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Sample records for open label randomised

  1. Supervised exercise therapy versus usual care for patellofemoral pain syndrome : an open label randomised controlled trial

    NARCIS (Netherlands)

    van Linschoten, R.; van Middelkoop, M.; Berger, M. Y.; Heintjes, E. M.; Verhaar, J. A. N.; Willemsen, S. P.; Koes, B. W.; Bierma-Zeinstra, S. M.

    2009-01-01

    Objective To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. Design Open label randomised controlled trial. Setting General practice and sport physician practice. Participants

  2. Supervised exercise therapy versus usual care for patellofemoral pain syndrome : an open label randomised controlled trial

    NARCIS (Netherlands)

    van Linschoten, R.; van Middelkoop, M.; Berger, M. Y.; Heintjes, E. M.; Verhaar, J. A. N.; Willemsen, S. P.; Koes, B. W.; Bierma-Zeinstra, S. M.

    2009-01-01

    Objective To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. Design Open label randomised controlled trial. Setting General practice and sport physician practice. Participants

  3. Supervised exercise therapy versus usual care for patellofemoral pain syndrome: an open label randomised controlled trial.

    NARCIS (Netherlands)

    R. van Linschoten (Robbart); M. van Middelkoop (Marienke); M.Y. Berger (Marjolein); E.M. Heintjes (Edith); J.A.N. Verhaar (Jan); S.P. Willemsen (Sten); B.W. Koes (Bart); S.M. Bierma-Zeinstra (Sita)

    2009-01-01

    textabstractOBJECTIVE: To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. DESIGN: Open label randomised controlled trial. SETTING: General practice and sport physician practic

  4. Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

    DEFF Research Database (Denmark)

    Chartier-Kastler, E; Lauge, I; Ruffion, A

    2011-01-01

    Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

  5. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

    Directory of Open Access Journals (Sweden)

    Tara Rheault

    2016-04-01

    Full Text Available This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611. Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1 at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score. Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54. Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37% and glycopyrronium (36%. Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  6. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

    Science.gov (United States)

    Rheault, Tara; Khindri, Sanjeev; Vahdati-Bolouri, Mitra; Church, Alison; Fahy, William A

    2016-04-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  7. Closure of mesenteric defects in laparoscopic gastric bypass: a multicentre, randomised, parallel, open-label trial.

    Science.gov (United States)

    Stenberg, Erik; Szabo, Eva; Ågren, Göran; Ottosson, Johan; Marsk, Richard; Lönroth, Hans; Boman, Lars; Magnuson, Anders; Thorell, Anders; Näslund, Ingmar

    2016-04-02

    Small bowel obstruction due to internal hernia is a common and potentially serious complication after laparoscopic gastric bypass surgery. Whether closure of surgically created mesenteric defects might reduce the incidence is unknown, so we did a large randomised trial to investigate. This study was a multicentre, randomised trial with a two-arm, parallel design done at 12 centres for bariatric surgery in Sweden. Patients planned for laparoscopic gastric bypass surgery at any of the participating centres were offered inclusion. During the operation, a concealed envelope was opened and the patient was randomly assigned to either closure of mesenteric defects beneath the jejunojejunostomy and at Petersen's space or non-closure. After surgery, assignment was open label. The main outcomes were reoperation for small bowel obstruction and severe postoperative complications. Outcome data and safety were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01137201. Between May 1, 2010, and Nov 14, 2011, 2507 patients were recruited to the study and randomly assigned to closure of the mesenteric defects (n=1259) or non-closure (n=1248). 2503 (99·8%) patients had follow-up for severe postoperative complications at day 30 and 2482 (99·0%) patients had follow-up for reoperation due to small bowel obstruction at 25 months. At 3 years after surgery, the cumulative incidence of reoperation because of small bowel obstruction was significantly reduced in the closure group (cumulative probability 0·055 for closure vs 0·102 for non-closure, hazard ratio 0·56, 95% CI 0·41-0·76, p=0·0002). Closure of mesenteric defects increased the risk for severe postoperative complications (54 [4·3%] for closure vs 35 [2·8%] for non-closure, odds ratio 1·55, 95% CI 1·01-2·39, p=0·044), mainly because of kinking of the jejunojejunostomy. The results of our study support the routine closure of the mesenteric defects in laparoscopic

  8. A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy.

    Science.gov (United States)

    Citerio, Giuseppe; Pesenti, Antonio; Latini, Roberto; Masson, Serge; Barlera, Simona; Gaspari, Flavio; Franzosi, Maria G

    2012-08-01

    A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension. The NeuroMorfeo trial was designed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery. This trial is a multicentre, randomised, open-label, equivalence design. A balanced stratified randomisation scheme was maintained using a centralised randomisation service. Equivalence was tested using the two one-sided tests procedure. Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009. Adults, 18 to 75 years old, scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension. Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane-remifentanil or sevoflurane-fentanyl were equivalent to propofol-remifentanil. The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation. Secondary endpoints included haemodynamic parameters, quality of the surgical field, perioperative neuroendocrine stress responses and routine postoperative assessments. Four hundred and eleven patients [51% men, mean age 54.8 (SD 13.3) years] were enrolled. Primary outcome data were available for 380. Median (interquartiles) times to reach an Aldrete score of at least 9 were 3.48 (2.02 to 7.56), 3.25 (1.21 to 6.45) and 3.32  min (1.40 to 8.33) for sevoflurane-fentanyl, sevoflurane-remifentanil and propofol-remifentanil anaesthesia respectively, which confirmed equivalence using the two one-sided tests approach. Between-treatment differences in haemodynamic variables were small and not clinically relevant. Urinary catecholamine and

  9. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial.

    Science.gov (United States)

    Jairath, Vipul; Kahan, Brennan C; Gray, Alasdair; Doré, Caroline J; Mora, Ana; James, Martin W; Stanley, Adrian J; Everett, Simon M; Bailey, Adam A; Dallal, Helen; Greenaway, John; Le Jeune, Ivan; Darwent, Melanie; Church, Nicholas; Reckless, Ian; Hodge, Renate; Dyer, Claire; Meredith, Sarah; Llewelyn, Charlotte; Palmer, Kelvin R; Logan, Richard F; Travis, Simon P; Walsh, Timothy S; Murphy, Michael F

    2015-07-11

    Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in

  10. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

    Science.gov (United States)

    Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

    2017-04-01

    Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AFrandomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months

  11. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma

    Directory of Open Access Journals (Sweden)

    Leelavathy Budamakuntla

    2013-01-01

    Full Text Available Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09% in the microinjections group, as compared to 12 patients (41.38% in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling.

  12. A Randomised, Open-label, Comparative Study of Tranexamic Acid Microinjections and Tranexamic Acid with Microneedling in Patients with Melasma

    Science.gov (United States)

    Budamakuntla, Leelavathy; Loganathan, Eswari; Suresh, Deepak Hurkudli; Shanmugam, Sharavana; Suryanarayan, Shwetha; Dongare, Aparna; Venkataramiah, Lakshmi Dammaningala; Prabhu, Namitha

    2013-01-01

    Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA) microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks) and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09%) in the microinjections group, as compared to 12 patients (41.38%) in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling. PMID:24163529

  13. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    Science.gov (United States)

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-03

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions.

  14. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial

    Science.gov (United States)

    Arjyal, Amit; Basnyat, Buddha; Nhan, Ho Thi; Koirala, Samir; Giri, Abhishek; Joshi, Niva; Shakya, Mila; Pathak, Kamal Raj; Mahat, Saruna Pathak; Prajapati, Shanti Pradhan; Adhikari, Nabin; Thapa, Rajkumar; Merson, Laura; Gajurel, Damodar; Lamsal, Kamal; Lamsal, Dinesh; Yadav, Bharat Kumar; Shah, Ganesh; Shrestha, Poojan; Dongol, Sabina; Karkey, Abhilasha; Thompson, Corinne N; Thieu, Nga Tran Vu; Thanh, Duy Pham; Baker, Stephen; Thwaites, Guy E; Wolbers, Marcel; Dolecek, Christiane

    2016-01-01

    Summary Background Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. Methods We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2–13 years) and adult (aged 14–45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2–13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. Findings Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi

  15. Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

    Science.gov (United States)

    Egede, Leonard E; Acierno, Ron; Knapp, Rebecca G; Lejuez, Carl; Hernandez-Tejada, Melba; Payne, Elizabeth H; Frueh, B Christopher

    2015-08-01

    Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in

  16. Dexmedetomidine versus midazolam for conscious sedation in endoscopic retrograde cholangiopancreatography: An open-label randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Sethi

    2014-01-01

    Full Text Available Background: Traditionally, midazolam has been used for providing conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Objective: The primary objective was to compare haemodynamic, respiratory and recovery profile of both drugs. Secondary objective was to compare the degree of comfort experienced by patients and the usefulness of the drug to endoscopist. Study Design: Open-label Randomised Controlled Trial. Methods: Subjects between 18 and 60 years of age with American Society of Anaesthesiologist Grade I-II requiring ERCP were enrolled in two groups (30 each. Both groups received fentanyl 1 μg/kg IV at the beginning of ERCP. Group M received IV midazolam (0.04 mg/kg and additional 0.5 mg doses until Ramsay Sedation Scale (RSS score reached 3-4. Group D received dexmedetomidine at loading dose of 1 μg/kg over 10 min followed by 0.5 μg/kg/h infusion until RSS reached 3-4. The vital parameters (heart rate (HR, blood pressure (BP, respiration rate, SpO 2 , time to achieve RSS 3-4 and facial pain score (FPS were compared during and after the procedure. In the recovery room, time to reach modified Aldrete score (MAS 9-10 and patient and surgeon′s satisfaction scores was also recorded and compared. Any complication during or after the procedure were also noted. Results: In Group D, patients had lower HR and FPS at 5, 10 and 15 min following the initiation of sedation (P<0.05. There was no statistically significant difference in BP and respiratory rate. The procedure elicited a gag response in 29 (97% and 7 (23% subjects in Group M and Group D respectively (P<0.05. MAS of 9-10 at 5 min during recovery was achieved in 27 (90% subjects in Group D in contrast to 5 (17% in Group M (P<0.05. Dexmedetomidine showed higher patient and surgeon satisfaction scores (P<0.05. Conclusion: Dexmedetomidine can be a superior alternative to midazolam

  17. Retraction statement: Manuka honey vs. hydrogel - a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers.

    Science.gov (United States)

    2015-09-01

    The following article from Journal of Clinical Nursing, 'Manuka honey vs. hydrogel - a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers' by Georgina Gethin and Seamus Cowman published online on 25 August 2008 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 18, pp. 466-474, has been retracted by agreement between the journal Editor-in-Chief, the authors and John Wiley & Sons, Ltd. The retraction has been agreed due to errors in the data analysis which affect the article's findings.

  18. Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

    NARCIS (Netherlands)

    F.W. Rozendaal (Frans); P.E. Spronk (Peter); F.F. Snellen (Ferdinand); A. Schoen (Adri); A.R.H. van Zanten (Arthur); N.A. Foudraine (Norbert); P.G.H. Mulder (Paul); J. Bakker (Jan)

    2009-01-01

    textabstractObjective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patie

  19. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

    2016-01-01

    BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous V...

  20. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

    Science.gov (United States)

    Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

    2016-11-01

    Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m(2) twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27

  1. Effectiveness of telemedicine and distance learning applications for patients with chronic heart failure. A protocol for prospective parallel group non-randomised open label study.

    Science.gov (United States)

    Vanagas, Giedrius; Umbrasiene, Jelena; Slapikas, Rimvydas

    2012-01-01

    Chronic heart failure in Baltic Sea Region is responsible for more hospitalisations than all forms of cancer combined and is one of the leading causes of hospitalisations in elderly patients. Frequent hospitalisations, along with other direct and indirect costs, place financial burden on healthcare systems. We aim to test the hypothesis that telemedicine and distance learning applications is superior to the current standard of home care. Prospective parallel group non-randomised open label study in patients with New York Heart Association (NYHA) II-III chronic heart failure will be carried out in six Baltic Sea Region countries. The study is organised into two 6-month follow-up periods. The first 6-month period is based on active implementation of tele-education and/or telemedicine for patients in two groups (active run period) and one standard care group (passive run period). The second 6-month period of observation will be based on standard care model (passive run period) to all three groups. Our proposed practice change is based on translational research with empirically supported interventions brought to practice and aims to find the home care model that is most effective to patient needs. This study has been approved by National Bioethics Committee (2011-03-07; Registration No: BE-2-11). This study has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) with registration number ACTRN12611000834954.

  2. A randomised, open-label, crossover study of the dopamine agonist, pramipexole, in patients with sleep bruxism.

    Science.gov (United States)

    Cahlin, Birgitta Johansson; Hedner, Jan; Dahlström, Lars

    2017-02-01

    Sleep bruxism bears several similarities to restless legs syndrome, and a link to changes in central dopamine activity has been considered in both conditions. The dopamine agonist pramipexole is currently indicated for the symptomatic treatment of restless legs. The effect of pramipexole on sleep bruxism was investigated in subjects with 'probable bruxism' recruited at the Orofacial Pain Clinic. Thirteen patients underwent polysomnographic recordings, including bilateral masseter electromyographic activity. Following habituation to the recording equipment, a baseline registration was used to confirm bruxism [total episodes per hour, mean 11.3 (6.3)]. Following randomisation, subjects received no treatment or pramipexole titrated from 0.09 to 0.54 mg, o.d., for 3 weeks according to a crossover procedure. A polysomnographic-electromyographic registration was performed at the end of each period. Pramipexole was associated with more frequent awakenings and a reduction in rapid eye movement sleep (both P ≤ 0.02). Sleep apnea decreased marginally after pramipexole (apnea-hypopnea index 17.1 compared with control 21.5, P ≤ 0.05). The number of bruxism episodes, phasic, tonic and mixed per hour, remained unchanged after pramipexole [total episodes per hour 12.7 (8.5) and 9.8 (5.2) during pramipexole and control conditions, respectively]. It is concluded, from this pilot study, that sleep bruxism is not affected by the dopaminergic agent, pramipexole.

  3. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

    Science.gov (United States)

    Fenaux, Pierre; Mufti, Ghulam J; Hellstrom-Lindberg, Eva; Santini, Valeria; Finelli, Carlo; Giagounidis, Aristoteles; Schoch, Robert; Gattermann, Norbert; Sanz, Guillermo; List, Alan; Gore, Steven D; Seymour, John F; Bennett, John M; Byrd, John; Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C L; Silverman, Lewis R

    2014-01-01

    Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most

  4. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Baharoglu, M Irem; Cordonnier, Charlotte; Al-Shahi Salman, Rustam; de Gans, Koen; Koopman, Maria M; Brand, Anneke; Majoie, Charles B; Beenen, Ludo F; Marquering, Henk A; Vermeulen, Marinus; Nederkoorn, Paul J; de Haan, Rob J; Roos, Yvo B

    2016-06-25

    Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the

  5. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial.

    Science.gov (United States)

    Kobayashi, Tohru; Saji, Tsutomu; Otani, Tetsuya; Takeuchi, Kazuo; Nakamura, Tetsuya; Arakawa, Hirokazu; Kato, Taichi; Hara, Toshiro; Hamaoka, Kenji; Ogawa, Shunichi; Miura, Masaru; Nomura, Yuichi; Fuse, Shigeto; Ichida, Fukiko; Seki, Mitsuru; Fukazawa, Ryuji; Ogawa, Chitose; Furuno, Kenji; Tokunaga, Hirohide; Takatsuki, Shinichi; Hara, Shinya; Morikawa, Akihiro

    2012-04-28

    Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, pKawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted. Japanese Ministry of Health, Labour and Welfare. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.

