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Sample records for multicenter randomized phase

  1. A phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis.

    PubMed

    McCarty, Nael A; Standaert, Thomas A; Teresi, Mary; Tuthill, Cynthia; Launspach, Janice; Kelley, Thomas J; Milgram, Laura J H; Hilliard, Kathleen A; Regelmann, Warren E; Weatherly, Mark R; Aitken, Moira L; Konstan, Michael W; Ahrens, Richard C

    2002-02-01

    CPX (8-cyclopentyl-1,3-dipropylxanthine) is a novel compound currently under development as a potential treatment for cystic fibrosis (CF). The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells. This phase I multicenter, single-dose, placebo-controlled trial was performed at four institutions. Thirty-seven subjects homozygous for the Delta F(508) allele were studied in an escalating dose protocol of seven single-dose cohorts (1, 3, 10, 30, 100, 300, and 1,000 mg) to evaluate the safety, pharmacokinetics, and efficacy of CPX. Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1, 2, and 4 hr postdose. The incidence of adverse events in the treatment group was similar to that with placebo, indicating safety of the single doses studied. One serious adverse event (an acute pulmonary exacerbation) occurred 13 days after dosing, and was not considered related to the study drug. The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose, but was highly variable throughout the dose range studied, suggesting inconsistent absorption. There was no apparent effect of single-dose administration on either nasal transepithelial potential difference or sweat chloride measurements. The positive safety and pharmacokinetic findings of this study support continued development of CPX as a potential therapeutic for CF. PMID:11802244

  2. Comparison of Iohexol-380 and Iohexol-350 for Coronary CT Angiography: A Multicenter, Randomized, Double-Blind Phase 3 Trial

    PubMed Central

    Park, Eun-Ah; Kang, Doo Kyoung; Kim, Sung Jin; Kim, Young-Ju; Kim, Yookyung; Sung, Yon Mi; Song, Soon-Young; Oh, Yu-Whan; Yong, Hwan Seok; Lee, Heon; Jeon, Eui-Yong; Jin, Gong-Yong; Choi, Byoung Wook; Choi, Sang-Il

    2016-01-01

    Objective This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Materials and Methods Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. Results A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Conclusion Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine. PMID:27134522

  3. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

    PubMed

    Scheller, Christian; Wienke, Andreas; Tatagiba, Marcos; Gharabaghi, Alireza; Ramina, Kristofer F; Ganslandt, Oliver; Bischoff, Barbara; Zenk, Johannes; Engelhorn, Tobias; Matthies, Cordula; Westermaier, Thomas; Antoniadis, Gregor; Pedro, Maria Teresa; Rohde, Veit; von Eckardstein, Kajetan; Kretschmer, Thomas; Kornhuber, Malte; Steighardt, Jörg; Richter, Michael; Barker, Fred G; Strauss, Christian

    2016-03-01

    OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the

  4. 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

  5. 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

  6. 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 Central

    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. PMID:25875868

  7. 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. PMID:25875868

  8. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    PubMed Central

    2013-01-01

    Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain. PMID:23414938

  9. 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. PMID:25547219

  10. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma

    PubMed Central

    Brown, Nicholas; McBain, Catherine; Nash, Stephen; Hopkins, Kirsten; Sanghera, Paul; Saran, Frank; Phillips, Mark; Dungey, Fiona; Clifton-Hadley, Laura; Wanek, Katharina; Krell, Daniel; Jeffries, Sarah; Khan, Iftekhar; Smith, Paul; Mulholland, Paul

    2016-01-01

    Background Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. Methods and Findings This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Conclusions Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. Trial Registration ClinicalTrials.gov NCT01310855 PMID:27232884

  11. 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

  12. 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

  13. 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

  14. A Randomized, Double Blind, Placebo-Controlled, Multicenter Phase II Trial of Allisartan Isoproxil in Essential Hypertensive Population at Low-Medium Risk

    PubMed Central

    Li, Ying; Li, Xiao-hui; Huang, Zhi-jun; Yang, Guo-ping; Zhang, Guo-gang; Zhao, Shui-ping; Guo, Ying; Lu, Shi-juan; Ma, Jian-lin; Meng, Fan-bo; Chen, Ping; Yuan, Hong

    2015-01-01

    Background Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk. Methods and Findings A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study. Conclusions/Significance Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. Trial Registration http

  15. 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

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

    PubMed

    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

  17. 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

  18. 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

  19. Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer

    PubMed Central

    Vergote, Ignace B.; Garcia, Agustin; Micha, John; Pippitt, Charles; Bendell, Johanna; Spitz, Daniel; Reed, Nicholas; Dark, Graham; Fracasso, Paula M.; Ibrahim, Emad N.; Armenio, Vincent A.; Duska, Linda; Poole, Chris; Gennigens, Christine; Dirix, Luc Y.; Leung, Abraham C.F.; Zhao, Carol; Soufi-Mahjoubi, Raoudha; Rustin, Gordon

    2013-01-01

    Purpose Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. Patients and Methods A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m2 every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS). Results The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days. Conclusion Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m2 once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum

  20. Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy

    PubMed Central

    2013-01-01

    Background Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy. Methods Patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1. Results Cycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (λ = −0.218 [95% confidence interval: –0.498%, 0.062%], p = 0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively. Conclusion This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Trial Registration Eudra EEACTA200901599910 The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees

  1. A Phase III, Randomized, Multi-Center, Double-Masked, Matched-Pairs, Active-Controlled Trial to Compare the Efficacy and Safety between Neuramis Deep and Restylane in the Correction of Nasolabial Folds

    PubMed Central

    Pak, Changsik; Park, Jihoon; Hong, Jinmyung; Jeong, Jaehoon; Bang, Saik

    2015-01-01

    Background We conducted this clinical study to compare the efficacy and safety between Neuramis Deep and Restylane in the correction of nasolabial folds. Methods In this phase III, randomized, multi-center, double-masked, matched-pairs, active-controlled trial (ClinicalTrials.gov Identifier: NCT01585220), we evaluated a total of 67 subjects (n=67). All the subjects underwent Neuramis Deep treatment on one side and Restylane on the contralateral side of the bilateral nasolabial folds at a ratio of 1:1. To compare the efficacy of Neuramis Deep and Restylane, we evaluated the Wrinkle Severity Rating Scale scores and those of the Global Aesthetic Improvement Scale. In addition, we compared the safety of Neuramis Deep and Restylane based on adverse events, physical examination, and clinical laboratory tests. Results Neuramis Deep was not inferior in improving the nasolabial folds as compared with Restylane. In addition, there was no significant difference in the efficacy between Neuramis Deep and Restylane. There were no significant differences in safety parameters between Neuramis Deep and Restylane. Conclusions In conclusion, our results indicate that Neuramis Deep may be a safe, effective material for improving the nasolabial folds. However, further studies are warranted to compare the tolerability of Neuramis Deep and Restylane based on histopathologic findings. PMID:26618119

  2. 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

  3. Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments

    PubMed Central

    Plomgaard, Anne M; Hagmann, Cornelia; Alderliesten, Thomas; Austin, Topun; van Bel, Frank; Claris, Olivier; Dempsey, Eugene; Franz, Axel; Fumagalli, Monica; Gluud, Christian; Greisen, Gorm; Hyttel-Sorensen, Simon; Lemmers, Petra; Pellicer, Adelina; Pichler, Gerhard; Benders, Manon

    2016-01-01

    Background: Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment. Methods: Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe. Results: Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively. Conclusion: There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials. PMID:26571218

  4. 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

  5. Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

    PubMed

    Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

    2016-03-01

    The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF).This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99).1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.). PMID:26945407

  6. LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

    PubMed Central

    2012-01-01

    Background 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory

  7. Impact of adjuvants on CD4(+) T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial.

    PubMed

    Leroux-Roels, Geert; Marchant, Arnaud; Levy, Jack; Van Damme, Pierre; Schwarz, Tino F; Horsmans, Yves; Jilg, Wolfgang; Kremsner, Peter G; Haelterman, Edwige; Clément, Frédéric; Gabor, Julian J; Esen, Meral; Hens, Annick; Carletti, Isabelle; Fissette, Laurence; Tavares Da Silva, Fernanda; Burny, Wivine; Janssens, Michel; Moris, Philippe; Didierlaurent, Arnaud M; Van Der Most, Robbert; Garçon, Nathalie; Van Belle, Pascale; Van Mechelen, Marcelle

    2016-08-01

    Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com. PMID:27236001

  8. Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    PubMed Central

    Kantarjian, Hagop M.; Thomas, Xavier G.; Dmoszynska, Anna; Wierzbowska, Agnieszka; Mazur, Grzegorz; Mayer, Jiri; Gau, Jyh-Pyng; Chou, Wen-Chien; Buckstein, Rena; Cermak, Jaroslav; Kuo, Ching-Yuan; Oriol, Albert; Ravandi, Farhad; Faderl, Stefan; Delaunay, Jacques; Lysák, Daniel; Minden, Mark; Arthur, Christopher

    2012-01-01

    Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). Conclusion In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis. PMID:22689805

  9. An International Randomized Multicenter Comparison of Nasal Potential Difference Techniques

    PubMed Central

    Solomon, George M.; Konstan, Michael W.; Wilschanski, Michael; Billings, Joanne; Sermet-Gaudelus, Isabelle; Accurso, Frank; Vermeulen, François; Levin, Elina; Hathorne, Heather; Reeves, Ginger; Sabbatini, Gina; Hill, Aubrey; Mayer-Hamblett, Nicole; Ashlock, Melissa; Clancy, John Paul

    2010-01-01

    Background: The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials. Methods: To determine whether a nonperfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at six different centers. Results: Artifact frequency was reduced by 75% (P < .001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, because Δ zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (224.2 ± 12.9 mV with agar vs 18.2 ± 9.1 mV with perfusion, P < .05). Conclusions: The agar nasal catheter approach demonstrates superior reliability compared with the perfusion nasal catheter method for measurement of NPD. This nonperfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials. PMID:20472865

  10. Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2.

    PubMed

    Mantovani, G; Gebbia, V; Airoldi, M; Bumma, C; Contu, P; Bianchi, A; Ghiani, M; Dessì, D; Massa, E; Curreli, L; Lampis, B; Lai, P; Mulas, C; Testa, A; Proto, E; Cadeddu, G; Tore, G

    1998-11-01

    We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m(-2) day(-1) 5-FU on days 1-5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8-12 and 15-19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients (20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients (13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus, there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were 2 toxic deaths (6.7%), 1 from hematological causes in group A and I from cardiac causes in group B. Myelosuppression and gastrointestinal toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable that a clinically significant difference between the two treatment groups will be observed even if the calculated patient sample size is achieved

  11. 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.

  12. Randomized, Double-Blind, Phase II, Multicenter Study Evaluating the Safety/Tolerability and Efficacy of JNJ-Q2, a Novel Fluoroquinolone, Compared with Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infection ▿ †

    PubMed Central

    Covington, Paul; Davenport, J. Michael; Andrae, David; O'Riordan, William; Liverman, Lisa; McIntyre, Gail; Almenoff, June

    2011-01-01

    JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature. PMID:21947389

  13. 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

  14. 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

  15. Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure

    PubMed Central

    Demetriou, Achilles A.; Brown, Robert S.; Busuttil, Ronald W.; Fair, Jeffrey; McGuire, Brendan M.; Rosenthal, Philip; Am Esch, Jan Schulte; Lerut, Jan; Nyberg, Scott L.; Salizzoni, Mauro; Fagan, Elizabeth A.; de Hemptinne, Bernard; Broelsch, Christoph E.; Muraca, Maurizio; Salmeron, Joan Manuel; Rabkin, John M.; Metselaar, Herold J.; Pratt, Daniel; De La Mata, Manuel; McChesney, Lawrence P.; Everson, Gregory T.; Lavin, Philip T.; Stevens, Anthony C.; Pitkin, Zorina; Solomon, Barry A.

    2004-01-01

    Objective: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure. PMID:15082970

  16. 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

  17. Open-Label, Phase II, Multicenter, Randomized Study of the Efficacy and Safety of Two Dose Levels of Pertuzumab, a Human Epidermal Growth Factor Receptor 2 Dimerization Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

    PubMed Central

    Gianni, Luca; Lladó, Anna; Bianchi, Giulia; Cortes, Javier; Kellokumpu-Lehtinen, Pirkko-Liisa; Cameron, David A.; Miles, David; Salvagni, Stefania; Wardley, Andrew; Goeminne, Jean-Charles; Hersberger, Veronica; Baselga, José

    2010-01-01

    Purpose Pertuzumab is a humanized monoclonal antibody inhibiting human epidermal growth factor receptor 2 (HER2) dimerization. The aim of this phase II trial was to assess the antitumor activity and safety profile of pertuzumab monotherapy in patients with HER2-negative metastatic breast cancer. The utility of biomarkers detected in paraffin-embedded tissue as predictors of response was also explored. Patients and Methods This was an international, multicenter, open-label, randomized phase II study. Patients (n = 79) with centrally confirmed HER2-negative metastatic breast cancer were randomly assigned to receive pertuzumab once every 3 weeks with a loading dose of 840 mg followed thereafter by either 420 mg (arm A) or 1,050 mg (arm B). Patients were stratified by country and prior taxane therapy. Results Of 79 patients who were randomly assigned, 78 were included in the intent-to-treat population. In arm A (n = 41), two patients had partial responses, and 18 patients (44%) experienced stable disease (SD) lasting ≥ 12 weeks. In arm B (n = 37), SD was observed in 14 patients (38%). Overall, six of 78 patients responded or had SD ≥ 6 months. Pertuzumab was generally well tolerated, and most adverse events were mild to moderate. Decline in left ventricular ejection fraction of ≥ 10% and/or to less than 50% was observed in eight patients, with one case of congestive heart failure in arm A. Pharmacokinetic data supported a fixed dose of pertuzumab once every 3 weeks. Conclusion The limited efficacy observed in this study, generally SD of relatively short duration, suggested little benefit of further investigation of single-agent pertuzumab in unselected patients with HER2-negative disease. PMID:20124183

  18. 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

  19. 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

  20. 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

  1. [Education programs on atopic eczema. Design and first results of the German Randomized Intervention Multicenter Study].

    PubMed

    Diepgen, T L; Fartasch, M; Ring, J; Scheewe, S; Staab, D; Szcepanski, R; Werfel, T; Wahn, U; Gieler, U

    2003-10-01

    Atopic eczema (AE) is a common, chronically relapsing, inflammatory skin disease with an early onset during infancy associated with a high loss of quality of life and socioeconomic burden. In the past few years, an Atopic Eczema Prevention Program was established to improve disease management and the quality of life of patients with atopic eczema. In Germany, the Task Force on Education Programs for Atopic Eczema (AGNES = Arbeitsgemeinschaft Neurodermitis Schulung) for children, youths, and parents was founded as well as the Task Force on Dermatological Prevention (ADP) for adults. These groups ensure structure and process quality of the prevention programs and organize train-the-trainer workshops. In a randomized prospective controlled trial (the German Randomized Intervention Multicenter Study = GRIMS), we are currently comparing the effectiveness of an atopic eczema group intervention program in (1) parents of atopic eczema children aged 0-7 years, (2) parents and children 7-12 years old, and (3) youths with AE aged between 13 and 18 years. The groups were randomized and compared with a waiting control group. The design and first results will be reported. PMID:14513241

  2. Daily Sodium Butyrate Enema for the Prevention of Radiation Proctitis in Prostate Cancer Patients Undergoing Radical Radiation Therapy: Results of a Multicenter Randomized Placebo-Controlled Dose-Finding Phase 2 Study

    SciTech Connect

    Maggio, Angelo; Magli, Alessandro; Rancati, Tiziana; Fiorino, Claudio; Valvo, Francesca; Fellin, Giovanni; Ricardi, Umberto; Munoz, Fernando; Cosentino, Dorian; Cazzaniga, Luigi Franco; Valdagni, Riccardo; Vavassori, Vittorio

    2014-07-01

    Purpose: To evaluate the efficacy of sodium butyrate enemas (NABUREN) in prostate cancer radiation therapy (RT) in reducing the incidence, severity, and duration of acute RT-induced proctitis. Methods and Materials: 166 patients, randomly allocated to 1 of 4 groups (rectal sodium butyrate 1 g, 2 g, or 4 g daily or placebo), were treated with NABUREN during and 2 weeks after RT. The grade of proctitis was registered in a daily diary. The correlation between NABUREN and proctitis was investigated through χ{sup 2} statistics. The toxicity endpoints considered were as follows: total number of days with grade ≥1 proctitis (≥G1); total number of days with grade ≥2 proctitis (≥G2); ≥G1 and ≥G2 proctitis lasting at least 3 and 5 consecutive days starting from week 4 (≥G1+3d, ≥G2+3d); damaging effects of RT on rectal mucosa as measured by endoscopy. The relationship between endpoints and pretreatment morbidities, hormonal therapy, presence of diabetes or hypertension, abdominal surgery, or hemorrhoids was investigated by univariate analysis. Results: The patients were randomly allocated to the 4 arms. No difference in the distribution of comorbidities among the arms was observed (P>.09). The mean ≥G1 and ≥G2 proctitis were 7.8 and 4.9 for placebo and 8.9 and 4.7 for the NABUREN group, respectively. No favorable trend in reduction of incidence, severity, and duration of ≥G1 and ≥G2 proctitis was observed with NABUREN use. In univariate analysis, ≥G1+3d toxicity was found to be related to hemorrhoids (P=.008), and a slight correlation was found between ≥G2 proctitis and hormonal therapy (P=.06). The RT effects on rectal mucosa as based on endoscopic assessment were mainly related to diabetes (P<.01). Endoscopy data at 6 week showed no significant difference between the placebo and butyrate arms. The other investigated endpoints were not correlated with any of the clinical risk factors analyzed. Conclusion: There was no evidence of efficacy

  3. Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial.

    PubMed

    Wendtner, Clemens M; Hallek, Michael; Fraser, Graeme A M; Michallet, Anne-Sophie; Hillmen, Peter; Dürig, Jan; Kalaycio, Matt; Gribben, John G; Stilgenbauer, Stephan; Buhler, Andreas; Kipps, Thomas J; Purse, Brendan; Zhang, Jennie; De Bedout, Sabine; Mei, Jay; Chanan-Khan, Asher

    2016-06-01

    The objective of this study was to evaluate the safety and efficacy of different lenalidomide starting doses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). CLL patients were randomized to receive lenalidomide at initial doses of 5, 10, or 15 mg/d (N = 103). Doses were escalated by 5 mg every 28-d up to a maximum of 25 mg/d; dose reductions in up to 5 mg decrements were permitted. The most common grade ≥3 adverse events (AEs) were neutropenia and thrombocytopenia. Ten patients died during therapy (four deaths considered as related to lenalidomide); 12 patients experienced second primary malignancies. The most common cause for treatment discontinuation was AEs. Overall response rates were similar across arms. Progression-free survival and overall survival rates were longer in patients who escalated treatment (to 15 or 20 mg/d) versus those who did not. Lower starting doses allowed subsequent dose escalation of lenalidomide while maintaining an acceptable tolerability profile in patients with relapsed/refractory CLL. PMID:26763349

  4. Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial.

    PubMed

    Huang, Liang; Chen, Sheng; Yang, Wentao; Xu, Binghe; Huang, Tao; Yang, Hongjian; Zheng, Hong; Wang, Yongsheng; Song, Erwei; Zhang, Jin; Cui, Shude; Pang, Da; Tang, Lili; Lei, Yutao; Geng, Cuizhi; Shao, Zhiming

    2015-07-30

    This trial was designed to compare the efficacy and safety between epirubicin (E) and carboplatin (C) in combination with paclitaxel (P) and trastuzumab (H) in neoadjuvant setting. In 13 Chinese cancer centers, 100 patients with HER2-positive, locally advanced breast cancer were 1:1 randomized to receive medication as follows: trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group, or epirubicin every 3 weeks for PEH group. Patients were given 4 to 6 cycles of chemotherapy. The primary endpoint was pathologic complete response (pCR) rate, which was no significant difference in PCH and PEH regimen (39.1% vs. 48.8%; p=0.365). However, PEH regimen achieved higher pCR in luminal-B (HER2-poitive) subgroup (55.0% vs. 24.0%; p = 0.033), but not in ERBB2+ subgroup (42.9% vs. 57.1%; p = 0.355). PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup (69.2% vs.23.5%, p=0.012). No significant difference was observed in the subgroup analysis of TP53 mutation status, PTEN expression, FCGR2A SNP and FCGR3A SNP. Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety. PEH might improve pCR rate, especially in the luminal-B subtype and PIK3CA mutation subtype. PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH. PMID:26084292

  5. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study

    PubMed Central

    Vici, P.; Brandi, M.; Giotta, F.; Foggi, P.; Schittulli, F.; Di Lauro, L.; Gebbia, N.; Massidda, B.; Filippelli, G.; Giannarelli, D.; Di Benedetto, A.; Mottolese, M.; Colucci, G.; Lopez, M.

    2012-01-01

    Background: The Gruppo Oncologico Italia Meridionale 9902 trial compared four cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of node-positive breast cancer. Patients and methods: Patients were randomly assigned to EC (E 120 mg/m2, C 600 mg/m2, arm A) for four cycles or four cycles of D (100 mg/m2) followed by four cycles of EC (arm B), both regimens every 21 days. Hormone receptor-positive patients were given hormonal therapy for 5 years. Primary end point was 5-year disease-free survival (DFS). Secondary objectives were overall survival (OS) and safety. Results: There were 750 patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was 0.99 (95% confidence interval for DFS 0.75–1.31; P = 0.95)], respectively. Grade 3–4 toxicity was more common in arm B. Conclusions: This study did not show advantages from the addition of docetaxel to high-dose EC as adjuvant chemotherapy in node-positive breast cancer. The small sample size and low number of DFS events may have limited the ability to observe statistically significant difference between the two arms. PMID:21965475

  6. China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

    PubMed Central

    Gao, Peng; Zhao, Zhenwei; Wang, Daming; Wu, Jian; Cai, Yiling; Li, Tianxiao; Wu, Wei; Shi, Huaizhang; He, Weiwen; Zhu, Fengshui; Ling, Feng

    2015-01-01

    Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The

  7. Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Patients With Biomarker-Selected Non–Small-Cell Lung Cancer

    PubMed Central

    Edelman, Martin J.; Tan, Ming T.; Fidler, Mary J.; Sanborn, Rachel E.; Otterson, Greg; Sequist, Lecia V.; Evans, Tracey L.; Schneider, Bryan J.; Keresztes, Roger; Rogers, John S.; de Mayolo, Jorge Antunez; Feliciano, Josephine; Yang, Yang; Medeiros, Michelle; Zaknoen, Sara L.

    2015-01-01

    Purpose Overexpression of COX-2 correlates with advanced stage and worse outcomes in non–small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2–dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. Patients and Methods Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m2 or pemetrexed 500 mg/m2 once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. Results In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). Conclusion Apricoxib did not improve PFS, despite biomarker-driven patient selection. PMID:25452446

  8. Final Report of Multicenter Canadian Phase III Randomized Trial of 3 Versus 8 Months of Neoadjuvant Androgen Deprivation Therapy Before Conventional-Dose Radiotherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Crook, Juanita Ludgate, Charles; Malone, Shawn; Perry, Gad; Eapen, Libni; Bowen, Julie; Robertson, Susan; Lockwood, Gina M.Math.

    2009-02-01

    Purpose: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. Methods and Materials: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. Results: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). Conclusion: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

  9. Evaluation of Immunogenicity and Safety of the New Tetanus-Reduced Diphtheria (Td) Vaccines (GC1107) in Healthy Korean Adolescents: A Phase II, Double-Blind, Randomized, Multicenter Clinical Trial

    PubMed Central

    Rhim, Jung-Woo; Lee, Kyung-Yil; Kim, Sang-Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Kim, Hwang Min; Choi, Young-Youn; Ma, Sang-Hyuk; Kim, Dong-Ho; Ahn, Dong Ho

    2013-01-01

    This phase II clinical trial was conducted to compare the immunogenicity and safety of a newly developed tetanus-reduced diphtheria (Td) vaccine (GC1107-T5.0 and GC1107-T7.5) and control vaccine. This study was also performed to select the proper dose of tetanus toxoid in the new Td vaccines. Healthy adolescents aged between 11 and 12 yr participated in this study. A total of 130 subjects (44 GC1107-T5.0, 42 GC1107-T7.5 and 44 control vaccine) completed a single dose of vaccination. Blood samples were collected from the subjects before and 4 weeks after the vaccination. In this study, all subjects (100%) in both GC1107-T5.0 and GC1107-T7.5 groups showed seroprotective antibody levels (≥ 0.1 U/mL) against diphtheria or tetanus toxoids. After the vaccination, the geometric mean titer (GMT) against diphtheria was significantly higher in Group GC1107-T5.0 (6.53) and GC1107-T7.5 (6.11) than in the control group (3.96). The GMT against tetanus was 18.6 in Group GC1107-T5.0, 19.94 in GC1107-T7.5 and 19.01 in the control group after the vaccination. In this study, the rates of local adverse reactions were 67.3% and 59.1% in GC1107-T5.0 and GC1107-7.5, respectively. No significant differences in the number of adverse reactions, prevalence and degree of severity of the solicited and unsolicited adverse reactions were observed among the three groups. Thus, both newly developed Td vaccines appear to be safe and show good immunogenicity. GC1107-T5.0, which contains relatively small amounts of tetanus toxoid, has been selected for a phase III clinical trial. PMID:23579367

  10. Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies.

    PubMed

    Zhao, Wenle; Mu, Yunming; Tayama, Darren; Yeatts, Sharon D

    2015-03-01

    Large multicenter acute stroke trials demand a randomization procedure with a high level of treatment allocation randomness, an effective control on overall and within-site imbalances, and a minimized time delay of study treatment caused by the randomization procedure. Driven by the randomization algorithm design of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients with Mild Stroke (PRISMS) (NCT02072226), this paper compares operational and statistical properties of different randomization algorithms in local, central, and step-forward randomization settings. Results show that the step-forward randomization with block urn design provides better performances over others. If the concern on the potential time delay is not serious and a central randomization system is available, the minimization method with an imbalance control threshold and a biased coin probability could be a better choice. PMID:25638754

  11. 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.

  12. Medialization vs. Reinnervation for Unilateral Vocal Fold Paralysis: A Multicenter Randomized Clinical Trial

    PubMed Central

    Paniello, Randal C.; Edgar, Julia D.; Kallogjeri, Dorina; Piccirillo, Jay F.

    2011-01-01

    Purpose Vocal fold medialization laryngoplasty (ML) and laryngeal reinnervation (LR) as treatments for unilateral vocal fold paralysis (UVFP) were compared in a multicenter, prospective, randomized clinical trial. Methods Previously untreated patients with UVFP were randomized to undergo either ML or LR. Voice results were compared pre-treatment and at 6 and 12 months post-treatment using perceptual ratings by untrained listeners (RUL), blinded speech pathologist GRBAS scores, and voice-related quality of life (VRQOL) scores. Other secondary data included maximum phonation time (MPT), cepstral analysis, and EMG findings. Results 24 patients from 9 sites completed the study, 12 in each group. There were no significant intergroup differences in pre-treatment variables. At 12 months, both study groups showed significant improvement in RUL, GRBAS and VRQOL scores, but no significant differences were found between the two groups. However, patient age significantly affected the LR, but not the ML, group results. The age<52 LR subgroup had significantly (p<0.05) better scores than the age>52 LR subgroup, and had better RUL and GRBAS scores than the age<52 ML subgroup. The age>52 ML subgroup results were significantly better than the age>52 LR subgroup. The secondary data generally followed the primary data, except that the MPTs for the ML patients were significantly longer than for the LR patients. Conclusion ML and LR are both effective surgical options for patients with UVFP. Laryngeal reinnervation should be considered in younger patients, while medialization laryngoplasty should be favored in older patients. PMID:21898419

  13. 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

    2016-01-01

    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. 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

  15. Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial

    PubMed Central

    2014-01-01

    Background Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. Methods/Design In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. Discussion This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Trial registration Chinese Clinical Trial Registry ChiCTR-TRC-12001971. PMID:24908241

  16. 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. PMID:16279258

  17. Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial

    PubMed Central

    Gonçalves-Ferri, W.A.; Martinez, F.E.; Caldas, J.P.S.; Marba, S.T.M.; Fekete, S.; Rugolo, L.; Tanuri, C.; Leone, C.; Sancho, G.A.; Almeida, M.F.B.; Guinsburg, R.

    2014-01-01

    This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min. PMID:24554040

  18. 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

  19. Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial

    PubMed Central

    2013-01-01

    Background More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. Methods/design In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. Discussion A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. Trial registration The trial was registered in Chinese Clinical Trial

  20. 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. PMID:24251724

  1. Biapenem versus meropenem in the treatment of bacterial infections: a multicenter, randomized, controlled clinical trial

    PubMed Central

    Wang, Xiaohui; Zhang, Xiaoke; Zong, Zhiyong; Yu, Rujia; Lv, Xiaoju; Xin, Jianbao; Tong, Chaohui; Hao, Qinglin; Qin, Zhiqiang; Xiong, Ying; Liu, Hong; Ding, Guohua; Hu, Chengping

    2013-01-01

    Background & objectives: Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China. Methods: Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed. Results: A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%). Interpretation & conclusions: Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs. PMID:24521647

  2. 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

  3. 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

  4. 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

  5. Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial

    PubMed Central

    Stephenson, Mary D.; Kutteh, William H.; Purkiss, Susan; Librach, Cliff; Schultz, Patricia; Houlihan, Edwina; Liao, Chuanhong

    2010-01-01

    BACKGROUND Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed. METHODS We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14–21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18–20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation. RESULTS A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41–4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06–18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59–3.48). CONCLUSIONS This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study

  6. 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

  7. Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial

    PubMed Central

    Burks, A. Wesley; Wood, Robert A.; Jones, Stacie M.; Sicherer, Scott H.; Fleischer, David M.; Scurlock, Amy M.; Vickery, Brian P.; Liu, Andrew H.; Henning, Alice K.; Lindblad, Robert; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A.

    2015-01-01

    Background We previously reported initial results of the first multi-center randomized, double blind, placebo controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year. Objective To provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key endpoints: (1) percentage of responders at 2 years (could consume 5g of peanut powder or a 10-fold increase from baseline), 2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic endpoints and (5) assessment of safety parameters. Methods Response to treatment was evaluated in 40 subjects aged 12-40 years by performing a 10g peanut powder oral food challenge (OFC) following 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks followed by another 10g OFC, and an open feeding of peanut butter to assess sustained unresponsiveness. Results Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study end, 4/37 (10.8%) of SLIT treated participants were fully desensitized to 10g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared to non-responders. Conclusions Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness. PMID:25656999

  8. Randomized Grain Boundary Liquid Crystal Phase

    NASA Astrophysics Data System (ADS)

    Chen, D.; Wang, H.; Li, M.; Glaser, M.; Maclennan, J.; Clark, N.

    2012-02-01

    The formation of macroscopic, chiral domains, in the B4 and dark conglomerate phases, for example, is a feature of bent-core liquid crystals resulting from the interplay of chirality, molecular bend and molecular tilt. We report a new, chiral phase observed in a hockey stick-like liquid crystal molecule. This phase appears below a smectic A phase and cools to a crystal phase. TEM images of the free surface of the chiral phase show hundreds of randomly oriented smectic blocks several hundred nanometers in size, similar to those seen in the twist grain boundary (TGB) phase. However, in contrast to the TGB phase, these blocks are randomly oriented. The characteristic defects in this phase are revealed by freeze-fracture TEM images. We will show how these defects mediate the randomized orientation and discuss the intrinsic mechanism driving the formation of this phase. This work is supported by NSF MRSEC Grant DMR0820579 and NSF Grant DMR0606528.

  9. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial

    PubMed Central

    Rossignol, Daniel A; Rossignol, Lanier W; Smith, Scott; Schneider, Cindy; Logerquist, Sally; Usman, Anju; Neubrander, Jim; Madren, Eric M; Hintz, Gregg; Grushkin, Barry; Mumper, Elizabeth A

    2009-01-01

    Background Several uncontrolled studies of hyperbaric treatment in children with autism have reported clinical improvements; however, this treatment has not been evaluated to date with a controlled study. We performed a multicenter, randomized, double-blind, controlled trial to assess the efficacy of hyperbaric treatment in children with autism. Methods 62 children with autism recruited from 6 centers, ages 2–7 years (mean 4.92 ± 1.21), were randomly assigned to 40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere (atm) and 24% oxygen ("treatment group", n = 33) or slightly pressurized room air at 1.03 atm and 21% oxygen ("control group", n = 29). Outcome measures included Clinical Global Impression (CGI) scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC). Results After 40 sessions, mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0008), receptive language (p < 0.0001), social interaction (p = 0.0473), and eye contact (p = 0.0102); 9/30 children (30%) in the treatment group were rated as "very much improved" or "much improved" compared to 2/26 (8%) of controls (p = 0.0471); 24/30 (80%) in the treatment group improved compared to 10/26 (38%) of controls (p = 0.0024). Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322). On the ABC, significant improvements were observed in the treatment group in total score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for each), but not in the control group. In the treatment group compared to the control group, mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability (p = 0.0311). On the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in the treatment group

  10. Phase transitions on random lattices: how random is topological disorder?

    PubMed

    Barghathi, Hatem; Vojta, Thomas

    2014-09-19

    We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω=(d-1)/(2d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d+1)ν>2 rather than the usual Harris criterion dν>2, making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d>1. These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. PMID:25279615

  11. High-fluoride toothpaste: a multicenter randomized controlled trial in adults

    PubMed Central

    Srinivasan, Murali; Schimmel, Martin; Riesen, Martine; Ilgner, Alexander; Wicht, Michael J; Warncke, Michael; Ellwood, Roger P; Nitschke, Ina; Müller, Frauke; Noack, Michael J

    2014-01-01

    Objective The aim of this single – blind, multicenter, parallel, randomized controlled trial was to evaluate the effectiveness of the application of a high-fluoride toothpaste on root caries in adults. Methods Adult patients (n = 130, ♂ = 74, ♀ = 56; mean age ± SD: 56.9 ± 12.9) from three participating centers, diagnosed with root caries, were randomly allocated into two groups: Test (n = 64, ♂ = 37, ♀ = 27; lesions = 144; mean age: 59.0 ± 12.1; intervention: high-fluoride toothpaste with 5000 ppm F), and Control (n = 66, ♂ = 37, ♀ = 29; lesions = 160; mean age: 54.8 ± 13.5; intervention: regular-fluoride toothpaste with 1350 ppm F) groups. Clinical examinations and surface hardness scoring of the carious lesions were performed for each subject at specified time intervals (T0 – at baseline before intervention, T1 – at 3 months and T2 – at 6 months after intervention). Mean surface hardness scores (HS) were calculated for each patient. Statistical analyses comprised of two-way analysis of variance and post hoc comparisons using the Bonferroni–Dunn correction. Results At T0, there was no statistical difference between the two groups with regard to gender (P = 0.0682, unpaired t-test), or age (P = 0.9786, chi-squared test), and for the overall HS (Test group: HS = 3.4 ± 0.61; Control group: HS = 3.4 ± 0.66; P = 0.8757, unpaired t-test). The anova revealed significantly better HS for the test group than for the control groups (T1: Test group: HS = 2.9 ± 0.67; Control group: HS = 3.1 ± 0.75; T2: Test group: HS = 2.4 ± 0.81; Control group: HS = 2.8 ± 0.79; P < 0.0001). However, the interaction term time-point*group was not significant. Conclusions The application of a high-fluoride containing dentifrice (5000 ppm F) in adults, twice daily, significantly improves the surface hardness of otherwise untreated root caries lesions when compared with the use of regular fluoride

  12. Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial

    PubMed Central

    Gajdos, Vincent; Katsahian, Sandrine; Beydon, Nicole; Abadie, Véronique; de Pontual, Loïc; Larrar, Sophie; Epaud, Ralph; Chevallier, Bertrand; Bailleux, Sylvain; Mollet-Boudjemline, Alix; Bouyer, Jean; Chevret, Sylvie; Labrune, Philippe

    2010-01-01

    Background Acute bronchiolitis treatment in children and infants is largely supportive, but chest physiotherapy is routinely performed in some countries. In France, national guidelines recommend a specific type of physiotherapy combining the increased exhalation technique (IET) and assisted cough (AC). Our objective was to evaluate the efficacy of chest physiotherapy (IET + AC) in previously healthy infants hospitalized for a first episode of acute bronchiolitis. Methods and Findings We conducted a multicenter, randomized, outcome assessor-blind and parent-blind trial in seven French pediatric departments. We recruited 496 infants hospitalized for first-episode acute bronchiolitis between October 2004 and January 2008. Patients were randomly allocated to receive from physiotherapists three times a day, either IET + AC (intervention group, n = 246) or nasal suction (NS, control group, n = 250). Only physiotherapists were aware of the allocation group of the infant. The primary outcome was time to recovery, defined as 8 hours without oxygen supplementation associated with minimal or no chest recession, and ingesting more than two-thirds of daily food requirements. Secondary outcomes were intensive care unit admissions, artificial ventilation, antibiotic treatment, description of side effects during procedures, and parental perception of comfort. Statistical analysis was performed on an intent-to-treat basis. Median time to recovery was 2.31 days, (95% confidence interval [CI] 1.97–2.73) for the control group and 2.02 days (95% CI 1.96–2.34) for the intervention group, indicating no significant effect of physiotherapy (hazard ratio [HR]  = 1.09, 95% CI 0.91–1.31, p = 0.33). No treatment by age interaction was found (p = 0.97). Frequency of vomiting and transient respiratory destabilization was higher in the IET + AC group during the procedure (relative risk [RR]  = 10.2, 95% CI 1.3–78.8, p = 0.005 and RR  = 5.4, 95% CI 1.6–18

  13. Acupuncture for patients with mild hypertension: study protocol of an open-label multicenter randomized controlled trial

    PubMed Central

    2013-01-01

    Background Several studies using acupuncture to treat essential hypertension have been carried out. However, whether acupuncture is efficacious for hypertension is still controversial. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for patients with mild hypertension. Methods/Design This is a large scale, open-label, multicenter, randomized controlled clinical trial with four parallel arms. We will recruit 428 hypertensive patients with systolic blood pressure (SBP) between 140 and 159 mmHg, diastolic blood pressure (DBP) between 90 and 99 mmHg. The participants will be randomly assigned to four different groups (three acupuncture groups and one waiting list group) (1).The affected meridian acupuncture group (n = 107) is treated with acupoints on the affected meridians (2).The non-affected meridian acupuncture group (n = 107) is treated with acupoints on the non-affected meridians (3).The invasive sham acupuncture group (n = 107) is provided with sham acupoints treatment (4).The waiting-list group (n = 107) is not offered any intervention until they complete the trial. Each patient allocated to acupuncture groups will receive 18 sessions of acupuncture treatment over 6 weeks. This trial will be conducted in 11 hospitals in China. The primary endpoint is the change in average 24-hSBP before and 6 weeks after randomization. The secondary endpoints are average SBP and average DBP during the daytime and night-time, and 36-Item Short Form Survey (SF-36), and so on. Discussion This is the first large scale, multicenter, randomized, sham controlled trial of acupuncture for essential hypertension in China. It may clarify the efficacy of acupuncture as a treatment for mild hypertension. Trial registration Clinicaltrials.gov Identifier: NCT01701726 PMID:24216113

  14. Entanglement of phase-random states

    NASA Astrophysics Data System (ADS)

    Nakata, Yoshifumi; Turner, Peter; Murao, Mio

    2014-12-01

    In order to study generic properties of time-evolving states by time-independent Hamiltonian dynamics, we introduce phase-random states, an ensemble of pure states with fixed amplitudes and uniformly distributed phases in a fixed basis. We compute the average amount of entanglement of phase-random states analytically, and show that the average can be extremely large when the amplitudes are equal and the basis is separable. We also study implications on Hamiltonian dynamics, in particular the realization of the canonical state in a subsystem.

  15. Phase Transitions on Random Lattices: How Random is Topological Disorder?

    NASA Astrophysics Data System (ADS)

    Barghathi, Hatem; Vojta, Thomas

    2015-03-01

    We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω = (d - 1) / (2 d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d + 1) ν > 2 rather than the usual Harris criterion dν > 2 , making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d > 1 . These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.

  16. The effect of small class sizes on mortality through age 29 years: evidence from a multicenter randomized controlled trial.

    PubMed

    Muennig, Peter; Johnson, Gretchen; Wilde, Elizabeth Ty

    2011-06-15

    Limiting the number of students per classroom in the early years has been shown to improve educational outcomes. Improved education is, in turn, hypothesized to improve health. The authors examined whether smaller class sizes affect mortality through age 29 years and whether cognitive factors play a role. They used data from the Project Student Teacher Achievement Ratio, a 4-year multicenter randomized controlled trial of reduced class sizes in Tennessee involving 11,601 students between 1985 and 1989. Children randomized to small classes (13-17 students) experienced improved measures of cognition and academic performance relative to those assigned to regular classes (22-25 students). As expected, these cognitive measures were significantly inversely associated with mortality rates (P < 0.05). However, through age 29 years, students randomized to small class size nevertheless experienced higher mortality rates than those randomized to regular size classes (hazard ratio (HR) = 1.58, 95% confidence interval (CI): 1.07, 2.32). The groups at risk included males (HR = 1.73, 95% CI: 1.05, 2.85), whites/Asians (HR = 1.68, 95% CI: 1.04, 2.72), and higher income students (HR = 2.20, 95% CI: 1.06, 4.57). The authors speculate that small classes might produce behavior changes that increase mortality through young adulthood that are stronger than the protective effects of enhanced cognition. PMID:21540326

  17. 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

  18. Random-phase metasurfaces at optical wavelengths

    PubMed Central

    Pors, Anders; Ding, Fei; Chen, Yiting; Radko, Ilya P.; Bozhevolnyi, Sergey I.

    2016-01-01

    Random-phase metasurfaces, in which the constituents scatter light with random phases, have the property that an incident plane wave will diffusely scatter, hereby leading to a complex far-field response that is most suitably described by statistical means. In this work, we present and exemplify the statistical description of the far-field response, particularly highlighting how the response for polarised and unpolarised light might be alike or different depending on the correlation of scattering phases for two orthogonal polarisations. By utilizing gap plasmon-based metasurfaces, consisting of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light, with statistics obeying the theoretical predictions. We foresee the use of random-phase metasurfaces for camouflage applications and as high-quality reference structures in dark-field microscopy, while the control of the statistics for polarised and unpolarised light might find usage in security applications. Finally, by incorporating a certain correlation between scattering by neighbouring metasurface constituents new types of functionalities can be realised, such as a Lambertian reflector. PMID:27328635

  19. Random-phase metasurfaces at optical wavelengths.

    PubMed

    Pors, Anders; Ding, Fei; Chen, Yiting; Radko, Ilya P; Bozhevolnyi, Sergey I

    2016-01-01

    Random-phase metasurfaces, in which the constituents scatter light with random phases, have the property that an incident plane wave will diffusely scatter, hereby leading to a complex far-field response that is most suitably described by statistical means. In this work, we present and exemplify the statistical description of the far-field response, particularly highlighting how the response for polarised and unpolarised light might be alike or different depending on the correlation of scattering phases for two orthogonal polarisations. By utilizing gap plasmon-based metasurfaces, consisting of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light, with statistics obeying the theoretical predictions. We foresee the use of random-phase metasurfaces for camouflage applications and as high-quality reference structures in dark-field microscopy, while the control of the statistics for polarised and unpolarised light might find usage in security applications. Finally, by incorporating a certain correlation between scattering by neighbouring metasurface constituents new types of functionalities can be realised, such as a Lambertian reflector. PMID:27328635

  20. Random-phase metasurfaces at optical wavelengths

    NASA Astrophysics Data System (ADS)

    Pors, Anders; Ding, Fei; Chen, Yiting; Radko, Ilya P.; Bozhevolnyi, Sergey I.

    2016-06-01

    Random-phase metasurfaces, in which the constituents scatter light with random phases, have the property that an incident plane wave will diffusely scatter, hereby leading to a complex far-field response that is most suitably described by statistical means. In this work, we present and exemplify the statistical description of the far-field response, particularly highlighting how the response for polarised and unpolarised light might be alike or different depending on the correlation of scattering phases for two orthogonal polarisations. By utilizing gap plasmon-based metasurfaces, consisting of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light, with statistics obeying the theoretical predictions. We foresee the use of random-phase metasurfaces for camouflage applications and as high-quality reference structures in dark-field microscopy, while the control of the statistics for polarised and unpolarised light might find usage in security applications. Finally, by incorporating a certain correlation between scattering by neighbouring metasurface constituents new types of functionalities can be realised, such as a Lambertian reflector.

  1. Random fields at a nonequilibrium phase transition.

    PubMed

    Barghathi, Hatem; Vojta, Thomas

    2012-10-26

    We study nonequilibrium phase transitions in the presence of disorder that locally breaks the symmetry between two equivalent macroscopic states. In low-dimensional equilibrium systems, such random-field disorder is known to have dramatic effects: it prevents spontaneous symmetry breaking and completely destroys the phase transition. In contrast, we show that the phase transition of the one-dimensional generalized contact process persists in the presence of random-field disorder. The ultraslow dynamics in the symmetry-broken phase is described by a Sinai walk of the domain walls between two different absorbing states. We discuss the generality and limitations of our theory, and we illustrate our results by large-scale Monte Carlo simulations. PMID:23215170

  2. Fast phase randomization via two-folds

    PubMed Central

    Jeffrey, M. R.