    Science.gov (United States)

    Qadri, Firdausi; Ali, Mohammad; Chowdhury, Fahima; Khan, Ashraful Islam; Saha, Amit; Khan, Iqbal Ansary; Begum, Yasmin A; Bhuiyan, Taufiqur R; Chowdhury, Mohiul Islam; Uddin, Md Jasim; Khan, Jahangir A M; Chowdhury, Atique Iqbal; Rahman, Anisur; Siddique, Shah Alam; Asaduzzaman, Muhammad; Akter, Afroza; Khan, Arifuzzaman; Ae You, Young; Siddik, Ashraf Uddin; Saha, Nirod Chandra; Kabir, Alamgir; Riaz, Baizid Khoorshid; Biswas, Shwapon Kumar; Begum, Farzana; Unicomb, Leanne; Luby, Stephen P; Cravioto, Alejandro; Clemens, John D

    2015-10-03

    Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting. We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845. Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events. Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations. Bill & Melinda Gates Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial.

    Science.gov (United States)

    Hillmen, Peter; Robak, Tadeusz; Janssens, Ann; Babu, K Govind; Kloczko, Janusz; Grosicki, Sebastian; Doubek, Michael; Panagiotidis, Panagiotis; Kimby, Eva; Schuh, Anna; Pettitt, Andrew R; Boyd, Thomas; Montillo, Marco; Gupta, Ira V; Wright, Oliver; Dixon, Iestyn; Carey, Jodi L; Chang, Chai-Ni; Lisby, Steen; McKeown, Astrid; Offner, Fritz

    2015-05-09

    Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; pchlorambucil plus ofatumumab group (109 [50

  8. Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

    Science.gov (United States)

    Hosseinipour, Mina C; Bisson, Gregory P; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, Fredrick K; Badal-Faesen, Sharlaa; Lagat, David; Nyirenda, Mulinda; Naidoo, Kogieleum; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, Paul D; Lama, Javier R; Mohapi, Lerato; Alave, Jorge; Mave, Vidya; Veloso, Valdilea G; Pillay, Sandy; Kumarasamy, Nagalingeswaran; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita

    2016-03-19

    Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. Between Oct 31, 2011, and June 9, 2014, we enrolled 850

  9. Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial

    Science.gov (United States)

    Puthanakit, Thanyawee; Vonthanak, Saphonn; Ananworanich, Jintanat; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Vibol, Ung; Kerr, Stephen J.; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Ngo-Giang-Huong, Nicole; Chettra, Kea; Cheunyam, Theshinee; Suwarnlerk, Tulathip; Ubolyam, Sasiwimol; Shearer, William T.; Paul, Robert; Mofenson, Lynne M.; Fox, Lawrence; Law, Matthew G.; Cooper, David A.; Phanuphak, Praphan; Vun, Mean Chhi; Ruxrungtham, Kiat

    2012-01-01

    Summary Background The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival. Methods In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1–12 years who were infected with HIV and had CD4 percentages of 15–24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091. Findings Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9–8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16–22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7–99·7; 148 of 150 patients) compared with 97·9% (93·7–99·3; 146 of 149 patients) in the early treatment group (p=0·6). Interpretation AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or

  10. Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.

    Science.gov (United States)

    Taniuchi, Mami; Famulare, Michael; Zaman, Khalequ; Uddin, Md Jashim; Upfill-Brown, Alexander M; Ahmed, Tahmina; Saha, Parimalendu; Haque, Rashidul; Bandyopadhyay, Ananda S; Modlin, John F; Platts-Mills, James A; Houpt, Eric R; Yunus, Mohammed; Petri, William A

    2017-07-07

    Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2). We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046. Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0

  11. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

    Science.gov (United States)

    Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

    2017-08-05

    Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m(2) once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62

  12. Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial.

    Science.gov (United States)

    Dávalos, Antoni; Cobo, Erik; Molina, Carlos A; Chamorro, Angel; de Miquel, M Angeles; Román, Luis San; Serena, Joaquín; López-Cancio, Elena; Ribó, Marc; Millán, Mónica; Urra, Xabier; Cardona, Pere; Tomasello, Alejandro; Castaño, Carlos; Blasco, Jordi; Aja, Lucía; Rubiera, Marta; Gomis, Meritxell; Renú, Arturo; Lara, Blanca; Martí-Fàbregas, Joan; Jankowitz, Brian; Cerdà, Neus; Jovin, Tudor G

    2017-05-01

    The REVASCAT trial and other studies have shown that the neurovascular thrombectomy improves outcomes at 90 days post stroke. However, whether the observed benefit is sustained in the long term remains unknown. We report the results of the prespecified 12-month analysis of the REVASCAT trial. Patients with acute ischaemic stroke who could be treated within 8 h of symptom onset were randomly assigned to medical therapy (including intravenous alteplase when eligible) and neurovascular thrombectomy with Solitaire FR or medical therapy alone. The main secondary outcome measure at 1 year follow-up was disability, measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) with categories 5 (severe disability) and 6 (death) collapsed into one category (severe disability or death), analysed as the distribution of the mRS. Additional prespecified secondary outcome measures included health-related quality of life measured with the EuroQol five dimensions questionnaire (EQ-5D) utility index (ranging from -0·3 to 1, higher values indicate better quality of life), the rate of functional independence (mRS 0-2), and cognitive function measured with the Trail Making Test (reported elsewhere). Treatment allocation was open label but endpoints at 12 months were assessed by masked investigators. The trial was registered at ClinicalTrials.gov, number NCT01692379. From Nov 24, 2012, to Dec 12, 2014, 206 patients were randomly assigned to medical therapy plus endovascular treatment (n=103) or medical treatment alone (n=103), at four centres in Catalonia, Spain. At 12 months post randomisation, based on 205 of 206 outcomes available at 12 months, thrombectomy reduced disability over the range of the mRS (common adjusted odds ratio [aOR] 1·80, 95% CI 1·09-2·99), and improved functional independence (mRS=0-2; 45 [44%] of 103 patients vs 31 [30%] of 103 patients; aOR 1·86, 95% CI 1·01-3·44). Health-related quality of life was superior in the

  13. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

    Science.gov (United States)

    Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

    2016-01-01

    Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

  14. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.

    Science.gov (United States)

    Todd, John A; Evangelou, Marina; Cutler, Antony J; Pekalski, Marcin L; Walker, Neil M; Stevens, Helen E; Porter, Linsey; Smyth, Deborah J; Rainbow, Daniel B; Ferreira, Ricardo C; Esposito, Laura; Hunter, Kara M D; Loudon, Kevin; Irons, Kathryn; Yang, Jennie H; Bell, Charles J M; Schuilenburg, Helen; Heywood, James; Challis, Ben; Neupane, Sankalpa; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Anselmiova, Katerina; Kennet, Jane; Brown, Judy; Caddy, Sarah L; Lu, Jia; Greatorex, Jane; Goodfellow, Ian; Wallace, Chris; Tree, Tim I; Evans, Mark; Mander, Adrian P; Bond, Simon; Wicker, Linda S; Waldron-Lynch, Frank

    2016-10-01

    Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2

  15. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.

    Directory of Open Access Journals (Sweden)

    John A Todd

    2016-10-01

    Full Text Available Interleukin-2 (IL-2 has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs. Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs to prevent autoimmune diseases, such as type 1 diabetes (T1D. Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2, which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs.To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D, a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39 found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254 and 0.497

  16. Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia;

    2016-01-01

    BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify...... an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days.......022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both...

  17. A two-centre, open-label, randomised study of ovulation inhibition with three transdermal contraceptive patches, each containing different amounts of ethinyl estradiol and gestodene in healthy, young women.

    Science.gov (United States)

    Waellnitz, K; Duijkers, I; Klipping, C; Rautenberg, T; Rohde, B; Zurth, C

    2016-01-01

    Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the 'EE/GSD patch') reliably inhibits ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18-35 years, were randomised to receive treatment with either the EE/GSD patch, a 'reduced-GSD patch' (delivering similar amounts of EE and approximately half the amount of GSD) or a 'reduced-EE/GSD patch' (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were also measured. Results indicated that the EE/GSD patch effectively suppressed ovulation, while patches delivering lower doses of EE and GSD were less effective for this purpose. All three patches showed comparable tolerability.

  18. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial

    DEFF Research Database (Denmark)

    Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning

    2009-01-01

    BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the comb......BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared...... with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. METHODS: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A(1c) (HbA(1c)) of 7.9% were randomly assigned to addition of rosiglitazone (n...... were increased mainly in women randomly assigned to rosiglitazone. Mean HbA(1c) was lower in the rosiglitazone group than in the control group at 5 years. INTERPRETATION: Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart...

  19. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial.

    Science.gov (United States)

    Reznik, Yves; Cohen, Ohad; Aronson, Ronnie; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; Lee, Scott W

    2014-10-04

    Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise). We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0-12·0% (64-108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493. 495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of -0·7% (95% CI -0·9 to -0·4; -8 mmol/mol, 95% CI -10 to -4, pinsulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (ppump treatment group compared with one in the multiple daily

  20. Integrated MRSA-Management (IMM with prolonged decolonization treatment after hospital discharge is effective: a single centre, non-randomised open-label trial

    Directory of Open Access Journals (Sweden)

    Bernhard Jahn

    2016-06-01

    Full Text Available Abstract Background Guidelines for the control of hospital-acquired MRSA include decolonization measures to end MRSA carrier status in colonized and infected patients. Successful decolonization typically requires up to 22 days of treatment, which is longer than the average hospital length of stay (LOS. Incomplete decolonization is therefore common, with long-term MRSA carriage as a consequence. To overcome this, we developed an integrated MRSA Management (IMM by extending MRSA decolonization to the outpatient and domestic setting. The protocol makes use of polyhexanide-based products, in view of reported qac-mediated resistance to chlorhexidine in S. aureus and MRSA. Methods This is a prospective, single centre, controlled, non-randomized, open-label study to evaluate the efficiency of the IMM concept. The outcome of guideline-approved decolonization during hospital stay only (control group; n = 201 was compared to the outcome following IMM treatment whereby decolonization was continued after discharge in the domestic setting or in a long-term care facility (study group; n = 99. As a secondary outcome, the effect of MRSA-status of skin alterations was assessed. Results The overall decolonization rate was 47 % in the IMM patient group compared to 12 % in the control group (p  0.05. For patients with skin alterations (e.g. wounds and entry sites, decolonization success was 50 % if the skin alterations were MRSA-negative at baseline, compared to 22 % success for patients entering the study with MRSA-positive skin alterations (p < 0.01. Conclusions The IMM strategy offers an MRSA decolonization protocol that is feasible in the domestic setting and is equally effective compared with inpatient decolonization treatment when hospital LOS is long enough to complete the treatment. Moreover, for patients with average LOS, decolonization rates obtained with IMM are significantly higher than for in-hospital treatment. IMM is a promising

  1. Vitamin D3 supplementation in healthy adults: a comparison between capsule and oral spray solution as a method of delivery in a wintertime, randomised, open-label, cross-over study.

    Science.gov (United States)

    Todd, Joshua J; McSorley, Emeir M; Pourshahidi, L Kirsty; Madigan, Sharon M; Laird, Eamon; Healy, Martin; Magee, Pamela J

    2016-10-01

    Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays - a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31-49 nmol/l) and clinical deficiency (capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.

  2. Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation

    Science.gov (United States)

    Hosgood, Sarah A; Saeb-Parsy, Kourosh; Wilson, Colin; Callaghan, Christopher; Collett, Dave; Nicholson, Michael L

    2017-01-01

    Introduction Ex vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice. Methods and analysis This is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020. Trial registration number ISRCTN15821205; Pre-results. PMID:28115329

  3. Evaluation of wet-cupping therapy for persistent non-specific low back pain: a randomised, waiting-list controlled, open-label, parallel-group pilot trial

    Directory of Open Access Journals (Sweden)

    Kim Kun

    2011-06-01

    Full Text Available Abstract Background Persistent non-specific low back pain (PNSLBP is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP. Methods We recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to100 numerical rating scale (NRS for pain, the McGill Pain Questionnaire for pain intensity (PPI and the Oswestry Disability Questionnaire (ODQ, and we assessed acetaminophen use and safety issues. Results The results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group, but there was no statistical difference between the groups (p = 0.52. However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p Conclusion This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention

  4. A multicentric, open label, randomised, postmarketing efficacy study comparing multidose of lincomycin hydrochloride capsule 500 mg with multidose cefpodoxime proxetil tablet 200 mg in patients with tonsillitis, sinusitis.

    Science.gov (United States)

    Kothadiya, Ajay

    2012-08-01

    Tonsillitis causes considerable short and medium term morbidity, and can be recurrent. Sinusitis can be acute (less than 4 weeks), subacute (4-8 weeks) or chronic (8 weeks or more). To study the comparative efficacy and safety of multidose treatments of lincomycin hydrochloride 500 mg capsules against cefpodoxime proxetil 200 mg tablets on its outcome in the Indian scenario are the aims and objective of the study. A total of 41 tonsillitis, sinusitis cases of either gender aged above 18 years were enrolled in the study. The diagnosis of sonsillitis, sinusitis was made based on examination of symptoms and throat swab. A randomised treatment of either lincomycin hydrochloride 500 mg capsules or cefpodoxime proxetil 200 mg tablets twice daily for five days alongwith other concomitant medications depending on related symptoms was given to 40 patients. At the end of study, all patients were re-evaluated and the response rate was assessed. The most common clinical symptoms were body temperature, headache, throat pain, postnasal discharge, mucopus, odynophagia, sinus tenderness, nasal congestion, pharyngeal congestion and tonsillar congestion. The overall response rate of lincomycin hydrochloride in all the symptoms except headache was more effective than cefpodoxime proxetil. Out of 100% (n = 20) patients in each group, 67.89% in lincomycin and 52.27% in cefpodoxime patients achieved complete relief, in all the clinical symptoms. The study suggests that lincomycin hydrochloride capsules, a conventional antibiotic indicates effective treatment for relief from tonsillitis and sinusitis, as compared to new third generation antibiotic.

  5. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine for treatment of malaria infection in pregnancy in Ghana: an open-label, randomised, non-inferiority trial.

    Science.gov (United States)

    Osarfo, Joseph; Tagbor, Harry; Cairns, Matthew; Alifrangis, Michael; Magnussen, Pascal

    2017-08-01

    To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy. A total of 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomised to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-week post-partum to ascertain the health status of the babies. Parasitological efficacy (PE) by days 28 and 42 were co-primary outcomes. Analysis was per-protocol (PP) and modified intention-to-treat (ITT). Non-inferiority was declared if the two-sided 95% confidence interval for PE at the endpoints excluded 5% lower efficacy for DHA-PPQ. Secondary outcomes were assessed for superiority. In PP analysis, PE was 91.6% for DHA-PPQ and 89.3% for ASAQ by day 28 and 89.0% and 86.5%, respectively, by day 42. DHA-PPQ was non-inferior to ASAQ with respect to uncorrected PE [adjusted difference by day 28 (DHA-PPQ-ASAQ); 3.5% (95%CI: -1.5, 8.5); and day 42: 3.9% (95%CI: -2.7, 10.4)]. ITT analysis gave similar results. PCR to distinguish recrudescence and reinfection was unsuccessful. DHA-PPQ recipients had fewer adverse events of vomiting, dizziness, and general weakness compared to ASAQ. Both drugs were well-tolerated, and there was no excess of adverse birth outcomes. DHA-PPQ was non-inferior to ASAQ for treatment of malaria infection during pregnancy. No safety concerns were identified. Our findings contribute to growing evidence that DHA-PPQ is useful for control of malaria in pregnancy. © 2017 John Wiley & Sons Ltd.