    2016-01-01

    A two-fold is a singular point on the discontinuity surface of a piecewise-smooth vector field, at which the vector field is tangent to the discontinuity surface on both sides. If an orbit passes through an invisible two-fold (also known as a Teixeira singularity) before settling to regular periodic motion, then the phase of that motion cannot be determined from initial conditions, and, in the presence of small noise, the asymptotic phase of a large number of sample solutions is highly random. In this paper, we show how the probability distribution of the asymptotic phase depends on the global nonlinear dynamics. We also show how the phase of a smooth oscillator can be randomized by applying a simple discontinuous control law that generates an invisible two-fold. We propose that such a control law can be used to desynchronize a collection of oscillators, and that this manner of phase randomization is fast compared with existing methods (which use fixed points as phase singularities), because there is no slowing of the dynamics near a two-fold. PMID:27118901

  3. Davunetide for Progressive Supranuclear Palsy: a multicenter, randomized, double-blind, placebo controlled trial

    PubMed Central

    Boxer, Adam L.; Lang, Anthony E.; Grossman, Murray; Knopman, David S.; Miller, Bruce L.; Schneider, Lon S.; Doody, Rachelle S.; Lees, Andrew; Golbe, Lawrence I.; Williams, David R.; Corvol, Jean-Cristophe; Ludolph, Albert; Burn, David; Lorenzl, Stefan; Litvan, Irene; Roberson, Erik D.; Höglinger, Günter U.; Koestler, Mary; Jack, Clifford R.; Van Deerlin, Viviana; Randolph, Christopher; Lobach, Iryna V.; Heuer, Hilary W.; Gozes, Illana; Parker, Lesley; Whitaker, Steve; Hirman, Joe; Stewart, Alistair J.; Gold, Michael; Morimoto, Bruce H.

    2014-01-01

    Summary Background Davunetide (AL-108, NAP) is an eightamino acid peptide that promotes microtubule stability and decreases tau phosphorylation in pre-clinical studies. Since PSP is tightly linked to tau pathology, davunetide could be an effective treatment for PSP.The goals of this study were to evaluate the efficacy and safety of davunetide in PSP. Methods A phase 2/3 double-blind, parallel group, clinical trial of davunetide 30 mg or placebo (randomized 1:1) administered intranasally twice daily for 52 weeks was conducted at 48centers. Participants met modifiedNNIPPS criteria for possible or probable PSP. Co-primary endpointswere the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England ADL(SEADL) scale at up to 52 weeks. Data from all individuals who received at least one dose of medication and had a post-baseline efficacy assessment were compared using a rank-based method.Secondary outcomes included the Clinical Global Impression of Change (CGIC) and the change in regional brain volumeon MRI. Clinicaltrials.gov identifier: NCT01110720. Findings 360 participants were screened, 313 were randomized and 243 (77.6%) completed the study. There were no group differences in PSPRS (mean difference: 0.49 [95% CI: −1.5, 2.5], p = 0.72) or SEADL (1% [−2, 4%], p = 0.76) change from baseline (CFB) and mean 52 week CFB PSPRS scores were similar between the davunetide (11.3 [9.8,12.8]) and placebo groups (10.9 [9.1, 13.0]). There wereno differences in any of the secondary or exploratory endpoints. There were 11deaths in the davunetide group and tenin the placebo group. There were more nasal adverse events in the davunetide group. Interpretation Davunetide is well tolerated but is not an effective treatment for PSP. Clinical trials of disease modifying therapy are feasible in PSP and should be pursued with other promising tau-directed therapies. Funding Allon Therapeutics PMID:24873720

  4. Evolutionary Phase Transitions in Random Environments.

    PubMed

    Skanata, Antun; Kussell, Edo

    2016-07-15

    We present analytical results for long-term growth rates of structured populations in randomly fluctuating environments, which we apply to predict how cellular response networks evolve. We show that networks which respond rapidly to a stimulus will evolve phenotypic memory exclusively under random (i.e., nonperiodic) environments. We identify the evolutionary phase diagram for simple response networks, which we show can exhibit both continuous and discontinuous transitions. Our approach enables exact analysis of diverse evolutionary systems, from viral epidemics to emergence of drug resistance. PMID:27472146

  5. Evolutionary Phase Transitions in Random Environments

    NASA Astrophysics Data System (ADS)

    Skanata, Antun; Kussell, Edo

    2016-07-01

    We present analytical results for long-term growth rates of structured populations in randomly fluctuating environments, which we apply to predict how cellular response networks evolve. We show that networks which respond rapidly to a stimulus will evolve phenotypic memory exclusively under random (i.e., nonperiodic) environments. We identify the evolutionary phase diagram for simple response networks, which we show can exhibit both continuous and discontinuous transitions. Our approach enables exact analysis of diverse evolutionary systems, from viral epidemics to emergence of drug resistance.

  6. Efficacy of Rifaximin Compared with Ciprofloxacin for the Treatment of Acute Infectious Diarrhea: A Randomized Controlled Multicenter Study

    PubMed Central

    Hong, Kyoung Sup; Kim, You Sun; Han, Dong Soo; Choi, Chang Hwan; Jang, Byung-Ik; Park, Young-Sook; Lee, Kang-Moon; Lee, Soo Teik; Kim, Hyun-Soo

    2010-01-01

    Background/Aims Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. Methods We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. Results Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. Conclusions These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea. PMID:20981213

  7. Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial

    PubMed Central

    Pakdaman, Hossein; Harandi, Ali Amini; Hatamian, Hamidreza; Tabatabae, Mojgan; Delavar Kasmaei, Hosein; Ghassemi, Amirhossein; Gharagozli, Koroush; Ashrafi, Farzad; Emami Naeini, Pardis; Tavakolian, Mehrnaz; Shahin, Darush

    2015-01-01

    Background MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale – Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs. PMID:25873931

  8. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy

    PubMed Central

    Kawamura, Tetsuya; Yoshimura, Mitsuhiro; Miyazaki, Yoichi; Okamoto, Hidekazu; Kimura, Kenjiro; Hirano, Keita; Matsushima, Masato; Utsunomiya, Yasunori; Ogura, Makoto; Yokoo, Takashi; Okonogi, Hideo; Ishii, Takeo; Hamaguchi, Akihiko; Ueda, Hiroyuki; Furusu, Akira; Horikoshi, Satoshi; Suzuki, Yusuke; Shibata, Takanori; Yasuda, Takashi; Shirai, Sayuri; Imasawa, Toshiyuki; Kanozawa, Koichi; Wada, Akira; Yamaji, Izumi; Miura, Naoto; Imai, Hirokazu; Kasai, Kenji; Soma, Jun; Fujimoto, Shouichi; Matsuo, Seiichi; Tomino, Yasuhiko

    2014-01-01

    Background The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). Methods Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. Results During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. Conclusions The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified. PMID:24596084

  9. Topical Administration of a Connexin43-based peptide Augments Healing of Chronic Neuropathic Diabetic Foot Ulcers: A Multicenter, Randomized Trial

    PubMed Central

    Grek, Christina L.; Prasad, G.M.; Viswanathan, Vijay; Armstrong, David G.; Gourdie, Robert G.; Ghatnekar, Gautam S.

    2015-01-01

    Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signaling accelerates wound reepithelialization. In a prospective, randomized, multi-center clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C-terminus of Cx43, ACT1, in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care protocols. Adults with DFUs of at least four weeks duration were randomized to receive standard of care with or without topical application of ACT1. Primary outcome was mean percent ulcer reepithelialization and safety variables included incidence of treatment related adverse events and detection of ACT1 immunogenicity. ACT1 treatment was associated with a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks (72.1% vs. 57.1%; p = 0.03). Analysis of incidence and median time-to-complete-ulcer closure revealed that ACT1 treatment was associated with a greater percentage of participants that reached 100% ulcer reepitheliazation and a reduced median time-to-complete-ulcer closure. No adverse events reported were treatment related, and ACT1 was not immunogenic. Treatment protocols that incorporate ACT1 may present a therapeutic strategy that safely augments the reepithelialization of chronic DFUs. PMID:25703647

  10. Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial

    PubMed Central

    Zhang, Xinchao; Lin, Peihong; Wei, Jie; Cao, Yu; Pan, Shuming; Walline, Joseph; Qian, Chuanyun; Shan, Zhigang

    2016-01-01

    The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369. PMID:27446222

  11. Random phase textures: theory and synthesis.

    PubMed

    Galerne, Bruno; Gousseau, Yann; Morel, Jean-Michel

    2011-01-01

    This paper explores the mathematical and algorithmic properties of two sample-based texture models: random phase noise (RPN) and asymptotic discrete spot noise (ADSN). These models permit to synthesize random phase textures. They arguably derive from linearized versions of two early Julesz texture discrimination theories. The ensuing mathematical analysis shows that, contrarily to some statements in the literature, RPN and ADSN are different stochastic processes. Nevertheless, numerous experiments also suggest that the textures obtained by these algorithms from identical samples are perceptually similar. The relevance of this study is enhanced by three technical contributions providing solutions to obstacles that prevented the use of RPN or ADSN to emulate textures. First, RPN and ADSN algorithms are extended to color images. Second, a preprocessing is proposed to avoid artifacts due to the nonperiodicity of real-world texture samples. Finally, the method is extended to synthesize textures with arbitrary size from a given sample. PMID:20550995

  12. Faddeev random-phase approximation for molecules

    SciTech Connect

    Degroote, Matthias; Van Neck, Dimitri; Barbieri, Carlo

    2011-04-15

    The Faddeev random-phase approximation is a Green's function technique that makes use of Faddeev equations to couple the motion of a single electron to the two-particle-one-hole and two-hole-one-particle excitations. This method goes beyond the frequently used third-order algebraic diagrammatic construction method: all diagrams involving the exchange of phonons in the particle-hole and particle-particle channel are retained, but the phonons are now described at the level of the random-phase approximation, which includes ground-state correlations, rather than at the Tamm-Dancoff approximation level, where ground-state correlations are excluded. Previously applied to atoms, this paper presents results for small molecules at equilibrium geometry.

  13. 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

  14. Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa

    PubMed Central

    Lentz, S R; Ehrenforth, S; Abdul Karim, F; Matsushita, T; Weldingh, K N; Windyga, J; Mahlangu, J N; For the Adept™2 Investigators

    2014-01-01

    Background Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. Objectives To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. Patients and methods In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept™2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg−1) or rFVIIa (one to three doses at 90 μg kg−1). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. Results In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24–48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. Conclusions This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit–risk profile is unlikely to be achieved with vatreptacog alfa. PMID:24931322

  15. Frovatriptan vs. other triptans for the acute treatment of oral contraceptive-induced menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies.

    PubMed

    Allais, G; Tullo, V; Omboni, S; Pezzola, D; Zava, D; Benedetto, C; Bussone, G

    2013-05-01

    Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans. PMID:23695052

  16. Double random phase encoding using phase reservation and compression

    NASA Astrophysics Data System (ADS)

    Chen, Wen; Chen, Xudong

    2014-02-01

    In recent years, various studies have been conducted to illustrate the vulnerability of double random phase encoding (DRPE). In this paper, we propose a novel method via phase reservation and compression to enhance DRPE security. Only a compressed phase distribution is available in the CCD plane, and the amplitude component is not available or requested for optical decryption. Since only noise-like distributions can be obtained by using the correct security keys during optical decryption, a nonlinear correlation algorithm is further applied for authenticating the decrypted image. It is demonstrated that valid conditions for attack algorithms are broken and high security can be achieved for the DRPE system.

  17. A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

    PubMed Central

    Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

    2014-01-01

    Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

  18. A short-term, multicenter, placebo-controlled, randomized withdrawal study of a metabotropic glutamate 2/3 receptor agonist using an electronic patient-reported outcome device in patients with schizophrenia.

    PubMed

    Stauffer, Virginia L; Baygani, Simin K; Kinon, Bruce J; Krikke-Workel, Judith O

    2014-10-01

    This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

  19. Change in clinical indices following laser or scalpel treatment for periodontitis: A split-mouth, randomized, multi-center trial

    NASA Astrophysics Data System (ADS)

    Harris, David M.; Nicholson, Dawn M.; McCarthy, Delwin; Yukna, Raymond A.; Reynolds, Mark A.; Greenwell, Henry; Finley, James; McCawley, Thomas K.; Xenoudi, Pinelopi; Gregg, Robert H.

    2014-02-01

    Data are presented from a multi-center, prospective, longitudinal, clinical trial comparing four different treatments for periodontitis, (1) the LANAPTM protocol utilizing a FR pulsed-Nd:YAG laser; (2) flap surgery using the Modified Widman technique (MWF); (3) traditional scaling and root planing (SRP); and (4) coronal debridement (CD). Each treatment was randomized to a different quadrant. Fifty-one (54) subjects were recruited at five centers that included both private practice and university-based investigators. At 6-months and 12 months post-treatment the LANAPTM protocol and MWF yielded equivalent results based on changes in probing depths. The major difference observed between the two procedures was that patients reported significantly greater comfort following the LANAP™ procedure than following the MWF (P<0.001). There was greater reduction in bleeding in the LANAPTM quadrant than in the other three at both 6 and 12 months. Improvements following SRP were better than expected at 6 months and continued to improve, providing outcomes that were equivalent to both LANAPTM and MWF at 12 months. The improvement in the SRP quadrants suggests the hypothesis that an aspect of the LANAPTM protocol generated a significant, positive and unanticipated systemic (or trans-oral) effect on sub-gingival wound healing.

  20. Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspective from a Multicenter Randomized Controlled Trial: PROMISE.

    PubMed

    Bittner, Daniel O; Ferencik, Maros; Douglas, Pamela S; Hoffmann, Udo

    2016-05-01

    The PROMISE (Prospective multicenter imaging study for evaluation of chest pain) trial compared the effectiveness of coronary CT angiography and functional testing as initial diagnostic test for patients with suspicion for stable coronary artery disease (CAD). With 10,003 patients randomized at 193 sites, the PROMISE trial provides a snapshot of real-world care for this very common presentation. Over a median follow-up of 25 months, PROMISE did not find significant differences in major clinical events (composite endpoint 164 vs. 151, HR 1.04 (0.83-1.29); p = 0.75) between the two strategies. Other major findings were the large discrepancy between estimates of pre-test likelihood and observed prevalence for obstructive CAD (≥50 %) and the proportion of noninvasive tests positive for ischemia or obstructive CAD (53 vs. 11 %; respectively) and the better efficiency of coronary computed tomography angiography (CTA) to select patients for invasive coronary angiography (ICA) who had obstructive CAD (72 vs. 48 % for coronary CTA and functional testing, respectively). Radiation exposure was higher in the CT arm compared to all functional testing but lower than for nuclear perfusion stress testing. Improvement of patient selection for diagnostic testing and risk stratification will be keys to increase efficacy and efficiency of management of patients with suspicion for stable CAD. PMID:26995403

  1. EDUC’AVK: Reduction of Oral Anticoagulant-related Adverse Events After Patient Education: A Prospective Multicenter Open Randomized Study

    PubMed Central

    Labarère, José; Yver, Jacqueline; Satger, Bernadette; Allenet, Benoit; Berremili, Touffek; Fontaine, Michèle; Franco, Guy; Bosson, Jean Luc

    2008-01-01

    Background Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown. Objective To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications. Design/Participants We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events. Results During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 – 0.7,  < 0.01). Conclusions Patient education using an educational program reduced VKA-related adverse event rates. PMID:18566863

  2. Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C.

    PubMed

    Castro, A; Suárez, D; Inglada, L; Carballo, E; Domínguez, A; Diago, M; Such, J; Del Olmo, J A; Pérez-Mota, A; Pedreira, J; Quiroga, J A; Carreño, V

    1997-01-01

    The intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months has been evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. Transaminase levels were significantly reduced in IFN-beta-treated patients (p = 0.015) and were significantly lower with respect to those of the untreated controls (p = 0.040 at 6 months). Four treated (8%) and one untreated (2.5%) patients had normal transaminase values after 6 months. At study end (12 months), three quarters of the IFN-beta-treated patients had sustained transaminase normalization, whereas the untreated case had relapsed. Hepatitis C viremia was cleared in 6 (12%) treated patients but in none of the untreated controls (p = 0.058). Side effects of IFN-beta were infrequent (a mild flu-like syndrome in < 10%, asthenia in 16%, anorexia in 8%, headaches and weight loss in 8%, and hair loss in 4%). Leukocyte and platelet counts decreased during IFN-beta treatment, but no dose modifications were necessary. Such decreases were not statistically significant when compared with the levels in the untreated controls. Intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C. Because of IFN-beta tolerance, higher doses and alternate routes of injection might prove beneficial for the treatment of this disease. PMID:9041468

  3. Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

    PubMed Central

    FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

    2010-01-01

    Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

  4. Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double-blind and placebo-controlled withdrawal study.

    PubMed

    DiBianco, R; Shabetai, R; Silverman, B D; Leier, C V; Benotti, J R

    1984-11-01

    A placebo-controlled study was employed to evaluate the effects of oral amrinone in patients with congestive heart failure. After a baseline period of at least 4 weeks of standard treatment for refractory congestive heart failure, oral amrinone was added to the treatment regimen of 173 patients. Patients were predominantly male (89%), aged 24 to 76 years (mean 54), with ischemic (52%) or idiopathic (37%) dilated cardiomyopathy, in New York Heart Association functional class II (40%), III (59%) and IV (1%) and having a mean (+/- standard deviation) left ventricular ejection fraction of 25 +/- 15%. Phase 1: After the addition of amrinone (113 +/- 33 mg three times daily), 52 patients (30%) showed a maximal increase in treadmill exercise time exceeding 2 minutes (Naughton protocol), 72 (42%) had a lesser increase, 24 (14%) developed limiting adverse reactions, 20 (12%) died and 5 dropped out of the study. Fifty-two "responders" (30%) who were free of limiting side effects and had a greater than 2 minute increase in exercise time were randomized in double-blind fashion to continued amrinone or switched to placebo (each plus standard treatment) for an additional 12 weeks. Phase 2: Comparison of 31 of these 52 responders who continued to receive amrinone with the remaining 21 randomized to placebo revealed no significant differences in vital signs, indexes of left ventricular size and function, systolic time intervals or maximal exercise time. Continued follow-up study of patients receiving either amrinone or placebo revealed decreases in exercise times of 7 and 10%, respectively (both p less than 0.05 compared with before randomization). Episodes of worsened congestive heart failure severe enough to mandate termination of double-blind treatment were as frequent in patients taking placebo (4[18%] of 21) as in those taking amrinone (4[13%] of 31; p = NS). The average symptom score and functional class of each treatment group remained comparable. Adverse effects such as

  5. Cost-Effectiveness of a Biodegradable Compared to a Titanium Fixation System in Maxillofacial Surgery: A Multicenter Randomized Controlled Trial

    PubMed Central

    van Bakelen, N. B.; Vermeulen, K. M.; Buijs, G. J.; Jansma, J.; de Visscher, J. G. A. M.; Hoppenreijs, Th. J. M.; Bergsma, J. E.; Stegenga, B.; Bos, R. R. M.

    2015-01-01

    Background Biodegradable fixation systems could reduce/delete the problems associated with titanium plate removal. This means less surgical discomfort, and a reduction in costs. Aim The aim of the present study was to compare the cost-effectiveness between a biodegradable and a titanium system in Maxillofacial surgery. Materials and Methods This multicenter RCT was performed in the Netherlands from December 2006 to July 2009. Included were 230 patients who underwent a bilateral sagittal split osteotomy (BSSO), a Le Fort-I osteotomy, or a bi-maxillary osteotomy and those treated for fractures of the mandible, maxilla, or zygoma. The patients were randomly assigned to a titanium group (KLS Martin) or to a biodegradable group (Inion CPS). Costs were assessed from a societal perspective. Health outcomes in the incremental cost-effectiveness ratio (ICER) were bone healing (8 weeks) and plate removal (2 years). Results In 25 out of the 117 patients who were randomized to the biodegradable group, the maxillofacial surgeon made the decision to switch to the titanium system intra-operatively. This resulted in an Intention-To-Treat (ITT-)analysis and a Treatment-Received (TR-) analysis. Both analyses indicated that operations performed with titanium plates and screws had better health outcomes. In the TR-analysis the costs were lower in the biodegradable group, in the ITT-analysis costs were lower in the titanium group. Conclusion and Discussion The difference in costs between the ITT and the TR analyses can be explained by the intra-operative switches: In the TR-analysis the switches were analysed in the titanium group. In the ITT-analysis they were analysed in the biodegradable group. Considering the cost-effectiveness the titanium system is preferable to the biodegradable system in the regular treatment spectrum of mandibular, Le Fort-I, and zygomatic fractures, and BSSO’s, Le Fort-I osteotomies and bimaxillary osteotomies. Trial Registration Controlled

  6. Endoscopic outcomes of resorbable nasal packing after functional endoscopic sinus surgery: a multicenter prospective randomized controlled study.

    PubMed

    Berlucchi, Marco; Castelnuovo, Paolo; Vincenzi, Andrea; Morra, Bruno; Pasquini, Ernesto

    2009-06-01

    Nasal packings can aid in control of postoperative bleeding and healing following functional endoscopic sinus surgery (FESS), but traditional non-resorbable stents have several inherent drawbacks. We performed a randomized, controlled, multicenter clinical trial to assess efficacy of resorbable nasal packing in patients undergoing FESS for chronic rhinosinusitis. A total of 66 patients for 88 nasal cavities were randomized to receive either hyaluronan resorbable packing (MeroGel) or standard non-resorbable nasal dressing after FESS. All underwent preoperative rhinoscopy, CT of sinuses, and, after surgery, were reassessed by rhinoscopy at 2, 4, and 12 weeks in blinded fashion. A total of 44 nasal cavities (MeroGel-group) received resorbable packing, whereas the remaining 44 were packed with non-resorbable nasal dressing. At follow-up endoscopic visit, the presence of nasal synechia was evaluated as primary outcome. Moreover, the tolerability and surgical handling properties of MeroGel and its comfort were assessed by surgeons and patients. Preoperative severity of rhinosinusitis was similar in both groups. No significant adverse events were observed in all patients. Follow-up endoscopy showed a lower proportion of nasal adhesions in MeroGel-group at both 4 (P = 0.041) and 12 weeks (P < 0.001). Moreover, an improvement of other endoscopic nasal findings such as re-epithelialization, presence of granulation tissue, and appearance of nasal mucosa of nasal cavities after FESS was observed in the MeroGel-group. Tolerability and surgical handling properties of MeroGel were positively rated by clinicians and the overall patient judged comfort of MeroGel was favorable. In conclusion, MeroGel can be considered a valid alternative to standard non-resorbable nasal dressings. It is safe, well-accepted, well-tolerated, and has significant advantage of being resorbable. Moreover, it may favor improved healing in patients undergoing FESS and reduce formation of adhesions. PMID

  7. A randomized, controlled, multicenter contraceptive efficacy clinical trial of the intravas device, a nonocclusive surgical male sterilization

    PubMed Central

    Lu, Wen-Hong; Liang, Xiao-Wei; Gu, Yi-Qun; Wu, Wei-Xiong; Bo, Li-Wei; Zheng, Tian-Gui; Chen, Zhen-Wen

    2014-01-01

    Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device (IVD) implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy (NSV). IVDs were categorized into two types: IVD-B has a tail used for fixing to the vas deferens (fixed wing) whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A (n = 487), IVD-B (n = 485) or NSV (n = 487) groups and underwent operation. Follow-up included visits at the 3rd–6th and 12th postoperative months. The assessments of the subjects involved regular physical examinations (including general and andrological examinations) and semen analysis. The subjects’ partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests. There were no significant differences in pregnancy rates (0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV) among the three groups (P > 0.05). The cumulative rates of complications at the 12th postoperative month were zero, 0.9% and 1.7% in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method. PMID:24589454

  8. Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Furuya, Motohide; Horiguchi, Jun; Hashioka, Sadayuki; Thoyama, Masaya; Murotani, Kenta; Mori, Norio; Minabe, Yoshio; Iyo, Masaomi; Ueno, Shuichi; Ezoe, Sachiko; Hoshino, Syuzo; Seno, Haruo

    2015-01-01

    Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: −0.23 ± 0.08; placebo: −0.03 ± 0.08, P < 0.018), tension (TJ-54: −0.42 ± 0.09; placebo: −0.18 ± 0.09, P < 0.045), and poor impulse control (TJ-54: −0.39 ± 0.10; placebo: −0.07 ± 0.10, P < 0.037). Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores. PMID:25954314

  9. A multicenter randomized controlled trial evaluating the effect of small stitches on the incidence of incisional hernia in midline incisions

    PubMed Central

    2011-01-01

    Background The median laparotomy is frequently used by abdominal surgeons to gain rapid and wide access to the abdominal cavity with minimal damage to nerves, vascular structures and muscles of the abdominal wall. However, incisional hernia remains the most common complication after median laparotomy, with reported incidences varying between 2-20%. Recent clinical and experimental data showed a continuous suture technique with many small tissue bites in the aponeurosis only, is possibly more effective in the prevention of incisional hernia when compared to the common used large bite technique or mass closure. Methods/Design The STITCH trial is a double-blinded multicenter randomized controlled trial designed to compare a standardized large bite technique with a standardized small bites technique. The main objective is to compare both suture techniques for incidence of incisional hernia after one year. Secondary outcomes will include postoperative complications, direct costs, indirect costs and quality of life. A total of 576 patients will be randomized between a standardized small bites or large bites technique. At least 10 departments of general surgery and two departments of oncological gynaecology will participate in this trial. Both techniques have a standardized amount of stitches per cm wound length and suture length wound length ratio's are calculated in each patient. Follow up will be at 1 month for wound infection and 1 year for incisional hernia. Ultrasound examinations will be performed at both time points to measure the distance between the rectus muscles (at 3 points) and to objectify presence or absence of incisional hernia. Patients, investigators and radiologists will be blinded during follow up, although the surgeon can not be blinded during the surgical procedure. Conclusion The STITCH trial will provide level 1b evidence to support the preference for either a continuous suture technique with many small tissue bites in the aponeurosis only or for

  10. Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

    PubMed Central

    Alkemade, Hans A.C; Maessen-Visch, Birgitte; Hendriks, Jan C.M; van Erp, Piet E.J; Adang, Eddy M.M; Gerritsen, Marie-Jeanne P

    2016-01-01

    Background Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis. Objective To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care). Study design: Randomized controlled multicenter trial. Methods On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM-9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection. Results This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018. Conclusions In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness. Trial Registration Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2) PMID:27363577

  11. A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine.

    PubMed

    Bartolini, Marco; Giamberardino, Maria Adele; Lisotto, Carlo; Martelletti, Paolo; Moscato, Davide; Panascia, Biagio; Savi, Lidia; Pini, Luigi Alberto; Sances, Grazia; Santoro, Patrizia; Zanchin, Giorgio; Omboni, Stefano; Ferrari, Michel D; Brighina, Filippo; Fierro, Brigida

    2011-06-01

    The objective of this study was to evaluate patients' satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1-3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment. PMID:21437714

  12. Internet-delivered cognitive-behavioral treatment for adolescents with chronic pain and their parents: a randomized controlled multicenter trial.

    PubMed

    Palermo, Tonya M; Law, Emily F; Fales, Jessica; Bromberg, Maggie H; Jessen-Fiddick, Tricia; Tai, Gabrielle

    2016-01-01

    Internet-delivered interventions are emerging as a strategy to address barriers to care for individuals with chronic pain. This is the first large multicenter randomized controlled trial of Internet-delivered cognitive-behavioral therapy (CBT) for pediatric chronic pain. Participants included were 273 adolescents (205 females and 68 males), aged 11 to 17 years with mixed chronic pain conditions and their parents, who were randomly assigned in a parallel-group design to Internet-delivered CBT (n = 138) or Internet-delivered Education (n = 135). Assessments were completed before treatment, immediately after treatment, and at 6-month follow-up. All data collection and procedures took place online. The primary analysis used linear growth models. Results demonstrated significantly greater reduction on the primary outcome of activity limitations from baseline to 6-month follow-up for Internet CBT compared with Internet education (b = -1.13, P = 0.03). On secondary outcomes, significant beneficial effects of Internet CBT were found on sleep quality (b = 0.14, P = 0.04), on reducing parent miscarried helping (b = -2.66, P = 0.007) and protective behaviors (b = -0.19, P = 0.001), and on treatment satisfaction (P values < 0.05). On exploratory outcomes, benefits of Internet CBT were found for parent-perceived impact (ie, reductions in depression, anxiety, self-blame about their adolescent's pain, and improvement in parent behavioral responses to pain). In conclusion, our Internet-delivered CBT intervention produced a number of beneficial effects on adolescent and parent outcomes, and could ultimately lead to wide dissemination of evidence-based psychological pain treatment for youth and their families. PMID:26335910

  13. Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study

    PubMed Central

    Karpecki, Paul M.; Majmudar, Parag A.; Nichols, Kelly K.; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P.

    2016-01-01

    Purpose: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. Methods: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. Results: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Conclusions: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events. PMID:27055211

  14. Diagnostic accuracy of the Eurotest for dementia: a naturalistic, multicenter phase II study

    PubMed Central

    Carnero-Pardo, Cristobal; Gurpegui, Manuel; Sanchez-Cantalejo, Emilio; Frank, Ana; Mola, Santiago; Barquero, M Sagrario; Montoro-Rios, M Teresa

    2006-01-01

    Background Available screening tests for dementia are of limited usefulness because they are influenced by the patient's culture and educational level. The Eurotest, an instrument based on the knowledge and handling of money, was designed to overcome these limitations. The objective of this study was to evaluate the diagnostic accuracy of the Eurotest in identifying dementia in customary clinical practice. Methods A cross-sectional, multi-center, naturalistic phase II study was conducted. The Eurotest was administered to consecutive patients, older than 60 years, in general neurology clinics. The patients' condition was classified as dementia or no dementia according to DSM-IV diagnostic criteria. We calculated sensitivity (Sn), specificity (Sp) and area under the ROC curves (aROC) with 95% confidence intervals. The influence of social and educational factors on scores was evaluated with multiple linear regression analysis, and the influence of these factors on diagnostic accuracy was evaluated with logistic regression. Results Sixteen neurologists recruited a total of 516 participants: 101 with dementia, 380 without dementia, and 35 who were excluded. Of the 481 participants who took the Eurotest, 38.7% were totally or functionally illiterate and 45.5% had received no formal education. Mean time needed to administer the test was 8.2+/-2.0 minutes. The best cut-off point was 20/21, with Sn = 0.91 (0.84–0.96), Sp = 0.82 (0.77–0.85), and aROC = 0.93 (0.91–0.95). Neither the scores on the Eurotest nor its diagnostic accuracy were influenced by social or educational factors. Conclusion This naturalistic and pragmatic study shows that the Eurotest is a rapid, simple and useful screening instrument, which is free from educational influences, and has appropriate internal and external validity. PMID:16606455

  15. Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com).

    PubMed

    Hutchinson, P J; Corteen, E; Czosnyka, M; Mendelow, A D; Menon, D K; Mitchell, P; Murray, G; Pickard, J D; Rickels, E; Sahuquillo, J; Servadei, F; Teasdale, G M; Timofeev, I; Unterberg, A; Kirkpatrick, P J

    2006-01-01

    The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study. PMID:16671415

  16. Echocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome

    PubMed Central

    Selamet Tierney, Elif Seda; Levine, Jami C.; Chen, Shan; Bradley, Timothy J.; Pearson, Gail D.; Colan, Steven D.; Sleeper, Lynn A.; Campbell, M. Jay; Cohen, Meryl S.; Backer, Julie De; Guey, Lin T.; Heydarian, Haleh; Lai, Wyman W.; Lewin, Mark B.; Marcus, Edward; Mart, Christopher R.; Pignatelli, Ricardo H.; Printz, Beth F.; Sharkey, Angela M.; Shirali, Girish S.; Srivastava, Shubhika; Lacro, Ronald V.

    2013-01-01

    Background The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Methods Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area–adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmax Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Results Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R2 = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmax Z scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmax Z scores < 4.5. Conclusions The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility. PMID:23582510

  17. Adolescent depressive disorders and family based interventions in the family options multicenter evaluation: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background There is increasing community and government recognition of the magnitude and impact of adolescent depression. Family based interventions have significant potential to address known risk factors for adolescent depression and could be an effective way of engaging adolescents in treatment. The evidence for family based treatments of adolescent depression is not well developed. The objective of this clinical trial is to determine whether a family based intervention can reduce rates of unipolar depressive disorders in adolescents, improve family functioning and engage adolescents who are reluctant to access mental health services. Methods/Design The Family Options study will determine whether a manualized family based intervention designed to target both individual and family based factors in adolescent depression (BEST MOOD) will be more effective in reducing unipolar depressive disorders than an active (standard practice) control condition consisting of a parenting group using supportive techniques (PAST). The study is a multicenter effectiveness randomized controlled trial. Both interventions are delivered in group format over eight weekly sessions, of two hours per session. We will recruit 160 adolescents (12 to 18 years old) and their families, randomized equally to each treatment condition. Participants will be assessed at baseline, eight weeks and 20 weeks. Assessment of eligibility and primary outcome will be conducted using the KID-SCID structured clinical interview via adolescent and parent self-report. Assessments of family mental health, functioning and therapeutic processes will also be conducted. Data will be analyzed using Multilevel Mixed Modeling accounting for time x treatment effects and random effects for group and family characteristics. This trial is currently recruiting. Challenges in design and implementation to-date are discussed. These include diagnosis and differential diagnosis of mental disorders in the context of adolescent

  18. Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL)

    PubMed Central

    2014-01-01

    Background Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. Methods RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers. Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. Discussion To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also

  19. Comparison of novel lipid-based eye drops with aqueous eye drops for dry eye: a multicenter, randomized controlled trial

    PubMed Central

    Simmons, Peter A; Carlisle-Wilcox, Cindy; Vehige, Joseph G

    2015-01-01

    Background Dry eye may be caused or exacerbated by deficient lipid secretion. Recently, lipid-containing artificial tears have been developed to alleviate this deficiency. Our study compared the efficacy, safety, and acceptability of lipid-containing eye drops with that of aqueous eye drops. Methods A non-inferiority, randomized, parallel-group, investigator-masked multicenter trial was conducted. Subjects with signs and symptoms of dry eye were randomized to use one of two lipid-containing artificial tears, or one of two aqueous artificial tears. Subjects instilled assigned drops in each eye at least twice daily for 30 days. The primary efficacy analysis tested non-inferiority of a preservative-free lipid tear formulation (LT UD) to a preservative-free aqueous tear formulation (AqT UD) for change in Ocular Surface Disease Index (OSDI) score from baseline at day 30. Secondary measures included OSDI at day 7, tear break-up time (TBUT), corneal and conjunctival staining, Schirmer’s test, acceptability and usage questionnaires, and safety assessments. Results A total of 315 subjects were randomized and included in the analyses. Subjects reported instilling a median of three doses of study eye drops per day in all groups. At days 7 and 30, all groups showed statistically significant improvements from baseline in OSDI (P<0.001) and TBUT (P≤0.005). LT UD was non-inferior to AqT UD for mean change from baseline in OSDI score at day 30. No consistent or clinically relevant differences for the other efficacy variables were observed. Acceptability was generally similar across the groups and there was a low incidence of adverse events. Conclusion In this heterogeneous population of dry eye subjects, there were no clinically significant differences in safety, effectiveness, and acceptability between lipid-containing artificial tears and aqueous eye drops. The results suggest that lipid-containing artificial tears can be used to counteract lipid deficiency that is common in

  20. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

    PubMed Central

    2012-01-01

    Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813 PMID:22225733

  1. Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers

    PubMed Central

    Pratschke, Sebastian; Arnold, Hannah; Zollner, Alfred; Heise, Michael; Pascher, Andreas; Schemmer, Peter; Scherer, Marcus N.; Bauer, Andreas; Jauch, Karl-Walter; Werner, Jens; Guba, Markus; Angele, Martin K.

    2016-01-01

    Background Organ shortage results in the transplantation of extended donor criteria (EDC) livers which is associated with increased ischemia-reperfusion injury (IRI). Experimental studies indicate that an organ rinse with the calcineurin inhibitor tacrolimus before implantation protects against IRI. The tacrolimus organ perfusion study was initiated to examine the effects of ex vivo tacrolimus perfusion on IRI in transplantation of EDC livers. Methods A prospective randomized multicenter trial comparing ex vivo perfusion of marginal liver grafts (≥2 EDC according to Eurotransplant manual) with tacrolimus (20 ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out at 5 German liver transplant centers (Munich Ludwig-Maximilians University, Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013. Primary endpoint was the maximum alanine transaminase (ALT) level within 48 hours after transplantation. Secondary endpoints were aspartate transaminase (AST), prothrombine ratio, and graft-patient survival within an observation period of 1 week. After an interim analysis, the study was terminated by the scientific committee after the treatment of 24 patients (tacrolimus n = 11, Control n = 13). Results Tacrolimus rinse did not reduce postoperative ALT peaks compared with control (P = 0.207; tacrolimus: median, 812; range, 362-3403 vs control: median, 652; range, 147-2034). Moreover, ALT (P = 0.100), prothrombine ratio (P = 0.553), and bilirubin (P = 0.815) did not differ between the groups. AST was higher in patients treated with tacrolimus (P = 0.011). Survival was comparable in both groups (P > 0.05). Conclusions Contrary to experimental findings, tacrolimus rinse failed to improve the primary endpoint of the study (ALT). Because 1 secondary endpoint (AST) was even higher in the intervention group, the study was terminated prematurely. Thus, tacrolimus rinse cannot be recommended in transplantation of EDC livers. PMID:27500266

  2. Evaluation of performance of the Omni mode for detecting video capsule endoscopy images: A multicenter randomized controlled trial

    PubMed Central

    Hosoe, Naoki; Watanabe, Kenji; Miyazaki, Takako; Shimatani, Masaaki; Wakamatsu, Takahiro; Okazaki, Kazuichi; Esaki, Motohiro; Matsumoto, Takayuki; Abe, Takayuki; Kanai, Takanori; Ohtsuka, Kazuo; Watanabe, Mamoru; Ikeda, Keiichi; Tajiri, Hisao; Ohmiya, Naoki; Nakamura, Masanao; Goto, Hidemi; Tsujikawa, Tomoyuki; Ogata, Haruhiko

    2016-01-01

    Background and study aims: Olympus recently developed a new algorithm called Omni mode that discards redundant video capsule endoscopy (VCE) images. The current study aimed to demonstrate the non-inferiority of the Omni mode in terms of true positives (TPs) and the superiority of the Omni mode with regard to reading time against a control (ordinary ES-10 system). Patients and methods: This multicenter prospective study included 40 patients with various small bowel diseases. VCE images were evaluated by 7 readers and 3 judging committee members. Two randomly allocated readers assessed the VCE images obtained using the 2 modalities for each patient. The order of the modalities was switched between the 2 readers and the interval between readings by the same reader was 2 weeks. The judging committee predefined clinically relevant lesions as major lesions and irrelevant lesions as minor lesions. The number of TPs for major and minor lesions and the reading times were compared between the modalities. The predefined non-inferiority margin for the TP ratio of the Omni mode compared with the control was 0.9. Results: The estimated TP ratios and 95 % confidence intervals for total, major, and minor lesions were 0.87 (0.80 – 0.95), 0.93 (0.83 – 1.04), and 0.83 (0.74 – 0.94), respectively. Although non-inferiority was not demonstrated, the rate of detection of major lesions was not significantly different between the modalities. The reading time was significantly lower when using the Omni mode than when using the control. Conclusions: The Omni mode may be only appropriate for the assessment of major lesions. PMID:27540577

  3. Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: a Multi-Center, Randomized, Controlled Study

    PubMed Central

    Talley, Nicholas J.; Locke, G. Richard; Saito, Yuri A.; Almazar, Ann E.; Bouras, Ernest P.; Howden, Colin W.; Lacy, Brian E.; DiBaise, John K.; Prather, Charlene M.; Abraham, Bincy P.; El-Serag, Hashem B.; Moayyedi, Paul; Herrick, Linda M.; Szarka, Lawrence A.; Camilleri, Michael; Hamilton, Frank A.; Schleck, Cathy D.; Tilkes, Katherine E.; Zinsmeister, Alan R.

    2015-01-01

    Background & Aims Anti-depressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or post-prandial fullness. However, there is little evidence for the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of anti-depressant therapy effects on symptoms, gastric emptying (GE), and mealinduced satiety in patients with FD. Methods We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use anti-depressants. Subjects (n=292; 44±15 y old, 75% female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary endpoint was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (out of 12). Secondary endpoints included GE time, maximum tolerated volume in a nutrient drink test, and FD-related quality of life. Results An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P=.05, following treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were more than 3-fold more likely to report adequate relief than those given placebo (odds ratio=3.1; 95% confidence interval, 1.1–9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10 week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio=0.4; 95% confidence interval, 0.2–0.8). Both anti-depressants improved overall quality-of-life. Conclusions Amitriptyline, but not escitalopram, appears to benefit some patients with FD— particularly those with ulcer-like (painful) FD. Patients

  4. 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

  5. Acute heart failure volume control multicenter randomized (AVCMA) trial: Comparison of tolvaptan and carperitide

    PubMed Central

    Suzuki, Satoshi; Yoshihisa, Akiomi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Abe, Yukihiko; Saito, Tomiyoshi; Ohwada, Takayuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Kubota, Isao; Takeishi, Yasuchika

    2013-01-01

    Backgroud Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide. Methods and Results One hundred and nine hospitalized ADHF patients were enrolled and randomly assigned to tolvaptan or carperitide treatment groups. Subjective symptoms and plasma BNP level were similarly improved by treatment in both groups. Urine volume was significantly higher in the tolvaptan group (P < .05), but volume of water intake was also higher in the tolvaptan group (P < .05). Blood pressure was significantly lower in the carperitide group than in the tolvaptan group after treatment (P < .05). Less adverse events such as worsening heart failure and hypotension requiring drug discontinuation were observed in the tolvaptan group (P = .027). The average drug cost of tolvaptan was lower than that of carperitide (P < .001). Conclusions Tolvaptan might be a novel promising agent for ADHF in terms of efficacy and safety compared to carperitide. PMID:24142853

  6. Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial

    PubMed Central

    Kremsner, Peter G.; Adegnika, Akim A.; Hounkpatin, Aurore B.; Zinsou, Jeannot F.; Taylor, Terrie E.; Chimalizeni, Yamikani; Liomba, Alice; Kombila, Maryvonne; Bouyou-Akotet, Marielle K.; Mawili Mboumba, Denise P.; Agbenyega, Tsiri; Ansong, Daniel; Sylverken, Justice; Ogutu, Bernhards R.; Otieno, Godfrey A.; Wangwe, Anne; Bojang, Kalifa A.; Okomo, Uduak; Sanya-Isijola, Frank; Newton, Charles R.; Njuguna, Patricia; Kazungu, Michael; Kerb, Reinhold; Geditz, Mirjam; Schwab, Matthias; Velavan, Thirumalaisamy P.; Nguetse, Christian; Köhler, Carsten; Issifou, Saadou; Bolte, Stefanie; Engleitner, Thomas; Mordmüller, Benjamin; Krishna, Sanjeev

    2016-01-01

    Background Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). Methods and Findings This randomized controlled trial included children (0.5–10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan–Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥99% reduction in parasitemia at 24 h compared to 263/331 (79

  7. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial

    PubMed Central

    Fleischer, David M.; Burks, A. Wesley; Vickery, Brian P.; Scurlock, Amy M.; Wood, Robert A.; Jones, Stacie M.; Sicherer, Scott H.; Liu, Andrew H.; Stablein, Donald; Henning, Alice K.; Mayer, Lloyd; Lindblad, Robert; Plaut, Marshall; Sampson, Hugh A.

    2012-01-01

    Background There are presently no available therapeutic options for peanut-allergic patients. Objective To investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). Methods After a baseline oral food challenge (OFC) of up to 2g of peanut powder (~50% protein) (median successfully consumed dose [SCD] 46mg), 40 subjects, aged 12–37 (median 15) years, were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5g OFC was performed after 44 weeks followed by unblinding; placebo subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5g OFC. Week 44 OFCs from both groups were compared to baseline OFCs; subjects successfully consuming 5g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results After 44 weeks of SLIT, 14/20 (70%) subjects receiving peanut SLIT were responders compared to 3/20 (15%) subjects receiving placebo (p<0.001). In peanut-SLIT responders, median SCD increased from 3.5mg to 496mg. After 68 weeks of SLIT, median SCD significantly increased to 996mg (compared to week 44, p=0.05). The median SCD at the Week 44 crossover OFC was significantly higher than baseline (603mg vs 71mg; p=0.02). 7/16 (44%) crossover subjects were responders; median SCD increased from 21mg to 496mg among responders. Of 10,855 peanut doses through Week 44 OFCs, 63.1% were symptom-free; excluding oral/pharyngeal symptoms, 95.2% were symptom-free. Conclusions Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared to placebo. Longer duration of therapy showed statistically significant increases in the SCD. PMID:23265698

  8. Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study

    PubMed Central

    Hanling, Steven; Bicket, Mark C; White, Ronald L; Veizi, Elias; Kurihara, Connie; Zhao, Zirong; Hayek, Salim; Guthmiller, Kevin B; Griffith, Scott R; Gordin, Vitaly; White, Mirinda Anderson; Vorobeychik, Yakov; Pasquina, Paul F

    2015-01-01

    Objective To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy. Design A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes. Settings Eight military, Veterans Administration, and civilian hospitals. Participants 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain. Interventions Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin. Main outcome measures Average leg pain one and three months after the injection on a 0-10 numerical rating scale. A positive outcome was defined as a ≥2 point decrease in leg pain coupled with a positive global perceived effect. All patients had one month follow-up visits; patients whose condition improved remained blinded for their three month visit. Results There were no significant differences for the primary outcome measure at one month (mean pain score 3.3 (SD 2.6) and mean change from baseline −2.2 (SD 2.4) in epidural steroid injection group versus 3.7 (SD 2.6) and −1.7 (SD 2.6) in gabapentin group; adjusted difference 0.4, 95% confidence interval −0.3 to 1.2; P=0.25) and three months (mean pain score 3.4 (SD 2.7) and mean change from baseline −2.0 (SD 2.6) versus 3.7 (SD 2.8) and −1.6 (SD 2.7), respectively; adjusted difference 0.3, −0.5 to 1.2; P=0.43). Among secondary outcomes, one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain (−3.0, SD 2.8) than those treated with gabapentin (−2.0, SD 2.9; P=0.04) and were more likely to experience a positive successful outcome (66% v 46%; number needed to treat=5.0, 95% confidence interval 2.8 to 27.0; P=0.02). At three

  9. The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study

    PubMed Central

    Hosomi, Naohisa; Nagai, Yoji; Kohriyama, Tatsuo; Ohtsuki, Toshiho; Aoki, Shiro; Nezu, Tomohisa; Maruyama, Hirofumi; Sunami, Norio; Yokota, Chiaki; Kitagawa, Kazuo; Terayama, Yasuo; Takagi, Makoto; Ibayashi, Setsuro; Nakamura, Masakazu; Origasa, Hideki; Fukushima, Masanori; Mori, Etsuro; Minematsu, Kazuo; Uchiyama, Shinichiro; Shinohara, Yukito; Yamaguchi, Takenori; Matsumoto, Masayasu

    2015-01-01

    Background Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. Methods This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. Finding Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. Interpretation Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. Funding This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and

  10. EFFECT OF GM-CSF ON CIRCULATING CD8+ AND CD4+ T CELL RESPONSES TO A MULTIPEPTIDE MELANOMA VACCINE: OUTCOME OF A MULTICENTER RANDOMIZED TRIAL

    PubMed Central

    Slingluff, Craig L.; Petroni, Gina R.; Olson, Walter C.; Smolkin, Mark E.; Ross, Merrick I.; Haas, Naomi B.; Grosh, William W.; Boisvert, Marc E; Kirkwood, John M.; Chianese-Bullock, Kimberly A.