  6. Maintenance of response after open-label treatment with atomoxetine hydrochloride in international European and non-European adult outpatients with attention-deficit/hyperactivity disorder: a placebo-controlled, randomised withdrawal study

    Directory of Open Access Journals (Sweden)

    Himanshu Upadhyaya

    2013-09-01

    Full Text Available Background and Objectives: We evaluated maintenance of response to atomoxetine during a 25-week, double-blind, placebo-controlled, randomised withdrawal period in adults with attention-deficit/hyperactivity disorder (ADHD who previously responded to atomoxetine during a 12 week open-label treatment period and maintained that response during a 12-week double-blind maintenance period. Methods: Patients (N = 2017, 18 to 50 years of age, diagnosed with ADHD from 152 outpatient sites in 18 countries received 12 weeks of open-label atomoxetine (40-100 mg/day followed by 12 weeks of double-blind maintenance (80 or 100 mg/day. Responders were randomized to atomoxetine (N = 266 or placebo (N = 258 for 25-weeks of double-blind treatment. The percentage of patients with a reduction >30% in their baseline Conners' ADHD Rating Scale Investigator-Rated: Screening Version (CAARS-Inv:SV total score and a score of <3 on the Clinical Global Impression ADHD-Severity (CGI-ADHD-S after 25 weeks was compared between treatment groups with a Fisher's exact test. Mean changes from baseline in the CAARS-Inv:SV and Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL were analysed. Results: Most patients enrolled (60% were from Europe. More atomoxetine- than placebo-treated patients maintained a satisfactory response postrandomisation (64.3% vs. 50.0%; p < .001. Time-to-relapse was significantly longer for atomoxetine than placebo (p = .004. Atomoxetine maintained greater improvements in ADHD symptoms compared with placebo (LS mean worsening in the CAARS-Inv:SV total score was 0.9 vs. 4.8 [ p < .001 ] and in the CGI-ADHD-S rating was 0.0 vs. 0.5 [ p < .001 ]. These results were supported by self- or observer-rated measures. Lastly, atomoxetine maintained greater improvements in quality of life compared with placebo (AAQoL total score was 0.4 vs. -4.0; p = .002. Conclusions: This study demonstrated that atomoxetine was superior to placebo in maintaining

  7. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial.

    Science.gov (United States)

    Grinsztejn, Beatriz; De Castro, Nathalie; Arnold, Vincent; Veloso, Valdiléa G; Morgado, Mariza; Pilotto, José Henrique; Brites, Carlos; Madruga, José Valdez; Barcellos, Nêmora Tregnago; Santos, Breno Riegel; Vorsatz, Carla; Fagard, Catherine; Santini-Oliveira, Marilia; Patey, Olivier; Delaugerre, Constance; Chêne, Geneviève; Molina, Jean-Michel

    2014-06-01

    Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis. We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315. Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the

  8. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.

    Science.gov (United States)

    Récher, Christian; Coiffier, Bertrand; Haioun, Corinne; Molina, Thierry Jo; Fermé, Christophe; Casasnovas, Olivier; Thiéblemont, Catherine; Bosly, André; Laurent, Guy; Morschhauser, Franck; Ghesquières, Hervé; Jardin, Fabrice; Bologna, Serge; Fruchart, Christophe; Corront, Bernadette; Gabarre, Jean; Bonnet, Christophe; Janvier, Maud; Canioni, Danielle; Jais, Jean-Philippe; Salles, Gilles; Tilly, Hervé

    2011-11-26

    The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Compared with standard R

  9. An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria.

    Directory of Open Access Journals (Sweden)

    Seth Owusu-Agyei

    Full Text Available BACKGROUND: Artesunate+amodiaquine (AS+AQ and artemether-lumefantrine (AL are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies. METHODS: Five hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups. MAIN FINDINGS: In a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28 was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005. In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2 primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4 The incidence of adverse events was comparable between the groups. CONCLUSIONS: AS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119145.

  10. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study

    Science.gov (United States)

    Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

    2016-01-01

    Introduction Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. Methods and analysis The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. Ethics and dissemination The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. Trial registration number 32017426, pre-results. PMID:27609859

  11. A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices.

    Science.gov (United States)

    van der Palen, Job; Thomas, Mike; Chrystyn, Henry; Sharma, Raj K; van der Valk, Paul Dlpm; Goosens, Martijn; Wilkinson, Tom; Stonham, Carol; Chauhan, Anoop J; Imber, Varsha; Zhu, Chang-Qing; Svedsater, Henrik; Barnes, Neil C

    2016-11-24

    Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all PELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), PELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers.

  12. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Gligorov, Joseph; Doval, Dinesh; Bines, José; Alba, Emilio; Cortes, Paulo; Pierga, Jean-Yves; Gupta, Vineet; Costa, Rômulo; Srock, Stefanie; de Ducla, Sabine; Freudensprung, Ulrich; Mustacchi, Giorgio

    2014-11-01

    Longer duration of first-line chemotherapy for patients with metastatic breast cancer is associated with prolonged overall survival and improved progression-free survival. We investigated capecitabine added to maintenance bevacizumab after initial treatment with bevacizumab and docetaxel in this setting. We did this open-label randomised phase 3 trial at 54 hospitals in Brazil, China, Egypt, France, Hong Kong, India, Italy, Poland, Spain, and Turkey. We enrolled patients with HER2-negative measurable metastatic breast cancer; each received three to six cycles of first-line bevacizumab (15 mg/kg) and docetaxel (75-100 mg/m(2)) every 3 weeks. Progression-free patients were randomly assigned with an interactive voice-response system by block (size four) randomisation (1:1) to receive either bevacizumab and capecitabine or bevacizumab only (bevacizumab 15 mg/kg on day 1; capecitabine 1000 mg/m(2) twice per day on days 1-14, every 3 weeks) until progression, stratified by oestrogen receptor status (positive vs negative), visceral metastases (present vs absent), response status (stable disease vs response vs non-measurable), and lactate dehydrogenase concentration (≤1·5 vs >1·5 × upper limit of normal). Neither patients nor investigators were masked to allocation. The primary endpoint was progression-free survival (from randomisation) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00929240. Between July 16, 2009, and March 7, 2011 (when enrolment was prematurely terminated), 284 patients received initial bevacizumab and docetaxel; 185 (65%) were randomly assigned (91 to bevacizumab and capecitabine versus 94 to bevacizumab only). Progression-free survival was significantly longer in the bevacizumab and capecitabine group than in the bevacizumab only group (median 11·9 months [95% CI 9·8-15·4] vs 4·3 months [3·9-6·8]; stratified hazard ratio 0·38 [95% CI 0·27-0·55]; two-sided log-rank p<0·0001), as was overall

  13. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Thatcher, Nick; Hirsch, Fred R; Luft, Alexander V; Szczesna, Aleksandra; Ciuleanu, Tudor E; Dediu, Mircea; Ramlau, Rodryg; Galiulin, Rinat K; Bálint, Beatrix; Losonczy, György; Kazarnowicz, Andrzej; Park, Keunchil; Schumann, Christian; Reck, Martin; Depenbrock, Henrik; Nanda, Shivani; Kruljac-Letunic, Anamarija; Kurek, Raffael; Paz-Ares, Luis; Socinski, Mark A

    2015-07-01

    Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients

  14. Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.

    Science.gov (United States)

    Wright, Peter F; Connor, Ruth I; Wieland-Alter, Wendy F; Hoen, Anne G; Boesch, Austin W; Ackerman, Margaret E; Oberste, M Steven; Gast, Chris; Brickley, Elizabeth B; Asturias, Edwin J; Rüttimann, Ricardo; Bandyopadhyay, Ananda S

    2016-12-01

    Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools. In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants. 210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (pBill & Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

  15. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.

    Science.gov (United States)

    de Boer, Stephanie M; Powell, Melanie E; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B; Ledermann, Jonathan A; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C; Nijman, Hans W; Kruitwagen, Roy F; Nout, Remi A; Verhoeven-Adema, Karen W; Smit, Vincent T; Putter, Hein; Creutzberg, Carien L

    2016-08-01

    About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48·6 Gy) in 1·8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for

  16. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial.

    Science.gov (United States)

    Goldstein, Joshua N; Refaai, Majed A; Milling, Truman J; Lewis, Brandon; Goldberg-Alberts, Robert; Hug, Bruce A; Sarode, Ravi

    2015-05-23

    Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures. In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than -10% for group difference) for both endpoints, then superiority (lower limit 95% CI >0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at ClinicalTrials.gov, number NCT00803101. 181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8-25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma

  17. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

    Science.gov (United States)

    Azzouzi, Abdel-Rahmène; Vincendeau, Sébastien; Barret, Eric; Cicco, Antony; Kleinclauss, François; van der Poel, Henk G; Stief, Christian G; Rassweiler, Jens; Salomon, Georg; Solsona, Eduardo; Alcaraz, Antonio; Tammela, Teuvo T; Rosario, Derek J; Gomez-Veiga, Francisco; Ahlgren, Göran; Benzaghou, Fawzi; Gaillac, Bertrand; Amzal, Billy; Debruyne, Frans M J; Fromont, Gaëlle; Gratzke, Christian; Emberton, Mark

    2017-02-01

    Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular

  18. Effect of a new insulin treatment regimen on glycaemic control and quality of life of Muslim patients with type 2 diabetes mellitus during Ramadan fast - an open label, controlled, multicentre, cluster randomised study.

    Science.gov (United States)

    Shehadeh, N; Maor, Y

    2015-11-01

    We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events.

  19. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial.

    Science.gov (United States)

    Hegewisch-Becker, Susanna; Graeven, Ullrich; Lerchenmüller, Christian A; Killing, Birgitta; Depenbusch, Reinhard; Steffens, Claus-Christoph; Al-Batran, Salah-Eddin; Lange, Thoralf; Dietrich, Georg; Stoehlmacher, Jan; Tannapfel, Andrea; Reinacher-Schick, Anke; Quidde, Julia; Trarbach, Tanja; Hinke, Axel; Schmoll, Hans-Joachim; Arnold, Dirk

    2015-10-01

    The definition of a best maintenance strategy following combination chemotherapy plus bevacizumab in metastatic colorectal cancer is unclear. We investigated whether no continuation of therapy or bevacizumab alone are non-inferior to fluoropyrimidine plus bevacizumab, following induction treatment with a fluoropyrimidine plus oxaliplatin plus bevacizumab. In this open-label, non-inferiority, randomised phase 3 trial, we included patients aged 18 years or older with histologically confirmed, previously untreated metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate bone marrow, liver, and renal function, no pre-existing neuropathy greater than grade 1, and measurable disease, from 55 hospitals and 51 private practices in Germany. After 24 weeks of induction therapy with either fluorouracil plus leucovorin plus oxaliplatin or capecitabine plus oxaliplatin, both with bevacizumab, patients without disease progression were randomly assigned centrally by fax (1:1:1) to standard maintenance treatment with a fluoropyrimidine plus bevacizumab, bevacizumab alone, or no treatment. Both patients and investigators were aware of treatment assignment. Stratification criteria were response status, termination of oxaliplatin, previous adjuvant treatment with oxaliplatin, and ECOG performance status. At first progression, re-induction with all drugs of the induction treatment was a planned part of the protocol. Time to failure of strategy was the primary endpoint, defined as time from randomisation to second progression after maintenance (and if applicable re-induction), death, or initiation of further treatment including a new drug. Time to failure of strategy was equivalent to time to first progression for patients who did not receive re-induction (for any reason). The boundary for assessment of non-inferiority was upper limit of the one-sided 98·8% CI 1·43. Analyses were done by intention to treat. The study has completed

  20. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728

    Directory of Open Access Journals (Sweden)

    Sheard Laura

    2004-04-01

    Full Text Available Abstract Background Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. Methods/design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

  1. Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial.

    Science.gov (United States)

    Asturias, Edwin J; Bandyopadhyay, Ananda S; Self, Steve; Rivera, Luis; Saez-Llorens, Xavier; Lopez, Eduardo; Melgar, Mario; Gaensbauer, James T; Weldon, William C; Oberste, M Steven; Borate, Bhavesh R; Gast, Chris; Clemens, Ralf; Orenstein, Walter; O'Ryan G, Miguel; Jimeno, José; Clemens, Sue Ann Costa; Ward, Joel; Rüttimann, Ricardo

    2016-07-09

    Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has

  2. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  3. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

    Science.gov (United States)

    Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

    2017-02-01

    Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and

  4. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial.

    Science.gov (United States)

    Marina, Neyssa M; Smeland, Sigbjørn; Bielack, Stefan S; Bernstein, Mark; Jovic, Gordana; Krailo, Mark D; Hook, Jane M; Arndt, Carola; van den Berg, Henk; Brennan, Bernadette; Brichard, Bénédicte; Brown, Ken L B; Butterfass-Bahloul, Trude; Calaminus, Gabriele; Daldrup-Link, Heike E; Eriksson, Mikael; Gebhardt, Mark C; Gelderblom, Hans; Gerss, Joachim; Goldsby, Robert; Goorin, Allen; Gorlick, Richard; Grier, Holcombe E; Hale, Juliet P; Hall, Kirsten Sundby; Hardes, Jendrik; Hawkins, Douglas S; Helmke, Knut; Hogendoorn, Pancras C W; Isakoff, Michael S; Janeway, Katherine A; Jürgens, Heribert; Kager, Leo; Kühne, Thomas; Lau, Ching C; Leavey, Patrick J; Lessnick, Stephen L; Mascarenhas, Leo; Meyers, Paul A; Mottl, Hubert; Nathrath, Michaela; Papai, Zsuzsanna; Randall, R Lor; Reichardt, Peter; Renard, Marleen; Safwat, Akmal Ahmed; Schwartz, Cindy L; Stevens, Michael C G; Strauss, Sandra J; Teot, Lisa; Werner, Mathias; Sydes, Matthew R; Whelan, Jeremy S

    2016-10-01

    We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m(2), doxorubicin 37·5 mg/m(2) per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m(2) over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m(2)) at 2·8 g/m(2) per day with equidose mesna uroprotection, followed by etoposide 100 mg/m(2) per day over 1 h on days 1-5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6-76·6); 62·3 months (IQR 46·9-77·1) for the MAP group and 61·1 months (IQR 46·5-75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event

  5. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

    Science.gov (United States)

    O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann

    2015-11-01

    Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups

  6. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  7. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

    Science.gov (United States)

    Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

    2017-03-01

    Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial

    DEFF Research Database (Denmark)

    Yeni, P; Cooper, DA; Aboulker, J-P

    2006-01-01

    BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretrov...

  9. Two-stage implant-based breast reconstruction compared with immediate one-stage implant-based breast reconstruction augmented with an acellular dermal matrix : An open-label, phase 4, multicentre, randomised, controlled trial

    NARCIS (Netherlands)

    Dikmans, Rieky E. G.; Negenborn, Vera L.; Bouman, Mark-Bram; Winters, Hay A. H.; Twisk, Jos W. R.; Ruhe, P. Quinten; Mureau, Marc A M; Smit, J.M.; Tuinder, Stefania; Eltahir, Yassir; Posch, Nicole A.; van Steveninck-Barends, Josephina M.; Meesters-Caberg, Marleen A.; van der Hulst, Rene R. W. J.; Ritt, Marco J. P. F.; Mullender, Margriet G.

    Background The evidence justifying the use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) is limited. We did a prospective randomised trial to compare the safety of IBBR with an ADM immediately after mastectomy with that of two-stage IBBR. Methods We did an

  10. A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

    Science.gov (United States)

    Borgatta, Lynn; Buhling, Kai J; Rybowski, Sarah; Roth, Katrin; Rosen, Kimberly

    2016-10-01

    To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

  11. Clinical and cost-effectiveness analysis of an open label, single-centre, randomised trial of spinal cord stimulation (SCS versus percutaneous myocardial laser revascularisation (PMR in patients with refractory angina pectoris: The SPiRiT trial

    Directory of Open Access Journals (Sweden)

    Khan SN

    2008-06-01

    Full Text Available Abstract Background Patients with refractory angina have significant morbidity. This study aimed to compare two of the treatment options, Spinal Cord Stimulation (SCS and Percutaneous Myocardial Laser Revascularisation (PMR in terms of clinical outcomes and cost-effectiveness. Methods Eligible patients were randomised to PMR or SCS and followed up for exercise tolerance time (ETT, Canadian Cardiovascular Society (CCS classification and the quality of life measures SF-36, Seattle Angina Questionnaire and the EuroQoL at 3, 12 and 24 months. Utilities were calculated using the EQ-5D and these and costs were compared between groups. The incremental cost-effectiveness ratio (ICER per QALY for SCS compared to PMR was also calculated. Results At 24 months post-randomisation, patients that had SCS and PMR had similar ETT (mean difference 0.05, 95% CI -2.08, 2.18, p = 0.96 and there was no difference in CCS classification or quality of life outcomes. The difference in overall mean costs when comparing SCS to PMR was GBP5,520 (95% CI GBP1,966 to GBP8,613; p Conclusion Outcomes after SCS did not differ appreciably from those after PMR, with the former procedure being less cost-effective as currently applied. Larger studies could clarify which patients would most benefit from SCS, potentially increasing cost-effectiveness. Trial registration Current Controlled Trials ISRCTN09648950

  12. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II: a multicentre, open-label randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Sporken Jan M J

    2011-07-01

    Full Text Available Abstract Background Gestational hypertension (GH and pre-eclampsia (PE can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Methods/Design Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS, neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that

  13. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial.

    Science.gov (United States)

    Haidar, Ahmad; Legault, Laurent; Messier, Virginie; Mitre, Tina Maria; Leroux, Catherine; Rabasa-Lhoret, Rémi

    2015-01-01

    The artificial pancreas is an emerging technology for the treatment of type 1 diabetes and two configurations have been proposed: single-hormone (insulin alone) and dual-hormone (insulin and glucagon). We aimed to delineate the usefulness of glucagon in the artificial pancreas system. We did a randomised crossover trial of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy (continuous subcutaneous insulin infusion) in participants aged 12 years or older with type 1 diabetes. Participants were assigned in a 1:1:1:1:1:1 ratio with blocked randomisation to the three interventions and attended a research facility for three 24-h study visits. During visits when the patient used the single-hormone artificial pancreas, insulin was delivered based on glucose sensor readings and a predictive dosing algorithm. During dual-hormone artificial pancreas visits, glucagon was also delivered during low or falling glucose. During conventional insulin pump therapy visits, patients received continuous subcutaneous insulin infusion. The study was not masked. The primary outcome was the time for which plasma glucose concentrations were in the target range (4·0-10·0 mmol/L for 2 h postprandially and 4·0-8·0 mmol/L otherwise). Hypoglycaemic events were defined as plasma glucose concentration of less than 3·3 mmol/L with symptoms or less than 3·0 mmol/L irrespective of symptoms. Analysis was by modified intention to treat, in which we included data for all patients who completed at least two visits. A p value of less than 0·0167 (0·05/3) was regarded as significant. This trial is registered with ClinicalTrials.gov, number NCT01754337. The mean proportion of time spent in the plasma glucose target range over 24 h was 62% (SD 18), 63% (18), and 51% (19) with single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional insulin pump therapy, respectively. The mean difference in time spent in the target

  14. The effect of a cinnamon-, chromium- and magnesium-formulated honey on glycaemic control, weight loss and lipid parameters in type 2 diabetes: an open-label cross-over randomised controlled trial.

    Science.gov (United States)

    Whitfield, Patricia; Parry-Strong, Amber; Walsh, Emily; Weatherall, Mark; Krebs, Jeremy D

    2016-04-01

    This randomised controlled trial assessed the acute and long-term effects of daily supplementation of kanuka honey, formulated with cinnamon, chromium and magnesium on glucose metabolism, weight and lipid parameters in individuals with type 2 diabetes. Twelve individuals with type 2 diabetes received 53.5 g of a formulated honey and a control (non-formulated) kanuka honey in a random order for 40 days, using cross-over design. Fasting glucose, insulin, HbA1c, lipids and anthropometric measures were measured at baseline and end of treatment. A meal tolerance test was performed at baseline to assess acute metabolic response. There was no statistically significant difference in acute glucose metabolism between treatment groups, as measured by the Matsuda index and AUC for glucose and insulin. After the 40-day intervention with honey, fasting glucose did not differ significantly between the two treatments (95 % CI -2.6 to 0.07). There was no statistically significant change in HbA1c or fasting insulin. There was a statistically significant reduction in total cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23), LDL cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23) and weight by -2.2 kg (95 % CI -4.2 to -0.1). There was a trend towards increased HDL and reduced systolic blood pressure in the intervention treatment. The addition of cinnamon, chromium and magnesium supplementation to kanuka honey was not associated with a significant improvement in glucose metabolism or glycaemic control in individuals with type 2 diabetes. Use of the formulated honey was associated with a reduction in weight and improvements in lipid parameters, and should be investigated further.

  15. Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

    Science.gov (United States)

    Pushpakom, Sudeep P; Taylor, Claire; Kolamunnage-Dona, Ruwanthi; Spowart, Catherine; Vora, Jiten; García-Fiñana, Marta; Kemp, Graham J; Whitehead, John; Jaki, Thomas; Khoo, Saye; Williamson, Paula; Pirmohamed, Munir

    2015-10-15

    Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West-Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. 04196/0024/001-0001; 2012-000935-18; 51069819. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  16. Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial.

    Science.gov (United States)

    Haidar, Ahmad; Legault, Laurent; Matteau-Pelletier, Laurence; Messier, Virginie; Dallaire, Maryse; Ladouceur, Martin; Rabasa-Lhoret, Rémi

    2015-08-01

    Additional benefits of the dual-hormone (insulin and glucagon) artificial pancreas compared with the single-hormone (insulin alone) artificial pancreas have not been assessed in young people in outpatient unrestricted conditions. We evaluated the efficacy of three systems for nocturnal glucose control in children and adolescents with type 1 diabetes. We did a randomised, three-way, crossover trial in children aged 9-17 years with type 1 diabetes attending a diabetes camp in Canada. With use of sealed envelopes, children were randomly assigned in a 1:1:1:1:1:1 ratio with blocks of six to different sequences of the three interventions (single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional continuous subcutaneous insulin pump therapy). Each intervention was applied for 3 consecutive nights. Participants, study staff, and endpoint assessors were not masked. The primary outcome was the percentage of time spent with glucose concentrations lower than 4·0 mmol/L from 2300 h to 0700 h. Analysis was by intention to treat. A p value of less than 0·0167 was regarded as significant. This study is registered with ClinicalTrials.gov, number NCT02189694. Between June 30, 2014, and Aug 9, 2014, we enrolled 33 children of mean age 13·3 years (SD 2·3; range 9-17). The time spent at a glucose concentration lower than 4·0 mmol/L was median 0% (IQR 0·0-2·4) during nights with the dual-hormone artificial pancreas, 3·1% (0·0-6·9) during nights with the single-hormone artificial pancreas (p=0·032), and 3·4% (0-11·0) during nights with conventional pump therapy (p=0·0048 compared with dual-hormone artificial pancreas and p=0·32 compared with single-hormone artificial pancreas). 15 hypoglycaemic events (pump therapy compared with four events with the single-hormone system and no events with the dual-hormone system. None of the assessed outcomes varied with the order in which children and young adults were assigned interventions. The dual

  17. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial.

    Science.gov (United States)

    Peter, Jonny G; Zijenah, Lynn S; Chanda, Duncan; Clowes, Petra; Lesosky, Maia; Gina, Phindile; Mehta, Nirja; Calligaro, Greg; Lombard, Carl J; Kadzirange, Gerard; Bandason, Tsitsi; Chansa, Abidan; Liusha, Namakando; Mangu, Chacha; Mtafya, Bariki; Msila, Henry; Rachow, Andrea; Hoelscher, Michael; Mwaba, Peter; Theron, Grant; Dheda, Keertan

    2016-03-19

    HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy. We therefore assessed a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality. We did a pragmatic, randomised, parallel-group, multicentre trial in ten hospitals in Africa--four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe. Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis (fever, cough, night sweats, or self-reported weightloss) and illness severity necessitating admission to hospital. Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment. We randomly assigned patients (1:1) to either LAM plus routine diagnostic tests for tuberculosis (smear microscopy, Xpert-MTB/RIF, and culture; LAM group) or routine diagnostic tests alone (no LAM group) using computer-generated allocation lists in blocks of ten. All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere, USA) at the bedside on enrolment. On the basis of a positive test result, the nurses made a recommendation for initiating anti-tuberculosis treatment. The attending physician made an independent decision about whether to start treatment or not. Neither patients nor health-care workers were masked to group allocation and test results. The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population (those who received their allocated intervention). This trial is registered with Clinical

  18. Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial.

    Science.gov (United States)

    García-Donas, Jesus; Font, Albert; Pérez-Valderrama, Begoña; Virizuela, José Antonio; Climent, Miquel Ángel; Hernando-Polo, Susana; Arranz, José Ángel; Del Mar Llorente, Maria; Lainez, Nuria; Villa-Guzmán, José Carlos; Mellado, Begoña; Del Alba, Aránzazu González; Castellano, Daniel; Gallardo, Enrique; Anido, Urbano; Del Muro, Xavier García; Domènech, Montserrat; Puente, Javier; Morales-Barrera, Rafael; Pérez-Gracia, Jose Luis; Bellmunt, Joaquim

    2017-05-01

    Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m(2) or at 280 mg/m(2) in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One

  19. Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

    Science.gov (United States)

    Desai, Meghna; Gutman, Julie; L'lanziva, Anne; Otieno, Kephas; Juma, Elizabeth; Kariuki, Simon; Ouma, Peter; Were, Vincent; Laserson, Kayla; Katana, Abraham; Williamson, John; ter Kuile, Feiko O

    2015-12-19

    Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine. We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941. Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine

  20. Open-Label Memantine in Fragile X Syndrome

    Science.gov (United States)

    Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

    2009-01-01

    Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). The purpose of this pilot study was to examine the effectiveness and tolerability of memantine for a number of target symptoms associated with FXS. Medical records describing open-label treatment with memantine in 6 patients with FXS and a comorbid…

  1. A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Abbott, Penelope; Gunasekera, Hasantha; Leach, Amanda Jane; Askew, Deborah; Walsh, Robyn; Kong, Kelvin; Girosi, Federico; Bond, Chelsea; Morris, Peter; Lujic, Sanja; Hu, Wendy; Usherwood, Tim; Tyson, Sissy; Spurling, Geoffrey; Douglas, Markeeta; Schubert, Kira; Chapman, Shavaun; Siddiqui, Nadeem; Murray, Reeion; Rabbitt, Keitha; Porykali, Bobby; Woodall, Cheryl; Newman, Tina; Reath, Jennifer

    2016-03-03

    Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 - 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. The trial will provide evidence for the safety and effectiveness of watchful waiting

  2. OpenCL based machine learning labeling of biomedical datasets

    Science.gov (United States)

    Amoros, Oscar; Escalera, Sergio; Puig, Anna

    2011-03-01

    In this paper, we propose a two-stage labeling method of large biomedical datasets through a parallel approach in a single GPU. Diagnostic methods, structures volume measurements, and visualization systems are of major importance for surgery planning, intra-operative imaging and image-guided surgery. In all cases, to provide an automatic and interactive method to label or to tag different structures contained into input data becomes imperative. Several approaches to label or segment biomedical datasets has been proposed to discriminate different anatomical structures in an output tagged dataset. Among existing methods, supervised learning methods for segmentation have been devised to easily analyze biomedical datasets by a non-expert user. However, they still have some problems concerning practical application, such as slow learning and testing speeds. In addition, recent technological developments have led to widespread availability of multi-core CPUs and GPUs, as well as new software languages, such as NVIDIA's CUDA and OpenCL, allowing to apply parallel programming paradigms in conventional personal computers. Adaboost classifier is one of the most widely applied methods for labeling in the Machine Learning community. In a first stage, Adaboost trains a binary classifier from a set of pre-labeled samples described by a set of features. This binary classifier is defined as a weighted combination of weak classifiers. Each weak classifier is a simple decision function estimated on a single feature value. Then, at the testing stage, each weak classifier is independently applied on the features of a set of unlabeled samples. In this work, we propose an alternative representation of the Adaboost binary classifier. We use this proposed representation to define a new GPU-based parallelized Adaboost testing stage using OpenCL. We provide numerical experiments based on large available data sets and we compare our results to CPU-based strategies in terms of time and

  3. Effects of interpretive front-of-pack nutrition labels on food purchases: protocol for the Starlight randomised controlled trial.

    Science.gov (United States)

    Volkova, Ekaterina; Neal, Bruce; Rayner, Mike; Swinburn, Boyd; Eyles, Helen; Jiang, Yannan; Michie, Jo; Ni Mhurchu, Cliona

    2014-09-18

    Interpretive front-of-pack nutrition labels are better understood than non-interpretive labels. However, robust evidence on the effects of such labels on consumer food purchases in the real-world is lacking. Our aim is to assess the effects of two interpretive front-of-pack nutrition labels, compared with a non-interpretive label, on the healthiness of consumer food purchases. A five-week (1-week baseline and 4-week intervention) three-arm parallel randomised controlled trial will be conducted using a bespoke smartphone application, which will administer study questionnaires and deliver intervention (Multiple Traffic Light and Health Star Rating) and control (Nutrition Information Panel) labels. To view their allocated nutrition label, participants scan the barcode of packaged food products using their smartphone camera. The assigned label is displayed instantly on the smartphone screen.1500 eligible participants (New Zealand adult smartphone owners who shop in a supermarket at least once a week and are main household shoppers) will be randomised in a 1:1:1 ratio to one of the three nutrition label formats, using computer-generated randomisation sequences. Randomisation will be stratified by ethnicity and interest in healthy eating. Food and beverage purchase data will be collected continuously throughout the study via hard copy till receipts and electronic grocery purchase lists recorded and transmitted using the smartphone application. The primary outcome will be healthiness of food purchases in each trial arm, assessed as mean Food Standards Australia New Zealand nutrient profiling score criterion score for all food and beverages purchased over the intervention period. Secondary outcomes will include saturated fat, sugar, sodium and energy content of food purchases; food expenditure; labelling profile of food purchases (i.e. mean number of Health Star Rating stars and proportion of red, green and amber traffic lights); nutrient profiling score over time and by

  4. Implementing Randomised Control Trials in Open and Distance Learning: A Feasibility Study

    Science.gov (United States)

    Herodotou, Christothea; Heiser, Sarah; Rienties, Bart

    2017-01-01

    Randomised control trials (RCTs) are an evidence-based research approach which has not yet been adopted and widely used in open and distance education to inform educational policy and practice. Despite the challenges entailed in their application, RCTs hold the power to robustly evaluate the effects of educational interventions in distance…

  5. Evaluation of efficacy and tolerability of eperisone and thiocolchicoside in treatment of low back pain associated with muscle spasm: An open label, prospective, randomized controlled trial

    OpenAIRE

    Syed H. Maaz; Prakash N. Khandelwal; Shiraz M. Baig; Sudhakar M. Doifode; Ulhas M. Ghotkar

    2016-01-01

    Background: Low back pain has a high prevalence in adult population. Because of reflex muscle spasm, muscle relaxants are frequently used either alone or in combination with analgesics. Eperisone inhibits voltage gated sodium channels in brain stem and Thiocolchicoside acts via GABA-mediated mechanism to relax muscle spasm and relieves pain. Methods: This was a prospective; open labeled, randomized, two-arm, parallel group, controlled, clinical trial. 113 patients were randomised to two gr...

  6. Endoscopic versus open release in patients with de Quervain's tenosynovitis: a randomised trial.

    Science.gov (United States)

    Kang, H J; Koh, I H; Jang, J W; Choi, Y R

    2013-07-01

    The purpose of this study was to compare the outcome and complications of endoscopic versus open release for the treatment of de Quervain's tenosynovitis. Patients with this condition were randomised to undergo either endoscopic (n = 27) or open release (n = 25). Visual Analogue Scale (VAS) pain and Disabilities of Arm, Shoulder, and Hand (DASH) scores were measured at 12 and 24 weeks after surgery. Scar satisfaction was measured using a VAS scale. The mean pain and DASH scores improved significantly at 12 weeks and 24 weeks (p Quervain's tenosynovitis seems to provide earlier improvement after surgery, with fewer superficial radial nerve complications and greater scar satisfaction, when compared with open release.