    2009-01-01

    Purpose GM-CSF administered locally together with vaccines can augment T cell responses in animal models. Human experience has been limited to small and uncontrolled trials. Thus, a multicenter randomized phase II trial was performed to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine. It also assessed immunogenicity of administration in one vs. two vaccine sites. Experimental Design 121 eligible patients with resected stage IIB-IV melanoma were vaccinated with 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CD8+ T cells, plus an HLA-DR restricted tetanus helper peptide to stimulate CD4+ T cells, emulsified in incomplete Freund’s adjuvant, with or without 110 mcg GM-CSF. Among 119 evaluable patients, T cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis. Clinical outcomes were recorded. Results CD8+ T cell response rates to the 12MP (by day 50), with or without GM-CSF were 34% and 73%, respectively (p<0.001) by direct ELIspot assay. Tetramer analyses corroborated the functional data. CD4+ T cell responses to tetanus helper peptide were higher without GM-CSF (95% vs. 77%, p=0.005). There was no significant difference by number of vaccine sites. Three-year overall and disease-free survival estimates [95% CI] were 76% [67, 83%] and 52% [43, 61%] respectively, with too few events to assess differences by study group. Conclusions High immune response rates for this multipeptide vaccine were achieved, but CD8+ and CD4+ T cell responses were lower when administered with GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. PMID:19903780

  11. Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial

    PubMed Central

    Palizas, Fernando; Dubin, Arnaldo; Regueira, Tomas; Bruhn, Alejandro; Knobel, Elias; Lazzeri, Silvio; Baredes, Natalio; Hernández, Glenn

    2009-01-01

    Introduction Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI). Methods The 130 septic-shock patients were randomized to two different resuscitation goals: CI ≥ 3.0 L/min/m2 (CI group: 66 patients) or intramucosal pH (pHi) ≥ 7.32 (pHi group: 64 patients). After correcting basic physiologic parameters, additional resuscitation consisting of more fluids and dobutamine was started if specific goals for each group had not been reached. Several clinical data were registered at baseline and during evolution. Hemodynamic data and pHi values were registered every 6 hours during the protocol. Primary end point was 28 days' mortality. Results Both groups were comparable at baseline. The most frequent sources of infection were abdominal sepsis and pneumonia. Twenty-eight day mortality (30.3 vs. 28.1%), peak Therapeutic Intervention Scoring System scores (32.6 ± 6.5 vs. 33.2 ± 4.7) and ICU length of stay (12.6 ± 8.2 vs. 16 ± 12.4 days) were comparable. A higher proportion of patients exhibited values below the specific target at baseline in the pHi group compared with the CI group (50% vs. 10.9%; P < 0.001). Of 32 patients with a pHi < 7.32 at baseline, only 7 (22%) normalized this parameter after resuscitation. Areas under the receiver operator characteristic curves to predict mortality at baseline, and at 24 and 48 hours were 0.55, 0.61, and 0.47, and 0.70, 0.90, and 0.75, for CI and pHi, respectively. Conclusions Our study failed to demonstrate any survival benefit of using pHi compared with CI as resuscitation goal in septic-shock patients. Nevertheless, a

  12. 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).

  13. Palonosetron versus ondansetron as rescue medication for postoperative nausea and vomiting: a randomized, multicenter, open-label study

    PubMed Central

    2014-01-01

    Background This study compared palonosetron and ondansetron as rescue medications for postoperative nausea and vomiting (PONV) in patients who received prophylactic ondansetron. Although guidelines recommend use of an agent from a different class when prophylaxis has failed, palonosetron has unique properties relative to other serotonin 5-HT3 receptor antagonists. Prior trials assessing its use for rescue have had conflicting results. Although palonosetron has compared favorably with ondansetron for PONV prevention, the drugs have not been compared in the rescue setting of failure of 5-HT3 receptor antagonist prophylaxis. Methods This was a randomized, open-label, multicenter trial comparing the efficacy and safety of intravenous palonosetron 0.075 mg and intravenous ondansetron 4 mg in patients experiencing PONV following laparoscopic abdominal or gynecological surgery despite prophylactic ondansetron. Results Of 239 patients screened, 220 were enrolled and 98 were treated for PONV: 48 and 50 in the palonosetron and ondansetron arms, respectively. Complete control during 72 hours after study drug administration was achieved in 25.0% of palonosetron recipients and 18.0% of ondansetron recipients (95% confidence interval [CI], -9.2, 23.3; p = 0.40). Corresponding incidences of vomiting were 29.2% for palonosetron and 48.0% for ondansetron (95% CI, -0.06, 37.7; p = 0.057), and 62.5% and 56.0% required additional rescue treatment, respectively (95% CI, -25.9, 12.9; p = 0.52). Other than a similar incidence of procedural pain in the 2 groups, the most common treatment-emergent adverse events, which were generally mild, were headache (14.6% vs 12.0%), constipation (8.3% vs 10.0%), and dizziness (6.3% vs 8.0%), for the palonosetron and ondansetron groups, respectively. Conclusions Palonosetron and ondansetron did not show differences in the primary efficacy endpoint of CC during the 72 hours after study drug administration. There was a trend toward less

  14. Trial to re-evaluate ultrasound in the treatment of tibial fractures (TRUST): a multicenter randomized pilot study

    PubMed Central

    2014-01-01

    Background The role of low-intensity pulsed ultrasound (LIPUS) in the management of fractures remains controversial. The purpose of this study was to assess the feasibility of a definitive trial to determine the effect of LIPUS on functional and clinical outcomes in tibial fractures managed operatively. Methods We conducted a multicenter, concealed, blinded randomized trial of 51 skeletally mature adults with operatively managed tibial fractures who were treated with either LIPUS or a sham device. All participating centers were located in Canada and site investigators were orthopedic surgeons specializing in trauma surgery. The goals of our pilot study were to determine recruitment rates in individual centers, investigators’ ability to adhere to study protocol and data collection procedures, our ability to achieve close to 100% follow-up rates, and the degree to which patients were compliant with treatment. Patients were followed for one year and a committee (blinded to allocation) adjudicated all outcomes. The committee adjudicators were experienced (10 or more years in practice) orthopedic surgeons with formal research training, specializing in trauma surgery. Results Our overall rate of recruitment was approximately 0.8 patients per center per month and site investigators successfully adhered to the study protocol and procedures. Our rate of follow-up at one year was 84%. Patient compliance, measured by an internal timer in the study devices, revealed that 39 (76%) of the patients were fully compliant and 12 (24%) demonstrated a greater than 50% compliance. Based on patient feedback regarding excessive questionnaire burden, we conducted an analysis using data from another tibial fracture trial that revealed the Short Musculoskeletal Function Assessment (SMFA) dysfunction index offered no important advantages over the SF-36 Physical Component Summary (PCS) score. No device-related adverse events were reported. Conclusions Our pilot study identified key issues

  15. Outcome of Burns Treated With Autologous Cultured Proliferating Epidermal Cells: A Prospective Randomized Multicenter Intrapatient Comparative Trial.

    PubMed

    Gardien, Kim L M; Marck, Roos E; Bloemen, Monica C T; Waaijman, Taco; Gibbs, Sue; Ulrich, Magda M W; Middelkoop, Esther

    2016-01-01

    Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5-7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound epithelialization after 5-7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only

  16. Random phase-shifting interferometry based on independent component analysis

    NASA Astrophysics Data System (ADS)

    Xu, Xiaofei; Lu, Xiaoxu; Tian, Jindong; Shou, Junwei; Zheng, Dejin; Zhong, Liyun

    2016-07-01

    In random phase-shifting interferometry, a novel phase retrieval algorithm is proposed based on the independent component analysis (ICA). By performing the recombination of pixel position, a sequence of phase-shifting interferograms with random phase shifts are decomposed into a group of mutual independent components, and then the background and the measured phase of interferogram can obtained with a simple arctangent operation. Compared with the conventional advanced iterative algorithm (AIA) with high accuracy, both the simulation and the experimental results demonstrate that the proposed ICA algorithm reveals high accuracy, rapid convergence, and good noise-tolerance in random phase-shifting interferometry.

  17. Phase Structure of the Random Zq Models in 2D

    NASA Astrophysics Data System (ADS)

    Sasamoto, T.; Nishimori, H.

    We discuss the phase diagram of the random Zq models in two dimensions. It is argued that, when q is large enough, there exist three phases in the phase diagram with two axes being the temperature and the strength of randomness. Our conlusions are derived based on the application of the duality arguments for random systems, which have been formulated recently by Maillard et al.

  18. Self-Consistent Random Phase Approximation

    NASA Astrophysics Data System (ADS)

    Rohr, Daniel; Hellgren, Maria; Gross, E. K. U.

    2012-02-01

    We report self-consistent Random Phase Approximation (RPA) calculations within the Density Functional Theory. The calculations are performed by the direct minimization scheme for the optimized effective potential method developed by Yang et al. [1]. We show results for the dissociation curve of H2^+, H2 and LiH with the RPA, where the exchange correlation kernel has been set to zero. For H2^+ and H2 we also show results for RPAX, where the exact exchange kernel has been included. The RPA, in general, over-correlates. At intermediate distances a maximum is obtained that lies above the exact energy. This is known from non-self-consistent calculations and is still present in the self-consistent results. The RPAX energies are higher than the RPA energies. At equilibrium distance they accurately reproduce the exact total energy. In the dissociation limit they improve upon RPA, but are still too low. For H2^+ the RPAX correlation energy is zero. Consequently, RPAX gives the exact dissociation curve. We also present the local potentials. They indicate that a peak at the bond midpoint builds up with increasing bond distance. This is expected for the exact KS potential.[4pt] [1] W. Yang, and Q. Wu, Phys. Rev. Lett., 89, 143002 (2002)

  19. 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…

  20. A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis.

    PubMed

    Piérard-Franchimont, Claudine; Goffin, Véronique; Decroix, Jacques; Piérard, Gérald E

    2002-01-01

    Ketoconazole (KET) and zinc pyrithione (ZPT) are compounds active against the Malassezia spp. yeasts, which are believed to play a major role in dandruff and seborrheic dermatitis. We compared the efficacy and safety of KET 2% and ZPT 1% in shampoo formulations for the alleviation of severe dandruff and seborrheic dermatitis. This open randomized, parallel-group trial began with a 2-week run-in phase during which subjects applied a neutral non-antidandruff shampoo. It was followed by a 4-week randomized treatment phase and a subsequent 4-week follow-up phase without treatment. Shampooing during the treatment period was carried out twice weekly for the KET group and at least twice weekly for the ZPT group in accordance with the label instructions. A total of 343 subjects were recruited to enter the trial. Of the 331 eligible volunteers, 171 were randomized to KET 2% and 160 to ZPT 1%. Clinical assessments were performed. Beneficial effects were evidenced for both medicated shampoos, but the effect was significantly better for KET 2%, which achieved a 73% improvement in the total dandruff severity score compared with 67% for ZPT 1% at week 4 (p < 0.02). The recurrence rate of the disease was also significantly lower following KET 2% treatment than following ZPT 1% treatment. As a consequence, the overall clearing of the skin condition at the end of treatment and follow-up phase was in favor of the KET 2% formulation (p = 0.004). Side effects were minimal. It is concluded that after a 4-week treatment, KET 2% shampoo was significantly superior to ZPT 1% shampoo in the treatment of subjects with severe dandruff or seborrheic dermatitis of the scalp. It is our assumption that this difference is noticeable for the patient and as a consequence relevant. Both formulations were well tolerated. PMID:12476017

  1. [Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study].

    PubMed

    Krege, S; Hinke, A; Otto, T; Rübben, H

    2002-03-01

    This is a prospective randomized multicenter trial for evaluation of the biological response modifier Factor AF2 in advanced urothelial cancer treated with chemotherapy. Main aim of the study was the analysis of supportive effects. Additionally patients were examined with regard to tumor response, time to progression and survival. 106 patients with advanced urothelial cancer received chemotherapy with cisplatin and methotrexate. They were randomized for additional Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was more common and severe in the group without Factor AF2 reaching statistical significance. Gastrointestinal side effects occurred in both groups, though grade III to IV toxicity was more common without Factor AF2. Overall remission rate was 38%, median survival 33 weeks, mean time to progression 20 weeks. There was no significant difference between the two groups with or without Factor AF2. PMID:11993095

  2. [Results of ventral hernia repair: comparison of suture repair with mesh implantation (onlay vs sublay) using open and laparoscopic approach--prospective, randomized, multicenter study].

    PubMed

    Wéber, György; Horváth, Ors Péter

    2002-10-01

    Incisional hernias is a frequent complication following abdominal surgery, it develops in 11-20% of patients who had laparotomies. Different operative techniques are used for repair but results are often poor. In the absence of valid scientific data, there is no general agreement on the best surgical treatment. To provide evidence based surgery a nation-wide multi-center, prospective, randomized study is set up. The present study compares suture and mesh repairs in different positions, using open and laparoscopic approach to define standard indication for the treatment of incisional hernias. The study was started in March, 2002, with 23 surgical departments participating. Each report about 100 patients with incisional hernia repair. The 2300 consecutive patients (who are 18 to 70 years old) with primary incisional hernia or first recurrent umbilical hernia are randomized. Patients are divided in two groups. If the hernia is between 5-25 cm2 (Group I) they are selected at random either for prosthetic (sublay) or suture repair. In patients with a hernia larger than 25 cm2 (Group II) mesh is implanted at random as either sublay or onlay position using a computer randomization program. After a short learning period, in Group II the laparoscopic approach will also be randomized. Postoperative outcome, complications and recurrence are recorded. The study will run for five years. All collected data are sent to the coordinating center via internet to be entered into database. PMID:12474512

  3. 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

  4. Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

    PubMed Central

    Bühler, A; Wendtner, C-M; Kipps, T J; Rassenti, L; Fraser, G A M; Michallet, A-S; Hillmen, P; Dürig, J; Gregory, S A; Kalaycio, M; Aurran-Schleinitz, T; Trentin, L; Gribben, J G; Chanan-Khan, A; Purse, B; Zhang, J; De Bedout, S; Mei, J; Hallek, M; Stilgenbauer, S

    2016-01-01

    Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (⩾3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105). PMID:26967821

  5. [Citalopram in depression (results of an open multicenter study in phase IV of the clinical trial)].

    PubMed

    Vinar, O; Svestka, J; Koníková, M

    1993-12-01

    249 depressed patients were treated by 35 psychiatrists in an open multicenter trial during 6 weeks with citalopram. The protocol enabled that naturalistic treatment conditions could be kept. The results were rated with the help of the Clinical Global Impression (CGI) scale. The treatment was successful in 77% of the patients. 5 patients dropped out because of adverse effects, 8 patients did not finish the trial due to insufficient efficacy. In 160 patients (64.2%) no adverse effects were registered. Transient mild headaches in 8.4% and nausea in 4% were the most frequent adverse events. The best effects were observed in patients who were rated as moderately ill (82.8% ameliorated) at pretreatment. Nevertheless, also 66.7% of those rated as severely ill before the treatment improved substantially. In patients treated with higher doses than 20 mg/day, the improvement rate was not higher than in those treated with 20 mg daily. PMID:8124734

  6. A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. Via the inhibition of inflammatory reactions and of apoptosis, stem cell recruitment, advancement of angiogenesis and growth factor release, EPO enhances healing and thus restitutio ad integrum after trauma. Human skin contains EPO receptors and is able to synthesize EPO. We therefore hypothesize that EPO is able to optimize wound healing in thermally injured patients. Methods/Design This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. Discussion We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. Trial registration EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT

  7. Multicenter randomized controlled trial of the management of unresectable malignant mesothelioma proposed by the British Thoracic Society and the British Medical Research Council.

    PubMed

    Girling, David J; Muers, Martin F; Qian, Wendi; Lobban, Dawn

    2002-02-01

    Malignant mesothelioma is almost invariably fatal. The incidence of the disease is rising rapidly in many countries, and there is no generally accepted standard treatment for patients with unresectable disease. According to current British Thoracic Society (BTS) guidelines, patients should be treated with active symptom control (ASC), involving (1) regular follow-up in a specialist clinic; (2) structured assessments of physical, psychological and social problems with appropriate action; (3) rapid involvement of additional specialists; and (4) parallel nursing support. Although many nonrandomized studies have reported tumor responses to anticancer chemotherapy, few have studied palliation and it is not known whether chemotherapy prolongs survival or provides clinically worthwhile palliation with acceptable toxicity when given in addition to ASC. We therefore plan to conduct a multicenter randomized controlled trial comparing (1) ASC alone, (2) ASC plus mitomycin vinblastine and cisplatin (MVP), and (3) ASC plus vinorelbine (N; Navelbine, Pierre Fabre Oncology, Winchester, UK). We chose these chemotherapy regimens because they have been shown in nonrandomized studies to provide good symptom control as recorded by patients. The outcome measures are overall survival, palliation of symptoms, performance status, analgesic usage, toxicity, quality of life, tumor response, and recurrence/progression-free survival. In a preliminary feasibility study, we are assessing the acceptability of the trial design to patients and the suitability of two standard quality-of-life instruments in mesothelioma. Data will help us to decide the final details of the large multicenter trial. PMID:11836674

  8. Double random-phase encoding in the Fresnel domain.

    PubMed

    Situ, Guohai; Zhang, Jingjuan

    2004-07-15

    A lensless optical security system based on double random-phase encoding in the Fresnel domain is proposed. This technique can encrypt a primary image to random noise by use of two statistically independent random-phase masks in the input and transform planes, respectively. In this system the positions of the significant planes and the operation wavelength, as well as the phase codes, are used as keys to encrypt and recover the primary image. Therefore higher security is achieved. The sensitivity of the decrypted image to shifting along the propagation direction and to the wavelength are also investigated. PMID:15309826

  9. Ordering and phase transitions in random-field Ising systems

    NASA Technical Reports Server (NTRS)

    Maritan, Amos; Swift, Michael R.; Cieplak, Marek; Chan, Moses H. W.; Cole, Milton W.; Banavar, Jayanth R.

    1991-01-01

    An exact analysis of the Ising model with infinite-range interactions in a random field and a local mean-field theory in three dimensions is carried out leading to a phase diagram with several coexistence surfaces and lines of critical points. The results show that the phase diagram depends crucially on whether the distribution of random fields is symmetric or not. Thus, Ising-like phase transitions in a porous medium (the asymmetric case) are in a different universality class from the conventional random-field model (symmetric case).

  10. Lower Bounds for Phase Estimation of PSK Packets with Random Phase

    NASA Technical Reports Server (NTRS)

    Drake, Jeffrey

    1999-01-01

    In this paper, we derive new Cramer-Rao bounds (CRBs) for the estimation of phase from a block of random M-PSK (M=2,4,8) symbols where the phase to be estimated is a random variable. Existing bounds for 2 and 4-PSK which model the phase as non-random are extended to obtain a new 8-PSK CRB. The new random phase bounds are compared to the new 8-PSK and existing 2,4-PSK bounds which model the phase as non-random. We see that the random phase CRBs more accurately model the behavior if the phase, as normally happens, is suppose to be constrained to the interval [-pi/M,pi/M).

  11. Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

    PubMed Central

    Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

    2015-01-01

    Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

  12. Rationale and design of a multicenter randomized clinical trial of extended release gabapentin in provoked vestibulodynia and biological correlates of response

    PubMed Central

    Brown, Candace S; Foster, David C; Wan, Jim Y; Rawlinson, Leslie; Bachmann, Gloria A

    2013-01-01

    Introduction Few randomized controlled trials (RCTs) have been conducted to establish evidence-based management protocols for provoked vestibulodynia (PVD), a chronic vulvar pain condition affecting approximately 14 million women in the U.S. We describe the rationale and design of an NIH funded multicenter clinical trial utilizing an extended release formulation of gabapentin (G-ER), an intervention that preliminary data suggest may be efficacious for this condition. Objectives 1) to determine if pain from tampon insertion (primary outcome measure) is lower in PVD patients when treated with G-ER compared to when treated with placebo and 2) to determine if G-ER reduces vulvar mechanical hyperalgesia, vaginal muscle pain to palpation, the number and intensity of somatic tenderpoints, spontaneous and provoked pain to intradermal capsaicin with an accompanying increase in cardiac beat-to-beat variability and to identify mechanistically-based PVD subtypes. Additional outcomes include subject reported intercourse pain and summative 24-hour pain. Methods This 16-week, randomized, double-blind, placebo-controlled, crossover study will enroll 120 women 18 years and older who report tenderness localized to the vulvar vestibule, pain with tampon insertion, and, when sexually active, insertional dyspareunia. Electronically entered daily diaries will be used to determine if pain is lower in PVD subjects when treated with G-ER (up to 3000 mg/d) compared to when treated with placebo. Psychophysiological measures will be obtained at baseline and after 2 weeks at the maximum tolerated dose. Conclusion We will conduct the first multicenter RCT to confirm efficacy of an agent that is currently used in clinical practice for treating PVD. PMID:23816491

  13. Cognitive Effects of High-Frequency rTMS in Schizophrenia Patients With Predominant Negative Symptoms: Results From a Multicenter Randomized Sham-Controlled Trial.

    PubMed

    Hasan, Alkomiet; Guse, Birgit; Cordes, Joachim; Wölwer, Wolfgang; Winterer, Georg; Gaebel, Wolfgang; Langguth, Berthold; Landgrebe, Michael; Eichhammer, Peter; Frank, Elmar; Hajak, Göran; Ohmann, Christian; Verde, Pablo E; Rietschel, Marcella; Ahmed, Raees; Honer, William G; Malchow, Berend; Karch, Susanne; Schneider-Axmann, Thomas; Falkai, Peter; Wobrock, Thomas

    2016-05-01

    Cognitive impairments are one of the main contributors to disability and poor long-term outcome in schizophrenia. Proof-of-concept trials indicate that repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) has the potential to improve cognitive functioning. We analyzed the effects of 10-Hz rTMS to the left DLPFC on cognitive deficits in schizophrenia in a large-scale and multicenter, sham-controlled study. A total of 156 schizophrenia patients with predominant negative symptoms were randomly assigned to a 3-week intervention (10-Hz rTMS, 15 sessions, 1000 stimuli per session) with either active or sham rTMS. The Rey Auditory Verbal Learning Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Digit Span Test, and the Regensburg Word Fluency Test were administered before intervention and at day 21, 45, and 105 follow-up. From the test results, a neuropsychological composite score was computed. Both groups showed no differences in any of the outcome variables before and after intervention. Both groups improved markedly over time, but effect sizes indicate a numeric, but nonsignificant superiority of active rTMS in certain cognitive tests. Active 10-Hz rTMS applied to the left DLPFC for 3 weeks was not superior to sham rTMS in the improvement of various cognitive domains in schizophrenia patients with predominant negative symptoms. This is in contrast to previous preliminary proof-of-concept trials, but highlights the need for more multicenter randomized controlled trials in the field of noninvasive brain stimulation. PMID:26433217

  14. Phase randomization of three-wave interactions in capillary waves.

    PubMed

    Punzmann, H; Shats, M G; Xia, H

    2009-08-01

    We present new experimental results on the transition from coherent-phase to random-phase three-wave interactions in capillary waves under parametric excitation. Above the excitation threshold, coherent wave harmonics spectrally broaden. An increase in the pumping amplitude increases spectral widths of wave harmonics and eventually causes a strong decrease in the degree of the three-wave phase coupling. The results point to the modulation instability of capillary waves, which leads to breaking of continuous waves into ensembles of short-lived wavelets or envelope solitons, as the reason for the phase randomization of three-wave interactions. PMID:19792572

  15. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine–cisplatin plus necitumumab versus gemcitabine–cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer

    PubMed Central

    Paz-Ares, L.; Socinski, M. A.; Shahidi, J.; Hozak, R. R.; Soldatenkova, V.; Kurek, R.; Varella-Garcia, M.; Thatcher, N.; Hirsch, F. R.

    2016-01-01

    Background SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. Patients and methods Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m2 i.v., days 1 and 8) and cisplatin (75 mg/m2 i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. Results A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine–cisplatin group than in the gemcitabine–cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%). Conclusions In line with SQUIRE ITT, addition of necitumumab to gemcitabine–cisplatin significantly prolonged OS and was

  16. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial

    PubMed Central

    2014-01-01

    Background Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. Methods The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. Discussion As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. Trial registration NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013. Recruiting. Randomisation commenced on 1 January 2014. PMID:24661817

  17. Continuity and Anomalous Fluctuations in Random Walks in Dynamic Random Environments: Numerics, Phase Diagrams and Conjectures

    NASA Astrophysics Data System (ADS)

    Avena, L.; Thomann, P.

    2012-07-01

    We perform simulations for one dimensional continuous-time random walks in two dynamic random environments with fast (independent spin-flips) and slow (simple symmetric exclusion) decay of space-time correlations, respectively. We focus on the asymptotic speeds and the scaling limits of such random walks. We observe different behaviors depending on the dynamics of the underlying random environment and the ratio between the jump rate of the random walk and the one of the environment. We compare our data with well known results for static random environment. We observe that the non-diffusive regime known so far only for the static case can occur in the dynamical setup too. Such anomalous fluctuations give rise to a new phase diagram. Further we discuss possible consequences for more general static and dynamic random environments.

  18. CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

    PubMed Central

    2014-01-01

    Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment

  19. Effects of Blockiness on the phase behavior of random copolymers

    NASA Astrophysics Data System (ADS)

    Vanderwoude, Gordon; Shi, An-Chang

    Theoretical study of random block copolymers remains a challenging topic due in part to the sheer enormity of their phase space. In this study we use the self-consistent field theory to investigate the phase behaviour of linear (AB)n-type and (AB)n-C-type multiblock copolymers with randomly distributed A and B blocks. In particular, we examine the effect of ``blockiness'' of the random copolymers on the formation of ordered phases. The blockiness can be quantified by the average length of individual A or B blocks, which can be taken as a measure of the heterogeneity of the random copolymers. We observed that the critical value of the χ parameter, at which the order-disorder transition occurs, decreases with increasing blockiness in the (AB)n copolymers. We also observed that the phase behaviour of the (AB)n-C copolymers depends strongly on the blockiness of the random chain. In particular, the blockiness governs whether or not the A/B blocks can phase separate within the A/B domains, thus dictating whether the (AB)n-C behaves as A/B-C diblock copolymers or as ABC terpolymers. The theoretical phase diagrams will be compared with available experiments.

  20. Spatial Distribution of Phase Singularities in Optical Random Vector Waves.

    PubMed

    De Angelis, L; Alpeggiani, F; Di Falco, A; Kuipers, L

    2016-08-26

    Phase singularities are dislocations widely studied in optical fields as well as in other areas of physics. With experiment and theory we show that the vectorial nature of light affects the spatial distribution of phase singularities in random light fields. While in scalar random waves phase singularities exhibit spatial distributions reminiscent of particles in isotropic liquids, in vector fields their distribution for the different vector components becomes anisotropic due to the direct relation between propagation and field direction. By incorporating this relation in the theory for scalar fields by Berry and Dennis [Proc. R. Soc. A 456, 2059 (2000)], we quantitatively describe our experiments. PMID:27610854

  1. Effectiveness of the Chest Pain Choice decision aid in emergency department patients with low-risk chest pain: study protocol for a multicenter randomized trial

    PubMed Central

    2014-01-01

    Background Chest pain is the second most common reason patients visit emergency departments (EDs) and often results in very low-risk patients being admitted for prolonged observation and advanced cardiac testing. Shared decision-making, including educating patients regarding their 45-day risk for acute coronary syndrome (ACS) and management options, might safely decrease healthcare utilization. Methods/Design This is a protocol for a multicenter practical patient-level randomized trial to compare an intervention group receiving a decision aid, Chest Pain Choice (CPC), to a control group receiving usual care. Adults presenting to five geographically and ethnically diverse EDs who are being considered for admission for observation and advanced cardiac testing will be eligible for enrollment. We will measure the effect of CPC on (1) patient knowledge regarding their 45-day risk for ACS and the available management options (primary outcome); (2) patient engagement in the decision-making process; (3) the degree of conflict patients experience related to feeling uninformed (decisional conflict); (4) patient and clinician satisfaction with the decision made; (5) the rate of major adverse cardiac events at 30 days; (6) the proportion of patients admitted for advanced cardiac testing; and (7) healthcare utilization. To assess these outcomes, we will administer patient and clinician surveys immediately after each clinical encounter, obtain video recordings of the patient-clinician discussion, administer a patient healthcare utilization diary, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. Discussion This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in low-risk chest pain patients from a variety of geographically and ethnically diverse EDs. Trial registration NCT01969240. PMID:24884807

  2. User assessment of Norditropin NordiFlex®, a new prefilled growth hormone pen: a Phase IV multicenter prospective study

    PubMed Central

    Tauber, Maithé; Jaquet, Delphine; Jesuran-Perelroizen, Monique; Petrus, Marc; Bertrand, Anne Marie; Coutant, Regis

    2013-01-01

    Background/aim In growth disorders, ensuring long-term growth hormone therapy (GHT) remains a challenge that might compromise the clinical outcome. Consequently, strategies aiming at alleviating the burden of daily injection might improve the treatment benefit. The study reported here was performed to assess the ease of use of Norditropin NordiFlex® (Novo Nordisk, Princeton, NJ, USA) compared with that of the devices previously used in children treated with GHT with recombinant somatropin. Methods This Phase IV prospective, multicenter, open-label study was conducted in France. All patients received Norditropin NordiFlex for 6 weeks. Oral questionnaires were administered by the physician to the patients and/or the parents at inclusion and at the final visit. Results This study included 103 patients aged between 6 and 17 years. The patients assessed Norditropin NordiFlex as significantly easier to use than their previous device (median value = 7.5, P < 0.001). Almost three-quarters of patients (64.4%) preferred Norditropin NordiFlex to their previous device. Among physicians and nurses, 73% assessed Norditropin NordiFlex training as “very easy” and 26% as “easy.” Norditropin NordiFlex improved patient autonomy, with 41% of patients able to self-inject the treatment. Conclusion This study has shown that Norditropin NordiFlex is reliable, safe, and easy to use and most study patients preferred it to their previous device. These characteristics may improve the adherence to GHT. PMID:23737664

  3. INTERBED: internet-based guided self-help for overweight and obese patients with full or subsyndromal binge eating disorder. A multicenter randomized controlled trial

    PubMed Central

    2012-01-01

    Background Binge eating disorder (BED) is a prevalent clinical eating disorder associated with increased psychopathology, psychiatric comorbidity, overweight and obesity, and increased health care costs. Since its inclusion in the DSM-IV, a few randomized controlled trials (RCTs) have suggested efficacy of book-based self-help interventions in the treatment of this disorder. However, evidence from larger RCTs is needed. Delivery of self-help through new technologies such as the internet should be investigated in particular, as these approaches have the potential to be more interactive and thus more attractive to patients than book-based approaches. This study will evaluate the efficacy of an internet-based guided self-help program (GSH-I) and cognitive-behavioral therapy (CBT), which has been proven in several studies to be the gold standard treatment for BED, in a prospective multicenter randomized trial. Methods The study assumes the noninferiority of GSH-I compared to CBT. Both treatments lasted 4 months, and maintenance of outcome will be assessed 6 and 18 months after the end of treatment. A total of 175 patients with BED and a body mass index between 27 and 40 kg/m2 were randomized at 7 centers in Germany and Switzerland. A 20% attrition rate was assumed. As in most BED treatment trials, the difference in the number of binge eating days over the past 28 days is the primary outcome variable. Secondary outcome measures include the specific eating disorder psychopathology, general psychopathology, body weight, quality of life, and self-esteem. Predictors and moderators of treatment outcome will be determined, and the cost-effectiveness of both treatment conditions will be evaluated. Results The methodology for the INTERBED study has been detailed. Conclusions Although there is evidence that CBT is the first-line treatment for BED, it is not widely available. As BED is still a recent diagnostic category, many cases likely remain undiagnosed, and a large number of

  4. A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction.

    PubMed

    Komrokji, Rami S; Mailloux, Adam W; Chen, Dung-Tsa; Sekeres, Mikkael A; Paquette, Ronald; Fulp, William J; Sugimori, Chiharu; Paleveda-Pena, Jennifer; Maciejewski, Jaroslaw P; List, Alan F; Epling-Burnette, Pearlie K

    2014-07-01

    Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, phase II trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary end point was hematologic response; secondary end points included duration of response, time to response, time to progression, and tolerance. Nine (33%;95% confidence interval=17%-54%) of the 27 patients treated experienced durable hematologic improvement in an intent-to-treat analysis with a median time to response and median response duration of 75 and 245 days, respectively. While younger age is the most significant factor favoring equine(e)-anti-thymocyte globulin response, treatment outcome on this study was independent of age (P=0.499). A shorter duration between diagnosis and treatment showed a positive trend (P=0.18), but International Prognostic Scoring System score (P=0.150), karyotype (P=0.319), and age-adjusted bone marrow cellularity (P=0.369) were not associated with response classification. Since activated T-lymphocytes are the primary cellular target of anti-thymocyte globulin, a T-cell expression profiling was conducted in a cohort of 38 patients consisting of rabbit and equine-antithymocyte globulin-treated patients. A model containing disease duration, CD8 terminal memory T cells and T-cell proliferation-associated-antigen expression predicted response with the greatest accuracy using a leave-one-out cross validation approach. This profile categorized patients independent of other covariates, including treatment type and age using a leave-one-out-cross-validation approach (75.7%). Therefore, rabbit-anti-thymocyte globulin has hematologic remitting activity in myelodysplastic syndrome and a T-cell activation profile has potential utility classifying those who are more likely to respond (NCT00466843 clinicaltrials.gov). PMID:24488560

  5. A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Duliang Soft Capsule in Patients with Chronic Daily Headache

    PubMed Central

    Yu, Shengyuan; Hu, Yueqing; Wan, Qi; Zhou, Jiying; Liu, Xinfeng; Qiao, Xiangyang; Yang, Xiaosu; Feng, Jiachun; Chen, Kangning; Pan, Xiaoping; Yang, Qingwu; Dou, Linsen; Liu, Ming; Chen, Yangmei; Yu, Tingmin; Yu, Juming; Li, Zhiwei; Bai, Xue; Duan, Jingfeng

    2015-01-01

    Objective. To investigate the efficacy and safety of traditional Chinese medicine Duliang soft capsule (DSC) in prophylactic treatment for patients with chronic daily headache (CDH). Methods. A multicenter, double-blind, randomized, placebo-controlled clinical study was conducted at 18 Chinese clinical centers. The participants received either DSC or placebo for 4 weeks. The primary efficacy measure was headache-free rate (HFR) in a 4-week period between the pretreatment and posttreatment stages. The secondary efficacy measures were the decrease of headache days, the duration of headache attacks, the frequency of analgesic usage, quality of life, disability, and the headache severity (VAS scores). The accompanying symptoms and adverse events were also assessed. Results. Of 584 CDH patients assessed, 468 eligible patients were randomized. 338 patients received DSC, while 111 patients were assigned in the placebo group. Following treatment, there was a 16.56% difference in HFR favoring DSC over placebo (P < 0.01). Significant differences were also observed between DSC and placebo groups in the secondary measures. However, no statistical difference was found between the two groups in the associated symptoms. No severe adverse effects were observed in the study. Conclusions. DSC might be an effective and well-tolerated option for the prophylactic treatment of patients with CDH. PMID:26101536

  6. Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial

    PubMed Central

    2012-01-01

    Background Nutritional support is an essential part of the management of critically ill patients. However, optimal caloric intake has not been systematically evaluated. We aim to compare two strategies of enteral feeding: permissive underfeeding versus target feeding. Method/Design This is an international multi-center randomized controlled trial in critically ill medical- surgical adult patients. Using a centralized allocation, 862 patients will be randomized to permissive underfeeding or target feeding. Patients in the permissive group receive 50% (acceptable range is 40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (acceptable range 70% to 100%) of the calculated caloric requirement. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05. Discussion Patient recruitment started in November 2009 and is currently active in five centers. The Data Monitoring Committee advised continuation of the trial after the first interim analysis. The study is expected to finish by November 2013. Trial registration Current Controlled Trials ISRCTN68144998 PMID:23057605

  7. Effect of Probiotic Lactobacillus (Lacidofil® Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

    PubMed Central

    Song, Hyun Joo; Kim, Jin-Yong; Kim, Seong-Eun; Park, Hye-Sook; Jeong, Yoolwon; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Hyo-Jong; Ye, Byong Duk; Yang, Suk-Kyun; Kim, Sang-Woo; Shin, Sung-Jae; Kim, Hyun-Soo; Sung, Jae-Kyu; Kim, Eun Young

    2010-01-01

    Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil® cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil® cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group. PMID:21165295

  8. VERTOS II: Percutaneous vertebroplasty versus conservative therapy in patients with painful osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial

    PubMed Central

    Klazen, CAH; Verhaar, HJJ; Lampmann, LEH; Juttmann, JR; Blonk, MC; Jansen, FH; Tielbeek, AV; Schoemaker, MC; Buskens, E; van der Graaf, Y; Janssens, X; Fransen, H; van Everdingen, KJ; Muller, AF; Mali, WPThM; Lohle, PNM

    2007-01-01

    Background The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is gaining popularity as a new treatment option. Many prospective and retrospective studies have reported on the effectiveness and safety of PV, but no large randomized controlled trial (RCT) has been published. Objective To estimate cost-effectiveness of PV compared to conservative therapy in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. Materials and methods The VERTOS II study is designed as a prospective, multicenter RCT. Patients with a painful VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent are included and randomized for PV or conservative therapy. In total 200 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with standard questionnaires, addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score, quality of life and cost-effectiveness. Secondary fractures, necessary additional therapies and complications are recorded. Conclusion The VERTOS II study is the first methodologically sound RCT designed to assess the cost-effectiveness of PV compared to conservative therapy in patients with an acute osteoporotic VCF. Trial registration , NCT00232466 PMID:17973983

  9. Patient Recruitment into a Multicenter Randomized Clinical Trial for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT)

    PubMed Central

    Ferris, Maria; Norwood, Victoria; Radeva, Milena; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

    2015-01-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. PMID:23399084

  10. Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

    PubMed

    Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

    2013-02-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. PMID:23399084

  11. Efficacy and Safety of “URSA Complex” in Subjects with Physical Fatigue: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

    PubMed Central

    Kim, Kwang-Min; Kim, Moon-Jong; Song, Sang-Wook; Cho, Doo-Yeoun; Park, Kyung-Chae; Yang, Sung-Won; Kim, Young-Sang; Kim, Kyung-Soo

    2016-01-01

    Background: Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS). Methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme. Results: The fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks. Conclusions: Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group. PMID:26830981

  12. Oats in the diet of children with celiac disease: preliminary results of a double-blind, randomized, placebo-controlled multicenter Italian study.

    PubMed

    Gatti, Simona; Caporelli, Nicole; Galeazzi, Tiziana; Francavilla, Ruggiero; Barbato, Maria; Roggero, Paola; Malamisura, Basilio; Iacono, Giuseppe; Budelli, Andrea; Gesuita, Rosaria; Catassi, Carlo; Lionetti, Elena

    2013-11-01

    A gluten-free diet (GFD) is currently the only available treatment for patients with celiac disease (CD). Several clinical trials have demonstrated that most celiac patients can tolerate a medium-high quantity of oats without any negative clinical effects; however, the inclusion of oats in GFD is still a matter of debate. In this study, Italian children with CD were enrolled in a 15-month, randomized, double-blind, placebo-controlled multicenter trial. Participants were randomized in two groups following either A-B treatment (6 months of diet "A", 3 months of standard GFD, 6 months of diet "B"), or B-A treatment (6 months of diet "B", 3 months of standard GFD, 6 months of diet "A"). A and B diets included gluten-free (GF) products (flour, pasta, biscuits, cakes and crisp toasts) with either purified oats or placebo. Clinical data (Gastrointestinal Symptoms Rate Scale [GSRS] score) and intestinal permeability tests (IPT), were measured through the study period. Although the study is still blinded, no significant differences were found in GSRS score or the urinary lactulose/mannitol (L/M) ratio between the two groups after 6 months of treatment. These preliminary results suggest that the addition of non-contaminated oats from selected varieties in the treatment of children with CD does not determine changes in intestinal permeability and gastrointestinal symptoms. PMID:24264227

  13. Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group.

    PubMed Central

    Bozzetti, F; Marubini, E; Bonfanti, G; Miceli, R; Piano, C; Crose, N; Gennari, L

    1997-01-01

    OBJECTIVE: The purpose of this study was to analyze postoperative morbidity and mortality of patients included in a randomized trial comparing total versus subtotal gastrectomy for gastric cancer. SUMMARY BACKGROUND DATA: There is controversy as to whether the optimal surgery for gastric cancer in the distal half of the stomach is subtotal or total gastrectomy. Although only a randomized trial can resolve this oncologic dilemma, the first step is to demonstrate whether the two procedures are penalized by different postoperative morbidity and mortality rates. METHODS: A total of 624 patients with cancer in the distal half of the stomach were randomized to subtotal gastrectomy (320) or total gastrectomy (304), both associated with a second-level lymphadenectomy, in a multicenter trial aimed at assessing the oncologic outcome after the two procedures. The end points considered were the occurrence of a postoperative event, complication, or death and length of postoperative stay. RESULTS: Nonfatal complications and death occurred in 9% and 1% of subtotal gastrectomy patients and in 13% and 2% of total gastrectomy patients, respectively. Multivariate analysis of postoperative events showed that splenectomy or resection of adjacent organs was associated with a twofold risk of postoperative complications. Random surgery and extension of surgery influenced the length of stay. The mean length of stay, adjusted for extension of surgery, was 13.8 days for subtotal gastrectomy and 15.4 days for total gastrectomy. CONCLUSIONS: Our data show that subtotal and total gastrectomies, with second-level lymphadenectomy, performed as an elective procedure have a similar postoperative complication rate and surgical outcome. A conclusive long-term evaluation of the two operations and an accurate estimate of the oncologic impact of surgery on long-term survival, not penalized by excess surgical risk of one of the two operations, are consequently feasible. PMID:9389395

  14. Randomized Multicenter Trial of the Effects of Melanoma-Associated Helper Peptides and Cyclophosphamide on the Immunogenicity of a Multipeptide Melanoma Vaccine

    PubMed Central

    Slingluff, Craig L.; Petroni, Gina R.; Chianese-Bullock, Kimberly A.; Smolkin, Mark E.; Ross, Merrick I.; Haas, Naomi B.; von Mehren, Margaret; Grosh, William W.

    2011-01-01

    Purpose This multicenter randomized trial was designed to test whether melanoma-associated helper peptides augment CD8+ T-cell responses to a melanoma vaccine and whether cyclophosphamide (CY) pretreatment augments CD4+ or CD8+ T-cell responses to that vaccine. Patients and Methods In all, 167 eligible patients with resected stage IIB to IV melanoma were randomly assigned to four vaccination study arms. Patients were vaccinated with 12 class I major histocompatibility complex–restricted melanoma peptides (12MP) to stimulate CD8+ T cells and were randomly assigned to receive a tetanus helper peptide or a mixture of six melanoma-associated helper peptides (6MHP) to stimulate CD4+ T cells. Before vaccination, patients were also randomly assigned to receive CY pretreatment or not. T-cell responses were assessed by an ex vivo interferon gamma ELISpot assay. Clinical outcomes and toxicities were recorded. Results Vaccination with 12MP plus tetanus induced CD8+ T-cell responses in 78% of patients and CD4+ T-cell responses to tetanus peptide in 93% of patients. Vaccination with 12MP plus 6MHP induced CD8+ responses in 19% of patients and CD4+ responses to 6MHP in 48% of patients. CY had no significant effect on T-cell responses. Overall 3-year survival was 79% (95% CI, 71% to 86%), with no significant differences (at this point) by study arm. Conclusion Melanoma-associated helper peptides paradoxically decreased CD8+ T-cell responses to a melanoma vaccine (P < .001), and CY pretreatment had no immunologic or clinical effect. Prior work showed immunologic and clinical activity of 6MHP alone. Possible explanations for negative effects on CD8 responses include modulation of homing receptor expression or induction of antigen-specific regulatory T cells. PMID:21690475

  15. The Condensation Phase Transition in Random Graph Coloring

    NASA Astrophysics Data System (ADS)

    Bapst, Victor; Coja-Oghlan, Amin; Hetterich, Samuel; Raßmann, Felicia; Vilenchik, Dan

    2016-01-01

    Based on a non-rigorous formalism called the "cavity method", physicists have put forward intriguing predictions on phase transitions in diluted mean-field models, in which the geometry of interactions is induced by a sparse random graph or hypergraph. One example of such a model is the graph coloring problem on the Erdős-Renyi random graph G( n, d/ n), which can be viewed as the zero temperature case of the Potts antiferromagnet. The cavity method predicts that in addition to the k-colorability phase transition studied intensively in combinatorics, there exists a second phase transition called the condensation phase transition (Krzakala et al. in Proc Natl Acad Sci 104:10318-10323, 2007). In fact, there is a conjecture as to the precise location of this phase transition in terms of a certain distributional fixed point problem. In this paper we prove this conjecture for k exceeding a certain constant k 0.