  7. Open-label escitalopram treatment for pathological skin picking.

    Science.gov (United States)

    Keuthen, Nancy J; Jameson, Mariko; Loh, Rebecca; Deckersbach, Thilo; Wilhelm, Sabine; Dougherty, Darin D

    2007-09-01

    Pathological skin picking is characterized by dysfunctional, repetitive and excessive manipulation of the skin resulting in noticeable tissue damage. This study sought to assess the effectiveness of escitalopram in treating pathological skin picking. Twenty-nine individuals with pathological skin picking were enrolled in an 18-week, open-label trial of escitalopram. Study measures assessing skin picking severity and impact, anxiety, depression, and quality of life were given at baseline and weeks 2, 4, 6, 10, 14, and 18. The mean maximally tolerated dose was 25.0 mg (standard deviation=8.4). For the 19 study completers, pre-post-treatment analyses revealed significant improvements (Ppicking severity and impact, quality of life, and self-rated anxiety and depression. Completer as well as intent-to-treat analyses indicated that approximately half of the sample satisfied full medication response criteria and one-quarter were partial medication responders. Correlational analyses indicated that changes in depression, anxiety, and quality of life co-occurred with reductions in skin picking severity but not impact. A high percentage of variance in severity, however, remained unexplained. These results suggest that escitalopram can be an effective agent in reducing pathological skin picking. The lack of medication response in a subset of our sample suggests the possibility of pathological skin picking subtypes.

  8. Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study.

    Science.gov (United States)

    Cheishvili, David; Maayan, Channa; Holzer, Naama; Tsenter, Jeanna; Lax, Elad; Petropoulos, Sophie; Razin, Aharon

    2016-07-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy, primarily presented in Ashkenazi Jews. The most common mutation in FD patients results from a single base pair substitution of an intronic splice site in the IKBKAP gene which disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP). To date, treatment of FD patients remains preventative, symptomatic and supportive. Based on previous in vitro evidence that tocotrienols, members of the vitamin E family, upregulate transcription of the IKBKAP gene, we aimed to investigate whether a similar effects was observed in vivo. In the current study, we assessed the effects of tocotrienol treatment on FD patients' symptoms and IKBKAP expression in white blood cells. The initial daily doses of 50 or 100 mg tocotrienol, doubled after 3 months, was administered to 32 FD patients. Twenty-eight FD patients completed the 6-month study. The first 3 months of tocotrienol treatment was associated with a significant increase in IKBKAP expression level in FD patients' blood. Despite doubling the dose after the initial 3 months of treatment, IKBKAP expression level returned to baseline by the end of the 6-month treatment. Clinical improvement was noted in the reported clinical questionnaire (with regard to dizziness, bloching, sweating, number of pneumonia, cough episodes, and walking stability), however, no significant effect was observed in any clinical measurements (weight, height, oxygen saturation, blood pressure, tear production, histamine test, vibration threshold test, nerve conduction, and heart rate variability) following Tocotrienol treatment. In conclusion, tocotrienol treatment appears significantly beneficial by clinical evaluation for some FD patients in a few clinical parameters; however it was not significant by clinical measurements. This open-label study shows the complexity of effect of tocotrienol treatment on FD patients' clinical outcomes and on

  9. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a d

  10. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a

  11. Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Samir Koirala

    Full Text Available BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day in a single dose or ofloxacin (20 mg/kg/day in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23 years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73. The median time to fever clearance was 4.70 days (IQR 2.98-5.90 in the ofloxacin group versus 3.31 days (IQR 2.29-4.75 in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004. The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com.

  12. Multi-atlas segmentation with joint label fusion and corrective learning-an open source implementation.

    Science.gov (United States)

    Wang, Hongzhi; Yushkevich, Paul A

    2013-01-01

    Label fusion based multi-atlas segmentation has proven to be one of the most competitive techniques for medical image segmentation. This technique transfers segmentations from expert-labeled images, called atlases, to a novel image using deformable image registration. Errors produced by label transfer are further reduced by label fusion that combines the results produced by all atlases into a consensus solution. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity is a simple and highly effective label fusion technique. However, one limitation of most weighted voting methods is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this problem, we recently developed the joint label fusion technique and the corrective learning technique, which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and Applications (SATA) challenge. To make our techniques more accessible to the scientific research community, we describe an Insight-Toolkit based open source implementation of our label fusion methods. Our implementation extends our methods to work with multi-modality imaging data and is more suitable for segmentation problems with multiple labels. We demonstrate the usage of our tools through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain image dataset and the 2013 SATA challenge canine leg image dataset. We report the best results on these two datasets so far.

  13. Multi-Atlas Segmentation with Joint Label Fusion and Corrective Learning - An Open Source Implementation

    Directory of Open Access Journals (Sweden)

    Hongzhi eWang

    2013-11-01

    Full Text Available Label fusion based multi-atlas segmentation has proven to be one of the most competitive techniques for medical image segmentation. This technique transfers segmentations from expert-labeled images, called atlases, to a novel image using deformable image registration. Errors produced by label transfer are further reduced by label fusion that combines the results produced by all atlases into a consensus solution. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity is a simple and highly effective label fusion technique. However, one limitation of most weighted voting methods is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this problem, we recently developed the joint label fusion technique and the corrective learning technique, which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and Applications (SATA challenge. To make our techniques more accessible to the scientific research community, we describe an Insight-Toolkit based open source implementation of our label fusion methods. Our implementation extends our methods to work with multi-modality imaging data and is more suitable for segmentation problems with multiple labels. We demonstrate the usage of our tools through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain image dataset and the 2013 SATA challenge canine leg image dataset. We report the best results on these two datasets so far.

  14. Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: An open-label study

    Institute of Scientific and Technical Information of China (English)

    Laurent Peyrin-Biroulet; Cécils Laclotte; Xavier Roblin; Marc-André Bigard

    2007-01-01

    AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant.METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4.RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4.CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebocontrolled trials.

  15. Laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study.

    Science.gov (United States)

    Simone, Giuseppe; Papalia, Rocco; Guaglianone, Salvatore; Ferriero, Mariaconsiglia; Leonardo, Costantino; Forastiere, Ester; Gallucci, Michele

    2009-09-01

    Laparoscopic nephroureterectomy (LNU) is increasingly being used instead of open nephroureterectomy (ONU) for the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT), but the evidence of equal oncologic effectiveness is still lacking. To present perioperative and oncologic results from a prospective randomised study comparing ONU and LNU. Eighty patients with nonmetastatic UUT UC and without previous history of UC were enrolled. Of those, 40 patients (group A) randomly received ONU and 40 patients (group B) randomly received LNU. ONU was performed through a flank incision with a lower quadrant incision to allow excision of a bladder cuff. Transperitoneal LNU was performed with a four-trocar technique, and bladder cuff was detached with a 10-mm LigaSure device. Perioperative data were compared with the student t test. Bladder tumour-free survival (BTFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) curves for both groups were compared with the log-rank test before and after stratifying patients for pT category and tumour grade. Operative times were comparable, while mean blood loss and mean time to discharge were significantly lower in group B (both p values ONU (p=0.039 and p=0.004, respectively, for pT3 tumours; p=0.078 and p=0.014, respectively, for high-grade tumours). The limitations of our study include the small sample size, the single-centre experience, the personal choice of laparoscopic technique, and not performing lymphadenectomies. Perioperative data and preliminary oncologic results were presented at 22nd Congress of the European Association of Urology, Berlin, Germany. In patients with organ-confined UUT UCs, LNU has the advantages of minimal invasiveness and oncologic outcomes comparable to those of ONU, while its effectiveness in patients with advanced stage diseases remains to be proven.

  16. An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

    Science.gov (United States)

    Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

    2005-01-01

    Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

  17. Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

    Science.gov (United States)

    Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

    2010-01-01

    Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

  18. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  19. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning

    NARCIS (Netherlands)

    Knegtering, H; Boks, M; Blijd, C; Castelein, S; Van den Bosch, RJ; Wiersma, D

    2006-01-01

    The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15mg/d) or risperidone (1-6mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview

  20. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.

    Science.gov (United States)

    Devinsky, Orrin; Marsh, Eric; Friedman, Daniel; Thiele, Elizabeth; Laux, Linda; Sullivan, Joseph; Miller, Ian; Flamini, Robert; Wilfong, Angus; Filloux, Francis; Wong, Matthew; Tilton, Nicole; Bruno, Patricia; Bluvstein, Judith; Hedlund, Julie; Kamens, Rebecca; Maclean, Jane; Nangia, Srishti; Singhal, Nilika Shah; Wilson, Carey A; Patel, Anup; Cilio, Maria Roberta

    2016-03-01

    Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy. In this open-label trial, patients (aged 1-30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2-5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test. Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n

  1. Randomised controlled trial of prophylactic antibiotic treatment for the prevention of endophthalmitis after open globe injury at Groote Schuur Hospital.

    Science.gov (United States)

    Du Toit, N; Mustak, S; Cook, C

    2017-07-01

    Most post-traumatic acute infectious endophthalmitis occur within a week of open globe trauma, necessitating early antibiotic prophylaxis. There are few randomised studies that demonstrate the benefits of prophylactic antibiotics. This randomised controlled non-inferiority trial was aimed at determining the incidence of post-traumatic endophthalmitis using established intravenous/oral prophylaxis and comparing this to the incidence using oral antibiotics only. All adult patients admitted with open globe injury were included. Those with proven endophthalmitis, high-risk features, who underwent primary evisceration and those allergic to the trial antibiotics were excluded. Patients were randomised to receive either intravenous cefazolin and oral ciprofloxacin or oral ciprofloxacin and oral cefuroxime for 3 days from admission. Acute endophthalmitis was the primary outcome. Patients completed the study if they were followed up for 6 weeks post injury. Three hundred patients were enrolled, with 150 in each arm. There were 99 exclusions. Seven patients developed endophthalmitis despite prophylaxis-2.0% (three cases) in the intravenous and oral arm, compared with 2.7% (four cases) in the oral-only arm-this difference was not statistically significant (p=0.703). The incidence of endophthalmitis with prophylaxis was 2-3%. Selected patients with open globe injuries (without high-risk features) may receive either intravenous cefazolin and oral ciprofloxacin, or oral cefuroxime and oral ciprofloxacin as prophylaxis against acute endophthalmitis-the latter regimen has the advantage of shortening patients' hospital stays and reducing costs. Non-inferiority study-design limitations should be taken into account, however. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study

    Science.gov (United States)

    Brodnicki, Elizabeth; Desai, Monica; McCormack, Sheena; Nutland, Will; Wayal, Sonali; White, Ellen; Wood, Gemma; Barber, Tristan; Bell, Gill; Clarke, Amanda; Dolling, David; Dunn, David; Fox, Julie; Haddow, Lewis; Lacey, Charles; Nardone, Anthony; Quinn, Killian; Rae, Caroline; Reeves, Iain; Rayment, Michael; White, David; Apea, Vanessa; Ayap, Wilbert; Dewsnap, Claire; Collaco-Moraes, Yolanda; Schembri, Gabriel; Sowunmi, Yinka; Horne, Rob

    2017-01-01

    Background PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. Methods Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. Results Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported ‘being deferred’ as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. Conclusion The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and

  3. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    OpenAIRE

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, def...

  4. A 10-Month, Open-Label Evaluation of Desvenlafaxine in Outpatients With Major Depressive Disorder

    Science.gov (United States)

    Pitrosky, Bruno; Padmanabhan, S. Krishna; Rosas, Gregory R.

    2011-01-01

    Background: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD). Method: Depressed adult outpatients (≥ 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings. Adverse events (AEs) and discontinuations due to AEs were monitored throughout the trial. The primary efficacy outcome was mean change from baseline on 17-item Hamilton Depression Rating Scale (HDRS-17) total score. The trial was conducted from August 2003 to March 2006. Results: The safety population included 1,395 patients who took at least 1 dose of open-label desvenlafaxine. Treatment-emergent AEs were reported by 1,238 of 1,395 patients (89%) during the open-label, on-therapy period. Treatment-emergent AEs reported by 10% or more patients were headache, nausea, hyperhidrosis, dizziness, dry mouth, insomnia, upper respiratory infection, nasopharyngitis, and fatigue. Adverse events were the primary reason for study discontinuation in 296 of 1,395 patients (21%). Ten patients (Desvenlafaxine can be safely administered for up to 12 months. No new safety findings were observed in this study. Trial Registration: clinicaltrials.gov Identifier: NCT01309542 PMID:21977353

  5. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    Science.gov (United States)

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-03-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. © 2016 The authors.

  6. Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial

    Directory of Open Access Journals (Sweden)

    Msika Simon

    2011-07-01

    Full Text Available Abstract Background Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma. Methods/Design The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A. Discussion Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery. Trial Registration NCT00937456 (ClinicalTrials.gov

  7. Sultone opening with [18F]fluoride: an efficient 18F-labelling strategy for PET imaging.

    Science.gov (United States)

    Schmitt, Sébastien; Bouteiller, Cédric; Barré, Louisa; Perrio, Cécile

    2011-11-01

    Sultones were subject to ring opening by nucleophilic attack with [(18)F]fluoride to afford easily purified (18)F-labelled hydrophilic sulfonated products in high yields. A two-step sequence including radiofluorination and coupling to lysine was then developed from a bis-sultone precursor as a model approach for the labelling of biopolymers.

  8. Systemic inflammatory responses during laparoscopic and open inguinal hernia repair: a randomised prospective study

    DEFF Research Database (Denmark)

    Jess, P; Schultz, Karen; Bendtzen, K

    2000-01-01

    To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed.......To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed....

  9. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    Science.gov (United States)

    Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

  10. A massive open online course (MOOC can be used to teach physiotherapy students about spinal cord injuries: a randomised trial

    Directory of Open Access Journals (Sweden)

    Mohammad S Hossain

    2015-01-01

    Full Text Available Question: Does a massive open online course (MOOC based around an online learning module about spinal cord injuries improve knowledge or confidence among physiotherapy students more than if physiotherapy students are left to work through the online learning module at their own pace. Which method of presenting the content leads to greater satisfaction among the students? Study design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty-eight physiotherapy students in Bangladesh. Intervention: Participants randomised to the control group were instructed to work at their own pace over a 5-week period through a physiotherapy-specific online learning module available at www.elearnSCI.org. Experimental participants were enrolled in a 5-week MOOC. The MOOC involved completing the same online learning module but experimental participants’ progress through the module was guided each week and they were provided with the opportunity to engage in online discussion through Facebook. Outcome measures: The primary outcome was knowledge, and the secondary outcomes were perceived confidence to treat people with spinal cord injuries and satisfaction with the learning experience. Results: The mean between-group difference for knowledge was 0.7 points (95% CI –1.3 to 2.6 on a 0 to 20-point scale. The equivalent results for perceived confidence and satisfaction with the learning experience were 0.4 points (95% CI –1.0 to 1.8 and 0.0 points (95% CI –1.1 to 1.2 on a 0 to 10-point scale. Conclusion: The MOOC was no better for students than working at their own pace through an online learning module for increasing knowledge, confidence or satisfaction. However, students in the MOOC group highlighted positive aspects of the course that were unique to their group, such as interacting with students from other countries through the MOOC Facebook group. Trial registration: ACTRN12614000422628. [Hossain MS, Islam

  11. Are open-Label Placebos Ethical? Informed Consent and Ethical Equivocations.

    Science.gov (United States)

    Blease, Charlotte; Colloca, Luana; Kaptchuk, Ted J

    2016-07-01

    The doctor-patient relationship is built on an implicit covenant of trust, yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.

  12. Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study.

    Science.gov (United States)

    Kluger, G; Glauser, T; Krauss, G; Seeruthun, R; Perdomo, C; Arroyo, S

    2010-09-01

    This open-label extension evaluated the long-term efficacy and tolerability of rufinamide in patients with Lennox-Gastaut syndrome (LGS) who had previously completed a 12-week double-blind study. In total, 124 patients (aged 4-37 years), receiving 1-3 concomitant antiepileptic drugs, were treated with rufinamide approximately 25-60 mg/kg/day. Efficacy was assessed by seizure frequency; tolerability by adverse events (AEs) and laboratory tests. Overall, patients were treated with rufinamide for a median (range) of 432 (10-1149) days. Reductions in seizure frequency were observed throughout the study; during the last 12 months of treatment, 41.0% and 47.9% of patients had > or = 50% reduction in total and tonic-atonic seizure frequency, respectively. The most common AEs were vomiting (30.6%) and pyrexia (25.8%). In this open-label extension, rufinamide appeared to be an effective long-term adjunctive therapy for the treatment of LGS-associated seizures in children and young adults.

  13. A massive open online course (MOOC) can be used to teach physiotherapy students about spinal cord injuries: a randomised trial.

    Science.gov (United States)

    Hossain, Mohammad S; Shofiqul Islam, Md; Glinsky, Joanne V; Lowe, Rachael; Lowe, Tony; Harvey, Lisa A

    2015-01-01

    Does a massive open online course (MOOC) based around an online learning module about spinal cord injuries improve knowledge or confidence among physiotherapy students more than if physiotherapy students are left to work through the online learning module at their own pace. Which method of presenting the content leads to greater satisfaction among the students? Randomised controlled trial with concealed allocation and intention-to-treat analysis. Forty-eight physiotherapy students in Bangladesh. Participants randomised to the control group were instructed to work at their own pace over a 5-week period through a physiotherapy-specific online learning module available at www.elearnSCI.org. Experimental participants were enrolled in a 5-week MOOC. The MOOC involved completing the same online learning module but experimental participants' progress through the module was guided each week and they were provided with the opportunity to engage in online discussion through Facebook. The primary outcome was knowledge, and the secondary outcomes were perceived confidence to treat people with spinal cord injuries and satisfaction with the learning experience. The mean between-group difference for knowledge was 0.7 points (95% CI -1.3 to 2.6) on a 0 to 20-point scale. The equivalent results for perceived confidence and satisfaction with the learning experience were 0.4 points (95% CI -1.0 to 1.8) and 0.0 points (95% CI -1.1 to 1.2) on a 0 to 10-point scale. The MOOC was no better for students than working at their own pace through an online learning module for increasing knowledge, confidence or satisfaction. However, students in the MOOC group highlighted positive aspects of the course that were unique to their group, such as interacting with students from other countries through the MOOC Facebook group. ACTRN12614000422628. Copyright © 2014. Published by Elsevier B.V.

  14. Open access follow-up care for early breast cancer: a randomised controlled quality of life analysis.

    Science.gov (United States)

    Kirshbaum, M N; Dent, J; Stephenson, J; Topping, A E; Allinson, V; McCoy, M; Brayford, S

    2017-07-01

    This study evaluated the acceptability of a supportive model of follow-up. One hundred and twelve women recovering from breast cancer were randomised to receive standard breast clinic aftercare (Control n = 56) or on demand by open access aftercare by breast care nurses (Intervention n = 56). Participants attended a support-based psycho-educational programme delivered in four half-day group sessions. Three quality of life questionnaires (EORTC QLQ-C30, QLQ-BR23, HADS) were administered at baseline and 6-monthly intervals for 2 years. Multilevel linear regression modelling methods were used for evaluation. Age was found to be a statistically significant predictor of quality of life in several sub-scales. Increasing age was negatively associated with sexual functioning, systematic therapy side effects and physical functioning, and positively associated with future perspective. Aftercare assignment was not found to be a statistically significant predictor. Women treated for early breast cancer were not disadvantaged by allocation to the open access supportive care model in terms of quality of life experienced. The model for follow-up was demonstrated to be a feasible alternative to routinised hospital-based follow-up and adds to the evidence for stratified follow-up for low-risk cancer patients, incorporating self-management education. Stratified follow-up pathways are viewed as a preferable approach. © 2016 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.

  15. Duloxetine in the treatment of major depressive disorder: an open-label study

    Directory of Open Access Journals (Sweden)

    Wang Fujun

    2007-08-01

    Full Text Available Abstract Background Major depressive disorder (MDD is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT and norepinephrine (NE may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined. Methods Patients (N = 533 meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD] for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17 total score ≥18 and a Clinical Global Impression of Severity (CGI-S score ≥4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I scale, Visual Analog Scales (VAS for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS. Quality of life was assessed using the Sheehan Disability Scale (SDS and the Quality of Life in Depression Scale (QLDS. Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF scale. Results The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of

  16. Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial).

    Science.gov (United States)

    Scarborough, Peter; Hodgkins, Charo; Raats, Monique M; Harrington, Richard A; Cowburn, Gill; Dean, Moira; Doherty, Aiden; Foster, Charlie; Juszczak, Edmund; Matthews, Anne; Mizdrak, Anja; Mhurchu, Cliona Ni; Shepherd, Richard; Tiomotijevic, Lada; Winstone, Naomi; Rayner, Mike

    2015-01-01

    Traffic light labelling of foods-a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods-has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions. The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial. The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be

  17. A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation.

    Science.gov (United States)

    White, William D; Crockford, David; Patten, Scott; El-Guebaly, Nady

    2005-10-01

    This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study. The primary outcome measure was smoking cessation. Secondary outcome measures included smoking reduction and withdrawal severity. Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects. Withdrawal severity was less with bupropion. Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation. Further study is required to determine if gabapentin has any useful role in smoking cessation. Based on our primary outcome measure, 79 subjects would be required in each treatment group of a two-armed study to achieve 90% power for detecting a difference in efficacy between gabapentin and bupropion.

  18. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Denton, C P; Engelhart, M; Tvede, N

    2008-01-01

    AIM: The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg...... of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred...... in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0...

  19. Open-label placebo treatment in chronic low back pain: a randomized controlled trial

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

    2016-01-01

    Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

  20. A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder.

    Science.gov (United States)

    Biederman, Joseph; Joshi, Gagan; Mick, Eric; Doyle, Robert; Georgiopoulos, Anna; Hammerness, Paul; Kotarski, Meghan; Williams, Courtney; Wozniak, Janet

    2010-04-01

    To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. This was a 12-week, open-label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Thirty-nine children with bipolar disorder (YMRS at entry: 31.6 +/- 5.5) were enrolled in the study and 22 (56%) completed the 12-week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 +/- 128.3 in subjects children 12-17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (-14.9 +/- 9.7, P disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 +/- 18.0 kg vs. 47.2 +/- 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Open-label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo-controlled, double-blind studies are warranted to confirm these findings.

  1. Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer

    NARCIS (Netherlands)

    Deijen, C.L. (Charlotte L.); Vasmel, J.E. (Jeanine E.); E.S.M. De Lange-De Klerk (E. S M); M.A. Cuesta (Miguel); P-P. Coene (Peter Paul); J.F. Lange (Johan); W.J.H.J. Meijerink (Jeroen); J.J. Jakimowicz; J. Jeekel (Hans); Kazemier, G. (Geert); Janssen, I.M.C. (Ignace M. C.); L. Påhlman (Lars); E. Haglind (Eva); H.J. Bonjer (H. Jaap); Hellberg, R.; Haglind, E.; Kurlberg, G.; P.G. Lindgren (P.); B. Lindholm (Bengt); L. Påhlman (Lars); C. Dahlberg (Caroline); M.S. Raab; B. Anderberg (Bo); Ewerth, S.; M. Janson (Martin); J.E. Åkerlund (J.); K. Smedh (K.); A. Montgomery; S. Skullman (Stefan); P.O. Nyström; A. Kald (A.); A. Wänström (A.); J. Dalén (Johan); I. Svedberg (I.); G. Edlund (G.); U. Kressner (U.); K. Öberg (Kjell); O. Lundberg (O.); G.E. Lindmark (G.); T. Heikkinen (T.); M. Morino (Mario); G. Giraudo (G.); Lacy, A.M.; S. Delgado (Salvadora); Macarulla Sanz, E.; Díez, J.M. (J. Medina); O. Schwandner (O.); T.H. Schiedeck (T.); Shekarriz, H.; Bloechle, C.; I. Baca (I.); Weiss, O.; S. Msika (Simon); G. Desvignes (G.); K.L. Campbell (K.); A. Cuschieri (A.); H.J. Bonjer (Jaap); W.R. Schouten (Ruud); G. Kazemier (Geert); J.F. Lange (Johan); E. van der Harst (Erwin); Coene, P.P.L.O.; P.W. Plaisier; M.J.O.E. Bertleff (Marietta); Cuesta, M.A.; W. van der Broek (W.); Meijerink, W.J.H.J.; J.J. Jakimowicz; G.A.P. Nieuwenhuijzen (Gerard); J.K. Maring (John); Kivit, J.; I.M.C. Janssen (Ignace); E.J. Spillenaar Bilgen (Ernst Jan); F.J. Berends (Frits)

    2016-01-01

    textabstractBackground: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch pa

  2. Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer

    NARCIS (Netherlands)

    Deijen, C.L. (Charlotte L.); Vasmel, J.E. (Jeanine E.); E.S.M. De Lange-De Klerk (E. S M); M.A. Cuesta (Miguel); P-P. Coene (Peter Paul); J.F. Lange (Johan); W.J.H.J. Meijerink (Jeroen); J.J. Jakimowicz; J. Jeekel (Hans); Kazemier, G. (Geert); Janssen, I.M.C. (Ignace M. C.); L. Påhlman (Lars); E. Haglind (Eva); H.J. Bonjer (H. Jaap)

    2016-01-01

    markdownabstractBackground: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the

  3. Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer

    NARCIS (Netherlands)

    Deijen, C.L.; Vasmel, J.E.; Lange-de Klerk, E.S. de; Cuesta, M.A.; Coene, P.L.O.; Lange, J.F.; Meijerink, W.J.H.J.; Jakimowicz, J.J.; Jeekel, J.; Kazemier, G.; Pahlman, L.; Haglind, E.; Bonjer, H.J.

    2017-01-01

    BACKGROUND: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients

  4. Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor.

    Science.gov (United States)

    Zhang, Bailin; Tamez-Vela, Juan Manuel; Solis, Steven; Bustamante, Gilbert; Peterson, Ralph; Rahman, Shafiqur; Morales, Andres; Tang, Liang; Ye, Jing Yong

    2013-01-01

    The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

  5. Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor

    Directory of Open Access Journals (Sweden)

    Bailin Zhang

    2013-01-01

    Full Text Available The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

  6. Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

    Science.gov (United States)

    Lecendreux, Michel; Berthier, Johanna; Corny, Jennifer; Bourdon, Olivier; Dossier, Claire; Delclaux, Christophe

    2017-01-01

    Study Objectives: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. Methods: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). Results: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg-treated patients achieved remission more rapidly than control patients. Commentary: A commentary on this article appears in this issue on page 363. Citation: Lecendreux M, Berthier J, Corny J, Bourdon O, Dossier C, Delclaux C. Intravenous immunoglobulin therapy in pediatric

  7. Six week open-label reboxetine treatment in children and adolescents with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Arabgol F

    2007-10-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a common psychiatric disorder among children and adolescents. This disorder causes difficulties in academic, behavioral, emotional, social and family performance. Stimulants show robust efficacy and a good safety profile in children with this disorder, but a significant percent of ADHD children do not respond adequately or cannot tolerate the associated adverse effects with stimulants. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention deficit hyperactivity disorder (ADHD."nMethods: Fifteen child and adolescent outpatients, aged 7 to 16 (Mean± SD=9.72±2.71 years, diagnosed with ADHD were enrolled in a six open-label study with reboxetine 4-6 mg/d. The principal measure of the outcome was the teacher and parent Attention Deficit Hyperactive Disorder Rating Scale (ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks of the medication started. Side effects questionnaire was used to detect side effects of reboxetine. Repeated measures Analysis of variance (ANOVA was done for comparison of Teacher and Parent ADHD Rating Scale scores during the intervention."nResults: Twelve of 15 (80% participants completed the treatment protocol. A significant decrease in ADHD symptoms on teacher (p=0.04 and parent (p=0.003 ADHD rating scale was noted. Adverse effects were mild to moderate in severity. The most common adverse effects were drowsiness/sedation and appetite decrease."nConclusion: The results of the current study suggest the effectiveness of reboxetine in the treatment of ADHD in children and adolescents. Double-blind, placebo-controlled studies and larger sample size with long duration of intervention are indicated to rigorously

  8. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

    NARCIS (Netherlands)

    Capelle, C.I. van; Beek, N.A. van der; Hagemans, M.L.; Arts, W.F.M.; Hop, W.C.J.; Lee, P.; Jaeken, J.; Frohn-Mulder, I.M.; Merkus, P.J.F.M.; Corzo, D.; Puga, A.C.; Reuser, A.J.J.; Ploeg, A.T. van der

    2010-01-01

    Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha-glucosidase. Treatment with recombinant human alpha-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response

  9. Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate

    DEFF Research Database (Denmark)

    Hengstman, G.J.; Bleecker, J.L. De; Feist, E.

    2008-01-01

    BACKGROUND/AIMS: To determine the efficacy of infliximab combined with weekly methotrexate in drug-naive recent-onset dermatomyositis and polymyositis. METHODS: A multicentre open-label controlled trial was conducted. Disease activity was assessed using patient's and physician's disease activity...

  10. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

    NARCIS (Netherlands)

    Capelle, C.I. van; Beek, N.A. van der; Hagemans, M.L.; Arts, W.F.M.; Hop, W.C.J.; Lee, P.; Jaeken, J.; Frohn-Mulder, I.M.; Merkus, P.J.F.M.; Corzo, D.; Puga, A.C.; Reuser, A.J.J.; Ploeg, A.T. van der

    2010-01-01

    Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha-glucosidase. Treatment with recombinant human alpha-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response

  11. An Open-Label Study of Aripiprazole : Pharmacokinetics, Tolerability, and Effectiveness in Children and Adolescents with Conduct Disorder

    NARCIS (Netherlands)

    Findling, Robert L.; Kauffman, Ralph; Sallee, Floyd R.; Salazar, Daniel E.; Sahasrabudhe, Vaishali; Kollia, Georgia; Kornhauser, David M.; Vachharajani, Nimish N.; Assuncao-Talbott, Sheila; Mallikaarjun, Suresh; Iwamoto, Taro; McQuade, Robert D.; Boulton, David W.; Blumer, Jeffrey

    2009-01-01

    Objectives: This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children and adolescents with conduct disorder (CD). Methods: This open-label, 15-day, three-center study with an optional 36-month extension enrolled a total of 23 patients: 12 children (6-

  12. An Open-Label Study of Aripiprazole : Pharmacokinetics, Tolerability, and Effectiveness in Children and Adolescents with Conduct Disorder

    NARCIS (Netherlands)

    Findling, Robert L.; Kauffman, Ralph; Sallee, Floyd R.; Salazar, Daniel E.; Sahasrabudhe, Vaishali; Kollia, Georgia; Kornhauser, David M.; Vachharajani, Nimish N.; Assuncao-Talbott, Sheila; Mallikaarjun, Suresh; Iwamoto, Taro; McQuade, Robert D.; Boulton, David W.; Blumer, Jeffrey

    Objectives: This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children and adolescents with conduct disorder (CD). Methods: This open-label, 15-day, three-center study with an optional 36-month extension enrolled a total of 23 patients: 12 children

  13. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa

    NARCIS (Netherlands)

    Olivennes, F.; Trew, G.; Borini, A.; Broekmans, F.; Arriagada, P.; Warne, D. W.; Howles, C. M.

    2015-01-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited (

  14. Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study.

    Science.gov (United States)

    Chen, Pei; Feng, Huiyu; Deng, Juan; Luo, Yufei; Qiu, Li; Ou, Changyi; Liu, Weibin

    2016-01-01

    Leflunomide is an effective drug used in the treatment of rheumatoid arthritis. Here we report the findings of an open-label pilot study, which found that leflunomide is also an effective treatment for myasthenia gravis (MG). This study recruited 15 corticosteroid-dependent MG patients. For 6 months, leflunomide 20 mg was given to these patients daily along with prednisone. The quantitative myasthenia gravis (QMG) scores and MG activities of daily living (MG-ADL) profiles were measured in these MG patients. After 6 months of treatment, 9 of the 15 patients enrolled in this study showed improvements in both QMG and MG-ADL. The mean QMG scores (13.4 to 8.5) and MG-ADL profiles (5.8 to 2.8) were significantly decreased (P = 0.01, 0.006 respectively). Furthermore, we found that the mean corticosteroid doses were reduced after treatment with leflunomide (24.3 to 12.3 mg per day). Leflunomide is a well-tolerated and efficacious treatment for corticosteroid-dependent MG, which may also enable lower doses of corticosteroids to be administered.