  16. Ultrafast quantum random number generation based on quantum phase fluctuations.

    PubMed

    Xu, Feihu; Qi, Bing; Ma, Xiongfeng; Xu, He; Zheng, Haoxuan; Lo, Hoi-Kwong

    2012-05-21

    A quantum random number generator (QRNG) can generate true randomness by exploiting the fundamental indeterminism of quantum mechanics. Most approaches to QRNG employ single-photon detection technologies and are limited in speed. Here, we experimentally demonstrate an ultrafast QRNG at a rate over 6 Gbits/s based on the quantum phase fluctuations of a laser operating near threshold. Moreover, we consider a potential adversary who has partial knowledge on the raw data and discuss how one can rigorously remove such partial knowledge with postprocessing. We quantify the quantum randomness through min-entropy by modeling our system and employ two randomness extractors--Trevisan's extractor and Toeplitz-hashing--to distill the randomness, which is information-theoretically provable. The simplicity and high-speed of our experimental setup show the feasibility of a robust, low-cost, high-speed QRNG. PMID:22714224

  17. An open-label, multicenter, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men naïve to phosphodiesterase 5 inhibitor therapy

    PubMed Central

    Bai, Wen-Jun; Li, Hong-Jun; Dai, Yu-Tian; He, Xue-You; Huang, Yi-Ran; Liu, Ji-Hong; Sorsaburu, Sebastian; Ji, Chen; Jin, Jian-Jun; Wang, Xiao-Feng

    2015-01-01

    The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe. PMID:25370206

  18. Random phase-free computer holography and its applications

    NASA Astrophysics Data System (ADS)

    Shimobaba, Tomoyoshi; Kakue, Takashi; Ito, Tomoyoshi

    2016-06-01

    Random phase is required in computer-generated hologram (CGH) to widely diffuse object light and to avoid its concentration on the CGH; however, the random phase causes considerable speckle noise in the reconstructed image and degrades the image quality. We introduce a simple and computationally inexpensive method that improves the image quality and reduces the speckle noise by multiplying the object light with the designed convergence light. We furthermore propose the improved method of the designed convergence light with iterative method to reduce ringing artifacts. Subsequently, as the application, a lensless zoomable holographic projection is introduced.

  19. A Placebo-Controlled, Multicenter, Randomized, Double-Blind, Flexible-Dose, Two-Way Crossover Study to Evaluate the Efficacy and Safety of Sildenafil in Men With Traumatic Spinal Cord Injury and Erectile Dysfunction

    PubMed Central

    Ergin, Sureyya; Gunduz, Berrin; Ugurlu, Hatice; Sivrioglu, Koncuy; Oncel, Sema; Gok, Haydar; Erhan, Belgin; Levendoglu, Funda; Senocak, Ozlem

    2008-01-01

    Background/Objective: To show the efficacy, safety, and tolerability of sildenafil in men with erectile dysfunction (ED) associated with complete or incomplete spinal cord injury (SCI) and to assess its effects on quality of life (QoL) using the Life-Satisfaction Check List. Methods: This was a placebo-controlled, multicenter, randomized, double-blind, flexible-dose, 2-way crossover study with a 2-week washout period between each phase. Patients with ED attributable to SCI (Sexual Health Inventory—Male score ≤21) received 50 to 100 mg sildenafil (n = 24) or placebo (n = 26). Results: Compared with placebo, sildenafil produced higher levels of successful sexual stimulation, intercourse success, satisfaction with sexual life and sexual relationship, erectile function, overall sexual satisfaction, and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score, with no clinically relevant effects on vital signs. Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI, producing significant improvements, compared with placebo, in a number of measures only in patients with incomplete SCI. All patients who expressed a preference selected sildenafil over placebo, although the drug had no effect on patient QoL. Sildenafil was well tolerated, with a profile comparable to that of placebo. Conclusions: Compared with placebo, treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI, especially in those with incomplete injury, and was the agent of choice in those who expressed a preference. PMID:19086709

  20. Results of a preclinical randomized controlled multicenter trial (pRCT): Anti-CD49d treatment for acute brain ischemia.

    PubMed

    Llovera, Gemma; Hofmann, Kerstin; Roth, Stefan; Salas-Pérdomo, Angelica; Ferrer-Ferrer, Maura; Perego, Carlo; Zanier, Elisa R; Mamrak, Uta; Rex, Andre; Party, Hélène; Agin, Véronique; Fauchon, Claudine; Orset, Cyrille; Haelewyn, Benoît; De Simoni, Maria-Grazia; Dirnagl, Ulrich; Grittner, Ulrike; Planas, Anna M; Plesnila, Nikolaus; Vivien, Denis; Liesz, Arthur

    2015-08-01

    Numerous treatments have been reported to provide a beneficial outcome in experimental animal stroke models; however, these treatments (with the exception of tissue plasminogen activator) have failed in clinical trials. To improve the translation of treatment efficacy from bench to bedside, we have performed a preclinical randomized controlled multicenter trial (pRCT) to test a potential stroke therapy under circumstances closer to the design and rigor of a clinical randomized control trial. Anti-CD49d antibodies, which inhibit the migration of leukocytes into the brain, were previously investigated in experimental stroke models by individual laboratories. Despite the conflicting results from four positive and one inconclusive preclinical studies, a clinical trial was initiated. To confirm the preclinical results and to test the feasibility of conducting a pRCT, six independent European research centers investigated the efficacy of anti-CD49d antibodies in two distinct mouse models of stroke in a centrally coordinated, randomized, and blinded approach. The results pooled from all research centers revealed that treatment with CD49d-specific antibodies significantly reduced both leukocyte invasion and infarct volume after the permanent distal occlusion of the middle cerebral artery, which causes a small cortical infarction. In contrast, anti-CD49d treatment did not reduce lesion size or affect leukocyte invasion after transient proximal occlusion of the middle cerebral artery, which induces large lesions. These results suggest that the benefits of immune-targeted approaches may depend on infarct severity and localization. This study supports the feasibility of performing pRCTs. PMID:26246166

  1. Effects of a Clinician Referral and Exercise Program for Men Who Have Completed Active Treatment for Prostate Cancer: A Multicenter Cluster Randomized Controlled Trial (ENGAGE)

    PubMed Central

    Livingston, Patricia M; Craike, Melinda J; Salmon, Jo; Courneya, Kerry S; Gaskin, Cadeyrn J; Fraser, Steve F; Mohebbi, Mohammadreza; Broadbent, Suzanne; Botti, Mari; Kent, Bridie

    2015-01-01

    BACKGROUND The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer. METHODS This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12-week exercise program comprising 2 supervised gym sessions and 1 home-based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self-reported physical activity; the secondary outcomes were quality of life, anxiety, and symptoms of depression. RESULTS A significant intervention effect was observed for vigorous-intensity exercise (effect size: Cohen's d, 0.46; 95% confidence interval [CI], 0.09-0.82; P = .010) but not for combined moderate and vigorous exercise levels (effect size: d, 0.08; 95% CI, −0.28 to 0.45; P = .48). Significant intervention effects were also observed for meeting exercise guidelines (≥150 min/wk; odds ratio, 3.9; 95% CI, 1.9-7.8; P = .002); positive intervention effects were observed in the intervention group for cognitive functioning (effect size: d, 0.34; 95% CI, −0.02 to 0.70; P = .06) and depression symptoms (effect size: d, −0.35; 95% CI, −0.71 to 0.02; P = .06). Eighty percent of participants reported that the clinician's referral influenced their decision to participate in the exercise program. CONCLUSIONS The clinician referral and 12-week exercise program significantly improved vigorous exercise levels and had a positive impact on mental health outcomes for men living with prostate cancer. Further research is needed to determine the sustainability of the exercise program and its generalizability to other cancer populations. Cancer 2015;121:2646–2654. © 2015 American Cancer Society. PMID:25877784

  2. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial

    PubMed Central

    Tomusiak, Anna; Strus, Magdalena; Heczko, Piotr B; Adamski, Paweł; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena

    2015-01-01

    Objective The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. Patients and methods The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4–6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag®, or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Results Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study. Conclusion The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota. PMID:26451088

  3. BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial

    PubMed Central

    Stanish, William D.; McCormack, Robert; Forriol, Francisco; Mohtadi, Nicholas; Pelet, Stéphane; Desnoyers, Jacques; Méthot, Stéphane; Vehik, Kendra; Restrepo, Alberto

    2015-01-01

    Objective The efficacy and safety of BST-CarGel®, a chitosan scaffold for cartilage repair was compared with microfracture alone at 1 year during a multicenter randomized controlled trial in the knee. This report was undertaken to investigate 5-year structural and clinical outcomes. Design The international randomized controlled trial enrolled 80 patients, aged 18 to 55 years, with grade III or IV focal lesions on the femoral condyles. Patients were randomized to receive BST-CarGel® treatment or microfracture alone, and followed standardized 12-week rehabilitation. Co-primary endpoints of repair tissue quantity and quality were evaluated by 3-dimensional MRI quantification of the degree of lesion filling (%) and T2 relaxation times. Secondary endpoints were clinical benefit measured with WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaires and safety. General estimating equations were used for longitudinal statistical analysis of repeated measures. Results Blinded MRI analysis demonstrated that BST-CarGel®-treated patients showed a significantly greater treatment effect for lesion filling (P = 0.017) over 5 years compared with microfracture alone. A significantly greater treatment effect for BST-CarGel® was also found for repair tissue T2 relaxation times (P = 0.026), which were closer to native cartilage compared to the microfracture group. BST-CarGel® and microfracture groups showed highly significant improvement at 5 years from pretreatment baseline for each WOMAC subscale (P < 0.0001), and there were no differences between the treatment groups. Safety was comparable for both groups. Conclusions BST-CarGel® was shown to be an effective mid-term cartilage repair treatment. At 5 years, BST-CarGel® treatment resulted in sustained and significantly superior repair tissue quantity and quality over microfracture alone. Clinical benefit following BST-CarGel® and microfracture treatment were highly significant over baseline

  4. Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention.

    PubMed

    Limburg, Paul J; Mahoney, Michelle R; Ziegler, Katie L Allen; Sontag, Stephen J; Schoen, Robert E; Benya, Richard; Lawson, Michael J; Weinberg, David S; Stoffel, Elena; Chiorean, Michael; Heigh, Russell; Levine, Joel; Della'Zanna, Gary; Rodriguez, Luz; Richmond, Ellen; Gostout, Christopher; Mandrekar, Sumithra J; Smyrk, Thomas C

    2011-02-01

    Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI®Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%ΔACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5-34) and 8 (0-37) at baseline and postintervention, respectively. The median (SD) for %ΔACF was 5.6 (-69% to 143%), -18.6 (-83% to 160%), -3.6 (-88% to 83%), and -10.0 (-100% to 117%) in the atorvastatin, sulindac, ORAFTI®Synergy1 and control arms, respectively. Neither within-arm (P = 0.12-0.59) nor between-arm (P = 0.30-0.92) comparisons of %ΔACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI®Synergy1, although statistical power was limited by the relatively small sample size. PMID:21209397

  5. Absolute uniqueness of phase retrieval with random illumination

    NASA Astrophysics Data System (ADS)

    Fannjiang, Albert

    2012-07-01

    Random illumination is proposed to enforce absolute uniqueness and resolve all types of ambiguity, trivial or nontrivial, in phase retrieval. Almost sure irreducibility is proved for any complex-valued object whose support set has rank ⩾ 2. While the new irreducibility result can be viewed as a probabilistic version of the classical result by Bruck, Sodin and Hayes, it provides a novel perspective and an effective method for phase retrieval. In particular, almost sure uniqueness, up to a global phase, is proved for complex-valued objects under general two-point conditions. Under a tight sector constraint absolute uniqueness is proved to hold with probability exponentially close to unity as the object sparsity increases. Under a magnitude constraint with random amplitude illumination, uniqueness modulo global phase is proved to hold with probability exponentially close to unity as object sparsity increases. For general complex-valued objects without any constraint, almost sure uniqueness up to global phase is established with two sets of Fourier magnitude data under two independent illuminations. Numerical experiments suggest that random illumination essentially alleviates most, if not all, numerical problems commonly associated with the standard phasing algorithms.

  6. The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

    PubMed Central

    Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2014-01-01

    Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

  7. Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients

    PubMed Central

    Miyake, Hideki; Kawano, Yuri; Tanaka, Hiroshi; Iwata, Akihiro; Imanaka, Takahiro; Nakamura, Masatsugu

    2016-01-01

    Purpose We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. Patients and methods A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. Results According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. Conclusion The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye. PMID:27257372

  8. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Sabate, A; Gutierrez, R; Beltran, J; Mellado, P; Blasi, A; Acosta, F; Costa, M; Reyes, R; Torres, F

    2016-08-01

    We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements. PMID:26880105

  9. Phase conjugation with random fields and with deterministic and random scatterers

    SciTech Connect

    Gbur, G.; Wolf, E.

    1999-01-01

    The theory of distortion correction by phase conjugation, developed since the discovery of this phenomenon many years ago, applies to situations when the field that is conjugated is monochromatic and the medium with which it interacts is deterministic. In this Letter a generalization of the theory is presented that applies to phase conjugation of partially coherent waves interacting with either deterministic or random weakly scattering nonabsorbing media. {copyright} {ital 1999} {ital Optical Society of America}

  10. Transformation of phase transitions driven by an anisotropic random field

    NASA Astrophysics Data System (ADS)

    Popa-Nita, V.; Kralj, Samo

    2005-04-01

    We carry out a comparative study of the influence of a random anisotropy field on continuous and discontinuous phase transitions. The ordered phase, which is reached via a continuous symmetry breaking phase transition, is characterized by an order parameter and by a corresponding hydrodynamic continuum field. We assume that the response of the hydrodynamic field to the imposed disorder results in a domainlike pattern of the system. For a strong enough disorder both transitions become gradual. For weaker disorder strengths the disorder converts a second order transition into a discontinuous one.

  11. A Multicenter, Randomized Clinical Trial of a Cognitive Remediation Program for Childhood Survivors of a Pediatric Malignancy

    ERIC Educational Resources Information Center

    Butler, Robert W.; Copeland, Donna R.; Fairclough, Diane L.; Mulhern, Raymond K.; Katz, Ernest R.; Kazak, Anne E.; Noll, Robert B.; Patel, Sunita K.; Sahler, Olle Jane Z.

    2008-01-01

    Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35%…

  12. Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial

    PubMed Central

    Marchand-Maillet, Florence; Baron, Gabriel; Douard, Richard; Béthoux, Jean-Pierre

    2016-01-01

    Objectives To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial). Design Multicenter, two-arm, parallel-group, open-label randomized controlled trial. Setting 11 university hospital ambulatory surgery units in Paris, France. Participants Patients scheduled for ambulatory surgery and able to be reached by telephone. Intervention A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone. Main Outcome Measures Rate of cancellation on the day of surgery or the day before. Results The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state. Conclusions A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes. Trial Registration ClinicalTrials.gov NCT01732159 PMID:26829478

  13. Pleiotropic effects of sitagliptin versus voglibose in patients with type 2 diabetes inadequately controlled via diet and/or a single oral antihyperglycemic agent: a multicenter, randomized trial

    PubMed Central

    Matsushima, Yukiko; Takeshita, Yumie; Kita, Yuki; Otoda, Toshiki; Kato, Ken-ichiro; Toyama-Wakakuri, Hitomi; Akahori, Hiroshi; Shimizu, Akiko; Hamaguchi, Erika; Nishimura, Yasuyuki; Kanamori, Takehiro; Kaneko, Shuichi; Takamura, Toshinari

    2016-01-01

    Purpose A step-up strategy for diet therapy and/or single oral antihyperglycemic agent (OHA) regimens has not yet been established. The aim of this study was to evaluate hemoglobin A1c (HbA1c) as a primary end point, and the pleiotropic effects on metabolic and cardiovascular parameters as secondary end points, of sitagliptin versus voglibose in patients with type 2 diabetes with inadequate glycemic control while on diet therapy and/or treatment with a single OHA. Methods In this multicenter, randomized, open-label, parallel-group trial, a total of 260 patients with inadequately controlled type 2 diabetes (HbA1c levels >6.9%) were randomly assigned to receive either sitagliptin (50 mg, once daily) or voglibose (0.6 mg, thrice daily) for 12 weeks. The primary end point was HbA1c levels. Results Patients receiving sitagliptin showed a significantly greater decrease in HbA1c levels (−0.78±0.69%) compared with those receiving voglibose (−0.30±0.78%). Sitagliptin treatment also lowered serum alkaline phosphatase levels and increased serum creatinine, uric acid, cystatin-C and homeostasis model assessment-β values. Voglibose increased low-density lipoprotein-cholesterol levels and altered serum levels of several fatty acids, and increased Δ-5 desaturase activity. Both drugs increased serum adiponectin. The incidence of adverse events (AEs) was significantly lower in the sitagliptin group, due to the decreased incidence of gastrointestinal AEs. Conclusions Sitagliptin shows superior antihyperglycemic effects compared with voglibose as a first-line or second-line therapy. However, both agents possess unique pleiotropic effects that lead to reduced cardiovascular risk in Japanese people with type 2 diabetes. Trial registration number UMIN 000003503. PMID:27110370

  14. Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

    PubMed Central

    Cao, Yuxue; Du, Yijie; Zhang, Hongying; Luo, Qingli; Li, Bei; Wu, Jinfeng; Lv, Yubao; Sun, Jing; Jin, Hualiang; Wei, Kai; Zhao, Zhengxiao; Kong, Lingwen; Zhou, Xianmei; Miao, Qing; Wang, Gang; Zhou, Qingwei; Dong, Jingcheng

    2014-01-01

    Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530 PMID:25118962

  15. Multicenter, randomized, placebo-controlled, double-blind study of the safety and efficacy of oral delapril in patients with congestive heart failure.

    PubMed

    Circo, A; Platania, F; Mangiameli, S; Putignano, E

    1995-06-16

    A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. If such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. There was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily and those finishing on 15 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7778529

  16. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial

    PubMed Central

    Jiang, Yan; Zhang, Zhen-Lin; Zhang, Zhong-Lan; Zhu, Han-Min; Wu, Yi-Yong; Cheng, Qun; Wu, Feng-Li; Xing, Xiao-Ping; Liu, Jian-Li; Yu, Wei; Meng, Xun-Wu

    2014-01-01

    Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. Method This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. Results A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women. PMID:24426779

  17. Prevention of Recurrent Foot Ulcers With Plantar Pressure–Based In-Shoe Orthoses: The CareFUL Prevention Multicenter Randomized Controlled Trial

    PubMed Central

    Ulbrecht, Jan S.; Hurley, Timothy; Mauger, David T.

    2014-01-01

    OBJECTIVE To assess the efficacy of in-shoe orthoses that were designed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes, peripheral neuropathy, and a history of similar prior ulceration. RESEARCH DESIGN AND METHODS Single-blinded multicenter randomized controlled trial with subjects randomized to wear shape- and pressure-based orthoses (experimental, n = 66) or standard-of-care A5513 orthoses (control, n = 64). Patients were followed for 15 months, until a study end point (forefoot plantar ulcer or nonulcerative plantar forefoot lesion) or to study termination. Proportional hazards regression was used for analysis. RESULTS There was a trend in the composite primary end point (both ulcers and nonulcerative lesions) across the full follow-up period (P = 0.13) in favor of the experimental orthoses. This trend was due to a marked difference in ulcer occurrence (P = 0.007) but no difference in the rate of nonulcerative lesions (P = 0.76). At 180 days, the ulcer prevention effect of the experimental orthoses was already significant (P = 0.003) when compared with control, and the benefit of the experimental orthoses with respect to the composite end point was also significant (P = 0.042). The hazard ratio was 3.4 (95% CI 1.3–8.7) for the occurrence of a submetatarsal head plantar ulcer in the control compared with experimental arm over the duration of the study. CONCLUSIONS We conclude that shape- and barefoot plantar pressure–based orthoses were more effective in reducing submetatarsal head plantar ulcer recurrence than current standard-of-care orthoses, but they did not significantly reduce nonulcerative lesions. PMID:24760263

  18. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment

    PubMed Central

    Yoshikawa, Norishige; Nakanishi, Koichi; Sako, Mayumi; Oba, Mari S; Mori, Rintaro; Ota, Erika; Ishikura, Kenji; Hataya, Hiroshi; Honda, Masataka; Ito, Shuichi; Shima, Yuko; Kaito, Hiroshi; Nozu, Kandai; Nakamura, Hidefumi; Igarashi, Takashi; Ohashi, Yasuo; Iijima, Kazumoto

    2015-01-01

    In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64–1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome. PMID:25054775

  19. Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies.

    PubMed

    Allais, Gianni; Tullo, Vincenzo; Omboni, Stefano; Benedetto, Chiara; Sances, Grazia; Zava, Dario; Ferrari, Michel D; Bussone, Gennaro

    2012-05-01

    The objective of this study was to review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), in women with menstrually related migraine (IHS criteria) through a pooled analysis of three individual studies. Subjects with a history of migraine with or without aura were randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double-blind, crossover design. After treating three episodes of migraine in no more than 3 months with the first treatment, patients had to switch to the next treatment for other 3 months. 346 subjects formed intention-to-treat population of the main study; 280 of them were of a female gender, 256 had regular menses and 187 were included in the menstrual migraine subgroup analysis. Rate of pain free at 2, 4 and 24 h was 23, 52 and 67 % with F and 30, 61 and 66 % with comparators (P = NS). Pain relief episodes at 2, 4 and 24 h were 37, 60 and 66 % for F and 43, 55 and 61 % for comparators (P = NS). Rate of recurrence was significantly (P < 0.05) lower under F either at 24 h (11 vs. 24 % comparators) or at 48 h (15 vs. 26 % comparators). Number of menstrual migraine attacks associated with drug-related adverse events was equally low (P = NS) between F (5 %) and comparators (4 %). PMID:22644174

  20. Frovatriptan versus other triptans in the acute treatment of migraine: pooled analysis of three double-blind, randomized, cross-over, multicenter, Italian studies.

    PubMed

    Cortelli, Pietro; Allais, Gianni; Tullo, Vincenzo; Benedetto, Chiara; Zava, Dario; Omboni, Stefano; Bussone, Gennaro

    2011-05-01

    The objective of the study is to systematically review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), through a pooled analysis of three individual studies. 414 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or R 10 mg (study 1), F 2.5 mg or Z 2.5 mg (study 2), and F 2.5 mg or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double blind, cross-over design, with each of the two treatment periods lasting not more than 3 months. The number of pain free (PF) and pain relief (PR) episodes at 2 h, and the number of sustained pain free (SPF) and recurrent episodes within the 48 h were the efficacy endpoints. 346 patients were included in the intention-to-treat analysis. Rate of PF episodes at 2 h was 30% with F and 34% with comparators (p = NS). PR episodes at 2 h were 55% for F and 59% for comparators (p = NS). SPF episodes at 48 h were also similar between the two groups (22% F vs. 21% comparators). Rate of recurrence was significantly (p < 0.001) lower under F (27 vs. 40% comparators). Drug-related adverse events were significantly (p < 0.05) less under F, particularly cardiovascular symptoms. Our systematic analysis of individual studies suggests that F has a similar immediate efficacy, but a more sustained effect and a better tolerability than R, Z and A. PMID:21533722

  1. Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study.

    PubMed

    Bartolini, Marco; Giamberardino, Maria Adelaide; Lisotto, Carlo; Martelletti, Paolo; Moscato, Davide; Panascia, Biagio; Savi, Lidia; Pini, Luigi Alberto; Sances, Grazia; Santoro, Patrizia; Zanchin, Giorgio; Omboni, Stefano; Ferrari, Michel D; Fierro, Brigida; Brighina, Filippo

    2012-07-01

    The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence. PMID:22592864

  2. Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

    PubMed Central

    Chow, Pierce K. H.; Poon, Donald Y. H.; Khin, Maung-Win; Singh, Harjit; Han, Ho-Seong; Goh, Anthony S. W.; Choo, Su-Pin; Lai, Hee-Kit; Lo, Richard H. G.; Tay, Kiang-Hiong; Lim, Teong-Guan; Gandhi, Mihir; Tan, Say-Beng; Soo, Khee-Chee

    2014-01-01

    Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790. PMID:24614178

  3. Urinary hMG (Meropur) versus recombinant FSH plus recombinant LH (Pergoveris) in IVF: a multicenter, prospective, randomized controlled trial.

    PubMed

    Pacchiarotti, Alessandro; Sbracia, Marco; Frega, Antonio; Selman, Helmy; Rinaldi, Leonardo; Pacchiarotti, Arianna

    2010-11-01

    To compare IVF outcome in ovarian stimulation protocols with recombinant FSH plus recombinant LH versus hMG, 122 patients were randomized into two study groups: group A, patients treated with urinary hMG, and group B, patients treated with rFSH plus rLH. The two groups proved to be comparable to the main IVF outcome (pregnancy rate, implantation rate, oocytes, and embryos quality), with an increasing risk of ovarian hyperstimulation in the Pergoveris group. PMID:20537626

  4. Strengthening of the Hip and Core Versus Knee Muscles for the Treatment of Patellofemoral Pain: A Multicenter Randomized Controlled Trial

    PubMed Central

    Ferber, Reed; Bolgla, Lori; Earl-Boehm, Jennifer E.; Emery, Carolyn; Hamstra-Wright, Karrie

    2015-01-01

    Context: Patellofemoral pain (PFP) is the most common injury in running and jumping athletes. Randomized controlled trials suggest that incorporating hip and core strengthening (HIP) with knee-focused rehabilitation (KNEE) improves PFP outcomes. However, no randomized controlled trials have, to our knowledge, directly compared HIP and KNEE programs. Objective: To compare PFP pain, function, hip- and knee-muscle strength, and core endurance between KNEE and HIP protocols after 6 weeks of rehabilitation. We hypothesized greater improvements in (1) pain and function, (2) hip strength and core endurance for patients with PFP involved in the HIP protocol, and (3) knee strength for patients involved in the KNEE protocol. Design: Randomized controlled clinical trial. Setting: Four clinical research laboratories in Calgary, Alberta; Chicago, Illinois; Milwaukee, Wisconsin; and Augusta, Georgia. Patients or Other Participants: Of 721 patients with PFP screened, 199 (27.6%) met the inclusion criteria (66 men [31.2%], 133 women [66.8%], age = 29.0 ± 7.1 years, height = 170.4 ± 9.4 cm, weight = 67.6 ± 13.5 kg). Intervention(s): Patients with PFP were randomly assigned to a 6-week KNEE or HIP protocol. Main Outcome Measure(s): Primary variables were self-reported visual analog scale and Anterior Knee Pain Scale measures, which were conducted weekly. Secondary variables were muscle strength and core endurance measured at baseline and at 6 weeks. Results: Compared with baseline, both the visual analog scale and the Anterior Knee Pain Scale improved for patients with PFP in both the HIP and KNEE protocols (P < .001), but the visual analog scale scores for those in the HIP protocol were reduced 1 week earlier than in the KNEE group. Both groups increased in strength (P < .001), but those in the HIP protocol gained more in hip-abductor (P = .01) and -extensor (P = .01) strength and posterior core endurance (P = .05) compared with the KNEE group. Conclusions: Both the HIP and KNEE

  5. Neutron diffusion in a randomly inhomogeneous multiplying medium with random phase approximation

    NASA Astrophysics Data System (ADS)

    Imre, Kaya; Akcasu, A. Ziya

    2012-06-01

    Neutron diffusion in a randomly inhomogeneous multiplying medium is studied. By making use of a random phase assumption we show that the average neutron density approximately satisfies an integral equation in Fourier space, which is solved using Kummer functions. We used multi-dimensional formulation. In the case of one dimension, we obtain the result of Rosenbluth and Tao for the mean total density for large t. In the three-dimensional case, a closed form of solution is derived for the mean total neutron density. Its asymptotic behavior is also investigated for large t.

  6. Neutron diffusion in a randomly inhomogeneous multiplying medium with random phase approximation

    SciTech Connect

    Imre, Kaya; Akcasu, A. Ziya

    2012-06-15

    Neutron diffusion in a randomly inhomogeneous multiplying medium is studied. By making use of a random phase assumption we show that the average neutron density approximately satisfies an integral equation in Fourier space, which is solved using Kummer functions. We used multi-dimensional formulation. In the case of one dimension, we obtain the result of Rosenbluth and Tao for the mean total density for large t. In the three-dimensional case, a closed form of solution is derived for the mean total neutron density. Its asymptotic behavior is also investigated for large t.

  7. 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

  8. Transdermal Wound Oxygen Therapy on Pressure Ulcer Healing: A Single-Blind Multi-Center Randomized Controlled Trial

    PubMed Central

    Azimian, Jalil; Dehghan Nayeri, Nahid; Pourkhaleghi, Enis; Ansari, Monireh

    2015-01-01

    Background: Although healthcare quality has considerably improved in many countries, pressure ulcer is still a major health challenge worldwide. Objectives: The current study aimed to evaluate the effects of TWOT on the healing of pressure ulcers. Patients and Methods: This study was a randomized controlled trial, and the convenient sample including 100 patients hospitalized in two university-affiliated medical-surgical intensive care units and one neurology unit located in Qazvin, Iran were studied. Patients with stage II-IV pressure ulcer on the sacral or ischial areas were randomly assigned to either the control or the experimental groups. The experimental group received a 12-day transdermal wound oxygen therapy. Wound status was assessed seven times before the intervention, as well as two, four, six, eight, ten, and twelve days after the intervention. Results: After 12 days of wound oxygen therapy, the number of patients with complete wound healing in the experimental group was significantly greater than that of the control group. Moreover, the total mean of wound area in the experimental group was significantly lower than that of the control group. Conclusions: Transdermal wound oxygen therapy can effectively promote wound healing in patients with pressure ulcers. PMID:26734476

  9. Three-dimensional photon counting double-random-phase encryption.

    PubMed

    Cho, Myungjin; Javidi, Bahram

    2013-09-01

    In this Letter, we present a three-dimensional (3D) photon counting double-random-phase encryption (DRPE) technique using passive integral imaging. A 3D photon counting DRPE can encrypt a 3D scene and provides more security and authentications due to photon counting Poisson nonlinear transformation on the encrypted image. In addition, 3D imaging allows verification of the 3D object at different depths. Preliminary results and performance evaluation have been presented. PMID:23988912

  10. A Randomized Multicenter Trial to Compare Long-Term Functional Outcome, Quality of Life, and Complications of Surgical Procedures for Low Rectal Cancers

    PubMed Central

    Fazio, Victor W.; Zutshi, Massarat; Remzi, Feza H.; Parc, Yann; Ruppert, Reinhard; Fürst, Alois; Celebrezze, James; Galanduik, Susan; Orangio, Guy; Hyman, Neil; Bokey, Leslie; Tiret, Emmanuel; Kirchdorfer, Boris; Medich, David; Tietze, Marcus; Hull, Tracy; Hammel, Jeff

    2007-01-01

    Introduction: Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer. More recently coloplasty has been advocated as an alternative to a colonic pouch. However there have been no long-term randomized, controlled trials to compare functional outcomes of coloplasty, colonic J-Pouch (JP), or a straight anastomosis (SA) after the treatment of low rectal cancer. Aim: To compare the complications, long-term functional outcome, and quality of life (QOL) of patients undergoing a coloplasty, JP, or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer. Methods: A multicenter study enrolled patients with low rectal cancer, who were randomized intraoperatively to coloplasty (CP-1) or SA if JP was not feasible, or JP or coloplasty (CP-2) if a JP was feasible. Patients were followed for 24 months with SF-36 surveys to evaluate the QOL. Bowel function was measured quantitatively and using Fecal Incontinence Severity Index (FISI). Urinary function and sexual function were also assessed. Results: Three hundred sixty-four patients were randomized. All patients were evaluated for complications and recurrence. Mean age was 60 ±12 years, 71% were male. Twenty-three (7.4%) died within 24 months of surgery. No significant difference was observed in the complications among the 4 groups. Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months. There was no difference in bowel function between the CP-1 and SA groups. JP patients had fewer bowel movements, less clustering, used fewer pads and had a lower FISI than the CP-2 group. Other parameters were not statistically different. QOL scores at 24 months were similar for each of the 4 groups. Conclusions: In patients undergoing a restorative resection for low rectal cancer, a colonic JP offers significant advantages in function over an SA or a coloplasty. In patients who cannot have a pouch

  11. Cervicothoracic Manual Therapy Plus Exercise Therapy Versus Exercise Therapy Alone in the Management of Individuals With Shoulder Pain: A Multicenter Randomized Controlled Trial.

    PubMed

    Mintken, Paul E; McDevitt, Amy W; Cleland, Joshua A; Boyles, Robert E; Beardslee, Amber R; Burns, Scott A; Haberl, Matthew D; Hinrichs, Lauren A; Michener, Lori A

    2016-08-01

    Study Design Multicenter randomized controlled trial. Background Cervicothoracic manual therapy has been shown to improve pain and disability in individuals with shoulder pain, but the incremental effects of manual therapy in addition to exercise therapy have not been investigated in a randomized controlled trial. Objectives To compare the effects of cervicothoracic manual therapy and exercise therapy to those of exercise therapy alone in individuals with shoulder pain. Methods Individuals (n = 140) with shoulder pain were randomly assigned to receive 2 sessions of cervicothoracic range-of-motion exercises plus 6 sessions of exercise therapy, or 2 sessions of high-dose cervicothoracic manual therapy and range-of-motion exercises plus 6 sessions of exercise therapy (manual therapy plus exercise). Pain and disability were assessed at baseline, 1 week, 4 weeks, and 6 months. The primary aim (treatment group by time) was examined using linear mixed-model analyses and the repeated measure of time for the Shoulder Pain and Disability Index (SPADI), the numeric pain-rating scale, and the shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH). Patient-perceived success was assessed and analyzed using the global rating of change (GROC) and the Patient Acceptable Symptom State (PASS), using chi-square tests of independence. Results There were no significant 2-way interactions of group by time or main effects by group for pain or disability. Both groups improved significantly on the SPADI, numeric pain-rating scale, and QuickDASH. Secondary outcomes of success on the GROC and PASS significantly favored the manual therapy-plus-exercise group at 4 weeks (P = .03 and P<.01, respectively) and on the GROC at 6 months (P = .04). Conclusion Adding 2 sessions of high-dose cervicothoracic manual therapy to an exercise program did not improve pain or disability in patients with shoulder pain, but did improve patient-perceived success at 4 weeks

  12. Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans.

    PubMed

    Franconi, Flavia; Finocchi, Cinzia; Allais, Gianni; Omboni, Stefano; Tullo, Vincenzo; Campesi, Ilaria; Reggiardo, Giorgio; Benedetto, Chiara; Bussone, Gennaro

    2014-05-01

    Migraine is three times as common in females as in males, and attacks may be more severe and difficult to treat in women. However, no study specifically addressed possible gender differences in response to antimigraine therapy. The objective of this study was to review the efficacy of frovatriptan vs. other triptans, in the acute treatment of migraine in subgroups of subjects classified according to gender (men vs. women) through a pooled analysis of three individual randomized Italian studies. 414 patients suffering from migraine with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in no more than 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, traditional migraine endpoints were compared between the 66 men and 280 women of the intent-to-treat population. At baseline, long-term and debilitating migraine attacks were more frequently reported by women than men. During the observation period, the proportion of pain-free attacks at 2 h did not significantly differ between frovatriptan and the comparators in either men (32 vs. 38 %, p = NS) or women (30 vs. 33 %, p = NS). Pain relief was also similar between treatments for both genders (men: 56 % frovatriptan vs. 57 % comparators; women: 55 vs. 57 %; p = NS for both). The rate of relapse was significantly lower with frovatriptan than with the comparators in men (24 h: 10 vs. 30 %; 48 h: 21 vs. 39 %; p < 0.05) as well as in women (24 h: 14 vs. 23 %; 48 h: 28 vs. 40 %; p < 0.05). The rate of adverse drug reactions was significantly larger with comparators, irrespectively of gender. Although migraine presents in a more severe form in women, frovatriptan seems to retain its good efficacy and

  13. Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

    PubMed Central

    2011-01-01

    Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation

  14. The Effect of Patient-Specific Cerebral Oxygenation Monitoring on Postoperative Cognitive Function: A Multicenter Randomized Controlled Trial

    PubMed Central

    Ellis, Lucy; Murphy, Gavin J; Culliford, Lucy; Dreyer, Lucy; Clayton, Gemma; Downes, Richard; Nicholson, Eamonn; Stoica, Serban; Reeves, Barnaby C

    2015-01-01

    Background Indices of global tissue oxygen delivery and utilization such as mixed venous oxygen saturation, serum lactate concentration, and arterial hematocrit are commonly used to determine the adequacy of tissue oxygenation during cardiopulmonary bypass (CPB). However, these global measures may not accurately reflect regional tissue oxygenation and ischemic organ injury remains a common and serious complication of CPB. Near-infrared spectroscopy (NIRS) is a noninvasive technology that measures regional tissue oxygenation. NIRS may be used alongside global measures to optimize regional perfusion and reduce organ injury. It may also be used as an indicator of the need for red blood cell transfusion in the presence of anemia and tissue hypoxia. However, the clinical benefits of using NIRS remain unclear and there is a lack of high-quality evidence demonstrating its efficacy and cost effectiveness. Objective The aim of the patient-specific cerebral oxygenation monitoring as part of an algorithm to reduce transfusion during heart valve surgery (PASPORT) trial is to determine whether the addition of NIRS to CPB management algorithms can prevent cognitive decline, postoperative organ injury, unnecessary transfusion, and reduce health care costs. Methods Adults aged 16 years or older undergoing valve or combined coronary artery bypass graft and valve surgery at one of three UK cardiac centers (Bristol, Hull, or Leicester) are randomly allocated in a 1:1 ratio to either a standard algorithm for optimizing tissue oxygenation during CPB that includes a fixed transfusion threshold, or a patient-specific algorithm that incorporates cerebral NIRS monitoring and a restrictive red blood cell transfusion threshold. Allocation concealment, Internet-based randomization stratified by operation type and recruiting center, and blinding of patients, ICU and ward care staff, and outcome assessors reduce the risk of bias. The primary outcomes are cognitive function 3 months after

  15. Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orthodontic appliances: a multicenter randomized clinical trial.

    PubMed

    Woodhouse, Neil R; DiBiase, Andrew T; Papageorgiou, Spyridon N; Johnson, Nicola; Slipper, Carmel; Grant, James; Alsaleh, Maryam; Cobourne, Martyn T

    2015-01-01

    This prospective randomized trial investigated the effect of supplemental vibrational force on orthodontic pain during alignment with fixed-appliances. Eighty-one subjects < 20 years-old undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20-minutes/day) use of an intra-oral vibrational device (AcceleDent(®)) (n = 29); an identical non-functional (sham) device (n = 25) or fixed-appliances only (n = 27). Each subject recorded pain intensity (using a 100-mm visual-analogue scale) and intake of oral analgesia in a questionnaire, following appliance-placement (T1) and first-adjustment (T2) for 1-week (immediately-after, 4, 24, 72-hours and at 1-week). Mean maximum-pain for the total sample was 72.96 mm [SD 21.59; 95%CI 68.19-77.74 mm] with no significant differences among groups (P = 0.282). Subjects taking analgesics reported slightly higher maximum-pain although this was not significant (P = 0.170). The effect of intervention was independent of analgesia (P = 0.883). At T1 and T2, a statistically and clinically significant increase in mean pain was seen at 4 and 24-hours, declining at 72-hours and becoming insignificant at 1-week. For mean alignment-rate, pain-intensity and use of analgesics, no significant differences existed between groups (P > 0.003). The only significant predictor for mean pain was time. Use of an AcceleDent vibrational device had no significant effect on orthodontic pain or analgesia consumption during initial alignment with fixed appliances. PMID:26610843

  16. Overcoming Disembodiment: The Effect of Movement Therapy on Negative Symptoms in Schizophrenia—A Multicenter Randomized Controlled Trial

    PubMed Central

    Martin, Lily A. L.; Koch, Sabine C.; Hirjak, Dusan; Fuchs, Thomas

    2016-01-01

    Objective: Negative symptoms of patients with Schizophrenia are resistant to medical treatment or conventional group therapy. Understanding schizophrenia as a form of disembodiment of the self, a number of scientists have argued that the approach of embodiment and associated embodied therapies, such as Dance and Movement Therapy (DMT) or Body Psychotherapy (BPT), may be more suitable to explain the psychopathology underlying the mental illness and to address its symptoms. Hence the present randomized controlled trial (DRKS00009828, http://apps.who.int/trialsearch/) aimed to examine the effectiveness of manualized movement therapy (BPT/DMT) on the negative symptoms of patients with schizophrenia. Method:A total of 68 out-patients with a diagnosis of a schizophrenia spectrum disorder were randomly allocated to either the treatment (n = 44, 20 sessions of BPT/DMT) or the control condition [n = 24, treatment as usual (TAU)]. Changes in negative symptom scores on the Scale for the Assessment of Negative Symptoms (SANS) were analyzed using Analysis of Covariance (ANCOVA) with Simpson-Angus Scale (SAS) scores as covariates in order to control for side effects of antipsychotic medication. Results:After 20 sessions of treatment (BPT/DMT or TAU), patients receiving movement therapy had significantly lower negative symptom scores (SANS total score, blunted affect, attention). Effect sizes were moderate and mean symptom reduction in the treatment group was 20.65%. Conclusion:The study demonstrates that embodied therapies, such as BPT/DMT, are highly effective in the treatment of patients with schizophrenia. Results strongly suggest that BPT/DMT should be embedded in the daily clinical routine. PMID:27064347

  17. A Multicenter Randomized Controlled Trial Comparing Treatment of Venous Leg Ulcers Using Mechanically Versus Electrically Powered Negative Pressure Wound Therapy

    PubMed Central

    Marston, William A.; Armstrong, David G.; Reyzelman, Alexander M.; Kirsner, Robert S.

    2015-01-01

    Objective: This study compares two different negative pressure wound therapy (NPWT) modalities in the treatment of venous leg ulcers (VLUs), the ultraportable mechanically powered (MP) Smart Negative Pressure (SNaP®) Wound Care System to the electrically powered (EP) Vacuum-Assisted Closure (V.A.C.®) System. Approach: Patients with VLUs from 13 centers participated in this prospective randomized controlled trial. Each subject was randomly assigned to treatment with either MP NPWT or EP NPWT and evaluated for 16 weeks or complete wound closure. Results: Forty patients (n=19 MP NPWT and n=21 EP NPWT) completed the study. Primary endpoint analysis of wound size reduction found wounds in the MP NPWT group had significantly greater wound size reduction than those in the EP NPWT group at 4, 8, 12, and 16 weeks (p-value=0.0039, 0.0086, 0.0002, and 0.0005, respectively). Kaplan–Meier analyses showed greater acceleration in complete wound closure in the MP NPWT group. At 30 days, 50% wound closure was achieved in 52.6% (10/19) of patients treated with MP NPWT and 23.8% (5/21) of patients treated with EP NPWT. At 90 days, complete wound closure was achieved in 57.9% (11/19) of patients treated with MP NPWT and 38.15% (8/21) of patients treated with EP NPWT. Innovation: These data support the use of MP-NPWT for the treatment of VLUs. Conclusions: In this group of venous ulcers, wounds treated with MP NPWT demonstrated greater improvement and a higher likelihood of complete wound closure than those treated with EP NPWT. PMID:25713749

  18. Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orthodontic appliances: a multicenter randomized clinical trial

    PubMed Central

    Woodhouse, Neil R.; DiBiase, Andrew T.; Papageorgiou, Spyridon N.; Johnson, Nicola; Slipper, Carmel; Grant, James; Alsaleh, Maryam; Cobourne, Martyn T.

    2015-01-01

    This prospective randomized trial investigated the effect of supplemental vibrational force on orthodontic pain during alignment with fixed-appliances. Eighty-one subjects < 20 years-old undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20-minutes/day) use of an intra-oral vibrational device (AcceleDent®) (n = 29); an identical non-functional (sham) device (n = 25) or fixed-appliances only (n = 27). Each subject recorded pain intensity (using a 100-mm visual-analogue scale) and intake of oral analgesia in a questionnaire, following appliance-placement (T1) and first-adjustment (T2) for 1-week (immediately-after, 4, 24, 72-hours and at 1-week). Mean maximum-pain for the total sample was 72.96 mm [SD 21.59; 95%CI 68.19–77.74 mm] with no significant differences among groups (P = 0.282). Subjects taking analgesics reported slightly higher maximum-pain although this was not significant (P = 0.170). The effect of intervention was independent of analgesia (P = 0.883). At T1 and T2, a statistically and clinically significant increase in mean pain was seen at 4 and 24-hours, declining at 72-hours and becoming insignificant at 1-week. For mean alignment-rate, pain-intensity and use of analgesics, no significant differences existed between groups (P > 0.003). The only significant predictor for mean pain was time. Use of an AcceleDent vibrational device had no significant effect on orthodontic pain or analgesia consumption during initial alignment with fixed appliances. PMID:26610843

  19. Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

    PubMed Central

    van Bergen, Christiaan JA; Blankevoort, Leendert; de Haan, Rob J; Sierevelt, Inger N; Meuffels, Duncan E; d'Hooghe, Pieter RN; Krips, Rover; van Damme, Geert; van Dijk, C Niek

    2009-01-01

    Background Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration Netherlands Trial Register (NTR1636) PMID:19591674

  20. Multifaceted Intervention to Prevent Venous Thromboembolism in Patients Hospitalized for Acute Medical Illness: A Multicenter Cluster-Randomized Trial

    PubMed Central

    Roy, Pierre-Marie; Rachas, Antoine; Meyer, Guy; Le Gal, Grégoire; Durieux, Pierre; El Kouri, Dominique; Honnart, Didier; Schmidt, Jeannot; Legall, Catherine; Hausfater, Pierre; Chrétien, Jean-Marie; Mottier, Dominique

    2016-01-01

    Background Misuse of thromboprophylaxis may increase preventable complications for hospitalized medical patients. Objectives To assess the net clinical benefit of a multifaceted intervention in emergency wards (educational lectures, posters, pocket cards, computerized clinical decision support systems and, where feasible, electronic reminders) for the prevention of venous thromboembolism. Patients/Methods Prospective cluster-randomized trial in 27 hospitals. After a pre-intervention period, centers were randomized as either intervention (n = 13) or control (n = 14). All patients over 40 years old, admitted to the emergency room, and hospitalized in a medical ward were included, totaling 1,402 (712 intervention and 690 control) and 15,351 (8,359 intervention and 6,992 control) in the pre-intervention and intervention periods, respectively. Results Symptomatic venous thromboembolism or major bleeding (primary outcome) occurred at 3 months in 3.1% and 3.2% of patients in the intervention and control groups, respectively (adjusted odds ratio: 1.02 [95% confidence interval: 0.78–1.34]). The rates of thromboembolism (1.9% vs. 1.9%), major bleedings (1.2% vs. 1.3%), and mortality (11.3% vs. 11.1%) did not differ between the groups. Between the pre-intervention and intervention periods, the proportion of patients who received prophylactic anticoagulant treatment more steeply increased in the intervention group (from 35.0% to 48.2%: +13.2%) than the control (40.7% to 44.1%: +3.4%), while the rate of adequate thromboprophylaxis remained stable in both groups (52.4% to 50.9%: -1.5%; 49.1% to 48.8%: -0.3%). Conclusions Our intervention neither improved adequate prophylaxis nor reduced the rates of clinical events. New strategies are required to improve thromboembolism prevention for hospitalized medical patients. Trial Registration ClinicalTrials.gov NCT01212393 PMID:27227406

  1. Efficacy and safety of two pH-dependent-release mesalamine doses in moderately active ulcerative colitis: a multicenter, randomized, double-blind, parallel-group study

    PubMed Central

    Suzuki, Yasuo; Iida, Mitsuo; Ito, Hiroaki; Saida, Isamu

    2016-01-01

    Background/Aims The therapeutic effect of mesalamine is considered to be dose-dependent; however, no consensus has been reached regarding the optimal doses for individual patients. This study aimed to provide new insight for dose optimization using two doses of pH-dependent release mesalamine for induction of remission of moderately active ulcerative colitis (UC). Methods In a multicenter, double-blind, randomized study, 110 patients with moderately active UC were assigned to two groups after treatment with a constant dose of mesalamine. Fifty-five patients were treated with a pH-dependent release formulation of 3.6 or 4.8 g/day for 8 weeks. The primary endpoint was a decrease in the UC disease activity index (UCDAI) adjusted by covariates. Results In the full analysis set (n=110), the mean decrease in UCDAI was 3.1 in the 3.6 g/day group and 3.4 in the 4.8 g/day group (P>0.05). In a subgroup analysis, the effectiveness of the 4.8 g/day dose was greater in particular populations, such as those who had been previously treated with a lower dose of mesalamine and those with more severe disease. The safety was comparable between the two groups. Conclusions The results suggest that treatment with pH-dependent release mesalamine at either 3.6 or 4.8 g/day was effective and safe for the induction of remission in patients with moderately active UC. However, the patients receiving mesalamine at 2.4 g/day but in whom the therapeutic effect is not sufficient and having more severe symptoms (UCDAI 9-10), benefit from higher doses of mesalamine compared to others. PMID:26884735

  2. Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial.

    PubMed

    Hifumi, Toru; Kuroda, Yasuhiro; Kawakita, Kenya; Yamashita, Susumu; Oda, Yasutaka; Dohi, Kenji; Maekawa, Tsuyoshi

    2016-06-01

    In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4). PMID:26413933

  3. Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.

    PubMed

    Benkert, Otto; Szegedi, Armin; Philipp, Michael; Kohnen, Ralf; Heinrich, Claus; Heukels, Anja; van der Vegte-Senden, Monique; Baker, Ross A; Simmons, John H; Schutte, Albert-Jan

    2006-02-01

    This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties. PMID:16415711

  4. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  5. Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial

    PubMed Central

    Wild, Sarah H.; Hanley, Janet; Lewis, Stephanie C.; McKnight, John A.; Padfield, Paul L.; Parker, Richard A.; Pinnock, Hilary; Sheikh, Aziz; McKinstry, Brian

    2016-01-01

    Background Self-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes. Methods and Findings We performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56–5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62–3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant

  6. Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

    PubMed Central

    Ruha, Anne-Michelle; Seifert, Steven A.; Morgan, David L.; Lewis, Brandon J.; Arnold, Thomas C.; Clark, Richard F.; Meggs, William J.; Toschlog, Eric A.; Borron, Stephen W.; Figge, Gary R.; Sollee, Dawn R.; Shirazi, Farshad M.; Wolk, Robert; de Chazal, Ives; Quan, Dan; García-Ubbelohde, Walter; Alagón, Alejandro; Gerkin, Richard D.; Boyer, Leslie V.

    2015-01-01

    Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation

  7. Daily Chlorhexidine Bathing To Reduce Bacteremia in Critically Ill Children: a Multicenter, Cluster-Randomized, Two-Period Crossover Trial

    PubMed Central

    Milstone, Aaron M.; Elward, Alexis; Song, Xiaoyan; Zerr, Danielle M.; Orscheln, Rachel; Speck, Kathleen; Obeng, Daniel; Reich, Nicholas G.; Coffin, Susan E; Perl, Trish M.

    2012-01-01

    Background Bacteremia is a significant cause of morbidity and mortality in critically ill children. Our objective was to assess whether daily chlorhexidine gluconate (CHG) bathing compared with standard bathing practices would reduce bacteremia in critically ill children. Methods In an unmasked, cluster-randomized, two-period crossover trial (Pediatric SCRUB), 10 pediatric intensive care units (ICUs) at 5 hospitals in the United States were randomly assigned to bathe patients > 2 months of age daily with a 2% CHG-impregnated cloth or with standard bathing practices for a six-month period. Units switched to the alternative bathing method during the second six-month period. Among 6,482 eligible patient admissions, 1521 were excluded due to a length of stay less than 2 days and 14 refused to participate. The primary outcome was an episode of bacteremia. This study is registered with ClinicalTrials.gov (Identifier: NCT00549393). Findings 4·947 patient admissions were eligible for analysis. In the intent to treat population, there was a non-statistically significant reduction in incidence of bacteremia among patients receiving daily CHG bathing (3·52 per 1,000 days, 95%CI 2·64–4·61) compared with patients receiving standard bathing practices (4·93 per 1,000 days, 95%CI 3·91–6·15) [adjusted incidence rate ratio (aIRR) 0·71, 95% CI 0·42–1·20]. In the per protocol population, the incidence of bacteremia was 36% lower among patients receiving daily CHG bathing (3·28 per 1,000 days, 95%CI 2·27–4·58)) compared with patients receiving standard bathing practices (4·93 per 1,000 days, 95%CI 3·91–6·15) [aIRR 0·64, 95% CI 0·42–0·98]. There were no serious study related adverse events, and the incidence of CHG-associated skin reactions was 1·2 per 1,000 days (95% CI 0·60–2·02). Interpretation Critically ill children receiving daily CHG bathing had a lower incidence of bacteremia, and the treatment was well tolerated. Funding Primarily by Sage

  8. [Felbinac gel for treatment of localized extra-articular rheumatic diseases--a multicenter, placebo controlled, randomized study].

    PubMed

    Bolten, W

    1991-01-01

    281 patients with extra-articular rheumatic disorders (enthesiopathy, bursitis, tendinosis, fibrositis) and moderate or severe localized pain during rest or movement in shoulder, neck, elbow or knee were randomized into groups and treated for 14 days in a double blind study with either 1 g Felbinac Gel 3% (biphenyl acetic acid) three times daily (N = 142) or with the gel formulation only (N = 139). In 50% of the patients treated with Felbinac Gel compared to 29% of the placebo treated patients (p = 0.001), the investigator assessed the global therapeutic success to be good or very good. The magnitude of complaints judged on the basis of a visual analogous scale by patients and doctor showed a significant improvement in pain reduction during rest or activity after 14 days of treatment in the Felbinac group. The rheumatic complaints diminished equally according to patient judgement in both treatment groups and the concomitant use of paracetamol was low in both groups. No significant side-effects or changes in laboratory parameters were observed during therapy. Felbinac Gel therefore is suitable for a low-risk topical therapy of soft tissue rheumatic disorders. PMID:1872042

  9. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial

    PubMed Central

    Ozawa, Hideki; Uemura, Naomi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the 13C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), 13C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  10. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial.

    PubMed

    Takagi, Atsushi; Yanagi, Hidetaka; Ozawa, Hideki; Uemura, Naomi; Nakajima, Shigemi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the (13)C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), (13)C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  11. Distal intramural spread of rectal cancer after preoperative radiotherapy: The results of a multicenter randomized clinical study

    SciTech Connect

    Chmielik, Ewa; Bujko, Krzysztof . E-mail: bujko@coi.waw.pl; Nasierowska-Guttmejer, Anna; Nowacki, Marek P.; Kepka, Lucyna; Sopylo, Rafal; Wojnar, Andrzej; Majewski, Przemyslaw; Sygut, Jacek; Karmolinski, Andrzej; Huzarski, Tomasz; Wandzel, Piotr

    2006-05-01

    Purpose: To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer. Methods and Materials: A total of 316 patients with T{sub 3-4} primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS. Results: The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001). Conclusions: Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

  12. Random and ordered phases of off-lattice rhombus tiles.

    PubMed

    Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter H; Garrahan, Juan P

    2012-01-20

    We study the covering of the plane by nonoverlapping rhombus tiles, a problem well studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations, we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on the tile shape and interactions, the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving "molecular rhombi." PMID:22400760

  13. Random and ordered phases of off-lattice rhombus tiles

    NASA Astrophysics Data System (ADS)

    Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter; Garrahan, Juan

    2012-02-01

    We study the covering of the plane by non-overlapping rhombus tiles, a problem well-studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on tile shape and interactions the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving ``molecular rhombi.''

  14. Random and Ordered Phases of Off-Lattice Rhombus Tiles

    NASA Astrophysics Data System (ADS)

    Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter H.; Garrahan, Juan P.

    2012-01-01

    We study the covering of the plane by nonoverlapping rhombus tiles, a problem well studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations, we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on the tile shape and interactions, the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving “molecular rhombi.”

  15. Phase diffusion and random walk interpretation of electromagnetic scattering

    NASA Astrophysics Data System (ADS)

    Bahcivan, Hasan; Hysell, David L.; Kelley, Michael C.

    2003-08-01

    The relaxation behavior of phase observables for different particle diffusion models is found to establish a ground for radioscience interpretations of coherent backscatter spectra. The characteristic function for a random walk process at twice the incident radiation wave number is associated with the complex amplitude of the scattered field from a medium containing refractive index fluctuations. The phase relaxation function can be connected to the evolution of the characteristic function and may describe the average regression of the scattered field from a spontaneous fluctuation undergoing turbulent mixing. This connection holds when we assume that the stochastic description of particle movements based on a diffusion model is valid. The phase relaxation function, when identified as the generalized susceptibility function of the fluctuation dissipation theorem, is related to the spectral density of the scattered field from steady-state fluctuations.

  16. Effect and safety of deep needling and shallow needling for functional constipation: a multicenter, randomized controlled trial.

    PubMed

    Wu, Jiani; Liu, Baoyan; Li, Ning; Sun, Jianhua; Wang, Lingling; Wang, Liping; Cai, Yuying; Ye, Yongming; Liu, Jun; Wang, Yang; Liu, Zhishun

    2014-12-01

    Aupuncture is widely used for functional constipation. Effect of acupuncture might be related to the depth of needling; however, the evidence is limited. This trial aimed to evaluate the effect and safety of deep needling and shallow needling for functional constipation, and to assess if the deep needling and shallow needling are superior to lactulose. We conducted a prospective, superiority-design, 5-center, 3-arm randomized controlled trial. A total of 475 patients with functional constipation were randomized to the deep needling group (237), shallow needling group (119), and lactulose-controlled group (119) in a ratio of 2:1:1. Sessions lasted 30 minutes each time and took place 5 times a week for 4 weeks in 2 acupuncture groups. Participants in the lactulose group took lactulose orally for 16 continuous weeks. The primary outcome was the change from baseline of mean weekly spontaneous bowel movements (SBMs) during week 1 to 4 (changes from the baselines of the weekly SBMs at week 8 and week 16 in follow-up period were also assessed simultaneously). Secondary outcomes were the weekly SBMs of each assessing week, the mean score change from the baseline of constipation-related symptoms over week 1 to 4, and the time to the first SBM. Emergency drug usage and adverse effects were monitored throughout the study.SBMs and constipation-related symptoms were all improved in the 3 groups compared with baseline at each time frame (P<0.01, all). The changes in the mean weekly SBMs over week 1 to 4 were 2 (1.75) in the deep needling group, 2 (1.75) in the shallow needling group, and 2 (2) in the lactulose group (P>0.05, both compared with the lactulose group). The changes of mean weekly SBMs at week 8 and week 16 in the follow-up period were 2 (2), 2 (2.5) in the deep needling group, 2 (3), 1.5 (2.5) in the shallow needling group, and 1 (2), 1 (2) in the lactulose group (P<0.05, all compared with the lactulose group). No significant difference was observed among the 3

  17. A multicenter, randomized, double-blind trial of a new porcine surfactant in premature infants with respiratory distress syndrome

    PubMed Central

    Rebello, Celso Moura; Precioso, Alexander Roberto; Mascaretti, Renata Suman

    2014-01-01

    Objective To compare the efficacy and safety of a new porcine-derived pulmonary surfactant developed by Instituto Butantan with those of animal-derived surfactants commercially available in Brazil, regarding neonatal mortality and the major complications of prematurity in preterm newborns with birth weight up to 1500g and diagnosed with respiratory distress syndrome. Methods Neonates diagnosed with respiratory distress syndrome were randomized to receive either Butantan surfactant (Butantan group) or one of the following surfactants: Survanta® or Curosurf®. Newborns receiving Survanta® or Curosurf® comprised the control group. The main outcome measures were mortality rates at 72 hours and at 28 days of life; the typical complications of prematurity as evaluated on the 28th day of life were defined as secundary outcomes. Results No differences were observed between the Butantan (n=154) and control (n=173) groups in relation to birth weight, gestational age, sex, and prenatal use of corticosteroids, or in mortality rates both at 72 hours (14.19% versus 14.12%; p=0.98) and at 28 days (39.86% versus 33.33%; p=0.24) of life. Higher 1- and 5-minute Apgar scores were observed among control group newborns. No differences were observed as regards the secondary outcomes, except for greater need for supplemental oxygen and a higher incidence of interstitial pulmonary emphysema in the Butantan group. Conclusion The mortality rates at 72 hours and 28 days of life and the incidence of major complications of prematurity were comparable to those found with the animal-derived surfactants commercially available in Brazil, showing the efficacy and safety of the new surfactant in the treatment of respiratory distress syndrome in newborns. PMID:25628188

  18. The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial

    PubMed Central

    Hua, Wei; Gao, Run-Lin; Zhao, Bu-Chang; Wang, Jing; Chen, Xu-Hua; Cai, Chi; Zhang, Shu

    2015-01-01

    Background: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. Methods: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. Results: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%, P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%, P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. Conclusions: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC

  19. Needle Sensation and Personality Factors Influence Therapeutic Effect of Acupuncture for Treating Bell's Palsy: A Secondary Analysis of a Multicenter Randomized Controlled Trial

    PubMed Central

    Zhang, Chen-Yan; Xu, Sha-Bei; Huang, Bo; Du, Peng; Zhang, Gui-Bin; Luo, Xiang; Huang, Guang-Ying; Xie, Min-Jie; Zhou, Zong-Kui; Wang, Wei

    2016-01-01

    Background: It has not been solved what kind of needle sensation might influence outcomes of acupuncture treatment. Effects of personality factors on the therapeutic effect of acupuncture have not been investigated. This study aimed to find the effects of the traits of personality on the objective outcome when different acupuncture techniques were used in treating patients with Bell's palsy. Methods: We performed a secondary analysis of a prospective multicenter randomized controlled trial of acupuncture for Bell's palsy. Patients were randomly assigned to the de qi and control groups, respectively. The primary outcome was facial nerve function at month 6. The intensity of each needle sensation was rated by a visual analog scale. Psychosocial factors were assessed by the pretreatment mediator questionnaire; 16 Personality Factor Questionnaire (16PF) was used for assessing personality factors and digit cancellation test for assessing attention. Results: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR]: 4.16, 95% confidence interval [CI]: 2.23–7.78). Path analysis showed that intensity of needle sensation of fullness had direct effect on House-Brackmann (HB) score at month 6. In de qi group, the low HB score on day 1 (OR: 0.13, 95% CI: 0.03–0.45) and the low Social Boldness score (OR: 0.63, 95% CI: 0.41–0.97) in 16PF were associated with better facial function. In control group, low HB score on day 1 (OR: 0.25, 95% CI: 0.13–0.50), low Vigilance score (OR: 0.66, 95% CI: 0.50–0.88), and high Tension score (OR: 1.41, 95% CI: 1.12–1.77) in 16PF were related to better facial function. Conclusions: The needle sensation of fullness could predict better facial function and personality traits might influence outcomes of acupuncture treatment. Both of them should be considered seriously in acupuncture treatment and research. PMID:27453226

  20. Primary hemiarthroplasty versus conservative treatment for comminuted fractures of the proximal humerus in the elderly (ProCon): A Multicenter Randomized Controlled trial

    PubMed Central

    2010-01-01

    Background Fractures of the proximal humerus are associated with a profound temporary and sometimes permanent, impairment of function and quality of life. The treatment of comminuted fractures of the proximal humerus like selected three-or four-part fractures and split fractures of the humeral head is a demanding and unresolved problem, especially in the elderly. Locking plates appear to offer improved fixation; however, screw cut-out rates ranges due to fracture collapse are high. As this may lead to higher rates of revision surgery, it may be preferable to treat comminuted fractures in the elderly primarily with a prosthesis or non-operatively. Results from case series and a small-sample randomized controlled trial (RCT) suggest improved function and less pain after primary hemiarthroplasty (HA); however these studies had some limitations and a RCT is needed. The primary aim of this study is to compare the Constant scores (reflecting functional outcome and pain) at one year after primary HA versus non-operative treatment in elderly patients who sustained a comminuted proximal humeral fracture. Secondary aims include effects on functional outcome, pain, complications, quality of life, and cost-effectiveness. Methods/Design A prospective, multi-center RCT will be conducted in nine centers in the Netherlands and Belgium. Eighty patients over 65 years of age, who have sustained a three-or four part, or split head proximal humeral fracture will be randomized between primary hemiarthroplasty and conservative treatment. The primary outcome is the Constant score, which indicates pain and function. Secondary outcomes include the Disability of the Arm and Shoulder (DASH) score, Visual Analogue Scale (VAS) for pain, radiographic healing, health-related quality of life (Short-form-36, EuroQol-5D) and healthcare consumption. Cost-effectiveness ratios will be determined for both trial arms. Outcome will be monitored at regular intervals over the subsequent 24 months (1, 3 and

  1. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

    PubMed Central

    Rauš, Karel; Pleschka, Stephan; Klein, Peter; Schoop, Roland; Fisher, Peter

    2015-01-01

    Background Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu. Objectives This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza. Methods Following informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea-based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (2-sided) and using a CI approach in the per-protocol sample. Results Recovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487–0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink. Conclusions Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive

  2. Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

    PubMed Central

    de Vos, Alexander M; Rutten, Annemarieke; van de Zaag-Loonen, Hester J; Bots, Michiel L; Dikkers, Riksta; Buiskool, Robert A; Mali, Willem P; Lubbers, Daniel D; Mosterd, Arend; Prokop, Mathias; Rensing, Benno J; Cramer, Maarten J; van Es, H Wouter; Moll, Frans L; van de Pavoordt, Eric D; Doevendans, Pieter A; Velthuis, Birgitta K; Mackaay, Albert J; Zijlstra, Felix; Oudkerk, Matthijs

    2008-01-01

    Background Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about

  3. Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind, double-dummy, randomized controlled clinical trial

    PubMed Central

    WANG, Zhiyang; XU, Xiufeng; TAN, Qingrong; LI, Keqing; MA, Cui; XIE, Shiping; GAO, Chengge; WANG, Gang; LI, Huafang

    2015-01-01

    Background This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603). Aims Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD). Methods This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40–60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial. Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention-to-treat (ITT) method with 146 in the experimental group and 150 in the control group. Results Both groups experienced 29 dropouts during the 8-week trial. HAMD-17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X2=0.62 p=0.433), remission rate (41.1% v. 51.3%, X2=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X2=0.14, p=0.705). Conclusions Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China. PMID:26549959

  4. A prospective, randomized, double-blind, and multicenter trial of prophylactic effects of ramosetronon postoperative nausea and vomiting (PONV) after craniotomy: comparison with ondansetron

    PubMed Central

    2014-01-01

    Background Craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). This prospective, randomized, double-blind, multi-center study was performed to evaluate the efficacy of prophylactic ramosetron in preventing PONV compared with ondansetron after elective craniotomy in adult patients. Methods A total of 160 American Society of Anesthesiologists physical status I–II patients aged 19–65 years who were scheduled to undergo elective craniotomy for various intracranial lesions were enrolled in this study. All patients received total intravenous anesthesia (TIVA) with propofol and remifentanil. Patients were randomly allocated into three groups to receive ondansetron (4 mg; group A, n  =  55), ondansetron (8 mg; group B, n  =  54), or ramosetron (0.3 mg; group C, n  =  51) intravenously at the time of dural closure. The incidence of PONV, the need for rescue antiemetics, pain score, patient-controlled analgesia (PCA) consumption, and adverse events were recorded 48 h postoperatively. Results Among the initial 160 patients, 127 completed the study and were included in the final analysis. The incidences of PONV were lower (nausea, 14% vs. 59% and 41%, respectively; P  <  0.001; vomiting, P  =  0.048) and the incidence of complete response was higher (83% vs. 37% and 59%, respectively; P  <  0.001) in group C than in groups A and B at 48 h postoperatively. There were no significant differences in the incidence of PONV or need for rescue antiemetics 0–2 h postoperatively, but significant differences were observed in the incidence of PONV and complete response among the three groups 2–48 h postoperatively. No statistically significant intergroup differences were observed in postoperative pain, PCA consumption, or adverse events. Conclusion Intravenous administration of ramosetron at 0.3 mg reduced the incidence of PONV and rescue antiemetic requirement in craniotomy patients

  5. Two-year clinical outcomes of a multicenter randomized controlled trial comparing two interspinous spacers for treatment of moderate lumbar spinal stenosis

    PubMed Central

    2014-01-01

    Background Interspinous spacers are a minimally invasive surgical alternative for patients with lumbar spinal stenosis (LSS) unresponsive to conservative care. The purpose of this prospective, multicenter, randomized, controlled trial was to compare 2-year clinical outcomes in patients with moderate LSS treated with the Superion® (Experimental) or the X-Stop®, a FDA-approved interspinous spacer (Control). Methods A total of 250 patients with moderate LSS unresponsive to conservative care were randomly allocated to treatment with the Experimental (n = 123) or Control (n = 127) interspinous spacer and followed through 2 years post-treatment. Complication data were available for all patients and patient-reported outcomes were available for 192 patients (101 Experimental, 91 Control) at 2 years. Results Zurich Claudication Questionnaire (ZCQ) Symptom Severity and Physical Function scores improved 34% to 36% in both groups through 2 years (all p < 0.001). Patient Satisfaction scores at 2 years were 1.8 ± 0.9 with Experimental and 1.6 ± 0.8 with Control. Axial pain decreased from 59 ± 26 mm at baseline to 21 ± 26 mm at 2 years with Experimental and from 55 ± 26 mm to 21 ± 25 mm with Control (both p < 0.001). Extremity pain decreased from 67 ± 24 mm to 14 ± 22 mm at 2 years with Experimental and from 63 ± 24 mm to 18 ± 23 mm with Control (both p < 0.001). Back function assessed with the Oswestry Disability Index similarly improved with Experimental (37 ± 12% to 18 ± 16%) and Control (39 ± 12% to 20 ± 16%) (both p < 0.001). Freedom from reoperation at the index level was 84% for Experimental and 83% for Control (log-rank: p = 0.38) at 2 years. Conclusions Both interspinous spacers effectively alleviated pain and improved back function to a similar degree through 2 years in patients with moderate LSS who were unresponsive to conservative care. Trial

  6. Effectiveness and safety of generic memantine hydrochloride manufactured in China in the treatment of moderate to severe Alzheimer's disease: a multicenter, double-blind randomized controlled trial

    PubMed Central

    Zhu, Minjie; Xiao, Shifu; Li, Guanjun; Li, Xia; Tang, Mouni; Yang, Siming; Xu, Xiufeng; Feng, Lianyuan; Liu, Kaixiang; Hu, Lianping

    2013-01-01

    Background Memantine hydrochloride is a N-methyl-D-aspartate (NMDA) antagonist that may be useful in the treatment of Alzheimer's disease. Aim Compare the efficacy and safety of generic memantine hydrochloride produced in China to that of the imported proprietary version of the medication (Ebixa) in the treatment of moderate to severe Alzheimer's disease (AD). Methods In this multicenter, double-blind randomized controlled trial 229 patients with moderate to severe AD were randomly assigned to a 16-week trial of either the generic preparation or the proprietary preparation of memantine hydrochloride. All participants were assessed at baseline and at 4, 8, 12 and 16 weeks after enrolment. The primary outcome variable was the Alzheimer Disease Assessment Scale-cognition (ADAS-Cog) score. Secondary outcomes were scores in the Mini-Mental State Examination (MMSE), the Activities of Daily Living (ADL) scale and the Clinical Global Impression (CGI) scale. Results Sample sizes for the safety set (SS) analysis, full analysis set (FAS) and per protocol set (PPS) analysis were 112, 109 and 103 in the generic medication group, and 111, 107 and 101 in the proprietary medication group, respectively. The ADAS-Cog and ADL total scores at the end of weeks 4, 8, 12, and 16 decreased significantly compared with baseline for both groups (p<0.001) and the MMSE total scores at the end of weeks 4, 8, 12, and 16 increased significantly compared with baseline for both groups (p<0.001). There were no significant differences in ADAS-Cog total scores, ADL total scores and level of improvement based on the CGI scores between the two groups at any of the follow-up assessments. The occurrence of adverse events was 20.5% in the generic medication group and 27.0% in the proprietary medication group; this difference was not statistically significant (χ2=1.30, p=0.255). Conclusion There are no significant differences in the effectiveness or safety between memantine that is generically produced in

  7. Laparoscopic bridging vs. anatomic open reconstruction for midline abdominal hernia mesh repair [LABOR]: single-blinded, multicenter, randomized, controlled trial on long-term functional results

    PubMed Central

    2013-01-01

    Background Re-approximation of the rectal muscles along the midline is recommended by some groups as a rule for incisional and ventral hernia repairs. The introduction of laparoscopic repair has generated a debate because it is not aimed at restoring abdominal wall integrity but instead aims just to bridge the defect. Whether restoration of the abdominal integrity has a real impact on patient mobility is questionable, and the available literature provides no definitive answer. The present study aims to compare the functional results of laparoscopic bridging with those of re-approximation of the rectal muscle in the midline as a mesh repair for ventral and incisional abdominal defect through an “open” access. We hypothesized that, for the type of defect suitable for a laparoscopic bridging, the effect of an anatomical reconstruction is near negligible, thus not a fixed rule. Methods and design The LABOR trial is a multicenter, prospective, two-arm, single-blinded, randomized trial. Patients of more than 60 years of age with a defect of less than 10 cm at its greatest diameter will be randomly submitted to open Rives or laparoscopic defect repair. All the participating patients will have a preoperative evaluation of their abdominal wall strength and mobility along with volumetry, respiratory function test, intraabdominal pressure and quality of life assessment. The primary outcome will be the difference in abdominal wall strength as measured by a double leg-lowering test performed at 12 months postoperatively. The secondary outcomes will be the rate of recurrence and changes in baseline abdominal mobility, respiratory function tests, intraabdominal pressure, CT volumetry and quality of life at 6 and 12 months postoperatively. Discussion The study will help to define the most suitable treatment for small-medium incisional and primary hernias in patients older than 60 years. Given a similar mid-term recurrence rate in both groups, if the trial shows no differences

  8. Wavefront watermarking of technical and biological samples using digital random phase modulation and phase retrieval

    NASA Astrophysics Data System (ADS)

    Carpio, Justine Patricia L.; Almoro, Percival F.

    2014-10-01

    A technique for digital watermarking of smooth object wavefronts using digital random phase modulation and multiple-plane iterative phase retrieval is demonstrated experimentally. A complex-valued watermark is first encrypted using two random phase masks of known distributions before being superposed onto a set of host wavefront intensity patterns. Encryption scaling factor and depth of randomization of the masks are optimized such that the amplitude and phase watermarks are decrypted successfully and are not distorting the host wavefront. Given that the watermarked intensity patterns and the numerous decryption keys are available (i.e. distances between recording planes, light source wavelength, pixel size, random phase masks and their distances to the planes are all known), increasing the number of watermarked patterns used results in enhanced quality of decrypted watermarks. The main advantage of wavefront watermarking via the phase retrieval approach compared to the holographic approach is the avoidance of reference wave-induced aberration. Watermarking of wavefronts from lenses and unstained human cheek cells demonstrate the effectiveness of the technique.

  9. Antireflux versus conventional self-expanding metallic Stents (SEMS) for distal esophageal cancer: results of a multicenter randomized trial

    PubMed Central

    Coron, E.; David, G.; Lecleire, S.; Jacques, J.; Le Sidaner, A.; Barrioz, T.; Coumaros, D.; Volteau, C.; Vedrenne, B.; Bichard, P.; Boustière, C.; Touchefeu, Y.; Brégeon, J.; Prat, F.; Le Rhun, M.

    2016-01-01

    Introduction: Self-expanding metal stents (SEMS) are commonly used in the palliation of dysphagia in patients with inoperable esophageal carcinoma. However, they predispose to gastroesophageal reflux when deployed across the gastroesophageal junction. The aims of this study were to: 1) assess the influence of the antireflux valve on trans-prosthetic reflux (primary outcome); and 2) compare the results of SEMS with and without antireflux valve in terms of reflux symptoms, quality of life (QOL), improvement of dysphagia and adverse events (secondary outcomes). Patients and methods: Thirty-eight patients were enrolled in nine centers. Carcinomas were locally advanced (47 %) or metastatic. After randomization, patients received either a covered SEMS with antireflux valve (n = 20) or a similar type of SEMS with no antireflux device but assigned to standard proton pump inhibitor therapy and postural advice (n = 18). Trans-prosthetic reflux was assessed at day 2 using a radiological score based on barium esophagography performed after Trendelenburg maneuver and graded from 0 (no reflux) to 12 (maximum). Monthly telephone interviews were conducted for Organisation Mondiale de la Santé (OMS) scoring from 0 (excellent) to 5 (poor), QOL assessment (based on the Reflux-Qual Simplifié scoring system) from 0 (poor) to 100 (excellent), dysphagia scoring from 0 (no dysphagia) to 5 (complete dysphagia) and regurgitation scoring from 0 (no regurgitation) to 16 (maximum). Results: No difference was noted in terms of age, sex, size of lesion, prosthesis length or need for dilation prior to SEMS placement. No difficulty in placing SEMS nor complications were noted. Radiological scores of reflux were found to be significantly lower in patients with an antireflux stent compared to the conventional stent and associated measures. The regurgitation scores were significantly decreased in patients with antireflux stents during the first 2 months after stent placement and

  10. Intravenous Ibuprofen for Treatment of Post-Operative Pain: A Multicenter, Double Blind, Placebo-Controlled, Randomized Clinical Trial

    PubMed Central

    Escontrela Rodriguez, Blanca; Planas Roca, Antonio; Martínez Ruiz, Alberto

    2016-01-01

    Background Non-steroidal anti-inflammatory drugs are often used as components of multimodal therapy for postoperative pain management, but their use is currently limited by its side effects. The specific objective of this study was to evaluate the efficacy and safety of a new formulation of intravenous (IV) ibuprofen for the management of postoperative pain in a European population. Methods and Findings A total of 206 patients from both abdominal and orthopedic surgery, were randomly assigned in 1:1 ratio to receive 800 mg IV-ibuprofen or placebo every 6 hours; all patients had morphine access through a patient controlled analgesia pump. The primary outcome measure was median morphine consumption within the first 24 hours following surgery. The mean±SEM of morphine requirements was reduced from 29,8±5,25 mg to 14,22±3,23 mg (p = 0,015) and resulted in a decrease in pain at rest (p = 0,02) measured by Visual Analog Scale (VAS) from mean±SEM 3.34±0,35 to 0.86±0.24, and also in pain during movement (p = 0,02) from 4.32±0,36 to 1.90±0,30 in the ibuprofen treatment arm; while in the placebo group VAS score at rest ranged from 4.68±0,40 to 2.12±0,42 and during movement from 5.66±0,42 to 3.38±0,44. Similar treatment-emergent adverse events occurred across both study groups and there was no difference in the overall incidence of these events. Conclusions Perioperative administration of IV-Ibuprofen 800 mg every 6 hours in abdominal surgery patient’s decreases morphine requirements and pain score. Furthermore IV-Ibuprofen was safe and well tolerate. Consequently we consider appropriate that protocols for management of postoperative pain include IV-Ibuprofen 800 mg every 6 hours as an option to offer patients an analgesic benefit while reducing the potentially risks associated with morphine consumption. Trial Registration EU Clinical Trials Register 2011-005007-33 PMID:27152748

  11. Efficacy of a dilemma-focused intervention for unipolar depression: study protocol for a multicenter randomized controlled trial

    PubMed Central

    2013-01-01

    Background Depression is one of the more severe and serious health problems because of its morbidity, disabling effects and for its societal and economic burden. Despite the variety of existing pharmacological and psychological treatments, most of the cases evolve with only partial remission, relapse and recurrence. Cognitive models have contributed significantly to the understanding of unipolar depression and its psychological treatment. However, success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them. One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence. Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory. We use a novel method for identifying those conflicts using the repertory grid technique (RGT). Preliminary results with depressive patients show that about 90% of them have one or more of those conflicts. This fact might explain the blockage and the difficult progress of these patients, especially the more severe and/or chronic. These results justify the need for specific interventions focused on the resolution of these internal conflicts. This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy (CBT) for depression. Design A therapy manual for a dilemma-focused intervention will be tested using a randomized clinical trial by comparing the outcome of two treatment conditions: combined group CBT (eight, 2-hour weekly sessions) plus individual dilemma-focused therapy (eight, 1-hour weekly sessions) and CBT alone (eight, 2-hour group weekly sessions plus eight, 1-hour individual weekly sessions). Method Participants are

  12. Efficacy and Safety of Domestic Leuprorelin in Girls with Idiopathic Central Precocious Puberty: A Multicenter, Randomized, Parallel, Controlled Trial

    PubMed Central

    Li, Wen-Jing; Gong, Chun-Xiu; Guo, Mei-Jie; Xing, Jie; Li, Tang; Song, Wen-Hui; Luo, Xiao-Ping; Wu, Di; Liang, Jian-Ping; Cao, Bing-Yan; Gu, Yi; Su, Chang; Liang, Xue-Jun; Liu, Min; Wang, Rui; Li, Feng-Ting

    2015-01-01

    Background: In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP. Methods: A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio <0.6, the improvements of secondary sexual characteristics, gonadal development and sex hormone levels, the change of growth rate of bone age (BA) and growth velocity, and drug adverse effects between two groups were compared. Results: After the treatment, the percentage of children with a suppressed LH response to GnRH, defined as a peak LH ≤3.3 U/L, at 6 months in test and control groups were 96.80% and 96.20%, respectively, and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%, respectively. The sizes of breast, uterus and ovary of children and the levels of estradiol (E2) were significantly reduced, and the growth rate of BA was also reduced. All the differences between pre- and post-treatment in each group were statistically significant (P < 0. 05), but the differences of the parameters between two groups were not significant (P > 0

  13. Doorway states in the random-phase approximation

    SciTech Connect

    De Pace, A.; Molinari, A.; Weidenmüller, H.A.

    2014-12-15

    By coupling a doorway state to a sea of random background states, we develop the theory of doorway states in the framework of the random-phase approximation (RPA). Because of the symmetry of the RPA equations, that theory is radically different from the standard description of doorway states in the shell model. We derive the Pastur equation in the limit of large matrix dimension and show that the results agree with those of matrix diagonalization in large spaces. The complexity of the Pastur equation does not allow for an analytical approach that would approximately describe the doorway state. Our numerical results display unexpected features: The coupling of the doorway state with states of opposite energy leads to strong mutual attraction.

  14. Laser-beam apodization with a graded random phase window.

    PubMed

    Haas, R A; Summers, M A; Linford, G J

    1986-10-01

    Experiments and analysis indicate that graded random phase modulation can be used to apodize a laser beam. In the case of an obscuration or a hard edge it can prevent the formation of Fresnel-diffraction ripples. For example, here the interaction of a 1-microm-wavelength laser beam with a central obscuration of half-width a = 100 microm is studied theoretically. It is found that if the exit surface of a window, placed immediately downstream of the obstacle, is randomly modulated with a Gaussian amplitude transverse correlation length l = 50 microm and a mean-square amplitude that decreases exponentially from a peak height of ~1 microm(2) away from the center of the obscuration with transverse scale length L = 500 microm, then the Fresnel-diffraction ripples normally produced by the obscuration are eliminated. The scaling of these results is also discussed. The calculations are in general agreement with experimental results. PMID:19738707

  15. The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study

    PubMed Central

    Brams, Matthew; Cutler, Andrew J.; Kollins, Scott H.; Northcutt, Jo; Padilla, Americo; Turnbow, John M.

    2015-01-01

    Abstract Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Methods: A total of 107 children ages 6–12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs). Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%). Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6–12 years with ADHD

  16. Finite amplitude method for the quasiparticle random-phase approximation

    SciTech Connect

    Avogadro, Paolo; Nakatsukasa, Takashi

    2011-07-15

    We present the finite amplitude method (FAM), originally proposed in Ref. [17], for superfluid systems. A Hartree-Fock-Bogoliubov code may be transformed into a code of the quasiparticle-random-phase approximation (QRPA) with simple modifications. This technique has advantages over the conventional QRPA calculations, such as coding feasibility and computational cost. We perform the fully self-consistent linear-response calculation for the spherical neutron-rich nucleus {sup 174}Sn, modifying the hfbrad code, to demonstrate the accuracy, feasibility, and usefulness of the FAM.

  17. Modified random phase approximation for multipole excitations at finite temperature

    SciTech Connect

    Dang, N.D. )

    1992-03-01

    The modified finite-temperature random phase approximation (FT-RPA) has been constructed by taking the influence of thermostat on the structure of quasiparticles into account. The modified FT-RPA linear response for electric quadrupole ({lambda}{sup {pi}}=2{sup +}) and octupole ({lambda}{sup {pi}}=3{sup {minus}}) excitations in {sup 58}Ni has been calculated as a function of the nuclear temperature. As compared to the conventional FT-RPA, the modified FT-RPA has given a stronger spreading for the strength distribution of quadrupole excitations at finite temperature {ital T}{le}3 MeV.

  18. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    HASSAN, S. S.; ROMERO, R.; VIDYADHARI, D.; FUSEY, S.; BAXTER, J. K.; KHANDELWAL, M.; VIJAYARAGHAVAN, J.; TRIVEDI, Y.; SOMA-PILLAY, P.; SAMBAREY, P.; DAYAL, A.; POTAPOV, V.; O’BRIEN, J.; ASTAKHOV, V.; YUZKO, O.; KINZLER, W.; DATTEL, B.; SEHDEV, H.; MAZHEIKA, L.; MANCHULENKO, D.; GERVASI, M. T.; SULLIVAN, L.; CONDE-AGUDELO, A.; PHILLIPS, J. A.; CREASY, G. W.

    2012-01-01

    Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the ef cacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10–20 mm) at 19 + 0to23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred rst. Randomization sequence was strati ed by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33–0.92; P = 0.02). The effect remained signi cant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31–0.91; P = 0.02). Vaginal progesterone was also associated with a signi cant reduction in the rate of preterm birth before 28 weeks(5.1%vs10.3%; RR, 0.50;95%CI, 0.25–0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42–0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17–0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33–0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26–0.85; P = 0.01). There were no differences

  19. A new phase of disordered phonons modelled by random matrices

    NASA Astrophysics Data System (ADS)

    Schmittner, Sebastian; Zirnbauer, Martin

    2015-03-01

    Starting from the clean harmonic crystal and not invoking two-level systems, we propose a model for phonons in a disordered solid. In this model the strength of mass and spring constant disorder can be increased separately. Both types of disorder are modelled by random matrices that couple the degrees of freedom locally. Treated in coherent potential approximation (CPA), the speed of sound decreases with increasing disorder until it reaches zero at finite disorder strength. There, a critical transition to a strong disorder phase occurs. In this novel phase, we find the density of states at zero energy in three dimensions to be finite, leading to a linear temperature dependence of the heat capacity, as observed experimentally for vitreous systems. For any disorder strength, our model is stable, i.e. masses and spring constants are positive, and there are no runaway dynamics. This is ensured by using appropriate probability distributions, inspired by Wishart ensembles, for the random matrices. The CPA self-consistency equations are derived in a very accessible way using planar diagrams. The talk focuses on the model and the results. The first author acknowledges financial support by the Deutsche Telekom Stiftung.

  20. The peculiar phase structure of random graph bisection

    SciTech Connect

    Percus, Allon G; Istrate, Gabriel; Goncalves, Bruno T; Sumi, Robert Z

    2008-01-01

    The mincut graph bisection problem involves partitioning the n vertices of a graph into disjoint subsets, each containing exactly n/2 vertices, while minimizing the number of 'cut' edges with an endpoint in each subset. When considered over sparse random graphs, the phase structure of the graph bisection problem displays certain familiar properties, but also some surprises. It is known that when the mean degree is below the critical value of 2 log 2, the cutsize is zero with high probability. We study how the minimum cutsize increases with mean degree above this critical threshold, finding a new analytical upper bound that improves considerably upon previous bounds. Combined with recent results on expander graphs, our bound suggests the unusual scenario that random graph bisection is replica symmetric up to and beyond the critical threshold, with a replica symmetry breaking transition possibly taking place above the threshold. An intriguing algorithmic consequence is that although the problem is NP-hard, we can find near-optimal cutsizes (whose ratio to the optimal value approaches 1 asymptotically) in polynomial time for typical instances near the phase transition.

  1. A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study

    PubMed Central

    Mishra, S; Xu, J; Agarwal, U; Gonzales, J; Levin, S; Barnard, N D

    2013-01-01

    Background/objectives: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. Subjects/methods: Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. Results: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01). Among study completers, mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P<0.01). Conclusions: An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight, plasma lipids, and, in individuals with diabetes, glycemic control. PMID:23695207

  2. Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial

    PubMed Central

    2013-01-01

    Background Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is a subtype of stroke that causes a great amount of disability and economic and social burden. This is particularly true in developing countries where it accounts for between 20% and 50% of all strokes. Pharmacological and surgical interventions have been attempted to reduce the mortality and disability caused by ICH, with unsuccessful results. Recently, the use of fluoxetine in addition to physical rehabilitation has been proven useful to improve motor recovery following cerebral infarct. The purpose of this study is to test whether a 3-month treatment with fluoxetine enhances motor recovery in nondepressed patients with acute intracerebral hemorrhage. Methods/design Our study is a randomized, double-blind, placebo-controlled, multicenter clinical trial. We will recruit 86 patients with intracerebral hemorrhage of both sexes, aged >18 years, from four Mexican hospitals. The patients will receive either 20 mg of fluoxetine or a placebo once daily for 90 days. The primary outcome is the mean change in the Fugl-Meyer Motor Scale score between inclusion (day 0) and day 90. The secondary outcomes will be changes in the Barthel Index, the Modified Rankin scale and the National Institutes of Health stroke scale. The outcomes will be measured at day 42 ± 7days and at day 90, for a total of four visits with each subject (at screening and at 0, 42 and 90 days). Discussion Current guidelines recommend early supported hospital discharge and home-based rehabilitation programs as the only cost-effective intervention to aid the recovery of patients with intracerebral hemorrhage. Nevertheless, such interventions are dependent on available resources and funding, which make them very difficult to implement in developing countries. We believe that the identification of a helpful pharmacological intervention to aid the motor recovery of these patients will constitute a breakthrough that will have a major impact in

  3. A prospective randomized multicenter trial of amnioreduction versus selective fetoscopic laser photocoagulation for the treatment of severe twin–twin transfusion syndrome

    PubMed Central

    Crombleholme, Timothy M.; Shera, David; Lee, Hanmin; Johnson, Mark; D’Alton, Mary; Porter, Flint; Chyu, Jacquelyn; Silver, Richard; Abuhamad, Alfred; Saade, George; Shields, Laurence; Kauffman, David; Stone, Joanne; Albanese, Craig T.; Bahado-Singh, Ray; Ball, Robert H.; Bilaniuk, Larissa; Coleman, Beverly; Farmer, Diana; Feldstein, Vickie; Harrison, Michael R.; Hedrick, Holly; Livingston, Jeffrey; Lorenz, Robert P.; Miller, David A.; Norton, Mary E.; Polzin, William J.; Robinson, Julian N.; Rychik, Jack; Sandberg, Per L.; Seri, Istvan; Simon, Erin; Simpson, Lynn L.; Yedigarova, Larisa; Wilson, R. Douglas; Young, Bruce

    2009-01-01

    Objective To examine the effect of selective fetoscopic laser photocoagulation (SFLP) versus serial amnioreduction (AR) on perinatal mortality in severe twin-twin transfusion syndrome (TTTS). Study Design 5-year multicenter prospective randomized controlled trial. The primary outcome variable was 30-day postnatal survival of donors and recipients. Results There is no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11/20) vs 55% (11/20) (p=1, OR=1, 95%CI=0.242 to 4.14) or recipients at 30% (6/20) vs 45% (9/20) (p=0.51, OR=1.88, 95%CI=0.44 to 8.64). There is no difference in 30-day survival of one or both twins on a per pregnancy basis between AR at 75% (15/20) and SFLP at 65% (13/20) (p=0.73, OR=1.62, 95%CI=0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) is not statistically significant for AR at 60% (24/40) vs SFLP 45% (18/40) (p=0.18, OR=2.01, 95%CI=0.76 to 5.44). There is a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14/20) versus the AR arm at 35% (7/20) (p=0.25, OR=5.31, 95%CI=1.19 to 27.6). This is offset by increased recipient neonatal mortality of 30% (6/20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality (p=0.055, OR=3.025/point) by logistic regression analysis. Conclusions The outcome of the trial does not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS. PMID:17904975

  4. Cefepime versus Imipenem-Cilastatin for Treatment of Nosocomial Pneumonia in Intensive Care Unit Patients: a Multicenter, Evaluator-Blind, Prospective, Randomized Study

    PubMed Central

    Zanetti, G.; Bally, F.; Greub, G.; Garbino, J.; Kinge, T.; Lew, D.; Romand, J.-A.; Bille, J.; Aymon, D.; Stratchounski, L.; Krawczyk, L.; Rubinstein, E.; Schaller, M.-D.; Chiolero, R.; Glauser, M.-P.; Cometta, A.