  15. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Sriram Ramaswamy

    2015-01-01

    Full Text Available Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS. RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS, Hamilton Depression Scale (HAM-D, Hamilton Anxiety Scale (HAM-A, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q, and Sheehan Disability Scale (SDS were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P<0.05, over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C and hyperarousal symptoms (CAPS-D, HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations.

  16. "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients.

    Science.gov (United States)

    Jackson, K; Ashby, M; Martin, P; Pisasale, M; Brumley, D; Hayes, B

    2001-10-01

    The results of a novel approach to the use of ketamine in refractory cancer pain are reported. In this prospective, multicenter, unblinded, open-label audit, 39 patients (with a total of 43 pains) received a short duration (3 to 5 days) ketamine infusion. The initial dose of 100 mg/24 hr was escalated if required to 300 mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response rate was 29/43 (67%). Analysis of results according to pain mechanisms showed that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared to respond, it is possible that another concurrent intervention may have contributed in whole or part for the pain relief observed. After cessation of ketamine, 24/29 maintained good pain control, with a maximum documented duration of eight weeks. However, 5 of the initial 29 responders experienced a recurrence of pain within 24 hours, and ketamine was recommenced. Of these, 2 underwent another intervention for pain control while 3 continued on ketamine until their deaths between two and four weeks later. Twelve patients reported adverse psychomimetic effects, with the incidence rising with increasing dose. Four of these were non-responders and the ketamine was stopped. Eight were responders, and in 3 the adverse effects were rendered acceptable with dose reduction; the other 5 rejected a dose reduction. The results reported suggest the need for further investigation of the place of ketamine in cancer pain management.

  17. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    Science.gov (United States)

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  18. Oral zinc sulfate treatment for viral warts: an open-label study.

    Science.gov (United States)

    Mun, Je-Ho; Kim, Su-Han; Jung, Do-Sang; Ko, Hyun-Chang; Kim, Byung-Soo; Kwon, Kyung-Sool; Kim, Moon-Bum

    2011-06-01

    Viral warts, which are caused by the human papilloma virus, are a common problem in dermatology. Various modalities have been used to treat warts, but none are uniformly effective or directly antiviral. Recent studies show that oral zinc sulfate could be effective in the treatment of viral warts. Thirty-one patients with multiple, non-genital viral warts were recruited in this open-label clinical study. The patients were treated with oral zinc sulfate (10 mg/kg to a maximum dose of 600 mg/day) for 2 months and followed up with assessments for the resolution of their warts and for any evidence of recurrence after treatment. Among the 31 patients, 18 patients showed low serum zinc levels (58%). Of 26 patients who completed the study (84%), 13 (50%) showed complete resolution of their warts after 2 months of treatment. Complete responders remained free of lesions at 6-month follow-up. No serious side-effects were reported apart from nausea (16%), mild gastric pain (3%) and itching sensation (3%). Oral zinc sulfate was found to be a good option in the treatment of viral warts, as it was safe and effective without important side-effects. © 2010 Japanese Dermatological Association.

  19. EFFICACY AND SAFETY OF SIMVASTATIN IN RHEUMATOID ARTHRITIS: AN OPEN-LABEL, CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    I. V. Shirinsky

    2008-01-01

    Full Text Available Abstract. Recently discovered immune–modulating and anti-inflammatory properties of statins have resulted in application of these drugs for treatment of autoimmune disorders. There are few studies investigating therapeutic potential of simvastatin in rheumatoid arthritis (RA. In present study, we investigated efficacy and safety of simvastatin in active RA patients treated with conventional disease-modifying antirheumatic drugs (DMARDs. Thirty-three patients were enrolled into an open-label, controlled study. The patients received treatment with 40 mg of simvastatin daily for 12 weeks. A group of historical controls consisted of nine patients taking placebo combined with disease-modifying therapy. No differences in demographic characteristics and disease activity were observed between the two groups. By the end of therapy (12 weeks, simvastatin-treated patients exhibited a significant reduction in disease activity scores with 28-joint counts (DAS28, and according to physician’s assessment of disease, as compared with control group. The estimate of trea tment effect (DAS28 scores was 0.76 (95% confidence interval 0.01-1.5, thus corresponding to moderate decrease in disease activity. In conclusion, combination therapy with simvastatin and conventional DMARDs results into decreased RA activity. However, additional studies are required in order to specify exact role of simvastatin in RA treatment. (Med. Immunol., vol. 10, N 4-5, pp 477-482.

  20. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial.

    Science.gov (United States)

    Nguyen, Liem Thanh; Nguyen, Anh Tuan; Vu, Chinh Duy; Ngo, Doan V; Bui, Anh V

    2017-04-12

    Stem cell therapy has emerged as a promising method for improving motor function of patients with cerebral palsy. The aim of this study is to assess the safety and effectiveness of autologous bone marrow mononuclear stem cell transplantation in patients with cerebral palsy related to oxygen deprivation. An open label uncontrolled clinical trial was carried out at Vinmec International Hospital. The intervention consisted of two administrations of stem cells, the first at baseline and the second 3 months later. Improvement was monitored at 3 months and 6 months after the first administration of stem cells, using the Gross Motor Function Measure (GMFM) and Modified Ashworth Score which measures muscle tone. No severe complications were recorded during the study. After transplantation, 12 patients encountered fever without infections and 9 patients experienced vomiting which was easily managed with medications. Gross motor function was markedly improved 3 months or 6 months after stem cell transplantation than at baseline. The post-transplantation GMFM-88 total score, each of its domains and the GMFM-66 percentile were all significantly higher (p-value  0.05). Autologous bone marrow mononuclear cell transplantation appears to be a safe and effective therapy for patients with cerebral palsy. ClinicalTrials.gov Identifier: NCT02569775 . Retrospectively registered on October 15, 2015.

  1. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    Science.gov (United States)

    Yari, Zahra; Rahimlou, Mehran; Eslamparast, Tannaz; Ebrahimi-Daryani, Naser; Poustchi, Hossein; Hekmatdoost, Azita

    2016-06-01

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

  2. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    Science.gov (United States)

    Ramaswamy, Sriram; Madabushi, Jayakrishna; Hunziker, John; Bhatia, Subhash C.; Petty, Frederick

    2015-01-01

    Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P < 0.05), over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C) and hyperarousal symptoms (CAPS-D), HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B) and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations. PMID:26064685

  3. Homoeopathic management of Schizophrenia: A prospective, non-comparative, open-label observational study

    Directory of Open Access Journals (Sweden)

    Praveen Oberai

    2016-01-01

    Full Text Available Objectives: To evaluate the usefulness of homoeopathic intervention in Schizophrenia, in untreated cases and antipsychotic treatment resistant cases, to verify indications of medicines, and to assess relapse, if any. Materials and Methods: A prospective, non-comparative, open-label observational study was carried out from October 2005-September 2010 by CCRH at Central Research Institute (H, Kottayam, Kerala, India. Patients between 20 and 60 years of age, presenting with symptoms of Schizophrenia were screened for inclusion and exclusion criteria. The patients who were on antipsychotic drugs were allowed to continue the same along with homoeopathic medicine, the dose of antipsychotics was monitored by the Psychiatrist. The symptoms of each patient were repertorized, and medicine was initially prescribed in 30C potency after consulting Materia Medica. Patients were followed up for 12 months. Outcome of treatment was assessed with Brief Psychiatric Rating Scales (BPRS. Analysis was done using Statistical Package for the Social Sciences  SPSS Version 20.0. Results: Out of 188 enrolled patients, 17 cases did not complete the baseline information. Total 171 patients were analysed as per modified Intention to Treat Principle. Significant difference (P = 0.0001, P < 0.05 in the mean scores of BPRS, using paired t test was observed at end of the study. Sulphur, Lycopodium, Natrum muriaticum, Pulsatilla and Phosphorus were found to be the most useful medicines in treating schizophrenic patients. Conclusion: The study reflects the positive role of homoeopathic medicines in the management of patients suffering from schizophrenia as measured by BPRS.

  4. Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Wolfgang Kruis; Robert L(o)fberg; Axel Dignass; Elisabeth Steinhagen-Thiessen; Julia Morgenstern; Joachim M(o)ssner; Stephan Schreiber; Maurizio Vecchi; Alberto Malesci; Max Reinshagen

    2005-01-01

    AIM:To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy.METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk).Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn(R), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life(IBDQ), and laboratory tests.RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01)at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia.CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

  5. An open-label conversion study of pramipexole to ropinirole prolonged release in Parkinson's disease.

    Science.gov (United States)

    Lyons, Kelly E; Pahwa, Rajesh

    2009-10-30

    Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved for the treatment of Parkinson's disease (PD). The goal of this 4 week, open-label study was to determine the most effective conversion ratio with the fewest adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty patients with PD taking pramipexole were converted overnight to ropinirole PR at ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to be well tolerated and AEs were typical for a dopamine agonist. The most common AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the majority of which resolved after dose adjustments. Thirteen subjects discontinued ropinirole PR before 4 weeks. These subjects were taking a significantly greater dose of pramipexole, the majority greater than 4 mg/day, and tended to have longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the fewest dose adjustments and the largest percentage of subjects that preferred ropinirole PR.

  6. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2013-01-01

    Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

  7. Open-label pilot study of memantine in the treatment of compulsive buying.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Mooney, Marc; O'Brien, Robert; Kim, Suck Won

    2012-05-01

    Although compulsive buying (CB) is relatively common, pharmacotherapy research for CB is limited. Memantine, an N-methyl-D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive behaviors, suggesting it may help individuals with CB. Nine patients (8 females) with CB were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/d). Participants were enrolled from December 2008 until May 2010. The primary outcome measure was change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (Y-BOCS-SV). Of the 9 participants, 8 (88.9%) completed the 10-week study. Y-BOCS-SV scores decreased from a mean of 22.0 ± 1.3 at baseline to 11.0 ± 5.3 at endpoint (P buying and improvements on cognitive tasks of impulsivity. In addition, the medication was well-tolerated. These findings suggest that pharmacologic manipulation of the glutamate system may target the impulsive behavior underlying CB. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

  8. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

    Science.gov (United States)

    Lally, Níall; Nugent, Allison C; Luckenbaugh, David A; Niciu, Mark J; Roiser, Jonathan P; Zarate, Carlos A

    2015-05-01

    Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC. © The Author(s) 2015.

  9. Open-label study of duloxetine for the treatment of obsessive-compulsive disorder.

    Science.gov (United States)

    Dougherty, Darin D; Corse, Andrew K; Chou, Tina; Duffy, Amanda; Arulpragasam, Amanda R; Deckersbach, Thilo; Jenike, Michael A; Keuthen, Nancy J

    2015-01-01

    This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (Pobsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (Pobsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  10. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

    NARCIS (Netherlands)

    Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

    2008-01-01

    Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial conduc

  11. Rufinamide for refractory focal seizures: an open-label, multicenter European study.

    Science.gov (United States)

    Coppola, Giangennaro; Zamponi, Nelia; Kluger, Gerhard; Mueller, Arndt; Anna Rita, Mazzotta; Parisi, Pasquale; Isone, Claudia; Santoro, Elena; Curatolo, Paolo; Verrotti, Alberto

    2013-01-01

    The present study aimed to assess the efficacy and tolerability of rufinamide as adjunctive drug for the treatment of a large series of children, adolescents and adults with refractory cryptogenic or symptomatic focal epilepsy. Patients were recruited in a prospective, add-on, open-label treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care. Inclusion criteria were: (1) age 3 years or more; (2) diagnosis of cryptogenic or symptomatic focal epilepsy refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than one seizure per month in the last 6 months; (4) use of at least one other AED, but no more than three, at baseline; (5) informed consent from parents and/or caregivers. Sixty-eight patients (40 males, 28 females), aged between 3 and 63 years (mean 19.9 years, median 16.0)±SD 12.58, with cryptogenic (28 pts, 41.2%) or symptomatic focal epilepsy (40 pts, 58.8%), were recruited in the study. After a mean follow-up period of 10.4±10.29 months, twenty-two patients (32.3%) had a 50-99% seizure reduction, and none became seizure-free. Twelve patients (17.6%) had a 25-49% seizure decrease, while in 30 (44.1%) seizure frequency was unchanged. A seizure worsening was reported in 5 patients (7.3%). A better response to rufinamide occurred in frontal lobe seizures (51.6%) and secondary generalized tonic-clonic seizures (50%). Rufinamide was effective against focal-onset seizures, particularly in the treatment of secondary generalized frontal lobe seizures. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study.

    Science.gov (United States)

    Stryjer, Rafael; Budnik, Dana; Ebert, Tania; Green, Tamar; Polak, Lea; Weizman, Shira; Spivak, Baruch

    2014-01-01

    It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.

  13. Dexmedetomidine versus propofol in dilatation and curettage: An open-label pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Sethi

    2015-01-01

    Full Text Available Background: Traditionally propofol has been used for providing sedation in dilatation and curettage (D and C. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Aims: The aim was to compare hemodynamic and recovery profile of both the drugs along with a degree of comfort experienced by patients and the usefulness of the drug to surgeons. Settings and Design: Tertiary care center and open-label randomized controlled trial. Materials and Methods: Patients posted for D and C were enrolled in two groups (25 each. Both groups received fentanyl 1 μg/kg intravenous (IV at the beginning of the procedure. Group P received IV propofol in dose of 1.5 mg/kg over 10-15 min and Group D received dexmedetomidine at a loading dose of 1 μg/kg over 10 min, followed by 0.5 μg/kg/h infusion until Ramsay sedation score reached 3-4. Hemodynamic vitals were compared during and after the procedure. In the recovery room time to reach modified Aldrete score (MAS of 9-10 and patient′s and surgeon′s satisfaction scores were also recorded and compared. Results: In Group D, patients had statistically significant lower heart rate at 2, 5, 10 and 15 min as compared to Group P. Hypotension was present in 52% in Group P and 4% in Group D (P < 0.05. MAS of 9-10 was achieved in 4.4 min in subjects in Group D in contrast to 16.2 min in Group P (P < 0.05. Group D showed higher patient and surgeon satisfaction scores (P < 0.05. Conclusion: Dexmedetomidine provide better hemodynamic and recovery profile than propofol. It can be a superior alternative for short surgical day care procedures.

  14. An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome.

    Science.gov (United States)

    Grieco, Joseph C; Ciarlone, Stephanie L; Gieron-Korthals, Maria; Schoenberg, Mike R; Smith, Amanda G; Philpot, Rex M; Heussler, Helen S; Banko, Jessica L; Weeber, Edwin J

    2014-12-10

    Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder. Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period. The clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted. NCT01531582 - clinicaltrials.gov.

  15. A 10-month, open-label evaluation of desvenlafaxine in Japanese outpatients with major depressive disorder.

    Science.gov (United States)

    Tourian, Karen; Wang, Ying; Ii, Yoichi

    2013-07-01

    The objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day). Japanese patients with MDD who had completed an 8-week, double-blind, placebo-controlled study in which patients received 25 or 50 mg/day desvenlafaxine or placebo were enrolled. In this study, patients received desvenlafaxine 25 mg/day from days 1 to 14, with subsequent upward titration, to a maximum of 100 mg/day, determined by clinical response. Of 304 patients, 75 (24.7%) discontinued during the on-therapy period; patient request was the most common reason (11.5%). Treatment-emergent adverse events were reported by 240 patients (78.9%) during the on-therapy period; the most common adverse events were nasopharyngitis (37.2%), somnolence (11.5%), headache (10.5%), and nausea (10.2%). For the ITT-LOCF population, the mean change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was -4.76 (95% confidence interval: -5.47 to -4.05); continued numerical improvements in the HAM-D₁₇ total scores and other depression outcome measures were observed irrespective of treatment in the previous study. Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations.