    2003-01-01

    In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (−16 to 8%) failed to exclude the predefined lower limit for noninferiority of −15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum β-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, −9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, −23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological

  5. Efficacy and Safety of Avandamet or Uptitrated Metformin Treatment in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Alone: A Multicenter, Randomized, Controlled Trial

    PubMed Central

    Cai, Xiao-Ling; Chen, Ying-Li; Zhao, Jia-Jun; Shan, Zhong-Yan; Qiu, Ming-Cai; Li, Cheng-Jiang; Gu, Wei; Tian, Hao-Ming; Yang, Hua-Zhang; Xue, Yao-Ming; Yang, Jin-Kui; Hong, Tian-Pei; Ji, Li-Nong

    2015-01-01

    Background: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. Methods: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5–9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. Results: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. Conclusions: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. Registration number: ChiCTR-TRC-13003776. PMID:25963345

  6. A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto™ (fluralaner) against Frontline™ (fipronil) in flea- and tick-infested dogs

    PubMed Central

    2014-01-01

    Background Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs. Methods A randomized, investigator-blinded, multi-centered field study compared the flea- and tick-control efficacy for dogs over a 12-week period with either a single oral dose of Bravecto™ (fluralaner) formulated as a chewable tablet or with three sequential topical Frontline™ (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto™ (fluralaner) and 54 tick-infested dogs were treated with Frontline™ (fipronil). Dogs in 115 flea-infested households received Bravecto™ (fluralaner) and dogs in 61 flea-infested households received Frontline™ (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tick-free and flea-free households were determined. Results At weeks 2, 4, 8, and 12, Bravecto™ (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline™ (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto™ (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and Frontline™ (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline™ (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion. Conclusions

  7. Treatment of Basal Cell Carcinoma Using a One-Stop-Shop With Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

    PubMed Central

    Wolkerstorfer, Albert; Elshot, Yannick; Zupan-Kajcovski, Biljana; Crijns, Marianne B; Starink, Markus V; Bekkenk, Marcel W; van der Wal, Allard C; Spuls, Phyllis I; de Rie, Menno A

    2015-01-01

    Background Basal cell carcinoma (BCC) is the most common cancer diagnosed in white populations worldwide. The rising incidence of BCC is becoming a major worldwide public health problem. Therefore, there is a need for more efficient management. Objective The aim of this research is to assess the efficacy and safety of a one-stop-shop (OSS) concept, using real-time in vivo reflectance confocal microscopy (RCM) (Vivascope 1500; Lucid Technologies, Henrietta, NY, USA) as a diagnostic tool, prior to surgical management of new primary BCCs. Methods This is a prospective non-inferiority multi-center RCT designed to compare the “OSS concept using RCM” to current standards of care in diagnosing and treating clinically suspected BCC. Patients ≥ 18 years attending our outpatient clinic at the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Department of Dermatology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (Amsterdam, The Netherlands) with a clinically suspected new primary BCC lesion will be considered for enrollment using predefined inclusion and exclusion criteria, and will be randomly allocated to the experimental or control group. The main outcome parameter is the assessment of incomplete surgical excision margins on the final pathology report of confirmed BCC lesions (either by punch biopsy or RCM imaging). Other outcome measures include diagnostic accuracy (sensitivity and specificity) of RCM for diagnosing BCC and dividing between subtypes, and throughput time. Patient satisfaction data will be collected postoperatively after 3 months during routine follow-up. Results This research is investigator-initiated and received ethics approval. Patient recruitment started in February 2015, and we expect all study-related activities to be completed by fall 2015. Conclusions This RCT is the first to examine an OSS concept using RCM for diagnosing and treating clinically suspected BCC lesions. Results of this

  8. ICT-based system to predict and prevent falls (iStoppFalls): study protocol for an international multicenter randomized controlled trial

    PubMed Central

    2014-01-01

    Background Falls are very common, especially in adults aged 65 years and older. Within the current international European Commission’s Seventh Framework Program (FP7) project ‘iStoppFalls’ an Information and Communication Technology (ICT) based system has been developed to regularly assess a person’s risk of falling in their own home and to deliver an individual and tailored home-based exercise and education program for fall prevention. The primary aims of iStoppFalls are to assess the feasibility and acceptability of the intervention program, and its effectiveness to improve balance, muscle strength and quality of life in older people. Methods/Design This international, multicenter study is designed as a single-blinded, two-group randomized controlled trial. A total of 160 community-dwelling older people aged 65 years and older will be recruited in Germany (n = 60), Spain (n = 40), and Australia (n = 60) between November 2013 and May 2014. Participants in the intervention group will conduct a 16-week exercise program using the iStoppFalls system through their television set at home. Participants are encouraged to exercise for a total duration of 180 minutes per week. The training program consists of a variety of balance and strength exercises in the form of video games using exergame technology. Educational material about a healthy lifestyle will be provided to each participant. Final reassessments will be conducted after 16 weeks. The assessments include physical and cognitive tests as well as questionnaires assessing health, fear of falling, quality of life and psychosocial determinants. Falls will be followed up for six months by monthly falls calendars. Discussion We hypothesize that the regular use of this newly developed ICT-based system for fall prevention at home is feasible for older people. By using the iStoppFalls sensor-based exercise program, older people are expected to improve in balance and strength outcomes. In addition, the exercise

  9. Increased masticatory activity and quality of life in elderly persons with dementia-a longitudinal matched cluster randomized single-blind multicenter intervention study

    PubMed Central

    2013-01-01

    Background Worldwide, millions of people are suffering from dementia and this number is rising. An index of quality of life (QoL) can describe the impact a disease or treatment has on a person’s wellbeing. QoL comprises many variables, including physical health and function, and mental health and function. QoL is related to masticatory ability and physical activity. Animal studies show that disruption of mastication due to loss of teeth or a soft diet leads to memory loss and learning problems. Since these are common complaints in dementia, it is hypothesized that improvement of masticatory function and normalization of diet consistency can increase QoL in elderly persons suffering from dementia. Therefore, the goal of the present study is to examine whether an increase in masticatory activity, achieved by increased food consistency and enhancement of masticatory function through improved oral health care has a positive effect on QoL, including cognition, mood, activities of daily living (ADL), and circadian rhythm in elderly persons with dementia. Methods and design The described study is a prospective longitudinal matched cluster randomized single-blind multicenter study. Participants are elderly persons living in the Netherlands, suffering from dementia and receiving psychogeriatric care. An intervention group will receive improved oral health care and a diet of increased consistency. A control group receives care as usual. Participants will be assessed four times; outcome variables besides QoL are cognition, mood, independence, rest-activity rhythm, blood pressure, and masticatory function. Discussion This research protocol investigates the effect of an intervention executed by daily caregivers. The intervention will increase masticatory activity, which is achieved by three different actions, (providing oral health care, increasing food consistency, or a combination of both). There is a certain amount of variety in the nature of the interventions due to local

  10. Effects of Poly-Bioactive Compounds on Lipid Profile and Body Weight in a Moderately Hypercholesterolemic Population with Low Cardiovascular Disease Risk: A Multicenter Randomized Trial

    PubMed Central

    Solà, Rosa; Valls, Rosa-M; Puzo, José; Calabuig, José-Ramón; Brea, Angel; Pedret, Anna; Moriña, David; Villar, José; Millán, Jesús; Anguera, Anna

    2014-01-01

    A dietary supplement (AP, Armolipid Plus) that combines red yeast rice extract, policosanol, berberine, folic acid, coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease (CVD) biomarkers. The aim of this study was to assess whether the intake of AP, in combination with dietary recommendations, reduces serum low density lipoprotein cholesterol (LDL-c) concentrations and other CVD biomarkers in patients with hypercholesterolemia. Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío (Sevilla); Hospital San Jorge (Huesca); Hospital San Pedro (Logroño); Hospital Gregorio Marañón (Madrid), Hospital la Fe (Valencia) and Hospital Universitari Sant Joan (Reus) as recruiting and coordinating center. 102 participants (mean age ± SD; 50.91±11.61; 32 men) with low CVD, with mild-to-moderately elevated LDL-c (between 3.35 mmol/L and 4.88 mmol/L) without hypolipemic therapy were randomized in a double-blind, parallel, controlled, multicenter trial commencing January 2012 and ending December 2012. Among the exclusion criteria were any concomitant chronic disease, triglycerides (TG) >3.97 mmol/L, pregnant or lactating, and history of CVD. At 12 weeks, compared to placebo, AP reduced LDL-c by −6.9%, apolipoprotein (Apo) B-100 by −6.6% and total cholesterol/HDL-c ratio by −5.5%, the ApoB/ApoA1 ratio by −8.6%, while increasing ApoA1 by +2.5% (p<0.05). AP consumption was associated with modest mean weight loss of −0.93 kg (95%CI: -1.74 to -0.12; P = 0.02) compared with control group while dietary composition remained unchanged in the AP group. The AP product was well tolerated. In conclusion, AP, combined with dietary recommendations, reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios, while increasing Apo A1, all of which are improvements in CVD risk indicators. AP is a product which could benefit patients having moderate hyperlipidemia and excess

  11. Glassy phases and driven response of the phase-field-crystal model with random pinning.

    PubMed

    Granato, E; Ramos, J A P; Achim, C V; Lehikoinen, J; Ying, S C; Ala-Nissila, T; Elder, K R

    2011-09-01

    We study the structural correlations and the nonlinear response to a driving force of a two-dimensional phase-field-crystal model with random pinning. The model provides an effective continuous description of lattice systems in the presence of disordered external pinning centers, allowing for both elastic and plastic deformations. We find that the phase-field crystal with disorder assumes an amorphous glassy ground state, with only short-ranged positional and orientational correlations, even in the limit of weak disorder. Under increasing driving force, the pinned amorphous-glass phase evolves into a moving plastic-flow phase and then, finally, a moving smectic phase. The transverse response of the moving smectic phase shows a vanishing transverse critical force for increasing system sizes. PMID:22060323

  12. NONLINEAR-OPTICS PHENOMENA: Phase fluctuations in waves reflected from a phase-conjugate mirror in a randomly inhomogeneous medium

    NASA Astrophysics Data System (ADS)

    Almaev, R. Kh; Suvorov, A. A.

    1993-09-01

    We investigate the statistical characteristics of the phase of a wave propagating along a ranging path that includes a phase-conjugate mirror through a medium whose complex permittivity ɛ varies randomly. We obtain expressions for the mean change and variance of fluctuations in the phase of a plane wave. We show that phase fluctuations caused by the random changes of the imaginary part of ɛ are not canceled by the phase-conjugate mirror. We obtain conditions for the appearance of enhanced backward scattering in comparison with the mean phase and variance of phase fluctuations for the reflected wave in this absorbing, randomly inhomogeneous medium.

  13. A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial

    PubMed Central

    Cusato, Maria; Ingelmo, Pablo; Niebel, Thekla Larissa; Somaini, Marta; Riva, Francesca; Tinelli, Carmine; De Andrés, José; Fanelli, Guido; Braschi, Antonio; Regazzi, Mario; Allegri, Massimo

    2015-01-01

    BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion

  14. A mathematical formulation of the random phase approximation for crystals

    NASA Astrophysics Data System (ADS)

    Cancès, Eric; Stoltz, Gabriel

    2012-11-01

    This works extends the recent study on the dielectric permittivity of crystals within the Hartree model [E. Cances and M. Lewin, Arch. Rational Mech. Anal., 197 (2010) 139--177] to the time-dependent setting. In particular, we prove the existence and uniqueness of the nonlinear Hartree dynamics (also called the random phase approximation in the physics literature), in a suitable functional space allowing to describe a local defect embedded in a perfect crystal. We also give a rigorous mathematical definition of the microscopic frequency-dependent polarization matrix, and derive the macroscopic Maxwell-Gauss equation for insulating and semiconducting crystals, from a first order approximation of the nonlinear Hartree model, by means of homogenization arguments.

  15. Continuum random-phase approximation for relativistic point coupling models

    SciTech Connect

    Daoutidis, J.; Ring, P.

    2009-08-15

    Continuum relativistic random-phase approximation (CRPA) is used to investigate collective excitation phenomena in several spherical nuclei along the periodic table. We start from relativistic mean-field calculations based on a covariant density functional with density-dependent zero-range forces. From the same functional an effective interaction is obtained as the second derivative with respect to the density. This interaction is used in relativistic CRPA calculations for the investigation of isoscalar monopole, isovector dipole, and isoscalar quadrupole resonances of spherical nuclei. In particular we study the low-lying E1 strength in the vicinity of the neutron evaporation threshold. The properties of the resonances, such as centroid energies and strengths distributions are compared with results of discrete RPA calculations for the same model as well as with experimental data.

  16. Phase transitions in the coloring of random graphs.

    PubMed

    Zdeborová, Lenka; Krzakała, Florent

    2007-09-01

    We consider the problem of coloring the vertices of a large sparse random graph with a given number of colors so that no adjacent vertices have the same color. Using the cavity method, we present a detailed and systematic analytical study of the space of proper colorings (solutions). We show that for a fixed number of colors and as the average vertex degree (number of constraints) increases, the set of solutions undergoes several phase transitions similar to those observed in the mean field theory of glasses. First, at the clustering transition, the entropically dominant part of the phase space decomposes into an exponential number of pure states so that beyond this transition a uniform sampling of solutions becomes hard. Afterward, the space of solutions condenses over a finite number of the largest states and consequently the total entropy of solutions becomes smaller than the annealed one. Another transition takes place when in all the entropically dominant states a finite fraction of nodes freezes so that each of these nodes is allowed a single color in all the solutions inside the state. Eventually, above the coloring threshold, no more solutions are available. We compute all the critical connectivities for Erdos-Rényi and regular random graphs and determine their asymptotic values for a large number of colors. Finally, we discuss the algorithmic consequences of our findings. We argue that the onset of computational hardness is not associated with the clustering transition and we suggest instead that the freezing transition might be the relevant phenomenon. We also discuss the performance of a simple local Walk-COL algorithm and of the belief propagation algorithm in the light of our results. PMID:17930223

  17. Exploring the Random Phase Approximately for materials chemistry and physics

    SciTech Connect

    Ruzsinsky, Adrienn

    2015-03-23

    This proposal focuses on improved accuracy for the delicate energy differences of interest in materials chemistry with the fully nonlocal random phase approximation (RPA) in a density functional context. Could RPA or RPA-like approaches become standard methods of first-principles electronic-structure calculation for atoms, molecules, solids, surfaces, and nano-structures? Direct RPA includes the full exact exchange energy and a nonlocal correlation energy from the occupied and unoccupied Kohn-Sham orbitals and orbital energies, with an approximate but universal description of long-range van der Waals attraction. RPA also improves upon simple pair-wise interaction potentials or vdW density functional theory. This improvement is essential to capture accurate energy differences in metals and different phases of semiconductors. The applications in this proposal are challenges for the simpler approximations of Kohn-Sham density functional theory, which are part of the current “standard model” for quantum chemistry and condensed matter physics. Within this project we already applied RPA on different structural phase transitions on semiconductors, metals and molecules. Although RPA predicts accurate structural parameters, RPA has proven not equally accurate in all kinds of structural phase transitions. Therefore a correction to RPA can be necessary in many cases. We are currently implementing and testing a nonempirical, spatially nonlocal, frequency-dependent model for the exchange-correlation kernel in the adiabatic-connection fluctuation-dissipation context. This kernel predicts a nearly-exact correlation energy for the electron gas of uniform density. If RPA or RPA-like approaches prove to be reliably accurate, then expected increases in computer power may make them standard in the electronic-structure calculations of the future.

  18. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

    PubMed Central

    Liu, Mei-Ching; Lee, Soo Chin; Vanlemmens, Laurence; Ferrero, Jean-Marc; Tabei, Toshio; Pivot, Xavier; Iwata, Hiroji; Aogi, Kenjiro; Lugo-Quintana, Roberto; Harbeck, Nadia; Brickman, Marla J.; Zhang, Ke; Kern, Kenneth A.; Martin, Miguel

    2010-01-01

    This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC. PMID:20339913

  19. A randomized phase II crossover study of imatinib or rituximab for cutaneous sclerosis after hematopoietic cell transplantation

    PubMed Central

    Arai, Sally; Pidala, Joseph; Pusic, Iskra; Chai, Xiaoyu; Jaglowski, Samantha; Khera, Nandita; Palmer, Jeanne; Chen, George L; Jagasia, Madan H; Mayer, Sebastian A; Wood, William A; Green, Michael; Hyun, Teresa S.; Inamoto, Yoshihiro; Storer, Barry E; Miklos, David B; Shulman, Howard M.; Martin, Paul J; Sarantopoulos, Stefanie; Lee, Stephanie J; Flowers, Mary E D

    2015-01-01

    Purpose Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design We conducted a prospective, multi-center, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 intravenously weekly × 4 doses, repeatable after 3 months) for treatment of CS diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary end points included changes of B cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and non-responders with each therapy. Results SCR was observed in 9 of 35 (26%, 95% CI 13-43%) participants randomized to imatinib and 10 of 37 (27%, 95% CI 14-44%) randomized to rituximab. Six (17%, 95% CI 7-34%) patients in the imatinib arm and 5 (14%, 95% CI 5-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (p = 0.01), but not in imatinib-treated patients. Conclusion These results support the need for more effective therapies for CS and suggest that activated B cells define a subgroup of patients with CS who are more likely to respond to rituximab. PMID:26378033

  20. Random Phase Approximation in Surface Chemistry: Water Splitting on Iron.

    PubMed

    Karlický, František; Lazar, Petr; Dubecký, Matúš; Otyepka, Michal

    2013-08-13

    The reaction of water with zero-valent iron (anaerobic corrosion) is a complex chemical process involving physisorption and chemisorption events. We employ random phase approximation (RPA) along with gradient-corrected and hybrid density functional theory (DFT) functionals to study the reaction of water with the Fe atom and Fe(100) surface. We show that the involvement of the exact electron exchange and nonlocal correlation effects in RPA improves the description of all steps of the reaction on the Fe surface with respect to standard [meaning local density approximation (LDA) or generalized gradient approximation (GGA)] DFT methods. The reaction profile calculated by range-separated hybrid functional HSE06 agrees reasonably well with the RPA profile, which makes HSE06 a computationally less demanding alternative to RPA. We also investigate the reaction of the Fe atom with water using DFT, RPA, and coupled-cluster through the perturbative triples complete basis set [CCSD(T)-3s3p-DKH/CBS] method. Local DFT methods significantly underestimate reaction barriers, while the reaction kinetics and thermodynamics from RPA agree with the reference CCSD(T) data. Both systems, i.e., the Fe atom and Fe(100), provide the same reaction mechanism, indicating that anaerobic corrosion is a stepwise process involving one-electron steps, with the first reaction step (formation of the HFeOH intermediate) representing the rate-limiting step. PMID:26584120

  1. Predicting the Catalytic Reactions using Random Phase Approximation

    NASA Astrophysics Data System (ADS)

    Yan, J.; Olsen, T.; Mortensen, J. J.; Jacobsen, K. W.; Thygesen, K. S.; Abild-Pedersen, F.; Norskov, J. K.

    2012-02-01

    Density functional theory has became the workhorse for simulations of catalytic reactions and computational design of novel catalysis. The generally applied semi-local exchange-correlation functionals have successfully predicted catalytic reaction trends over a variety of surfaces. However, in order to achieve quantitative predictions of reaction rates for molecule-surface systems, in particular where there is weak Van der Waals interactions or strong correlation, it is of vital importance to include non-local correlation effects. The use of random phase approximation (RPA) to construct the correlation energy, combined with the exact, self-interaction free exchange energy, offers a non-empirical way for accurately describe the adsorption energies [1] and dispersion forces [2]. We have recently implemented RPA in the GPAW code [3-4], an electronic structure package using projector augmented wave method and real space grids. In this talk I will present our initial results comparing RPA and generalized gradient functionals for the activation energies and reaction energies for transition metal or metal oxide surfaces. [4pt] [1] L. Schimka, et.al, Nature Mat. 9, 741 (2010) [2] T. Olsen, et.al, Phys. Rev. Lett. 107, 156401 (2011) [3] J. Yan, et.al, Phys. Rev. B 83, 245122 (2011). [4] J. Yan, et.al, Phys. Rev. Lett. 106, 146803 (2011)

  2. Separable pairing force for relativistic quasiparticle random-phase approximation

    SciTech Connect

    Tian Yuan; Ma Zhongyu; Ring, Peter

    2009-06-15

    We have introduced a separable pairing force, which was adjusted to reproduce the pairing properties of the Gogny force in nuclear matter. This separable pairing force is able to describe in relativistic Hartree-Bogoliubov (RHB) calculations the pairing properties in the ground state of finite nuclei on almost the same footing as the original Gogny interaction. In this work we investigate excited states using the Relativistic Quasiparticle Random-Phase Approximation (RQRPA) with the same separable pairing force. For consistency the Goldstone modes and the convergence with various cutoff parameters in this version of RQRPA are studied. The first excited 2{sup +} states for the chain of Sn isotopes with Z=50 and the chain of isotones with N=82 isotones are calculated in RQRPA together with the 3{sup -} states of Sn isotopes. By comparing our results with experimental data and with the results of the original Gogny force we find that this simple separable pairing interaction is very successful in depicting the pairing properties of vibrational excitations.

  3. Communication: Random phase approximation renormalized many-body perturbation theory

    SciTech Connect

    Bates, Jefferson E.; Furche, Filipp

    2013-11-07

    We derive a renormalized many-body perturbation theory (MBPT) starting from the random phase approximation (RPA). This RPA-renormalized perturbation theory extends the scope of single-reference MBPT methods to small-gap systems without significantly increasing the computational cost. The leading correction to RPA, termed the approximate exchange kernel (AXK), substantially improves upon RPA atomization energies and ionization potentials without affecting other properties such as barrier heights where RPA is already accurate. Thus, AXK is more balanced than second-order screened exchange [A. Grüneis et al., J. Chem. Phys. 131, 154115 (2009)], which tends to overcorrect RPA for systems with stronger static correlation. Similarly, AXK avoids the divergence of second-order Møller-Plesset (MP2) theory for small gap systems and delivers a much more consistent performance than MP2 across the periodic table at comparable cost. RPA+AXK thus is an accurate, non-empirical, and robust tool to assess and improve semi-local density functional theory for a wide range of systems previously inaccessible to first-principles electronic structure calculations.

  4. Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

    PubMed Central

    De Grève, Jacques; Van Meerbeeck, Jan; Vansteenkiste, Johan F.; Decoster, Lore; Meert, Anne-Pascale; Vuylsteke, Peter; Focan, Christian; Canon, Jean-Luc; Humblet, Yves; Berchem, Guy; Colinet, Benoit; Galdermans, Danny; Bosquée, Lionel; Vermeij, Joanna; Dewaele, Alex; Geers, Caroline; Schallier, Denis; Teugels, Erik

    2016-01-01

    Introduction Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. Methods Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. Results Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. Conclusion The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. Trial Registration ClinicalTrials.gov NCT00339586 PMID:27032107

  5. 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.

  6. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933

    PubMed Central

    Martinez-Torres, Francisco; Menon, Sanjay; Pritsch, Maria; Victor, Norbert; Jenetzky, Ekkehart; Jensen, Katrin; Schielke, Eva; Schmutzhard, Erich; de Gans, Jan; Chung, Chin-Hee; Luntz, Steffen; Hacke, Werner; Meyding-Lamadé, Uta

    2008-01-01

    Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933 PMID:18959773

  7. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.

    PubMed

    Yamaue, Hiroki; Tsunoda, Takuya; Tani, Masaji; Miyazawa, Motoki; Yamao, Kenji; Mizuno, Nobumasa; Okusaka, Takuji; Ueno, Hideki; Boku, Narikazu; Fukutomi, Akira; Ishii, Hiroshi; Ohkawa, Shinichi; Furukawa, Masayuki; Maguchi, Hiroyuki; Ikeda, Masafumi; Togashi, Yosuke; Nishio, Kazuto; Ohashi, Yasuo

    2015-07-01

    Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486-1.557). Median survival time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival. PMID:25867139

  8. 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.

  9. Multicenter Phase II Study of Nedaplatin and Irinotecan for Patients with Squamous Cell Carcinoma of the Lung: Thoracic Oncology Research Group 0910.

    PubMed

    Yamada, Kouzo; Saito, Haruhiro; Kondo, Tetsuro; Murakami, Shuji; Masuda, Noriyuki; Yamamoto, Michiko; Igawa, Satoshi; Katono, Ken; Takiguchi, Yuichi; Iwasawa, Shunichiro; Kurimoto, Ryota; Okamoto, Hiroaki; Shimokawa, Tsuneo; Hosomi, Yukio; Takagi, Yusuke; Kishi, Kazuma; Ohba, Mari; Oshita, Fumihiro; Watanabe, Koshiro

    2015-12-01

    Squamous cell carcinoma (SCC) of the lung is moderately responsive to anticancer drugs, but no specific chemotherapy regimens have yet been established. We conducted a multicenter phase II study of nedaplatin (NP) and irinotecan (CPT) for SCC of the lung. Fifty patients underwent 4 to 6 cycles of chemotherapy comprising of NP at 100 mg/m(2) on day 1 and CPT at 60 mg/m(2) on days 1 and 8 every 4 weeks. Twenty-seven patients received 4 to 6 cycles of chemotherapy (median=4 cycles). Major toxicities included neutropenia (46.0%), grade 3 or 4 anorexia (22.0%), febrile neutropenia (16.0%), diarrhea (12.0%), hyponatremia (12.0%), grade 4 anemia (10.0%), thrombocytopenia (10.0%) and infection (10.0%). There were no treatment-related deaths. One patient achieved a complete response and 16 a partial response, with an overall response rate of 34.0%. The median survival time was 11.8 months (95% CI=8.3-15.8 months) and the 2-year survival rate was 22.0%. In conclusion, the NP and CPT regimen is not recommend for further evaluation for patients with advanced SCC of the lung. PMID:26637886

  10. The 2 + 1 paradigm: an efficient algorithm for central reading of Mayo endoscopic subscores in global multicenter phase 3 ulcerative colitis clinical trials.

    PubMed

    Ahmad, Harris A; Gottlieb, Klaus; Hussain, Fez

    2016-02-01

    Despite its importance and potential impact in clinical trials, central reading continues to be an under-represented topic in the literature about inflammatory bowel disease (IBD) clinical trials. Although several IBD studies have incorporated central reading to date, none have fully detailed the specific methodology with which the reads were conducted. Here we outline key principles for designing an efficient central reading paradigm for an ulcerative colitis (UC) study that addresses regulatory, operational and clinical expectations. As a step towards standardization of read methodology for the growing number of multicenter phase 3 clinical trials in IBD, we have applied these principles to the design of an optimal read methodology that we call the '2 + 1 paradigm.' The 2 + 1 paradigm involves the use of both site and central readers, validated scoring criteria and multiple measures for blinding readers, all of which contribute to reducing bias and generating a reliable endoscopic subscore that reflects endoscopic disease severity. The paradigm can be utilized while maintaining a practical workflow compatible with an operationally feasible clinical trial. The 2 + 1 paradigm represents a logical approach to endoscopic assessment in IBD clinical trials, one that should be considered attractive to prospective sponsors, contract research organizations, key opinion leaders and regulatory authorities and be ready for implementation and further evaluation. PMID:26361984

  11. Laser-Supported CD133+ Cell Therapy in Patients with Ischemic Cardiomyopathy: Initial Results from a Prospective Phase I Multicenter Trial

    PubMed Central

    Kröpil, Patric; Ptok, Lena; Hafner, Dieter; Ohmann, Christian; Martens, Andreas; Karluß, Antje; Emmert, Maximilian Y.; Kutschka, Ingo; Sievers, Hans-Hinrich; Klein, Hans-Michael

    2014-01-01

    Objectives This study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy. Methods Forty-two patients with severe ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) >15% and <35%) were included in this prospective multicenter phase I trial. They underwent coronary artery bypass grafting (CABG) with subsequent transepicardial low-energy laser treatment and autologous CD133+ cell transplantation, and were followed up for 12 months. To evaluate segmental myocardial contractility as well as perfusion and to identify the areas of scar tissue, cardiac MRI was performed at 6 months and compared to the preoperative baseline. In addition, clinical assessment comprising of CCS scoring, blood and physical examination was performed at 3, 6 and 12 months, respectively. Results Intraoperative cell isolation resulted in a mean cell count of 9.7±1.2×106. Laser treatment and subsequent CD133+ cell therapy were successfully and safely carried out in all patients and no procedure-related complications occurred. At 6 months, the LVEF was significantly increased (29.7±1.9% versus 24.6±1.5% with p = 0.004). In addition, freedom from angina was achieved, and quality of life significantly improved after therapy (p<0.0001). Interestingly, an extended area of transmural delayed enhancement (>3 myocardial segments) determined in the preoperative MRI was inversely correlated with a LVEF increase after laser-supported cell therapy (p = 0.024). Conclusions This multicenter trial demonstrates that laser-supported CD133+ cell transplantation is safe and feasible in patients with ischemic cardiomyopathy undergoing CABG, and in most cases, it appears to significantly improve the myocardial function. Importantly, our data show that the beneficial effect was significantly related to the extent of transmural delayed enhancement, suggesting that MRI

  12. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  13. Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

    PubMed Central

    Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

    2012-01-01

    In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

  14. Electron correlation effects beyond the random phase approximation

    NASA Astrophysics Data System (ADS)

    Fan, J. D.; Malozovsky, Y. M.

    2016-04-01

    The methods that have been used to deal with a many-particle system can be basically sorted into three types: Hamiltonian, field theory and phenomenological method. The first two methods are more popular. Traditionally, the Hamiltonian method has been widely adopted in the conventional electronic theory for metals, alloys and semiconductors. Basically, the mean-field approximation (MFA) that has been working well for a weakly coupled system like a metal is employed to simplify a Hamiltonian corresponding to a particular electron system. However, for a strongly coupled many-particle system like a cuprate superconductor MFA should in principle not apply. Therefore, the field theory on the basis of Green’s function and the Feynman diagrams must be invoked. In this method, one is however more familiar with the random phase approximation (RPA) that gives rise to the same results as MFA because of being short of the information for higher-order terms of interaction. For a strongly coupled electron system, it is obvious that one has to deal with higher-order terms of a pair interaction to get a correct solution. Any ignorance of the higher-order terms implies that the more sophisticated information contained in those terms is discarded. However, to date one has not reached a consensus on how to deal with the higher-order terms beyond RPA. We preset here a method that is termed the diagrammatic iteration approach (DIA) and able to derive higher-order terms of the interaction from the information of lower-order ones on the basis of Feynman diagram, with which one is able to go beyond RPA step by step. It is in principle possible that all of higher-order terms can be obtained, and then sorted to groups of diagrams. It turns out that each of the groups can be replaced by an equivalent one, forming a diagrammatic Dyson-equation-like relation. The diagrammatic solution is eventually “translated” to a four-dimensional integral equation. The method can be applied to a

  15. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial

    PubMed Central

    2011-01-01

    Background Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation. Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. Methods/Design ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool. The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central

  16. A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

    PubMed

    Takashima, Tsutomu; Tokunaga, Shinya; Tei, Seika; Nishimura, Shigehiko; Kawajiri, Hidemi; Kashiwagi, Shinichiro; Yamagata, Shigehito; Noda, Satoru; Nishimori, Takeo; Mizuyama, Yoko; Sunami, Takeshi; Tezuka, Kenji; Ikeda, Katsumi; Ogawa, Yoshinari; Onoda, Naoyoshi; Ishikawa, Tetsuro; Kudoh, Shinzoh; Takada, Minoru; Hirakawa, Kosei

    2016-01-01

    The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC. PMID:27026861

  17. Acute and late complications after radiotherapy for prostate cancer: Results of a multicenter randomized trial comparing 68 Gy to 78 Gy

    SciTech Connect

    Peeters, Stephanie T.H.; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Tabak, Hans; Mens, Jan Willem; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Koper, Peter C.M.

    2005-03-15

    Purpose: To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy. Methods and materials: Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA {<=}4 ng/mL. Stratification was done for four dose-volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV-planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria. Results: The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity

  18. Truly random number generation based on measurement of phase noise of a laser.

    PubMed

    Guo, Hong; Tang, Wenzhuo; Liu, Yu; Wei, Wei

    2010-05-01

    We present a simple approach to realize truly random number generator based on measuring the phase noise of a single-mode vertical cavity surface emitting laser. The true randomness of the quantum phase noise originates from the spontaneous emission of photons and the random bit generation rate is ultimately limited only by the laser linewidth. With the final bit generation rate of 20 Mbit/s, the truly random bit sequence guaranteed by the uncertainty principle of quantum mechanics passes the three standard randomness tests (ENT, Diehard, and NIST Statistical Test Suites). Moreover, a continuously generated random bit sequence, with length up to 14 Gbit, is verified by two additional criteria for its true randomness. PMID:20866215

  19. Phase transition in the assignment problem for random matrices

    NASA Astrophysics Data System (ADS)

    Esteve, J. G.; Falceto, F.

    2005-12-01

    We report an analytic and numerical study of a phase transition in a P problem (the assignment problem) that separates two phases whose representatives are the simple matching problem (an easy P problem) and the traveling-salesman problem (a NP-complete problem). Like other phase transitions found in combinatoric problems (K-satisfiability, number partitioning) this can help to understand the nature of the difficulties in solving NP problems an to find more accurate algorithms for them.

  20. The PanAM study: a multi-center, double-blinded, randomized, non-inferiority study of paracetamol versus non-steroidal anti-inflammatory drugs in treating acute musculoskeletal trauma

    PubMed Central

    2013-01-01

    Background Acute musculoskeletal trauma, including strains, sprains or contusions, occur frequently. Pain management is a crucial component of treatment. However, there is no convincing evidence which drug is superior in managing pain in these patients. The aim of the PanAM Study is to compare analgesic efficacy of three strategies of pain management: paracetamol, diclofenac, or a combination of both in patients with acute musculoskeletal trauma. Methods/design The PanAM Study is a multi-center, double blind randomized controlled trial with non-inferiority design. Included are adult patients presenting to an academic, urban Emergency Department or to a General Practice with acute, blunt, traumatic limb injury. In total, 547 patients will be included using a predefined list of exclusion criteria, to be allocated by randomization to treatment with paracetamol + placebo diclofenac, diclofenac + placebo paracetamol or paracetamol + diclofenac. The hypothesis is that paracetamol will not be inferior to treatment with diclofenac, or the combination of both. Primary outcome will be between-group differences in decrease in pain, measured with Numerical Rating Scales at baseline and at 90 minutes after study drug administration. Secondary outcomes are Numerical Rating Scales at 30 and 60 minutes and measured frequently during three consecutive days after discharge; occurrence of adverse effects; patient satisfaction and an analysis of quality of life and cost-effectiveness. Recruitment started July 2013 and is expected to last a year. Discussion With this multi-center randomized clinical trial we will investigate whether treatment with paracetamol alone is not inferior to diclofenac alone or a combination of both drugs in adult patients with acute musculoskeletal trauma. The main relevance of the trial is to demonstrate the benefits and risks of three commonly used treatment regimens for musculoskeletal trauma. Data that lead to the prevention of severe Non

  1. The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

    PubMed Central

    Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

    2015-01-01

    Background Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. Methods A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated. Results At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Conclusion Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Trial Registration Chinese Clinical Trial Register

  2. Anomalously elastic intermediate phase in randomly layered superfluids, superconductors, and planar magnets.

    PubMed

    Mohan, Priyanka; Goldbart, Paul M; Narayanan, Rajesh; Toner, John; Vojta, Thomas

    2010-08-20

    We show that layered quenched randomness in planar magnets leads to an unusual intermediate phase between the conventional ferromagnetic low-temperature and paramagnetic high-temperature phases. In this intermediate phase, which is part of the Griffiths region, the spin-wave stiffness perpendicular to the random layers displays anomalous scaling behavior, with a continuously variable anomalous exponent, while the magnetization and the stiffness parallel to the layers both remain finite. Analogous results hold for superfluids and superconductors. We study the two phase transitions into the anomalous elastic phase, and we discuss the universality of these results, and implications of finite sample size as well as possible experiments. PMID:20868107

  3. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study.

    PubMed

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (> or =18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  4. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study

    PubMed Central

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (≥18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  5. MIOTIC study: a prospective, multicenter, randomized study to evaluate the long-term efficacy of mobile phone-based Internet of Things in the management of patients with stable COPD.

    PubMed

    Zhang, Jing; Song, Yuan-Lin; Bai, Chun-Xue

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the 'MIOTIC study' to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. PMID:24082784

  6. Statistical analysis plan for the Stroke Oxygen Study (SO2S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome

    PubMed Central

    2014-01-01

    Background The Stroke Oxygen Study (SO2S) is a multi-center randomized controlled trial of oxygen supplementation in patients with acute stroke. The main hypothesis for the trial is that fixed-dose oxygen treatment during the first 3 days after an acute stroke improves outcome. The secondary hypothesis is that restricting oxygen supplementation to night time only is more effective than continuous supplementation. This paper describes the statistical analysis plan for the study. Methods and design Patients (n = 8000) are randomized to three groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen supplementation for three nights; and (3) no routine oxygen supplementation. Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary outcome measure is the modified Rankin scale at 90 days. Data will be analyzed according to the intention-to-treat principle. Methods of statistical analysis are described, including the handling of missing data, the covariates used in adjusted analyses, planned subgroups analyses, and planned sensitivity analyses. Trial registration This trial is registered with the ISRCTN register, number ISRCTN52416964 (30 September 2005). PMID:24939648

  7. Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial.

    PubMed

    Banovic, Marko; Iung, Bernard; Bartunek, Jozef; Asanin, Milika; Beleslin, Branko; Biocina, Bojan; Casselman, Filip; da Costa, Mark; Deja, Marek; Gasparovic, Hrvoje; Kala, Petr; Labrousse, Lois; Loncar, Zlatibor; Marinkovic, Jelena; Nedeljkovic, Ivana; Nedeljkovic, Milan; Nemec, Peter; Nikolic, Serge D; Pencina, Michael; Penicka, Martin; Ristic, Arsen; Sharif, Faisal; Van Camp, Guy; Vanderheyden, Marc; Wojakowski, Wojtek; Putnik, Svetozar

    2016-04-01

    Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients. PMID:26995381

  8. MIOTIC study: a prospective, multicenter, randomized study to evaluate the long-term efficacy of mobile phone-based Internet of Things in the management of patients with stable COPD

    PubMed Central

    Zhang, Jing; Song, Yuan-lin; Bai, Chun-xue

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. PMID:24082784

  9. A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients

    PubMed Central

    ARIDOME, KUNIAKI; MORI, SHIN-ICHIROU; BABA, KENJI; YANAGI, MASAYUKI; HAMANOUE, MASAHIRO; MIYAZONO, FUTOSHI; TOKUDA, KOUKI; IMAMURA, HIROSHI; OGURA, YOSHITO; KANEKO, KOUICHI; KIJIMA, FUMIO; MAEMURA, KOUSEI; ISHIGAMI, SUMIYA; NATSUGOE, SHOJI

    2016-01-01

    The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC. PMID:26998290

  10. Partition function for a two dimensional plasma in the random phase approximation

    NASA Technical Reports Server (NTRS)

    Seyler, C. E., Jr.

    1974-01-01

    The partition function for a two-dimensional plasma is evaluated within the random phase approximation. The periodic boundary conditions are fully taken into account by including the periodic image interactions. In the guiding-center limit, the negative temperature threshold energy is evaluated, and a value different from previous calculations results. When an identical random phase evaluated, and a value different from previous calculations results. When an identical random phase evaluation is applied to the finite gyroradius plasma, the Salzberg-Prager-May equation of state is recovered.

  11. Final results of a multicenter phase 1 study of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia.

    PubMed

    Wendtner, Clemens-Martin; Hillmen, Peter; Mahadevan, Daruka; Bühler, Andreas; Uharek, Lutz; Coutré, Steven; Frankfurt, Olga; Bloor, Adrian; Bosch, Francesc; Furman, Richard R; Kimby, Eva; Gribben, John G; Gobbi, Marco; Dreisbach, Luke; Hurd, David D; Sekeres, Mikkael A; Ferrajoli, Alessandra; Shah, Sheetal; Zhang, Jennie; Moutouh-de Parseval, Laure; Hallek, Michael; Heerema, Nyla A; Stilgenbauer, Stephan; Chanan-Khan, Asher A

    2012-03-01

    Based on clinical activity in phase 2 studies, lenalidomide was evaluated in a phase 2/3 study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Following tumor lysis syndrome (TLS) complications, the protocol was amended to a phase 1 study to identify the maximum tolerated dose-escalation level (MTDEL). Fifty-two heavily pretreated patients, 69% with bulky disease and 48% with high-risk genomic abnormalities, initiated lenalidomide at 2.5 mg/day, with dose escalation until the MTDEL or the maximum assigned dose was attained. Lenalidomide was safely titrated to 20 mg/day; the MTDEL was not reached. Most common grade 3-4 adverse events were neutropenia and thrombocytopenia; TLS was mild and rare. The low starting dose and conservative dose escalation strategy resulted in six partial responders and 30 patients obtaining stable disease. In summary, lenalidomide 2.5 mg/day is a safe starting dose that can be titrated up to 20 mg/day in patients with CLL. PMID:21879809

  12. 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.

  13. Multicenter phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide.

    PubMed

    Yoo, Changhoon; Lee, Jeeyun; Rha, Sun Young; Park, Kyong Hwa; Kim, Tae Min; Kim, Yu Jung; Lee, Hyo Jin; Lee, Kyung Hee; Ahn, Jin-Hee

    2013-12-01

    This multicenter, phase II trial evaluated the efficacy and safety of everolimus, an mTOR inhibitor, in patients with metastatic or recurrent bone and soft-tissue sarcoma after the failure of anthracycline- and ifosfamide-containing regimens. Everolimus was administered orally as 10 mg once daily. The primary endpoint was the progression-free rate (PFR) at 16 weeks, assessed by computed tomography scan according to RECIST v1.0. Between July 2010 and May 2011, 41 patients were enrolled in this study. Among them, 83% received two or more regimens of chemotherapy prior to study entry. In 38 patients who the primary endpoint was evaluable, 11 patients reached 16 weeks progression-free (one with partial response and 10 with stable disease), indicating a PFR at 16 weeks of 27% (95% confidence interval [CI], 16-42%). The PFR at 16 weeks was highest in patients with angiosarcoma (2 of 3, 67%). With a median follow-up of 10.9 months (range, 2.3-23.9 months) in living patients, the median progression-free survival was 1.9 months (95% CI, 1.3-2.4 months) and the median overall survival was 5.8 months (95% CI, 3.6-8.0 months). Most adverse events were generally mild and tolerable. Grade 3/4 toxicities included hyperglycemia (15%), stomatitis (7%), pain (5%), and asthenia (5%). Everolimus shows modest antitumor activity with manageable toxicities in heavily pretreated patients with bone and soft-tissue sarcoma. PMID:24037083

  14. 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. PMID:26211987

  15. 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.

  16. A Prospective, Multicenter, Phase I Matched-Comparison Group Trial of Safety, Pharmacokinetics, and Preliminary Efficacy of Riluzole in Patients with Traumatic Spinal Cord Injury

    PubMed Central

    Fehlings, Michael G.; Frankowski, Ralph F.; Burau, Keith D.; Chow, Diana S.L.; Tator, Charles; Teng, Angela; Toups, Elizabeth G.; Harrop, James S.; Aarabi, Bizhan; Shaffrey, Christopher I.; Johnson, Michele M.; Harkema, Susan J.; Boakye, Maxwell; Guest, James D.; Wilson, Jefferson R.

    2014-01-01

    Abstract A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A–C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14–70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group. PMID:23859435

  17. The safety and effectiveness of a long-acting transdermal fentanyl solution compared with oxymorphone for the control of postoperative pain in dogs: a randomized, multicentered clinical study

    PubMed Central

    Martinez, S A; Wilson, M G; Linton, D D; Newbound, G C; Freise, K J; Lin, T-L; Clark, T P

    2014-01-01

    A prospective, double-blinded, positive-controlled, multicenter, noninferiority study was conducted to evaluate the safety and effectiveness of transdermal fentanyl solution (TFS) compared with oxymorphone for the control of postoperative pain in dogs. Five hundred and two (502) client-owned dogs were assigned to a single dose of TFS (2.7 mg/kg) applied 2–4 h prior to surgery or oxymorphone hydrochloride (0.22 mg/kg) administered subcutaneously 2–4 h prior to surgery and q6h through 90 h. Pain was evaluated over 4 days by blinded observers using a modified Glasgow composite pain scale, and the a priori criteria for treatment failure was a pain score ≥8 or adverse event necessitating withdrawal. Four TFS- and eight oxymorphone-treated dogs were withdrawn due to lack of pain control. Eighteen oxymorphone-treated, but no TFS-treated dogs were withdrawn due to severe adverse events. The one-sided upper 95% confidence interval of the difference between TFS and oxymorphone treatment failure rates was −5.3%. Adverse events associated with oxymorphone were greater in number and severity compared with TFS. It was concluded that a single administration of TFS was safe and noninferior to repeated injections of oxymorphone for the control of postoperative pain over 4 days at the dose rates of both formulations used in this study. PMID:24344787

  18. 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

  19. Ultra-fast quantum randomness generation by accelerated phase diffusion in a pulsed laser diode.

    PubMed

    Abellán, C; Amaya, W; Jofre, M; Curty, M; Acín, A; Capmany, J; Pruneri, V; Mitchell, M W

    2014-01-27

    We demonstrate a high bit-rate quantum random number generator by interferometric detection of phase diffusion in a gain-switched DFB laser diode. Gain switching at few-GHz frequencies produces a train of bright pulses with nearly equal amplitudes and random phases. An unbalanced Mach-Zehnder interferometer is used to interfere subsequent pulses and thereby generate strong random-amplitude pulses, which are detected and digitized to produce a high-rate random bit string. Using established models of semiconductor laser field dynamics, we predict a regime of high visibility interference and nearly complete vacuum-fluctuation-induced phase diffusion between pulses. These are confirmed by measurement of pulse power statistics at the output of the interferometer. Using a 5.825 GHz excitation rate and 14-bit digitization, we observe 43 Gbps quantum randomness generation. PMID:24515170

  20. Design Features of the Diabetes and Periodontal Therapy Trial (DPTT): A Multicenter Randomized Single-Masked Clinical Trial Testing the Effect of Non-surgical Periodontal Therapy on Glycosylated Hemoglobin (HbA1c) Levels in Subjects with Type 2 Diabetes and Chronic Periodontitis

    PubMed Central

    2013-01-01

    Background Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. Purpose The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. Methods DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. Conclusion Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other. PMID:24080100

  1. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970

  2. Chiral random grain boundary phase of achiral hockey-stick liquid crystals.

    PubMed

    Chen, Dong; Wang, Haitao; Li, Min; Glaser, Matthew A; Maclennan, Joseph E; Clark, Noel A

    2014-12-01

    A disordered chiral conglomerate, the random grain boundary (RGB) phase, has been observed below the smectic A liquid crystal phase of an achiral, hockey-stick molecule. In cells, the RGB phase appears dark between crossed polarizers but decrossing the polarizers reveals large left- and right-handed chiral domains with opposite optical rotation. Freeze-fracture transmission electron microscopy reveals that the RGB phase is an assembly of randomly oriented blocks of smectic layers, an arrangement that distinguishes the RGB from the dark, chiral conglomerate phases of bent-core mesogens. X-ray diffraction indicates that there is significant layer shrinkage at the SmA-RGB phase transition, which is marked by the collapse of layers with long-range order into small, randomly oriented smectic blocks. PMID:25310113

  3. Variance of phase fluctuations of waves propagating through a random medium

    NASA Technical Reports Server (NTRS)

    Chu, Nelson C.; Kong, Jin AU; Yueh, Simon H.; Nghiem, Son V.; Fleischman, Jack G.; Ayasli, Serpil; Shin, Robert T.

    1992-01-01

    As an electromagnetic wave propagates through a random scattering medium, such as a forest, its energy is attenuated and random phase fluctuations are induced. The magnitude of the random phase fluctuations induced is important in estimating how well a Synthetic Aperture Radar (SAR) can image objects within the scattering medium. The two-layer random medium model, consisting of a scattering layer between free space and ground, is used to calculate the variance of the phase fluctuations induced between a transmitter located above the random medium and a receiver located below the random medium. The scattering properties of the random medium are characterized by a correlation function of the random permittivity fluctuations. The effective permittivity of the random medium is first calculated using the strong fluctuation theory, which accounts for large permittivity fluctuations of the scatterers. The distorted Born approximation is used to calculate the first-order scattered field. A perturbation series for the phase of the received field in the Rytov approximation is then introduced and the variance of the phase fluctuations is also calculated assuming that the transmitter and receiver are in the paraxial limit of the random medium, which allows an analytic solution to be obtained. Results are compared using the paraxial approximation, scalar Green's function formulation, and dyadic Green's function formulation. The effects studied are the dependence of the variance of the phase fluctuations on receiver location in lossy and lossless regions, medium thickness, correlation length and fractional volume of scatterers, depolarization of the incident wave, ground layer permittivity, angle of incidence, and polarization.

  4. Self-consistent continuum random-phase approximation calculations with finite-range interactions

    SciTech Connect

    De Donno, V.; Co', G.; Anguiano, M.; Lallena, A. M.

    2011-04-15

    We present a technique that treats, without approximations, the continuum part of the excitation spectrum in random phase approximation calculations with finite-range interactions. The interaction used in Hartree-Fock calculations to generate the single-particle basis is also used in continuum random phase approximation calculations. We show results for electric dipole and quadrupole excitations in {sup 16}O, {sup 22}O, {sup 24}O, {sup 40}Ca, {sup 48}Ca, and {sup 52}Ca nuclei. We compare our results with those of the traditional discrete random phase approximation, with continuum independent-particle model results, and with results obtained by a phenomenological random phase approximation approach. We study the relevance of the continuum, of the residual interaction, and of the self-consistency. We also compare our results with the available total photoabsorption cross-section data.

  5. Arandomized multicenter Phase II study of perioperative tiotropium intervention in gastric cancer patients with chronic obstructive pulmonary disease

    PubMed Central

    Fushida, Sachio; Oyama, Katsunobu; Kaji, Masahide; Hirono, Yasuo; Kinoshita, Jun; Tsukada, Tomoya; Nezuka, Hideaki; Nakano, Tatsuo; Noto, Masahiro; Nishijima, Koji; Fujimura, Takashi; Ohta, Tetsuo

    2015-01-01

    Background Tiotropium, a long-acting inhaled anticholinergic drug, has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the issue of whether perioperative tiotropium improves postoperative outcomes for gastric cancer patients with COPD remains unclear. Thus, the aim of this study was to determine the efficacy of perioperative tiotropium intervention for gastric cancer patients with COPD. Patients and methods Eighty-four gastric cancer patients with mild-to-moderate COPD were randomly assigned to receive perioperative pulmonary rehabilitation alone (control group) or pulmonary rehabilitation with 18 µg of tiotropium once daily (tiotropium group). The patients in the tiotropium group received tiotropium for more than 1 week before surgery and for 2 weeks after surgery. Spirometry was performed prior to group assignment and at 2 weeks after surgery. Postoperative complications, forced expiratory volume in 1 second, forced vital capacity, and the ratio of forced expiratory volume in second to forced vital capacity (%) were compared between the two groups. Results There were no significant differences between the two groups in terms of age, body mass index, smoking, gastrectomy incision, operation time, and bleeding volume (all P>0.05). Postoperative complications and pulmonary functions did not differ significantly between the control and tiotropium groups. A subgroup analysis of gastric cancer patients with moderate COPD showed that perioperative tiotropium intervention significantly decreased the rate of postoperative complications compared with the control group (P=0.046). However, even after gastrectomy, many patients with mild COPD in both the control and tiotropium groups showed improved pulmonary function. Conclusion Although perioperative tiotropium intervention had no significant effects in gastric cancer patients with mild COPD, it may be beneficial in those with moderate COPD. Therefore, the next prospective study

  6. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

    PubMed

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-07-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC. PMID:25872578

  7. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron

    PubMed Central

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-01-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval [CI]: −7.8%–12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC. PMID:25872578

  8. Phase-change Random Access Memory: A Scalable Technology

    SciTech Connect

    Raoux, S.; Burr, G; Breitwisch, M; Rettner, C; Chen, Y; Shelby, R; Salinga, M; Krebs, D; Chen, S; Lung, H

    2008-01-01

    Nonvolatile RAM using resistance contrast in phase-change materials [or phase-change RAM (PCRAM)] is a promising technology for future storage-class memory. However, such a technology can succeed only if it can scale smaller in size, given the increasingly tiny memory cells that are projected for future technology nodes (i.e., generations). We first discuss the critical aspects that may affect the scaling of PCRAM, including materials properties, power consumption during programming and read operations, thermal cross-talk between memory cells, and failure mechanisms. We then discuss experiments that directly address the scaling properties of the phase-change materials themselves, including studies of phase transitions in both nanoparticles and ultrathin films as a function of particle size and film thickness. This work in materials directly motivated the successful creation of a series of prototype PCRAM devices, which have been fabricated and tested at phase-change material cross-sections with extremely small dimensions as low as 3 nm x 20 nm. These device measurements provide a clear demonstration of the excellent scaling potential offered by this technology, and they are also consistent with the scaling behavior predicted by extensive device simulations. Finally, we discuss issues of device integration and cell design, manufacturability, and reliability.

  9. Phase transitions, magnetism and surface adsorptions assessed by meta-GGA functionals and random phase approximation

    NASA Astrophysics Data System (ADS)

    Xiao, Bing

    The meta-GGA functionals and random phase approximation are tested for phase transitions and a strongly correlated transition metal oxide in this dissertation. One of the latest meta-GGA functionals is also employed to study the van der Waals bound system in surface science. Our main purpose is to reveal the performance of new exchange-correlation functionals on various properties and systems. We are also interested in seeking the possible relationship between the performance of a semilocal functional and its exchange enhancement factor. We have studied the structural phase transitions in crystalline Si (insulator to metal), SiO2 (insulator to insulator) and Zr (metal to metal) systems, as a test of exchange energy semilocal functionals on Jacob's ladder. Our results confirm the energy-geometry delimma of GGAs in three systems. The most sophisticated non-empirical meta-generalized gradient approximations (meta-GGAs) such as TPSS (Tao-Perdew-Staroveov-Scuseria) and revTPSS (revised TPSS) give better lattice constants than PBE, but the phase transition parameters (energy difference and transition pressure) are smaller and less realistic than those from the latter GGA. However, the recent functionals of meta-GGA made simple family (MGGA_MS) behave differently to those previous meta-GGAs, predicting larger and more realistic phase transition parameters. Meanwhile, MGGA_MS also delivers the equilibrium geometry of crystalline materials similar to previous non-empirical meta-GGAs. In contrast to semilocal functionals, the nonlocal functionals such as the range-separated hybrid functional HSE06 (Heyd-Scuseria-Ernzerhof) and non-self consistent random phase approximation (RPA) are not only able to give the accurate equilibrium geometry , but also predict the realistic phase transition parameters for Si and SiO2 systems. The ground state of rutile-type vanadium dioxide (R-VO2) represents a great challenge to the current density functional theory. In this dissertation, we

  10. Non-equilibrium Phase Transitions: Activated Random Walks at Criticality

    NASA Astrophysics Data System (ADS)

    Cabezas, M.; Rolla, L. T.; Sidoravicius, V.

    2014-06-01

    In this paper we present rigorous results on the critical behavior of the Activated Random Walk model. We conjecture that on a general class of graphs, including , and under general initial conditions, the system at the critical point does not reach an absorbing state. We prove this for the case where the sleep rate is infinite. Moreover, for the one-dimensional asymmetric system, we identify the scaling limit of the flow through the origin at criticality. The case remains largely open, with the exception of the one-dimensional totally-asymmetric case, for which it is known that there is no fixation at criticality.

  11. Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study

    PubMed Central

    Gutierrez, Juan E; Rosenberg, Martin; Seemann, Jörg; Breuer, Josy; Haverstock, Daniel; Agris, Jacob; Balzer, Thomas; Anzalone, Nicoletta

    2015-01-01

    PURPOSE Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood–brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. MATERIALS AND METHODS Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. RESULTS Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). CONCLUSION Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity. PMID:25922578

  12. DHA-enriched high–oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial123

    PubMed Central

    Jones, Peter JH; Senanayake, Vijitha K; Pu, Shuaihua; Jenkins, David JA; Connelly, Philip W; Lamarche, Benoît; Couture, Patrick; Charest, Amélie; Baril-Gravel, Lisa; West, Sheila G; Liu, Xiaoran; Fleming, Jennifer A; McCrea, Cindy E; Kris-Etherton, Penny M

    2014-01-01

    Background: It is well recognized that amounts of trans and saturated fats should be minimized in Western diets; however, considerable debate remains regarding optimal amounts of dietary n−9, n−6, and n−3 fatty acids. Objective: The objective was to examine the effects of varying n−9, n−6, and longer-chain n−3 fatty acid composition on markers of coronary heart disease (CHD) risk. Design: A randomized, double-blind, 5-period, crossover design was used. Each 4-wk treatment period was separated by 4-wk washout intervals. Volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in beverages: 1) conventional canola oil (Canola; n−9 rich), 2) high–oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n−9 and n−3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n−6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n−6 and short-chain n−3 rich), or 5) high–oleic acid canola oil (CanolaOleic; highest in n−9). Results: One hundred thirty individuals completed the trial. At endpoint, total cholesterol (TC) was lowest after the FlaxSaff phase (P < 0.05 compared with Canola and CanolaDHA) and highest after the CanolaDHA phase (P < 0.05 compared with CornSaff, FlaxSaff, and CanolaOleic). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were highest, and triglycerides were lowest, after CanolaDHA (P < 0.05 compared with the other diets). All diets decreased TC and LDL cholesterol from baseline to treatment endpoint (P < 0.05). CanolaDHA was the only diet that increased HDL cholesterol from baseline (3.5 ± 1.8%; P < 0.05) and produced the greatest reduction in triglycerides (−20.7 ± 3.8%; P < 0.001) and in systolic blood pressure (−3.3 ± 0.8%; P < 0.001) compared with the other diets (P < 0.05). Percentage reductions in Framingham 10-y CHD risk scores (FRS) from

  13. Optical Security Card by Three-dimensional Random Phase Distribution

    NASA Astrophysics Data System (ADS)

    Matoba, Osamu; Nitta, Kouichi

    2007-10-01

    An optical security card based on a three-dimensional (3D) phase object is presented. This card enables us to develop a personal authentification system and secure data storage in a highly scattering medium. The authentification is implemented by the correlation between a speckle pattern of the 3D phase object and stored speckle patterns. For secure data storage, absorption distribution is involved in a scattering volume medium. Appropriate user can only reconstruct the absorption distribution by solving inverse problem. Experimental and numerical results are presented to show the effectiveness of the proposed system.

  14. A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

    PubMed Central

    Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

    2010-01-01

    Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

  15. Evaluation of oral care to prevent oral mucositis in estrogen receptor-positive metastatic breast cancer patients treated with everolimus (Oral Care-BC): randomized controlled phase III trial.

    PubMed

    Niikura, Naoki; Ota, Yoshihide; Hayashi, Naoki; Naito, Mariko; Kashiwabara, Kosuke; Watanabe, Ken-Ichi; Yamashita, Toshinari; Mukai, Hirofumi; Umeda, Masahiro

    2016-09-01

    This is a randomized, multi-center, open-label, phase III study to evaluate the efficacy of professional oral care in preventing oral mucositis induced by everolimus in postmenopausal estrogen receptor-positive metastatic breast cancer. Patients will be randomized into professional oral care and control groups (1:1 ratio). All patients will receive everolimus with exemestane and will continue everolimus until disease progression. In the professional oral care group, patients will receive teeth surface cleaning, scaling and tongue cleaning before starting everolimus, and will continue to receive professional oral care weekly from oral surgeons throughout the 8 week treatment. In the control group, patients will brush their own teeth and gargle with 0.9% sodium chloride solution or water. The primary endpoint is the incidence of all grades of oral mucositis. Target accrual is 200 patients with a two-sided type I error rate of 5% and 80% power to detect 25% risk reduction. PMID:27365521

  16. A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive Medullary Thyroid Carcinoma: MC057H

    PubMed Central

    Suman, Vera J.; Molina, Julian R.; Smallridge, Robert C.; Maples, William J.; Menefee, Michael E.; Rubin, Joseph; Karlin, Nina; Sideras, Kostandinos; Morris, John C.; McIver, Bryan; Hay, Ian; Fatourechi, Vahab; Burton, Jill K.; Webster, Kevin P.; Bieber, Carolyn; Traynor, Anne M.; Flynn, Patrick J.; Cher Goh, Boon; Isham, Crescent R.; Harris, Pamela; Erlichman, Charles

    2014-01-01

    Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%–27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. PMID:24606083

  17. Experimental demonstration of an active phase randomization and monitor module for quantum key distribution

    NASA Astrophysics Data System (ADS)

    Sun, Shi-Hai; Liang, Lin-Mei

    2012-08-01

    Phase randomization is a very important assumption in the BB84 quantum key distribution (QKD) system with weak coherent source; otherwise, eavesdropper may spy the final key. In this Letter, a stable and monitored active phase randomization scheme for the one-way and two-way QKD system is proposed and demonstrated in experiments. Furthermore, our scheme gives an easy way for Alice to monitor the degree of randomization in experiments. Therefore, we expect our scheme to become a standard part in future QKD systems due to its secure significance and feasibility.

  18. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris – A randomized phase II study

    PubMed Central

    Koo, John; Tyring, Stephen; Werschler, William P.; Bruce, Suzanne; Olesen, Martin; Villumsen, John; Bagel, Jerry

    2016-01-01

    Abstract Background: An aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment. Objectives: To compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks. Methods: In this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician’s global assessment of disease severity. Results: In total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference –0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch). Conclusions: Cal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment. PMID:26444907

  19. Coherent-phase or random-phase acceleration of electron beams in solar flares

    NASA Technical Reports Server (NTRS)

    Aschwanden, Markus J.; Benz, Arnold O.; Montello, Maria L.

    1994-01-01

    Time structures of electron beam signatures at radio wavelengths are investigated to probe correlated versus random behavior in solar flares. In particular we address the issue whether acceleration and injection of electron beams is coherently modulated by a single source, or whether the injection is driven by a stochastic (possibly spatially fragmented) process. We analyze a total of approximately = 6000 type III bursts observed by Ikarus (Zurich) in the frequency range of 100-500 MHz, during 359 solar flares with simultaneous greater than or = 25 keV hard X-ray emission, in the years 1890-1983. In 155 flares we find a total of 260 continuous type III groups, with an average number of 13 +/- 9 bursts per group, a mean duration of D = 12 +/- 14 s, a mean period of P = 2.0 +/- 1.2 s, with the highest burst rate at a frequency of nu = 310 +/- 120 MHz. Pulse periods have been measured between 0.5 and 10 s, and can be described by an exponential distribution, i.e., N(P) varies as e (exp -P/1.0s). The period shows a frequency dependence of P(nu)=46(exp-0.6)(sub MHz)s for different flares, but is invariant during a particular flare. We measure the mean period P and its standard deviation sigma (sub p) in each type III group, and quantify the degree of periodicity (or phase-coherence) by the dimensionless parameter sigma (sub p)P. The representative sample of 260 type III burst groups shows a mean periodicity of sigma (sub p/P) = 0.37 +/- 0.12, while Monte Carlo simulations of an equivalent set of truly random time series show a distinctly different value of sigma (sub p)P = 0.93 +/- 0.26. This result indicates that the injection of electron beams is coherently modulated by a particle acceleration source which is either compact or has a global organization on a timescale of seconds, in contrast to an incoherent acceleration source, which is stochastic either in time or space. We discuss the constraints on the size of the acceleration region resulting from electron beam

  20. 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

  1. Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

    PubMed

    Flowers, Christopher R; Costa, Luciano J; Pasquini, Marcelo C; Le-Rademacher, Jennifer; Lill, Michael; Shore, Tsiporah B; Vaughan, William; Craig, Michael; Freytes, Cesar O; Shea, Thomas C; Horwitz, Mitchell E; Fay, Joseph W; Mineishi, Shin; Rondelli, Damiano; Mason, James; Braunschweig, Ira; Ai, Weiyun; Yeh, Rosa F; Rodriguez, Tulio E; Flinn, Ian; Comeau, Terrance; Yeager, Andrew M; Pulsipher, Michael A; Bence-Bruckler, Isabelle; Laneuville, Pierre; Bierman, Philip; Chen, Andy I; Kato, Kazunobu; Wang, Yanlin; Xu, Cong; Smith, Angela J; Waller, Edmund K

    2016-07-01

    Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM. PMID:27040394

  2. Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: a phase II multicenter study.

    PubMed

    Ahluwalia, Manmeet S; Xie, Hao; Dahiya, Saurabh; Hashemi-Sadraei, Nooshin; Schiff, David; Fisher, Paul G; Chamberlain, Marc C; Pannullo, Susan; Newton, Herbert B; Brewer, Cathy; Wood, Laura; Prayson, Richard; Elson, Paul; Peereboom, David M

    2015-03-01

    Standard initial therapy for patients with pure and mixed anaplastic oligodendrogliomas (AO/MAO) includes chemotherapy and radiation therapy. Anaplastic oligodendrogliomas with 1p/19q co-deletion are more responsive to chemotherapy. There is concern for potential long-term CNS toxicity of radiation. Hence an approach using chemotherapy initially and reserving radiation for progressive disease is attractive. This multicenter phase II trial included patients with newly diagnosed AO/MAO with central pathology review and 1p/19q assay. Temozolomide was given 150 mg/m(2) days 1-7 and 15-21, every 28 days for 8 cycles. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate, overall survival (OS), treatment toxicity and health-related quality of life (HRQL). Data from 62 patients enrolled between December 2001 and April 2007 at seven centers were analyzed. Among patients with measurable disease, 8 % achieved complete remission, 56 % had stable disease and 36 % had progression. The median PFS and OS were 27.2 months (95 % CI 11.9-36.3) and 105.8 months (95 % CI 51.5-N/A), respectively. Both 1p loss and 1p/19q co-deletion were positive prognostic factors for PFS (p < 0.001) and OS (p < 0.001); and there was some suggestion that 1p/19q co-deletion also predicted better response to chemotherapy (p = 0.007). Grade 3/4 toxicities were mainly hematological. Significantly improved HRQL in the future uncertainty domain of the brain cancer module was seen after cycle 4 (p < 0.001). This trial achieved outcomes similar to those reported previously. Toxicities from dose-intense temozolomide were manageable. Improvement in at least one HRQL domain increased over time. This trial supports the further study of first-line temozolomide monotherapy as an alternative to radiation therapy for patients with newly diagnosed AO/MAO with 1p 19q co-deleted tumors. PMID:25534576

  3. Dabrafenib in BRAF V600E–Mutant Advanced Non-Small Cell Lung Cancer: an Open-label, Single arm, Multicenter, Phase 2 Trial

    PubMed Central

    Planchard, David; Kim, Tae Min; Mazieres, Julien; Quoix, Elisabeth; Riely, Gregory; Barlesi, Fabrice; Souquet, Pierre-John; Smit, Egbert F.; Groen, Harry J. M.; Kelly, Ronan J.; Cho, B. C.; Socinski, Mark A.; Pandite, Lini; Nase, Christine; Ma, Bo; D’Amelio, Anthony; Mookerjee, Bijoyesh; Curtis, C. Martin; Johnson, Bruce E.

    2016-01-01

    Background Activating BRAF V600E mutations are found in approximately 1–2% of adenocarcinomas of the lung offering an opportunity to test targeted therapy for this disease. Dabrafenib is an oral selective inhibitor of the BRAF kinase. The aim of this study was to assess the clinical activity of dabrafenib in patients with advanced BRAF V600E-mutant non-small cell lung cancer (NSCLC). Methods In this phase 2, multicenter, nonrandomized, open-label study of previously treated and untreated patients with stage IV, metastatic NSCLC and BRAF V600E mutation, we evaluated the antitumor activity and safety of oral dabrafenib (150 mg twice daily). The primary endpoint was investigator-assessed overall response rate (ORR) in patients receiving ≥ 1 dose of study drug. Safety analysis was performed on the all-treated population (all previously treated and untreated patients receiving ≥ 1 dose of study drug). The study is ongoing but not enrolling participants in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Between August 2011 and February 2014 a total of 84 previously treated and untreated patients were enrolled. Investigator-assessed ORR for 78 pretreated patients was 33% (95% confidence interval [CI], 23·1 to 44·9). Independent review committee assessment of ORR was consistent with investigator-based assessment. Four of the six previously untreated patients had an objective response. One patient died on study due to intracranial hemorrhage that was considered by the investigator to be due to study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or higher adverse events were cutaneous squamous cell carcinoma (10 [12%] of 84 patients), asthenia (4 [5%] of 84 patients), and basal cell carcinoma (4 [5%] of 84 patients). Interpretation This is, to our knowledge, the first prospective trial focusing on BRAF V600E-mutant NSCLC to show clinical activity of a BRAF inhibitor. The

  4. 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.

  5. Comparison of efficacy and safety of choline fenofibrate (fenofibric acid) to micronized fenofibrate in patients of mixed dyslipidemia: A randomized, open-label, multicenter clinical trial in Indian population

    PubMed Central

    Patel, Piyush; Barkate, Hanmant

    2016-01-01

    Introduction: Choline fenofibrate is a newly developed choline salt of fenofibric acid, which is more hydrophilic than fenofibrate. This study was initiated to evaluate the safety and efficacy of choline fenofibrate in comparison to micronized fenofibrate among Indian patients of mixed dyslipidemia. Methods: A multicenter, open-label, randomized, active controlled, comparative, parallel group study was conducted at around 10 centers spread all across the country. Mixed dyslipidemia patients (serum triglycerides [TG] levels between 150 and 500 mg/dl), aged 18–70 years and taking stable statin dose for 8 weeks were randomized to choline fenofibrate 135 mg delayed release tablets and micronized fenofibrate 160 mg tablets once daily for 12 weeks. The primary endpoint of the study was percentage change in serum TG level at the end of 12 weeks. Results: A total of 226 patients were enrolled in this study, of which 116 patients were administered choline fenofibrate and 110 patients were administered micronized fenofibrate. At the end of 12 weeks, there was a significant reduction in TG level (34.24% in choline fenofibrate group and 38.13% reduction in micronized fenofibrate group). However, the difference between group was not statistically different (P = 0.471). Similarly, there was a significant increase in high-density lipoprotein cholesterol at the end of 12 weeks (10% increase in choline fenofibrate group and 9% increase in micronized fenofibrate group); but the difference between the group was not statistically significant (P = 0.598). Both the treatment was safe and well tolerated. Conclusion: Choline fenofibrate delayed release 135 mg is as safe and effective as 160 mg of micronized fenofibrate in Indian patients with mixed dyslipidemia. PMID:26904471

  6. A Randomized, Double-blind, Placebo-controlled, Multi-center, Extension Trial Evaluating the Efficacy of a New Oral Supplement in Women with Self-perceived Thinning Hair

    PubMed Central

    Dayan, Steven

    2015-01-01

    Objective: The purpose of this six-month, randomized, double-blind, multi-center, placebo-controlled study was to determine if the administration of a new oral supplement will promote terminal hair growth. Design: A randomized, double-blind study. Setting: Two private practices (dermatology and facial plastics). Participants: Women 21 to 75 years of age with self-perceived thinning hair. Measurements: The primary efficacy endpoint was the change in terminal and vellus hairs in a 4cm2 target area of the scalp after 90 and 180 days of treatment. Secondary endpoints were change in hair diameter and responses to Quality of Life and Self-Assessment questionnaires. Results: Subjects treated with the new oral supplement achieved a significant increase in the number of baseline terminal hairs at 90 and 180 days (for each, p<0.0001, respectively) and were significantly greater then placebo (p<0.0001). Treatment with the new oral supplement was also associated with a significant increase in baseline terminal hair diameter after 90 (p=0.006) and 180 days of treatment (p=0.001) which was significantly greater than placebo at the end of the study (p=0.003). Improvements in hair growth and hair diameter were associated with significant improvement in most responses to Self-Assessment and Quality of Life Questionnaire responses. There were no adverse events. Conclusion: The daily administration of a new oral supplement was associated with significant increases in the number of terminal and vellus hairs and hair diameter. Most study participants believed the use of the oral supplement resulted in significant improvement in skin and hair quality and quality of life. PMID:26705444

  7. Treatment of children with attention-deficit/hyperactivity disorder: results of a randomized, multicenter, double-blind, crossover study of extended-release dexmethylphenidate and D,L-methylphenidate and placebo in a laboratory classroom setting.

    PubMed

    Silva, Raul; Muniz, Rafael; McCague, Kevin; Childress, Ann; Brams, Matthew; Mao, Alice

    2008-01-01

    The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. This multicenter, double-blind, crossover study randomized 82 children, 6 to 12 years of age, stabilized on a total daily dose to the nearest equivalent of 40 to 60 mg of d,l-MPH or 20 or 30 mg/day of d-MPH. Patients participated in a screening day and practice day, and were randomized to 1 of 10 sequences of all five treatments in five separate periods. Treatments included d-MPH-ER (20 mg/day), d-MPH-ER (30 mg/day), d,l-MPH-ER (36 mg/day), d,l-MPH-ER (54 mg/day), and placebo. Primary efficacy was measured by the change from predose on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2-h postdose during the 12-h laboratory assessment (d-MPH-ER 20 mg/day vs. d,l-MPH-ER 36 mg/day). Adverse events were monitored throughout the study period. d-MPH-ER (20 mg/day) was significantly more effective than d,l-MPH-ER (36 mg/day) in the primary efficacy variable, change from predose to 2-h postdose in SKAMP-combined score. In general, d-MPH-ER had an earlier onset of action than d,l-MPH-ER, while d,l-MPH-ER had a stronger effect at 12-h postdose. No serious adverse events were reported. Treatment with either agent was associated with significant improvements in ADHD symptoms. d-MPH-ER and d,l-MPH-ER can be differentiated on what part of the day each is more effective. PMID:18362868

  8. A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy

    PubMed Central

    Lee, Hee Yeon; Lee, Kyung Hee; Kim, Bong-Seog; Song, Hong Suk; Yang, Sung Hyun; Kim, Joon Hee; Kim, Yeul Hong; Kim, Jong Gwang; Kim, Sang-We; Kim, Dong-Wan; Kim, Si-Young; Park, Hee Sook

    2014-01-01

    Purpose This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. Results Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. Conclusion In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups. PMID:24520219

  9. Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxinA in the treatment of glabellar lines: a multicenter, randomized, double-blind, active-controlled study.

    PubMed

    Won, Chong Hyun; Kim, Hyun Kyu; Kim, Beom Joon; Kang, Hoon; Hong, Joon Pio; Lee, Su-Young; Kim, Chung-Sei

    2015-02-01

    A novel botulinum neurotoxin type A (DWP450; Daewoong Pharmaceutical, Seoul, Korea) has recently been introduced for the treatment of facial wrinkles. The efficacy of this agent has previously been demonstrated in an in vivo study using an electrophysiological protocol in a rat model. To compare the efficacy and safety of DWP450 with onabotulinumtoxinA (OBoNT) for use in the treatment of glabellar lines, we performed a multicenter, double-blind, randomized, active-controlled trial comparing DWP450 and OBoNT (Allergan Inc., Irvine, CA, USA). A total of 268 subjects with moderate to severe glabellar lines were randomized at a 1:1 ratio. Each patient received treatment with 20 U of study medication. Maximum frown responder rates at week 4 were measured to analyze the primary efficacy endpoint. To evaluate secondary efficacy endpoints, response rates were measured at weeks 8, 12, and 16, at maximum frown and rest. Specifically, responder rates at both maximum frown and at rest were assessed based on clinical photography. Subject degree of satisfaction and self-assessed rate of response were also measured. Adverse events (AEs) were documented to evaluate safety. Responder rate by physician-rating severity at maximal contraction at week 4 was 93.89% in the DWP450 group and 88.64% in OBoNT group. As the lower limit of the 97.5% one-sided confidence interval (-1.53%) surpassed the -15% threshold, we determined that DWP450 was not inferior to OBoNT. For the secondary efficacy endpoint analyses, no significant differences were observed between the two groups for any variable at any point in time. The incidences of AEs were similar for the two groups. Most of AEs were considered mild. DWP450 and OBoNT were comparable in efficacy and safety in the treatment of glabellar lines. PMID:25311357

  10. A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial

    PubMed Central

    Meng, Wenxia; Dong, Yi; Liu, Jie; Wang, Zhi; Zhong, Xiaobo; Chen, Ruiyang; Zhou, Hongmei; Lin, Mei; Jiang, Lu; Gao, Feng; Xu, Tao; Chen, Qianming; Zeng, Xin

    2009-01-01

    Background Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS) in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox. Methods We performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU) were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets. Results Amlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6) and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6). No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox. Conclusions Amlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients. Trials registration Nederlands Trial Register NTR1727. PMID:19419555

  11. Comparison of 1470 nm Laser and Radial 2ring Fiber with 980 nm Laser and Bare-Tip Fiber in Endovenous Laser Ablation of Saphenous Varicose Veins: A Multicenter, Prospective, Randomized, Non-Blind Study

    PubMed Central

    Ogawa, Tomohiro; Sugawara, Hiromitsu; Shokoku, Shintaro; Sato, Shoji

    2015-01-01

    Objective: The aim of this study is to compare the clinical efficacy and safety of two laser wavelengths and fiber types in endovenous laser ablation (EVLA) of saphenous varicose veins of the lower limb. Design: Multi-center prospective randomized non-blind clinical trial. Patients and Methods: From January 2007 to December 2011, 113 patients (113 limbs) with primary varicose veins were randomized into two groups. They were treated with radial 2ring fiber and 1470 nm laser in Group I (57 limbs) and bare-tip fiber and 980 nm laser in Group E (56 limbs) in order to ablate the saphenous vein. Vein occlusion rates at 12 weeks and pain in treated region were recorded as primary endpoint. Visual analogue scale (VAS) for assessment of pain, rates of bruising, complications and equipment failure were recorded as secondary endpoint of safety. Results: Occlusion rates at 12 weeks were 100% in both groups. Rates of pain (0% vs. 25.0%) and bruising (7.0% vs. 57.1%) were significantly lower in Group I (p <0.0001). VAS of pain was significantly lower on postoperative day 1, day 5 and 2nd week in Group I. Conclusion: Treatment of saphenous varicose veins by EVLA using a 1470 nm laser and a radial 2ring fiber resulted in comparable occlusion rates at 12 weeks and less postoperative pain and bruising than EVLA with a 980 nm laser and a bare-tip fiber. (This article is a translation of Jpn J Vasc Surg 2014; 23: 964–971.) PMID:26730252

  12. Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basal-bolus regimen for type 2 diabetes: a multicenter, randomized, parallel, open-label study (NCT00135096)

    PubMed Central

    Ratner, R; Wynne, A; Nakhle, S; Brusco, O; Vlajnic, A; Rendell, M

    2011-01-01

    Aim: Insulin therapy is commonly associated with weight gain. The timing of prandial insulin administration may enhance its efficacy/safety and maintain effective weight control. This study examined the effect of postprandial vs. preprandial insulin glulisine on weight gain and glycaemic control in type 2 diabetes patients taking basal insulin. Methods: This was a multicenter, randomized, open-label trial conducted in 45 centres in the USA. A total of 716 patients with type 2 diabetes and glycated haemoglobin A1c (HbA1c) ≥7.5% and ≤10.0% were screened; 345 were randomized and 322 comprised the intent-to-treat group (premeal, 163; postmeal, 159). Insulin glargine once daily, ±metformin and subcutaneous injections of premeal or postmeal insulin glulisine were given for 52 weeks. Main outcome measures included changes in HbA1c, fasting plasma glucose and weight from study baseline to endpoint (week 52). Results: At study end, insulin glulisine achieved similar glycaemic control whether it was administered before or after meals (HbA1c: 7.04% premeal vs. 7.16% postmeal, p = NS). Overall hypoglycaemia incidence and severe hypoglycaemia rates were not significantly different between premeal and postmeal groups; however, symptomatic and nocturnal hypoglycaemia rates were higher in the postprandial group. Mean body weight was lower in the postmeal group, with the difference between postmeal and premeal weight change from baseline to week 52 of −0.87 kg (p = 0.243). Conclusion: Postprandial glulisine administration provided similar glycaemic control and was non-inferior to preprandial administration on weight gain, without additional risk of severe hypoglycaemia, showing dosing flexibility and the feasibility of such approach when clinically indicated. PMID:21812890

  13. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    PubMed

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). PMID:26696251

  14. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    PubMed Central

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Background Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. Conclusion While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer. PMID:26109878

  15. Smeared quantum phase transition in the dissipative random quantum Ising model

    NASA Astrophysics Data System (ADS)

    Vojta, Thomas; Hoyos, José A.

    2010-01-01

    We investigate the quantum phase transition in the random transverse-field Ising model under the influence of Ohmic dissipation. To this end, we numerically implement a strong-disorder renormalization-group scheme. We find that Ohmic dissipation destroys the quantum critical point and the associated quantum Griffiths phase by smearing. Our results quantitatively confirm a recent theory [J.A. Hoyos, T. Vojta, Phys. Rev. Lett. 100 (2008) 240601] of smeared quantum phase transitions.

  16. Phase transitions in optimal search times: How random walkers should combine resetting and flight scales

    NASA Astrophysics Data System (ADS)

    Campos, Daniel; Méndez, Vicenç

    2015-12-01

    Recent works have explored the properties of Lévy flights with resetting in one-dimensional domains and have reported the existence of phase transitions in the phase space of parameters which minimizes the mean first passage time (MFPT) through the origin [L. Kusmierz et al., Phys. Rev. Lett. 113, 220602 (2014), 10.1103/PhysRevLett.113.220602]. Here, we show how actually an interesting dynamics, including also phase transitions for the minimization of the MFPT, can also be obtained without invoking the use of Lévy statistics but for the simpler case of random walks with exponentially distributed flights of constant speed. We explore this dynamics both in the case of finite and infinite domains, and for different implementations of the resetting mechanism to show that different ways to introduce resetting consistently lead to a quite similar dynamics. The use of exponential flights has the strong advantage that exact solutions can be obtained easily for the MFPT through the origin, so a complete analytical characterization of the system dynamics can be provided. Furthermore, we discuss in detail how the phase transitions observed in random walks with resetting are closely related to several ideas recurrently used in the field of random search theory, in particular, to other mechanisms proposed to understand random search in space as mortal random walks or multiscale random walks. As a whole, we corroborate that one of the essential ingredients behind MFPT minimization lies in the combination of multiple movement scales (regardless of their specific origin).

  17. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use

    PubMed Central

    Wun, Ted; McCavit, Timothy L.; De Castro, Laura M.; Krishnamurti, Lakshmanan; Lanzkron, Sophie; Hsu, Lewis L.; Smith, Wally R.; Rhee, Seungshin; Magnani, John L.; Thackray, Helen

    2015-01-01

    Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833. PMID:25733584

  18. Masking property of quantum random cipher with phase mask encryption

    NASA Astrophysics Data System (ADS)

    Sohma, Masaki; Hirota, Osamu

    2014-10-01

    The security analysis of physical encryption protocol based on coherent pulse position modulation (CPPM) originated by Yuen is one of the most interesting topics in the study of cryptosystem with a security level beyond the Shannon limit. Although the implementation of CPPM scheme has certain difficulty, several methods have been proposed recently. This paper deals with the CPPM encryption in terms of symplectic transformation, which includes a phase mask encryption as a special example, and formulates a unified security analysis for such encryption schemes. Specifically, we give a lower bound of Eve's symbol error probability using reliability function theory to ensure that our proposed system exceeds the Shannon limit. Then we assume the secret key is given to Eve after her heterodyne measurement. Since this assumption means that Eve has a great advantage in the sense of the conventional cryptography, the lower bound of her error indeed ensures the security level beyond the Shannon limit. In addition, we show some numerical examples of the security performance.

  19. All-optical quantum random bit generation from intrinsically binary phase of parametric oscillators.

    PubMed

    Marandi, Alireza; Leindecker, Nick C; Vodopyanov, Konstantin L; Byer, Robert L

    2012-08-13

    We demonstrate a novel all-optical quantum random number generator (RNG) based on above-threshold binary phase state selection in a degenerate optical parametric oscillator (OPO). Photodetection is not a part of the random process, and no post processing is required for the generated bit sequence. We show that the outcome is statistically random with 99% confidence, and verify that the randomness is due to the phase of initiating photons generated through spontaneous parametric down conversion of the pump, with negligible contribution of classical noise sources. With the use of micro- and nanoscale OPO resonators, this technique offers a promise for simple, robust, and high-speed on-chip all-optical quantum RNGs. PMID:23038574

  20. Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

    PubMed Central

    2013-01-01

    Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary

  1. Security authentication with a three-dimensional optical phase code using random forest classifier.

    PubMed

    Markman, Adam; Carnicer, Artur; Javidi, Bahram

    2016-06-01

    An object with a unique three-dimensional (3D) optical phase mask attached is analyzed for security and authentication. These 3D optical phase masks are more difficult to duplicate or to have a mathematical formulation compared with 2D masks and thus have improved security capabilities. A quick response code was modulated using a random 3D optical phase mask generating a 3D optical phase code (OPC). Due to the scattering of light through the 3D OPC, a unique speckle pattern based on the materials and structure in the 3D optical phase mask is generated and recorded on a CCD device. Feature extraction is performed by calculating the mean, variance, skewness, kurtosis, and entropy for each recorded speckle pattern. The random forest classifier is used for authentication. Optical experiments demonstrate the feasibility of the authentication scheme. PMID:27409445

  2. Effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial

    SciTech Connect

    Coy, P.; Hodson, I.; Payne, D.G.; Evans, W.K.; Feld, R.; MacDonald, A.S.; Osoba, D.; Pater, J.L.

    1988-02-01

    Patients with limited stage small cell lung cancer were initially randomized to receive either three courses of Cyclophosphamide, Adriamycin, and Vincristine (CAV) followed by three courses of VP-16 and Cis-platin (VP-PT) or six courses of alternating CAV and VP-PT. Responding patients received prophylactic cranial radiation (PCI) after three courses of chemotherapy (CT) and loco-regional thoracic radiation (LRTR) after six courses. No maintenance chemotherapy was given. Patients receiving LRTR were randomized to receive either 25 Gy in ten fractions over 2 weeks (SD) or 37.5 Gy in 15 fractions over 3 weeks (HD). In both arms the pre-chemotherapy disease was treated with a 2 cm margin around the primary tumor volume. The mediastinum was included in the treatment volume and the supraclavicular nodes were also included if involved originally. The spinal cord was shielded after 32 Gy. Of the 333 patients enrolled by the time the trial closed in October 1984, 168 were eventually randomized to LRTR and are eligible for response assessment. The overall response rate after combined RT and CT was 94% (CR 67%, PR 27%). The CR rate for SD was 65% and for HD 69%. The combined treatment was well tolerated by most patients. Forty-nine percent of HD patients developed dysphagia compared to 26% of those SD (p less than 0.01). At the time of this analysis the median duration of follow-up since randomization to radiotherapy is 30 months. The median local progression-free survival on HD is 49 weeks. On SD it is 38 weeks (p = 0.05, one sided). The actuarial incidence of local progression by 2 years is 69% on HD and 80% on LD. There is as yet no significant difference in overall survival between the two arms. It appears that HD radiotherapy as administered in this study may have an impact on local control, but it is too early to determine if this will translate into a survival benefit.

  3. Multiple-wavelength double random phase encoding with CCD-plane sparse-phase multiplexing for optical information verification.

    PubMed

    Chen, Wen

    2015-12-20

    A novel method is proposed by using multiple-wavelength double random phase encoding (MW-DRPE) with CCD-plane sparse-phase multiplexing for optical information verification. Two different strategies are applied to conduct sparse-phase multiplexing in the CCD plane. The results demonstrate that large capacity can be achieved for optical multiple-image verification. The proposed optical verification strategy is implemented based on optical encoding, and the keys generated by optical encryption can further guarantee the safety of the designed optical multiple-image verification system. The proposed method provides a novel alternative for DRPE-based optical information verification. PMID:26837040

  4. Simultaneous transmission for an encrypted image and a double random-phase encryption key

    NASA Astrophysics Data System (ADS)

    Yuan, Sheng; Zhou, Xin; Li, Da-Hai; Zhou, Ding-Fu

    2007-06-01

    We propose a method to simultaneously transmit double random-phase encryption key and an encrypted image by making use of the fact that an acceptable decryption result can be obtained when only partial data of the encrypted image have been taken in the decryption process. First, the original image data are encoded as an encrypted image by a double random-phase encryption technique. Second, a double random-phase encryption key is encoded as an encoded key by the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. Then the amplitude of the encrypted image is modulated by the encoded key to form what we call an encoded image. Finally, the encoded image that carries both the encrypted image and the encoded key is delivered to the receiver. Based on such a method, the receiver can have an acceptable result and secure transmission can be guaranteed by the RSA cipher system.

  5. Randomized, Multicenter, Double–Blind Study of the Safety and Efficacy of 1%D-3-Hydroxybutyrate eye drops for Dry Eye Disease

    PubMed Central

    Kawakita, Tetsuya; Uchino, Miki; Fukagawa, Kazumi; Yoshino, Kenichi; Shimazaki, Seika; Toda, Ikuko; Tanaka, Mari; Arai, Hiroyuki; Sakatani, Keiko; Hata, Seiichiro; Okano, Takashi; Tsubota, Kazuo

    2016-01-01

    In a previous study, we demonstrated that topical D-beta-hydroxybutyrate ameliorates corneal epithelial erosion and superficial punctate keratopathy in a rat model of dry eye disease. In the current investigation, we performed a prospective, randomized, multicentre, double-blind, placebo-controlled study to assess the safety and efficacy of 1% D-3-hydroxybutyrate eye drops in patients with dry eye disease. A total of 65 patients were randomly assigned to either the placebo group or the 1% D-3-hydroxybutyrate group, and the treatments were administered 6 times a day for 4 weeks. We then evaluated corneal fluorescein staining, corneal and conjunctival rose Bengal staining, tear film break-up time (BUT), Schirmer score, and subjective symptoms. At both 2 and 4 weeks, the corneal rose Bengal score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group. Among patients with an initial Schirmer score of ≤5 mm, the corneal fluorescein staining score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group at two weeks. Mild ocular symptoms occurred in both groups, and these spontaneously resolved. The present study suggested that 1% D-3-hydroxybutyrate eye drops are safe and effective in treating ocular surface disorders in patients with tear-deficient dry eye disease. PMID:26865350

  6. A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction.

    PubMed

    Lee, Jun-Won; Lee, Seung-Hwan; Youn, Young-Jin; Ahn, Min-Soo; Kim, Jang-Young; Yoo, Byung-Su; Yoon, Junghan; Kwon, Woocheol; Hong, In-Soo; Lee, Kyounghoon; Kwan, Jun; Park, Keum Soo; Choi, Donghoon; Jang, Yang Soo; Hong, Mun K

    2014-01-01

    Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9% ± 8.5% vs 1.6% ± 7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105). PMID:24431901

  7. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

    PubMed

    Park, Sat Byul; Kim, Kyu-Nam; Sung, Eunju; Lee, Suk Young; Shin, Ho Cheol

    2016-05-01

    Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS. PMID:26911970

  8. Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial

    PubMed Central

    Thomas, Pierre; Vieta, Eduard

    2008-01-01

    The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400–800 mg/day) or haloperidol (5–15 mg/day) for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of ≥50% of the Y-MRS) in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009) more frequently in the haloperidol group (86.4%) than in the amisulpride group (66.1%). In conclusion, the valproate–amisulpride combination was as effective as the valproate – haloperidol combination in bipolar I patients, with a better safety profile. PMID:18830442

  9. Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: a multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial.

    PubMed

    Habib, G B; Dunbar, L M; Rodrigues, R; Neale, A C; Friday, K J

    1995-05-01

    This study was a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of oral nicardipine for the treatment of urgent hypertension in the emergency department. Of 57 patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women, 43 black and 10 white, age range 48 +/- 11 years, and diastolic blood pressure 128 +/- 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or placebo in blind fashion followed by 30 mg open-label nicardipine in nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg nicardipine three times a day for 1 week after discharge from the emergency department. Adequate blood pressure reduction, defined as a reduction of diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo (p = 0.002). Adequate blood pressure reduction after administration of open-label nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure reductions were maintained at 1 week after discharge. The drug was well tolerated, and no significant adverse events occurred. We conclude that oral nicardipine is a safe and effective drug for the initial treatment of urgent hypertension. PMID:7732981

  10. A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction

    PubMed Central

    Lee, Jun-Won; Youn, Young-Jin; Ahn, Min-Soo; Kim, Jang-Young; Yoo, Byung-Su; Yoon, Junghan; Kwon, Woocheol; Hong, In-Soo; Lee, Kyounghoon; Kwan, Jun; Park, Keum Soo; Choi, Donghoon; Jang, Yang Soo; Hong, Mun K.

    2014-01-01

    Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%±8.5% vs 1.6%±7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105) PMID:24431901

  11. Universal polarization terahertz phase controllers using randomly aligned liquid crystal cells with graphene electrodes.

    PubMed

    Sasaki, Tomoyuki; Noda, Kohei; Kawatsuki, Nobuhiro; Ono, Hiroshi

    2015-04-01

    We present a universal polarization terahertz (THz) phase controller using a randomly aligned liquid crystal (LC) cell with graphene electrodes. The LC cell was fabricated using a nematic LC and two quartz substrates that were coated with a monolayer of graphene as the transparent electrode. The LC in the cell was prepared without any alignment treatments and was randomly aligned. The size of the random domains and the width of the disclination lines in the LC layer were several tens of microns. These textures disappeared when an alternating voltage was applied to the LC through the graphene layers. Using a THz time domain spectroscopic technique, we investigated the complex transmittance of the LC cell. The LC cell was highly transparent in the THz frequency range, and there was little change in the transmittance with the applied voltage. This indicated that the scattering loss originating in the randomly aligned LC molecules was small for the THz waves. We also demonstrated that the THz phase shift could be controlled by the applied voltage. The amplitude of the phase shift was explained by the ordinary and extraordinary refractive indices of the LC. These LC cells with graphene electrodes can be used to realize universal polarization THz phase controllers because of the random alignment. PMID:25831380

  12. Single-shot phase imaging with randomized light (SPIRaL).

    PubMed

    Horisaki, Ryoichi; Egami, Riki; Tanida, Jun

    2016-02-22

    We present a method for single-shot phase imaging with randomized light (SPIRaL). In SPIRaL, the complex (amplitude and phase) field of an object illuminated with a randomized coherent beam is captured with an image sensor, without the need for any reference light. The object field is retrieved from the single captured intensity image by a compressive sensing-based algorithm with a sparsity constraint. SPIRaL has higher observation speed, light efficiency, and flexibility of the implementation compared with previous methods. We demonstrate SPIRaL numerically and experimentally. PMID:26907032

  13. Random exchange interaction effects on the phase transitions in frustrated classical Heisenberg model

    SciTech Connect

    Li, W. C.; Song, X.; Feng, J. J.; Zeng, M.; Gao, X. S.; Qin, M. H.; Jia, X. T.

    2015-07-07

    In this work, the effects of the random exchange interaction on the phase transitions and phase diagrams of classical frustrated Heisenberg model are investigated by Monte Carlo simulation in order to simulate the chemical doping effect in real materials. It is observed that the antiferromagnetic transitions shift toward low temperature with the increasing magnitude of the random exchange interaction, which can be qualitatively understood from the competitions among local spin states. This study is related to the magnetic properties in the doped iron-based superconductors.

  14. The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol

    PubMed Central

    2014-01-01

    Background Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion. Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. Methods/Design This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18–75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. Discussion In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled

  15. The efficacy of a health-related quality-of-life intervention during 48 weeks of biologic treatment of patients with moderate to severe psoriasis: study protocol for a multicenter randomized controlled trial

    PubMed Central

    2012-01-01

    Background Interest in health-related quality of life (HRQoL) outcome research in dermatology is increasing, especially in the systemic treatment of psoriasis with biologic agents. In other specialties, such as oncology, the application of a HRQoL intervention is considered to be an aid for monitoring disease and treatment over time, for the communication with the patient, and for improving treatment outcome. However, in dermatology practice, the application of this intervention is relatively new. Moreover, evidence on the effectiveness of a HRQoL intervention in dermatology is missing. It is hypothesized that the application of a HRQoL intervention in dermatology practice will have a positive impact on patients’ HRQoL as well as on doctor-patient communication. Methods/design In a prospective multicenter cluster randomized controlled trial, patients diagnosed with moderate to severe psoriasis who receive biologic treatment, will be followed for 48 weeks. The study sites, and not the patients, will be randomly allocated via a computer-based randomization system to either the intervention (treatment with etanercept and standardized HRQoL assessment and communication) or the control group (treatment with etanercept alone). The HRQoL intervention will include 1) the electronic assessment of the Skindex-29, a well-studied dermatology-specific HRQoL questionnaire, and 2) the communication of the resulting Skindex-29 data with the patient. Prior to study start, dermatologists in the intervention group will be educated and trained in standardized HRQoL assessment and communication using the Skindex-29. At six consecutive visits, patients at study sites in the intervention group will be asked to complete the Skindex-29 on a desk-top pc at the clinic, just before their consultation with the dermatologist. A print-out of the completed questionnaire will be made and, guided by this print-out, feedback on the HRQoL scores will be given during the consultation. Primary

  16. The Effectiveness of Parent Training as a Treatment for Preschool Attention-Deficit/Hyperactivity Disorder: Study Protocol for a Randomized Controlled, Multicenter Trial of the New Forest Parenting Program in Everyday Clinical Practice

    PubMed Central

    Daley, David; Frydenberg, Morten; Rask, Charlotte U; Sonuga-Barke, Edmund; Thomsen, Per H

    2016-01-01

    Background Parent training is recommended as the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD. Objective The objective of this trial is to investigate whether the NFPP can be effectively delivered for children referred through official community pathways in everyday clinical practice. Methods A multicenter randomized controlled parallel arm trial design is employed. There are two treatment arms, NFPP and treatment as usual. NFPP consists of eight individually delivered parenting sessions, where the child attends during three of the sessions. Outcomes are examined at three time points (T1, T2, T3): T1 (baseline), T2 (week 12, post intervention), and T3 (6 month follow/up). 140 children between the ages of 3-7, with a clinical diagnosis of ADHD, informed by the Development and Well Being Assessment, and recruited from three child and adolescent psychiatry departments in Denmark will take part. Randomization is on a 1:1 basis, stratified for age and gender. Results The primary endpoint is change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (ADHD-RS) by T2. Secondary outcome measures include: effects on this measure at T3 and T2 and T3 measures of teacher reported Preschool ADHD-RS scores, parent and teacher rated scores on the Strength & Difficulties Questionnaire, direct observation of ADHD behaviors during Child’s Solo Play, observation of parent-child interaction, parent sense of competence, and family stress. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of nonpharmacological treatments. Conclusions The trial will provide evidence as to whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice. Trial

  17. Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study.

    PubMed

    Bourin, Michel S; Severus, Emanuel; Schronen, Juan P; Gass, Peter; Szamosi, Johan; Eriksson, Hans; Chandrashekar, Hongally

    2014-01-01

    Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was -22.8 for add-on lithium and -20.1 for add-on placebo, a statistically significant treatment group difference of -2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials

  18. Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term Premature Rupture of Membranes: A Randomized Multicenter Trial.

    PubMed

    Kruit, Heidi; Tihtonen, Kati; Raudaskoski, Tytti; Ulander, Veli-Matti; Aitokallio-Tallberg, Ansa; Heikinheimo, Oskari; Paavonen, Jorma; Rahkonen, Leena

    2016-07-01

    Objectives To compare the Foley catheter and misoprostol for induction of labor in term women with premature rupture of membranes. Study Design A randomized controlled trial was performed in three university hospitals in Finland between March 2012 and September 2014. A total of 202 term women with ruptured membranes >18 hours, singleton pregnancies in cephalic presentation, unfavorable cervix, and no prior cesarean section were enrolled. Participants were randomly allocated to induction of labor by Foley catheter or oral misoprostol in a 1:1 ratio. All women received prophylactic antibiotics. The main outcomes were cesarean section and maternal and neonatal infections. Results Labor induction by Foley catheter or misoprostol showed no difference in cesarean delivery rates (23.6 vs. 18.2%; odds ratio [OR], 1.39; 95% confidence interval [CI], 0.69-2.82; p = 0.36), maternal intrapartum infections (2.2 vs. 2%; OR, 1.12; 95% CI, 0.15-8.9; p = 1.00), postpartum infections (1.1 vs. 2.0%; OR, 0.55; 95% CI, 0.05-6.18; p = 1.00), or neonatal infections (1.1 vs. 5.1%; OR, 0.21; 95% CI, 0.24-1.87; p = 0.22). The total time from induction to delivery was similar (1,311 vs. 1,435 minutes; p = 0.31) in the two groups. Conclusions Foley catheter or misoprostol can both be used for induction of labor in women with term premature rupture of membranes. PMID:27031055

  19. Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

    PubMed Central

    Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

    2012-01-01

    Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

  20. Efficacy of oral antibiotics on acne vulgaris and their effects on quality of life: a multicenter randomized controlled trial using minocycline, roxithromycin and faropenem.

    PubMed

    Hayashi, Nobukazu; Kawashima, Makoto

    2011-02-01

    There are few clinical studies which compare the efficacy and patient satisfaction for oral antibiotics to treat inflammatory acne. To clarify the difference between oral antibiotics, acne patients with moderate to severe inflammatory eruptions were randomized into three groups, and each patient was given minocycline (MINO), roxithromycin (RXM) or faropenem (FRPM) for 4 weeks, followed by 4 weeks of observation without any oral antibiotics. We estimated the reduction rate of inflammatory lesion counts, the scale of Skindex-16 which represents patient quality of life (QOL), and minimum inhibitory concentrations required to inhibit the growth of 90% of Propionibacterium acnes isolated from acne patients (MIC(90) ). In all three groups, inflammatory lesion counts, and emotional and total score of Skindex-16 were significantly improved (P<0.05) after 4 weeks treatment, and these effects were maintained for the following 4 weeks. Dizziness/nausea in two patients (4.1%) of the MINO group and diarrhea in three patients (5.9%) of the FRPM group were observed. There was no significant difference of percentage reduction in inflammatory lesion counts and incident rates of side-effects between these three oral antibiotics. MIC(90) of MINO was 0.25 μg/mL before and after treatment, but MIC(90) of RXM had increased from 0.25 μg/mL to more than 32 μg/mL after treatment. MIC(90) of FRPM was 0.06 μg/mL or less for all strains before and after treatment. Our randomized controlled clinical trial suggested that MINO, RXM and FRPM were efficient to improve inflammatory acne and patient QOL, and there was no significant difference between them. PMID:21269305

  1. Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia

    PubMed Central

    Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

    2015-01-01

    Background/Aims Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Methods Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients’ quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. Results We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. Conclusions DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety. PMID:26130637

  2. The generation of 68 Gbps quantum random number by measuring laser phase fluctuations.

    PubMed

    Nie, You-Qi; Huang, Leilei; Liu, Yang; Payne, Frank; Zhang, Jun; Pan, Jian-Wei

    2015-06-01

    The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high-speed quantum random number generators are ready for practical usage. PMID:26133826

  3. The generation of 68 Gbps quantum random number by measuring laser phase fluctuations

    SciTech Connect

    Nie, You-Qi; Liu, Yang; Zhang, Jun Pan, Jian-Wei; Huang, Leilei; Payne, Frank

    2015-06-15

    The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high-speed quantum random number generators are ready for practical usage.

  4. Improvement in Growth After 1 Year of Growth Hormone Therapy in Well-Nourished Infants with Growth Retardation Secondary to Chronic Renal Failure: Results of a Multicenter, Controlled, Randomized, Open Clinical Trial

    PubMed Central

    Moreno, M. Llanos; Neto, Arlete; Ariceta, Gema; Vara, Julia; Alonso, Angel; Bueno, Alberto; Afonso, Alberto Caldas; Correia, António Jorge; Muley, Rafael; Barrios, Vicente; Gómez, Carlos; Argente, Jesús

    2010-01-01

    Background and objectives: Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management. Design, setting, participants, & measurements: The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12 ± 3 months, had CRF (GFR ≤60 ml/min per 1.73 m2), and had adequate nutritional intake and good metabolic control were recruited from eight pediatric nephrology departments from Spain and Portugal. Main outcome measures were body length, body weight, bone age, biochemical and hormonal analyses, renal function, bone mass, and adverse effects. Results: Length gain in infants who were treated with GH was statistically greater (P < 0.05) than that of nontreated children (14.5 versus 9.5 cm/yr; SD score 1.43 versus −0.11). The GH-induced stimulation of growth was associated with no undesirable effects on bone maturation, renal failure progression, or metabolic control. In addition, GH treatment improved forearm bone mass and increased serum concentrations of total and free IGF-I and IGF-binding protein 3 (IGFBP-3), whereas IGF-II, IGFBP-1, IGFBP-2, GH-binding protein, ghrelin, and leptin were not modified. Conclusions: Infants with CRF and growth retardation despite good metabolic and nutritional control benefit from GH treatment without adverse effects during 12 months of therapy. PMID:20522533

  5. Efficacy and Safety of Low-Dose Propiverine in Patients with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia with Storage Symptoms: A Prospective, Randomized, Single-Blinded and Multicenter Clinical Trial

    PubMed Central

    Bae, Jae Hyun; Kim, Sun Ouck; Yoo, Eun Sang; Moon, Kyung Hyun; Kyung, Yoon Soo

    2011-01-01

    Purpose The aim of this study was to evaluate whether low-dose anticholinergics combined with an α1-receptor antagonist would continue the effect of an alpha-blocker, decrease the side effects of anticholinergics, and improve the symptoms of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Materials and Methods Two hundred nine men with LUTS/BPH with storage symptoms (International Prostate Symptom Score [IPSS] ≥12; storage symptoms ≥4) were randomly assigned in a prospective, multicentered, and single-blind fashion to either the control group (alfuzosin 10 mg, once daily) or the combined group (alfuzosin 10 mg, once daily, and propiverine 10 mg, once daily) for 2 months. IPSS, maximal urinary flow rate (Qmax), and postvoid residual volume (PVR) were used to grade symptoms, side effects, and the impact on quality of life (QoL) at the start of the study and after 1 and 2 months. Results There were no significant differences in patient background, including age, prostate size, Qmax, and PVR, between the control group and the combined group. In the combined group, the IPSS total score and the IPSS storage symptom score were significantly improved compared with the control group. The IPSS voiding symptom score, QoL, Qmax, and PVR did not differ significantly. There were no serious side effects in either group. Conclusions Management with an α1-receptor antagonist combined with a low-dose anticholinergic improved the total score and storage symptom score of the IPSS compared with α1-receptor antagonist only group without causing serious side effects. This initial combination medication can be considered an effective and safe treatment modality for LUTS/BPH patients with storage symptoms. PMID:21556215

  6. Implementation and Operational Research: Computer-Assisted Intervention for Safer Sex in HIV-Positive Men Having Sex With Men: Findings of a European Randomized Multi-Center Trial

    PubMed Central

    Platteau, Tom; Bogner, Johannes; Buyze, Jozefien; Dec-Pietrowska, Joanna; Dias, Sonia; Newbury-Helps, John; Kocsis, Agnes; Mueller, Matthias; Rojas, Daniela; Stanekova, Danica; van Lankveld, Jacques; Colebunders, Robert

    2016-01-01

    Objective: Men who have sex with men (MSM) are the key population most affected by HIV in Europe. We performed the first European multicenter, simple-randomized parallel-group study to test the effectiveness of a theory-guided computer-assisted intervention to improve safer sex among HIV-positive men who have sex with men. Methods: Between February, 2011 and February, 2013, 112 participants were enrolled in 8 different European HIV-care settings. Intervention participants received 3 individual counseling sessions facilitated by trained service providers using computer-assisted tools. The control-group received sexual health advice delivered as part of regular HIV care. Outcome behavior (self-reported condom use at last intercourse; combined HIV transmission risk score), its influencing factors, and mediating variables were assessed at baseline, and at 3 and 6 months follow-up. Mixed effects models were used to compare primary outcomes (condom use at last intercourse, HIV transmission risk score), and mediation analysis to explore intervention effects. Results: Condom use at last intercourse increased more among intervention than control participants at 3 months follow-up (odds ratio of 3.83; P = 0.03), but not significantly at 6 months follow-up. Intervention participants reported a lower transmission risk at 3 months follow-up than controls (odds ratio compared with baseline of 11.53 and 1.28, respectively; P = 0.008), but this effect became nonsignificant at 6 months. Intervention effects were mediated by the proximal variables, self-efficacy to negotiate condom use and condom attitudes. Conclusions: This intervention showed short-term effectiveness. The intervention should be replicated in other settings, eventually investigating if booster-counseling sessions would yield a longer lasting effect. PMID:26866955

  7. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

    PubMed Central

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-01-01

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

  8. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

    PubMed

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-02-01

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

  9. Multi-center, Prospective, Randomized, Controlled Investigational Device Exemption Clinical Trial Comparing Mobi-C Cervical Artificial Disc to Anterior Discectomy and Fusion in the Treatment of Symptomatic Degenerative Disc Disease in the Cervical Spine

    PubMed Central

    Bae, Hyun W.; Davis, Reginald; Gaede, Steven; Hoffman, Greg; Kim, Kee; Nunley, Pierce D.; Peterson, Daniel; Rashbaum, Ralph; Stokes, John

    2014-01-01

    Background Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating symptomatic cervical disc degeneration. Cervical total disc replacements (TDRs) have emerged as an alternative for some patients. The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating single-level cervical disc degeneration. Methods This was a prospective, randomized, controlled, multicenter Food and Drug Administration (FDA) regulated Investigational Device Exemption (IDE) study. A total of 245 patients were treated (164 TDR: 81 ACDF). The primary outcome measure was overall success based on improvement in Neck Disability Index (NDI), no subsequent surgical interventions, and no adverse events (AEs) classified as major complications. Secondary outcome measures included SF-12, visual analog scale (VAS) assessing neck and arm pain, patient satisfaction, radiographic range of motion, and adjacent level degeneration. Patients were evaluated preoperatively and postoperatively at 6 weeks, 3, 6, 12, 18, and 24 months. The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months. Results Overall success rates were 73.6% for TDR and 65.3% for ACDF, confirming non-inferiority (p < 0.0025). TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months, and VAS neck pain and SF-12 PCS scores at 6 weeks (p<0.05). Operative level range of motion in the TDR group was maintained throughout follow-up. Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months (p < 0.05). AE rates were similar. Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration, producing outcomes similar to ACDF with less adjacent segment degeneration. Level of Evidence: Level I. Clinical relevance: This study adds to the literature supporting cervical TDR as a viable option to ACDF in

  10. Phase Separation Kinetics of a Binary Polymer Blend with Added Random Copolymer

    NASA Astrophysics Data System (ADS)

    Waldow, Dean; Barham, Bethany; Halasa, Adel

    1998-03-01

    The phase separation kinetics of a polymer blend with increasing amounts of random copolymer was studied using wide angle light scattering. The system is a blend of polystyrene and polybutadiene, and the copolymer is an asymmetric random styrene-butadiene copolymer (80/20). The composition of the blend is near critical and the weight percentages of the added copolymer vary from 0.0 to 2.5 percent. The temperature of the cloud point increases with increasing copolymer amount indicating a destabilizing effect. Light scattering data was collected while temperature was jumped from the one-phase region into the two-phase region near the phase boundary. Early stage and intermediate stage kinetics were analyzed using Cahn-Hillard-Cook theory and scaling theory. The early stage kinetics indicate a slowing of the diffusion constants with added copolymer, and the intermediate stage kinetics suggest that the scaling theory doesn't accurately describe the data.

  11. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases.

    PubMed

    Lasser, Robert A; Dirks, Bryan; Nasrallah, Henry; Kirsch, Courtney; Gao, Joseph; Pucci, Michael L; Knesevich, Mary A; Lindenmayer, Jean-Pierre

    2013-10-01

    Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted. PMID:23756608

  12. Efficacy and Safety of Tangshen Formula on Patients with Type 2 Diabetic Kidney Disease: A Multicenter Double-Blinded Randomized Placebo-Controlled Trial

    PubMed Central

    Li, Ping; Chen, Yiping; Liu, Jianping; Hong, Jing; Deng, Yueyi; Yang, Fang; Jin, Xiuping; Gao, Jing; Li, Jing; Fang, Hui; Liu, Geling; Shi, Liping; Du, Jinhang; Li, Yang; Yan, Meihua; Wen, Yumin; Yang, Wenying

    2015-01-01

    Background Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. Methods The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. Findings After 24 weeks of treatment, no statistically significant difference in UAER (TSF −19.53 μg/min compared with placebo −7.01 μg/min, with a mean difference of −12.52 μg/min; 95%CI, −68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF−0.21 g compared with placebo 0.36 g, with a mean difference of −0.57g; 95%CI, −1.05 to −0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, −0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. Conclusions Based on conventional

  13. A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

    PubMed Central

    Vinh, Ha; Anh, Vo Thi Cuc; Anh, Nguyen Duc; Campbell, James I.; Hoang, Nguyen Van Minh; Nga, Tran Vu Thieu; Nhu, Nguyen Thi Khanh; Minh, Pham Van; Thuy, Cao Thu; Duy, Pham Thanh; Phuong, Le Thi; Loan, Ha Thi; Chinh, Mai Thu; Thao, Nguyen Thi Thu; Tham, Nguyen Thi Hong; Mong, Bui Li; Bay, Phan Van Be; Day, Jeremy N.; Dolecek, Christiane; Lan, Nguyen Phu Huong; Diep, To Song; Farrar, Jeremy J.; Chau, Nguyen Van Vinh; Wolbers, Marcel; Baker, Stephen

    2011-01-01

    Background The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children. Methodology/Principal Findings We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n  =  249) or ciprofloxacin (n  =  245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p  =  0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66–126) hours for gatifloxacin recipients and 93 (68–120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]  =  0.98 [0.82–1.17], p  =  0.83). Conclusions We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the

  14. Rationale and design of a multicenter randomized controlled trial on a 'minimal intervention' in Dutch army personnel with nonspecific low back pain [ISRCTN19334317

    PubMed Central

    Helmhout, Pieter H; Harts, Chris C; Staal, J Bart; de Bie, Rob A

    2004-01-01

    Background Researchers from the Royal Netherlands Army are studying the potential of isolated lumbar extensor training in low back pain in their working population. Currently, a randomized controlled trial is carried out in five military health centers in The Netherlands and Germany, in which a 10-week program of not more than 2 training sessions (10–15 minutes) per week is studied in soldiers with nonspecific low back pain for more than 4 weeks. The purpose of the study is to investigate the efficacy of this 'minimal intervention program', compared to usual care. Moreover, attempts are made to identify subgroups of different responders to the intervention. Methods Besides a baseline measurement, follow-up data are gathered at two short-term intervals (5 and 10 weeks after randomization) and two long-term intervals (6 months and one year after the end of the intervention), respectively. At every test moment, participants fill out a compound questionnaire on a stand-alone PC, and they undergo an isometric back strength measurement on a lower back machine. Primary outcome measures in this study are: self-assessed degree of complaints and degree of handicap in daily activities due to back pain. In addition, our secondary measurements focus on: fear of movement/(re-) injury, mental and social health perception, individual back extension strength, and satisfaction of the patient with the treatment perceived. Finally, we assess a number of potential prognostic factors: demographic and job characteristics, overall health, the degree of physical activity, and the attitudes and beliefs of the physiotherapist towards chronic low back pain. Discussion Although a substantial number of trials have been conducted that included lumbar extension training in low back pain patients, hardly any study has emphasized a minimal intervention approach comparable to ours. For reasons of time efficiency and patient preferences, this minimal sports medicine approach of low back pain

  15. Midterm comparison of posterior cruciate-retaining versus -substituting total knee arthroplasty using the Genesis II prosthesis. A multicenter prospective randomized clinical trial.

    PubMed

    Harato, Kengo; Bourne, Robert B; Victor, Jan; Snyder, Mark; Hart, John; Ries, Michael D

    2008-06-01

    The purpose of the current study was to compare midterm outcomes of posterior cruciate-retaining (CR) versus posterior cruciate-substituting (PS) procedures using the Genesis II total knee arthroplasty (TKA) system (Smith and Nephew, Memphis, TN). Ninety-nine (99) CR and 93 PS TKA's were analyzed in this prospective, randomized clinical trial. Surgeries were performed at seven medical centers by participating surgeons. Clinical outcomes (Knee Society Score, Range of Motion, WOMAC, SF-12, and Radiographic Findings), in addition to postoperative complications, were evaluated with a minimum follow-up of 5 years. Following data analysis, there were no significant differences in patient demographics or preoperative clinical measures between the two groups. At the latest follow-up interval, no significant differences were found between the CR and PS groups with regards to functional assessment, patient satisfaction, or postoperative complication. However, the PS group did display statistically significant improvements in range of motion when compared with the CR group. The results of this investigation would suggest that, while comparable in regards to supporting good clinical outcomes, the PS Genesis II design does appear to support significantly improved postoperative range of motion when compared with the CR design. PMID:18325770

  16. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial.

    PubMed

    Abdelkefi, Abderrahman; Ladeb, Saloua; Torjman, Lamia; Othman, Tarek Ben; Lakhal, Amel; Romdhane, Neila Ben; Omri, Halima El; Elloumi, Moez; Belaaj, Hatem; Jeddi, Ramzi; Aissaouï, Lamia; Ksouri, Habib; Hassen, Assia Ben; Msadek, Fahmi; Saad, Ali; Hsaïri, Mohamed; Boukef, Kamel; Amouri, Ahlem; Louzir, Hechmi; Dellagi, Koussay; Abdeladhim, Abdeladhim Ben

    2008-02-15

    From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805). PMID:17875806

  17. Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome.

    PubMed

    Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R

    2013-08-01

    Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481

  18. Prospective, Multi-center Randomized Intermediate Biomarker Study of Oral Contraceptive vs. Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome

    PubMed Central

    Lu, Karen H.; Loose, David S.; Yates, Melinda S.; Nogueras-Gonzalez, Graciela M.; Munsell, Mark F.; Chen, Lee-may; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S.; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M.; Broaddus, Russell R.

    2013-01-01

    Women with Lynch syndrome have a 40–60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have demonstrated that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown if they are effective in women with Lynch syndrome. Asymptomatic women age 25–50 with Lynch syndrome were randomized to receive the progestin compounds depo-Provera (depoMPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were performed before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depoMPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results demonstrate that women with Lynch syndrome do show an endometrial response to short term exogenous progestins, suggesting that OCP and depoMPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481

  19. Deferiprone versus deferoxamine in sickle cell disease: results from a 5-year long-term Italian multi-center randomized clinical trial.

    PubMed

    Calvaruso, Giusi; Vitrano, Angela; Di Maggio, Rosario; Ballas, Samir; Steinberg, Martin H; Rigano, Paolo; Sacco, Massimiliano; Telfer, Paul; Renda, Disma; Barone, Rita; Maggio, Aurelio

    2014-12-01

    Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although the basal serum ferritin levels were higher in transfused compared with non-transfused group (p=0.031), the changes over time in serum ferritin levels were not statistically significantly different between transfused and non-transfused cohort of patients (p=0.389). Kaplan-Meier curve, during 5-years of study, suggests that Deferiprone does not alter survival in comparison with Deferoxamine (p=0.38). In conclusion, long-term iron chelation therapy with Deferiprone was associated with efficacy and safety similar to that of Deferoxamine. Therefore, in patients with Sickle-Cell-Disease, Deferiprone may represent an effective long-term treatment option. PMID:24814618

  20. Intravenous acetaminophen is superior to ketamine for postoperative pain after abdominal hysterectomy: results of a prospective, randomized, double-blind, multicenter clinical trial

    PubMed Central

    Faiz, Hamid Reza; Rahimzadeh, Poupak; Visnjevac, Ognjen; Behzadi, Behzad; Ghodraty, Mohammad Reza; Nader, Nader D

    2014-01-01

    Background In recent years, intravenously (IV) administered acetaminophen has become one of the most common perioperative analgesics. Despite its now-routine use, IV acetaminophen’s analgesic comparative efficacy has never been compared with that of ketamine, a decades-old analgesic familiar to obstetricians, gynecologists, and anesthesiologists alike. This doubleblind clinical trial aimed to evaluate the analgesic effects of ketamine and IV acetaminophen on postoperative pain after abdominal hysterectomy. Methods Eighty women aged 25–70 years old and meeting inclusion and exclusion criteria were randomly allocated into two groups of 40 to receive either IV acetaminophen or ketamine intraoperatively. Postoperatively, each patient had patient-controlled analgesia. Pain and sedation (Ramsay Sedation Scale) were documented based on the visual analog scale in the recovery room and at 4 hours, 6 hours, 12 hours, and 24 hours after the surgery. Hemodynamic changes, adverse medication effects, and the need for breakthrough meperidine were also recorded for both groups. Data were analyzed by repeated-measures analysis of variance. Results Visual analog scale scores were significantly lower in the IV acetaminophen group at each time point (P<0.05), and this group required significantly fewer doses of breakthrough analgesics compared with the ketamine group (P=0.039). The two groups had no significant differences in terms of adverse effects. Conclusion Compared with ketamine, IV acetaminophen significantly improved postoperative pain after abdominal hysterectomy. PMID:24465135

  1. A Multicenter, Randomized, Parallel-Group Trial Assessing Compliance, Tolerability, Safety, and Efficacy to Treatment with Grass Allergy Tablets in 261 Patients with Grass Pollen Rhinoconjunctivitis

    PubMed Central

    Alesina, Roberta; Milani, Massimo; Pecora, Silvia

    2012-01-01

    Background. Allergen-specific sublingual immunotherapy (SLIT) is considered a causal treatment of respiratory allergies. Compliance to the SLIT is an important aspect for a positive clinical outcome. Study Aim. To evaluate if compliance with grass Allergy Immunotherapy Tablet (AIT) can be increased by providing an electronic compliance device (CED) (Memozax; a tablet-container with a programmable daily acoustic alarm). Patients and Methods. 261 patients with grass allergy were enrolled and randomized (1 : 1) to 1-year treatment with AIT (Grazax) using a CED (group A; n = 122) or without (Group B, n = 139). Compliance was measured through tablet count at each visit. Results. The 12-month compliance, mean (SD), in group A was 83% (21) and 83% (24) in group B. A total of 81% of patients reported a significant clinical improvement of symptoms after treatment in comparison with the previous year. No severe adverse reactions were observed in the study. Conclusion. Compliance to the treatment with AIT administered for 12 consecutive months is in general good. The use of CED is not associated with a greater compliance. AIT treatment was associated with a significant clinical improvement in >80% of patients with a good tolerability and safety profile. PMID:22131999

  2. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP

    PubMed Central

    Zhou, Hai; Xu, Miao; Qin, Ping; Zhang, Hai-yan; Yuan, Cheng-lu; Zhao, Hong-guo; Cui, Zhong-guang; Meng, Yue-sheng; Wang, Lei; Zhou, Fang; Wang, Xin; Li, Da-qi; Bi, Ke-hong; Zhu, Chuan-sheng; Guo, Cheng-shan; Chu, Xiao-xia; Wu, Qing-chao; Liu, Xin-guang; Dong, Xiao-yuan; Li, Jie; Peng, Jun

    2015-01-01

    This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836. PMID:25575541

  3. Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

    PubMed Central

    Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

    2013-01-01

    In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

  4. Optical information authentication using compressed double-random-phase-encoded images and quick-response codes.

    PubMed

    Wang, Xiaogang; Chen, Wen; Chen, Xudong

    2015-03-01

    In this paper, we develop a new optical information authentication system based on compressed double-random-phase-encoded images and quick-response (QR) codes, where the parameters of optical lightwave are used as keys for optical decryption and the QR code is a key for verification. An input image attached with QR code is first optically encoded in a simplified double random phase encoding (DRPE) scheme without using interferometric setup. From the single encoded intensity pattern recorded by a CCD camera, a compressed double-random-phase-encoded image, i.e., the sparse phase distribution used for optical decryption, is generated by using an iterative phase retrieval technique with QR code. We compare this technique to the other two methods proposed in literature, i.e., Fresnel domain information authentication based on the classical DRPE with holographic technique and information authentication based on DRPE and phase retrieval algorithm. Simulation results show that QR codes are effective on improving the security and data sparsity of optical information encryption and authentication system. PMID:25836845

  5. Single-random phase encoding architecture using a focus tunable lens

    NASA Astrophysics Data System (ADS)

    Mosso, E. F.; Bolognini, N.; Pérez, D. G.

    2016-02-01

    We propose a new nonlinear optical architecture based on a focus tunable lens and an iterative phase retrieval algorithm. It constitutes a compact encryption system that uses a single-random phase key to simultaneously encrypt (decrypt) amplitude and phase data. Summarily, the information encoded in a transmittance object (phase and amplitude) is randomly modulated by a diffuser when a laser beam illuminates it; once the beam reaches a focus tunable lens, different subjective speckle distributions are registered at some image plane as the focal length is tuned to different values. This set of speckle patterns constitutes a delocalized ciphertext, which is used in an iterative phase retrieval algorithm to reconstruct a complex ciphertext. The original data are decrypted propagating this ciphertext through a virtual optical system. In this system, amplitude data are straightforwardly decrypted while phase data can only be restored if the random modulation produced in the encryption process is compensated. Thus, an encryption-decryption process and authentication protocol can simultaneously be performed. We validate the feasibility of our proposal with simulated and experimental results.

  6. Effect of Certolizumab Pegol on Multiple Facets of Psoriatic Arthritis as Reported by Patients: 24-Week Patient-Reported Outcome Results of a Phase III, Multicenter Study

    PubMed Central

    Gladman, D; Fleischmann, R; Coteur, G; Woltering, F; Mease, P J

    2014-01-01

    Objective To examine the effect of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with and without prior tumor necrosis factor (TNF) inhibitor exposure. Methods The ongoing phase III RAPID-PsA trial was double blind and placebo controlled to week 24. Patients were randomized 1:1:1 to placebo every 2 weeks or CZP 400 mg at weeks 0, 2, and 4, followed by either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks. PRO measures evaluated were the Health Assessment Questionnaire (HAQ) disability index (DI), health status (measured by the Short Form 36 [SF-36] health survey), Psoriatic Arthritis Quality of Life (PsAQOL), Fatigue Assessment Scale, patient assessment of pain (visual analog scale), and Dermatology Life Quality Index (DLQI). Post hoc analyses of PROs in patients with and without prior TNF inhibitor exposure were conducted. Change from baseline for all PROs was analyzed for the randomized population using analysis of covariance with last observation carried forward imputation. Results A total of 409 patients were randomized. Twenty percent had received a prior TNF inhibitor. Baseline demographics were similar between the treatment groups. At week 24, clinically meaningful differences in HAQ DI, SF-36, PsAQOL, fatigue, pain, and DLQI were observed in both CZP arms versus placebo (P < 0.001), irrespective of prior TNF inhibitor exposure. More CZP-treated patients reached SF-36 general population norms than placebo-treated patients. Conclusion Both CZP dosing schedules provided rapid improvements in PROs across multiple disease aspects in patients with PsA. The benefits of CZP treatment for health-related quality of life were seen across generic, PsA-specific, and dermatology-specific measures and were observed in patients regardless of prior TNF inhibitor exposure. PMID:24339179

  7. Security enhanced optical encryption system by random phase key and permutation key.

    PubMed

    He, Mingzhao; Tan, Qiaofeng; Cao, Liangcai; He, Qingsheng; Jin, Guofan

    2009-12-01

    Conventional double random phase encoding (DRPE) encrypts plaintext to white noise-like ciphertext which may attract attention of eavesdroppers, and recent research reported that DRPE is vulnerable to various attacks. Here we propose a security enhanced optical encryption system that can hide the existence of secret information by watermarking. The plaintext is encrypted using iterative fractional Fourier transform with random phase key, and ciphertext is randomly permuted with permutation key before watermarking. Cryptanalysis shows that linearity of the security system has been broken and the permutation key prevent the attacker from accessing the ciphertext in various attacks. A series of simulations have shown the effectiveness of this system and the security strength is enhanced for invisibility, nonlinearity and resistance against attacks. PMID:20052170

  8. Continuous and discontinuous absorbing-state phase transitions on Voronoi-Delaunay random lattices.

    PubMed

    de Oliveira, Marcelo M; Alves, Sidiney G; Ferreira, Silvio C

    2016-01-01

    We study absorbing-state phase transitions (APTs) in two-dimensional Voronoi-Delaunay (VD) random lattices with quenched coordination disorder. Quenched randomness usually changes the criticality and destroys discontinuous transitions in low-dimensional nonequilibrium systems. We performed extensive simulations of the Ziff-Gulari-Barshad model, and verified that the VD disorder does not change the nature of its discontinuous transition. Our results corroborate recent findings of Barghathi and Vojta [H. Barghathi and T. Vojta, Phys. Rev. Lett. 113, 120602 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.120602], stating the irrelevance of topological disorder in a class of random lattices that includes VD, and raise the interesting possibility that disorder in nonequilibrium APT may, under certain conditions, be irrelevant for the phase coexistence. We also verify that the VD disorder is irrelevant for the critical behavior of models belonging to the directed percolation and Manna universality classes. PMID:26871027

  9. Continuous and discontinuous absorbing-state phase transitions on Voronoi-Delaunay random lattices

    NASA Astrophysics Data System (ADS)

    de Oliveira, Marcelo M.; Alves, Sidiney G.; Ferreira, Silvio C.

    2016-01-01

    We study absorbing-state phase transitions (APTs) in two-dimensional Voronoi-Delaunay (VD) random lattices with quenched coordination disorder. Quenched randomness usually changes the criticality and destroys discontinuous transitions in low-dimensional nonequilibrium systems. We performed extensive simulations of the Ziff-Gulari-Barshad model, and verified that the VD disorder does not change the nature of its discontinuous transition. Our results corroborate recent findings of Barghathi and Vojta [H. Barghathi and T. Vojta, Phys. Rev. Lett. 113, 120602 (2014), 10.1103/PhysRevLett.113.120602], stating the irrelevance of topological disorder in a class of random lattices that includes VD, and raise the interesting possibility that disorder in nonequilibrium APT may, under certain conditions, be irrelevant for the phase coexistence. We also verify that the VD disorder is irrelevant for the critical behavior of models belonging to the directed percolation and Manna universality classes.

  10. Phase Transitions for the Cavity Approach to the Clique Problem on Random Graphs

    NASA Astrophysics Data System (ADS)

    Gaudillière, Alexandre; Scoppola, Benedetto; Scoppola, Elisabetta; Viale, Massimiliano

    2011-12-01

    We give a rigorous proof of two phase transitions for a disordered statistical mechanics system used to define an algorithm to find large cliques inside Erdös random graphs. Such a system is a conservative probabilistic cellular automaton inspired by the cavity method originally introduced in spin glass theory.

  11. The PRESLO study: evaluation of a global secondary low back pain prevention program for health care personnel in a hospital setting. Multicenter, randomized intervention trial

    PubMed Central

    2012-01-01

    Background Common low back pain represents a major public health problem in terms of its direct cost to health care and its socio-economic repercussions. Ten percent of individuals who suffer from low back pain evolve toward a chronic case and as such are responsible for 75 to 80% of the direct cost of low back pain. It is therefore imperative to highlight the predictive factors of low back pain chronification in order to lighten the economic burden of low back pain-related invalidity. Despite being particularly affected by low back pain, Hospices Civils de Lyon (HCL) personnel have never been offered a specific, tailor-made treatment plan. The PRESLO study (with PRESLO referring to Secondary Low Back Pain Prevention, or in French, PREvention Secondaire de la LOmbalgie), proposed by HCL occupational health services and the Centre Médico-Chirurgical et de Réadaptation des Massues – Croix Rouge Française, is a randomized trial that aims to evaluate the feasibility and efficiency of a global secondary low back pain prevention program for the low back pain sufferers among HCL hospital personnel, a population at risk for recurrence and chronification. This program, which is based on the concept of physical retraining, employs a multidisciplinary approach uniting physical activity, cognitive education about low back pain and lumbopelvic morphotype analysis. No study targeting populations at risk for low back pain chronification has as yet evaluated the efficiency of lighter secondary prevention programs. Methods/Design This study is a two-arm parallel randomized controlled trial proposed to all low back pain sufferers among HCL workers, included between October 2008 and July 2011 and followed over two years. The personnel following their usual treatment (control group) and those following the global prevention program in addition to their usual treatment (intervention group) are compared in terms of low back pain recurrence and the impairments measured at the

  12. Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: A phase-1, single-dose, randomized, open-label study.

    PubMed

    Ravenstijn, Paulien; Remmerie, Bart; Savitz, Adam; Samtani, Mahesh N; Nuamah, Isaac; Chang, Cheng-Tao; De Meulder, Marc; Hough, David; Gopal, Srihari

    2016-03-01

    This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18-65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single-dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75-525 mg eq) separated by a washout of 7-21 days. Overall, 245 of 308 (79.5%) PP3M-dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half-life was ∼2-4 months. Mean plasma AUC∞ and Cmax of paliperidone appeared to be dose-proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment-emergent adverse events. Overall, safety and tolerability were similar to those of the 1-month formulation. Results support a once-every-3-months dosing interval in patients with schizophrenia or schizoaffective disorder. PMID:26189570

  13. Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial

    PubMed Central

    2014-01-01

    Background HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders. Methods Sixty-eight HD patients who were maintained on calcium carbonate (n = 33) or sevelamer hydrochloride (n = 35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23. Results Sixty-three patients chewed either HS219 (n = 35) or placebo (n = 28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels. Conclusions The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels. Trail registration ClinicalTrials.gov NCT01039428, 24 December, 2009. PMID:24968790

  14. A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis.

    PubMed

    Truitt, K E; Sperling, R S; Ettinger, W H; Greenwald, M; DeTora, L; Zeng, Q; Bolognese, J; Ehrich, E

    2001-04-01

    This 6-week study was conducted to test the efficacy, safety, and tolerability of rofecoxib (a selective COX-2 inhibitor) compared to nabumetone (a non-selective NSAID) and placebo in osteoarthritis (OA) patients aged 80 and older. Three hundred forty-one patients, mean age 83 years, were randomized. Allocations were made in an approximately 1:2:1:2 ratio (placebo: 12.5 mg rofecoxib: 25 mg rofecoxib: 1500 mg nabumetone). Least square mean changes from baseline in the primary efficacy endpoint, Patient Global Assessment of Disease Status, were as follows (with negative numbers indicating improvement): -14.85 mm for placebo; -25.34 mm for 12.5 mg rofecoxib; -25.40 mm for 25 mg of rofecoxib; and -25.95 mm for nabumetone (p<0.001 for all active treatments vs placebo.) Results from secondary endpoints, including the 3 WOMAC sub-scales (pain, stiffness, and disability) and the Investigator Global Assessment of Disease Status, were consistent with those for the primary endpoint. No significant between-group differences were observed in the proportions of patients who discontinued treatment due to either clinical or laboratory adverse experiences. Renal safety (edema and hypertension adverse experiences) was similar for rofecoxib and nabumetone. No gastroduodenal ulcers occurred; however, the demonstration of gastrointestinal risk with rofecoxib or nabumetone was beyond the scope of this trial. We conclude that in patients 80 years and older, rofecoxib, 12.5 mg and 25 mg once daily, demonstrated clinical efficacy for the treatment for OA as did 1500 mg of nabumetone. Rofecoxib and nabumetone were generally well tolerated in this elderly population. PMID:11405384

  15. Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor–Induced Musculoskeletal Pain: SWOG S0927

    PubMed Central

    Hershman, Dawn L.; Unger, Joseph M.; Crew, Katherine D.; Awad, Danielle; Dakhil, Shaker R.; Gralow, Julie; Greenlee, Heather; Lew, Danika L.; Minasian, Lori M.; Till, Cathee; Wade, James L.; Meyskens, Frank L.; Moinpour, Carol M.

    2015-01-01

    Purpose Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in decreasing arthralgia resulting from rheumatologic conditions and reducing serum triglycerides. Patients and Methods Women with early-stage breast cancer receiving an AI who had a worst joint pain/stiffness score ≥ 5 of 10 using the Brief Pain Inventory–Short Form (BPI-SF) were randomly assigned to receive either O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically significant change was defined as ≥ 2-point drop from baseline. Patients also completed quality-of-life (Functional Assessment of Cancer Therapy–Endocrine Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12, and 24. Serial fasting blood was collected for lipid analysis. Results Among 262 patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127 in the placebo arm. Compared with baseline, the mean observed BPI-SF score decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and by 1.49 and 1.81 points, respectively, with placebo. In a linear regression adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12-week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased in patients receiving O3-FA treatment and remained the same for those receiving placebo (P = .01). No between-group differences were seen for HDL, LDL, or C-reactive protein. Conclusion We found a substantial (> 50%) and sustained improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful difference between the groups. PMID:25940724

  16. A multi-center randomized trial of buprenorphine–naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network

    PubMed Central

    Ling, Walter; Amass, Leslie; Shoptaw, Steve; Annon, Jeffrey J.; Hillhouse, Maureen; Babcock, Dean; Brigham, Greg; Harrer, Judy; Reid, Malcolm; Muir, Joan; Buchan, Betty; Orr, Debbie; Woody, George; Krejci, Jonathan; Ziedonis, Douglas; Group, the Buprenorphine Study Protocol

    2005-01-01

    Aims The clinical effectiveness of buprenorphine–naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. Design Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2:1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. Methods A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. Findings A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. Conclusion The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs. PMID:16042639

  17. Short-term effectiveness of an individual counseling program for impaired fasting glucose and mild type 2 diabetes in Japan: a multi-center randomized control trial.

    PubMed

    Watanabe, Makoto; Okayama, Akira; Shimamoto, Kazuaki; Ueshima, Hirotsugu

    2007-01-01

    The aim of this study is to evaluate the short-term effectiveness of our individual-based counseling program and tools among individuals in ordinary Japanese communities with impaired fasting glucose (IFG) and mild type 2 diabetes. A tota