  16. Nerve Growth Factor for the Treatment of Spinocerebellar Ataxia Type 3: An Open-label Study

    Institute of Scientific and Technical Information of China (English)

    Song Tan; Rui-Hao Wang; Hui-Xia Niu; Chang-He Shi; Cheng-Yuan Mao; Rui Zhang; Bo Song

    2015-01-01

    Background:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide,and runs a slowly progressive and unremitting disease course.There is currently no curable treatment available.Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases,and possibly also in SCA3.The objective of this study was to test the efficacy of NGF in SCA3 patients.Methods:We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients.NGF was administered by intramuscular injection (18 μg once daily) for 28 days consecutively.All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA).Results:Twenty-one SCA3 patients (10 men and 11 women,mean age 39.14 ± 7.81 years,mean disease duration 4.14 ± 1.90 years,mean CAG repeats number 77.57 ± 2.27) were enrolled.After 28 days of NGF treatment,the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001).Subsections SARA scores also showed significant improvements in stance (P =0.003),speech (P =0.023),finger chase (P =0.015),fast alternating hand movements (P =0.009),and heel-shin slide (P =0.001).Conclusions:Our preliminary data suggest that NGF may be effective in treating patients with SCA3.

  17. An open-label study of quetiapine in the treatment of fibromyalgia.

    Science.gov (United States)

    Hidalgo, Javier; Rico-Villademoros, Fernando; Calandre, Elena Pita

    2007-01-30

    The aim of this exploratory study was to systematically assess the potential effectiveness and tolerability of quetiapine, an atypical antipsychotic, for the treatment of patients with fibromyalgia. This was a unicentre, open-label study conducted in thirty-five outpatients, 18 years or older, who met the ACR criteria for fibromyalgia and who had not satisfactorily responded to their previous fibromyalgia treatment. Quetiapine, flexibly dosed (25-100 mg/day), was added to their original treatment regimen for 12 weeks. The primary outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) total score. Secondary efficacy measures included mean changes from baseline to endpoint in the scores of the Clinical Global Impression (CGI) of Severity scale, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), 12-Item Short Form Health Survey (SF-12), and individual items of the FIQ. Thirty (85.7%) patients (mean age 47+/-7.9, 93.3% females) had a postbaseline evaluation and constituted the intent-to-treat efficacy sample. Mean FIQ total score decreased significantly by 10.2 points from a baseline of 63.2 to 53.0 at study endpoint (pfatigue subscores but not in FIQ pain subscore. Large effect sizes were observed for the FIQ total (1.04), CGI-severity (1.00) and PSQI (1.07), while moderate effect sizes (i.e.> or =0.50) were encountered in the FIQ fatigue, FIQ stiffness and SF-12 mental component summary. Quetiapine was safely administered and well tolerated. Despite the lack of effect on pain, the significant and relevant improvement in overall efficacy measures and quality of life suggests that quetiapine may be a valuable drug for treatment of patients with fibromyalgia that should be further tested in double-blind, placebo-controlled trials.

  18. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

    Science.gov (United States)

    Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

    2016-07-01

    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

  19. Efficacy and safety of tolterodine in subjects with symptoms of overactive bladder: An open label, noncomparative, prospective, multicentric study

    OpenAIRE

    Anant Kumar

    2002-01-01

    Objective: To evaluate the clinical efficacy and safety of Tolterodine 2 mg twice daily in Indian subjects with symptoms of overactive bladder including frequency, ur-gency with or without urge incontinence. Methods: This multicentric open-label, noncompara-tive, prospective study was conducted at 7 centers across India. Eligible patients were assigned to treatment with Tab. Tolterodine 2 mg twice daily for 8 weeks. Subjects were seen at visit ](day 3 to 10), visit 2 (day 1) and after 8...

  20. An open-label,randomized,cross-over bioequivalence study of lafutidine 10 mg under fasting condition

    Institute of Scientific and Technical Information of China (English)

    Bhupesh; Dewan; Raghuram; Chimata

    2010-01-01

    AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.

  1. Safety of long-term use of linezolid: results of an open-label study

    Directory of Open Access Journals (Sweden)

    Vazquez JA

    2016-09-01

    Full Text Available Jose A Vazquez,1 Anthony C Arnold,2 Robert N Swanson,3 Pinaki Biswas,3 Matteo Bassetti4 1Section of Infectious Diseases, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2UCLA Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA, USA; 3Clinical Research, Global Innovative Pharmaceutical, Pfizer Inc., New York, NY, USA; 4Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Objective: The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods: This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results: The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days. In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk

  2. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOSan open-label, international, randomised controlled trial-1): an open-label, international, randomised controlled trial

    DEFF Research Database (Denmark)

    Marina, Neyssa M; Smeland, Sigbjørn; Bielack, Stefan S

    2016-01-01

    doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. INTERPRETATION: EURAMOS-1...

  3. Cervical radiculopathy: Study protocol of a randomised clinical trial evaluating the effect of mobilisations and exercises targeting the opening of intervertebral foramen [NCT01500044

    Directory of Open Access Journals (Sweden)

    Langevin Pierre

    2012-01-01

    Full Text Available Abstract Background Cervical radiculopathy is a common form of neck pain and has been shown to lead to severe disability. Clinical rehabilitation approaches for cervical radiculopathies commonly include exercise and manual therapy interventions targeting the opening of intervertebral foramen, but evidence regarding their effectiveness is scarce. The primary objective of this randomised clinical trial is to compare, in terms of pain and disability, a rehabilitation program targeting the opening of intervertebral foramen to a conventional rehabilitation program, for patients presenting acute or subacute cervical radiculopathies. The hypothesis is that the rehabilitation program targeting the opening of intervertebral foramen will be significantly more effective in reducing pain and disability than the conventional rehabilitation program. Methods/Design This study is a double-blind (participants and evaluators blinded randomised clinical trial that will allow the comparison of patients with a cervical radiculopathy randomly assigned to one of two groups: one group will receive a 4-week rehabilitation program targeting the opening of intervertebral foramen, and the second group will receive a 4-week conventional rehabilitation program. Thirty-six subjects with cervical radiculopathy will be recruited from participating medical and physiotherapy clinics and will be evaluated at baseline, at the end of the 4-week program and four weeks following the end of the program. The primary outcome measure will be the validated Neck Disability Index questionnaire. Secondary outcome measures will include the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire, a numerical pain rating scale, cervicothoracic mobility and patients' perceived global rating of change. During the 4-week rehabilitation program, each participant will take part in eight physiotherapy treatment sessions (2 session/week and will perform a home exercise program. A

  4. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial.

    NARCIS (Netherlands)

    Ruslami, R.; Ganiem, A.R.; Dian, S.; Apriani, L.; Achmad, T.H.; Ven, A.J.A.M. van der; Borm, G.F.; Aarnoutse, R.E.; Crevel, R. van

    2013-01-01

    BACKGROUND: Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting. M

  5. Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study) : an open-label, multicentre, randomised controlled trial

    NARCIS (Netherlands)

    Mol, Femke; van Mello, Norah M.; Strandell, Annika; Strandell, Karin; Jurkovic, Davor; Ross, Jackie; Barnhart, Kurt T.; Yalcinkaya, Tamer M.; Verhoeve, Harold R.; Graziosi, Giuseppe C. M.; Koks, Carolien A. M.; Klinte, Ingmar; Hogstrom, Lars; Janssen, Ineke C. A. H.; Kragt, Harry; Hoek, Annemieke; Trimbos-Kemper, Trudy C. M.; Broekmans, Frank J. M.; Willemsen, Wim N. P.; Ankum, Willem M.; Mol, Ben W.; van Wely, Madelon; van der Veen, Fulco; Hajenius, Petra J.

    2014-01-01

    Background Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred

  6. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II) : an open-label randomised trial

    NARCIS (Netherlands)

    Klazen, Caroline A. H.; Lohle, Paul N. M.; de Vries, Jolanda; Jansen, Frits H.; Tielbeek, Alexander V.; Blonk, Marion C.; Venmans, Alexander; van Rooij, Willem Jan J.; Schoemaker, Marinus C.; Juttmann, Job R.; Lo, Tjoen H.; Verhaar, Harald J. J.; van der Graaf, Yolanda; van Everdingen, Kaspar J.; Muller, Alex F.; Elgersma, Otto E. H.; Halkema, Dirk R.; Fransen, Hendrik; Janssens, Xavier; Buskens, Erik; Mali, Willem P. Th M.

    2010-01-01

    Background Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compare

  7. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

    Directory of Open Access Journals (Sweden)

    Fornaro M

    2013-02-01

    Full Text Available Michele Fornaro,1 Michael J McCarthy,2,3 Domenico De Berardis,4 Concetta De Pasquale,1 Massimo Tabaton,5 Matteo Martino,6 Salvatore Colicchio,7 Carlo Ignazio Cattaneo,8 Emanuela D'Angelo,9 Pantaleo Fornaro61Department of Formative Sciences, University of Catania, Catania, Italy; 2Department of Psychiatry, Veteran's Affairs San Diego Healthcare System, 3University of California San Diego, La Jolla, CA, USA; 4Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "ASL 4", Teramo, Italy; 5Department of Internal Medicine and Medical Specialties, University of Genova, Genoa, Italy; 6Department of Neurosciences, Section of Psychiatry, University of Genova, Genoa, Italy; 7Unit of Sleep Medicine, Department of Neuroscience, Catholic University, Rome, Italy; 8National Health System, "ASL 13", Novara, Italy; 9National Health System, "ASL 3", Genoa, ItalyPurpose: The circadian rhythm hypothesis of bipolar disorder (BD suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute or II cases of bipolar depression.Patients and methods: Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale–Bipolar Version, Young Mania Rating Scale, and body mass index.Results: Intent to treat analysis results demonstrated that 18 of the 28 subjects (64% showed medication response after 6 weeks (primary study endpoint, while 24 of the 28 subjects (86% responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6% valproate and six of the 11 (54.5% lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4% and 10 lithium

  8. Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

    Science.gov (United States)

    Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

    2017-08-01

    Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p Epilepsy.

  9. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  10. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial.

    Science.gov (United States)

    2015-06-13

    The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590. Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassified the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; pcoronary heart disease increased (1·09, 1·02-1·17; p=0·0172), the certainty increased (1·79, 1·62-1·96; pcoronary heart disease. This changed planned investigations (15% vs 1%; pcoronary heart disease, CTCA clarifies the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funded the trial

  11. A parallel group randomised open blinded evaluation of Acceptance and Commitment Therapy for depression after psychosis: Pilot trial outcomes (ADAPT).

    Science.gov (United States)

    Gumley, Andrew; White, Ross; Briggs, Andy; Ford, Ian; Barry, Sarah; Stewart, Corinna; Beedie, Sara; McTaggart, Jacqueline; Clarke, Caoimhe; MacLeod, Rachel; Lidstone, Emma; Riveros, Bruno Salgado; Young, Robin; McLeod, Hamish

    2017-05-01

    Depression is one of the major contributors to poorer quality of life amongst individuals with psychosis and schizophrenia. The study was designed as a Pilot Trial to determine the parameters of a larger, definitive pragmatic multi-centre randomised controlled trial of Acceptance and Commitment Therapy for depression after psychosis (ACTdp) for individuals with a diagnosis of schizophrenia who also meet diagnostic criteria for major depression. Participants were required to meet criteria for schizophrenia and major depression. Blinded follow-ups were undertaken at 5-months (end of treatment) and at 10-months (5-months posttreatment). Primary outcomes were depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck Depression Inventory (BDI). A total of 29 participants were randomised to ACTdp + Standard Care (SC) (n=15) or SC alone (n=14). We did not observe significant differences between groups on the CDSS total score at 5-months (Coeff=-1.43, 95%CI -5.17, 2.32, p=0.45) or at 10-months (Coeff=1.8, 95%CI -2.10, 5.69, p=0.36). In terms of BDI, we noted a statistically significant effect in favour of ACTdp+SC at 5-months (Coeff=-8.38, 95%CI -15.49, -1.27, p=0.02) but not at 10-months (Coeff=-4.85, 95%CI -12.10, 2.39, p=0.18). We also observed significant effects on psychological flexibility at 5-months (Coeff=-8.83, 95%CI -14.94, -2.71, ptherapy with depression as the primary outcome, ACT is a promising intervention for depression in the context of psychosis. A further large-scale definitive randomised controlled trial is required to determine effectiveness. ISRCTN: 33306437. Copyright © 2016. Published by Elsevier B.V.

  12. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Berlant Jeffrey L

    2004-08-01

    Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

  13. Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study.

    Science.gov (United States)

    Coelho, Claudia; Figueiredo, Ricardo; Frank, Elmar; Burger, Julia; Schecklmann, Martin; Landgrebe, Michael; Langguth, Berthold; Elgoyhen, Ana Belen

    2012-01-01

    Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open-label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials.

  14. Pregabalin augmentation of antidepressants in older patients with comorbid depression and generalized anxiety disorder-an open-label study.

    Science.gov (United States)

    Karaiskos, Dimitrios; Pappa, Dimitra; Tzavellas, Elias; Siarkos, Kostas; Katirtzoglou, Everina; Papadimitriou, George N; Politis, Antonios

    2013-01-01

    The objective of this 12-week open-label study was to evaluate the efficacy, safety, and tolerability of pregabalin as an adjunctive treatment to antidepressants in older patients suffering from depression and comorbid generalized anxiety disorder (GAD). The initial sample of this open-label study consisted of 94 older patients fulfilling criteria for depression with comorbid GAD who were treated with antidepressants. Twenty of them who had received antidepressant monotherapy for an adequate time and shown partial response to the antidepressant prescribed, in terms of either anxiety or depressive symptomatology, followed the next phase. During the 12-week study period, pregabalin was gradually added to the previously prescribed antidepressant, reaching 225 mg/day over 4 weeks. Depression and anxiety scores as well as side effects were monitored. Within groups, differences of depression and anxiety scores at baseline and during the following 12 weeks of treatment were estimated with repeated-measure analysis of variance. A statistical significant reduction in depression scores was observed after the 4th week of treatment (p anxiety scores, a statistically significant improvement was noted between the 2nd and 4th weeks (p anxiety and depressive symptomatology significantly improved, and minimal side effects were observed. Copyright © 2012 John Wiley & Sons, Ltd.

  15. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopatholog......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...... causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration...

  16. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

    Science.gov (United States)

    Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

    2015-01-01

    Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  17. Mesh fixation methods in open inguinal hernia repair: a protocol for network meta-analysis and trial sequential analysis of randomised controlled trials

    Science.gov (United States)

    Ge, Long; Tian, Jin-hui; Li, Lun; Wang, Quan; Yang, Ke-hu

    2015-01-01

    Introduction Randomised clinical trials (RCTs) have been used to compare and evaluate different types of mesh fixation usually employed to repair open inguinal hernia. However, there is no consensus among surgeons on the best type of mesh fixation method to obtain optimal results. The choice often depends on surgeons’ personal preference. This study aims to compare different types of mesh fixation methods to repair open inguinal hernias and their role in the incidences of chronic groin pain, risk of hernia recurrence, complications, operative time, length of hospital stay and postoperative pain, using Bayesian network meta-analysis and trial sequential analysis of RCTs. Methods and analysis A systematic search will be performed using PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM) and Chinese Journal Full-text Database, to include RCTs of different mesh fixation methods (or fixation vs no fixation) during open inguinal hernia repair. The risk of bias in included RCTs will be evaluated according to the Cochrane Handbook V.5.1.0. Standard pairwise meta-analysis, trial sequential analysis and Bayesian network meta-analysis will be performed to compare the efficacy of different mesh fixation methods. Ethics and dissemination Ethical approval and patient consent are not required since this study is a meta-analysis based on published studies. The results of this network meta-analysis and trial sequential analysis will be submitted to a peer-reviewed journal for publication. Protocol registration number PROSPERO CRD42015023758. PMID:26586326

  18. An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

    Directory of Open Access Journals (Sweden)

    Pandina Gahan

    2012-06-01

    Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

  19. Rifaximin Is Effective for the Treatment of Clostridium difficile—Associated Diarrhea: Results of an Open-Label Pilot Study

    Directory of Open Access Journals (Sweden)

    David T. Rubin

    2011-01-01

    Full Text Available Objectives. This open-label trial assessed the efficacy and safety of rifaximin as first-line therapy in hospitalized patients with Clostridium difficile-associated diarrhea (CDAD. Methods. We enrolled thirteen patients who had a confirmed diagnosis of CDAD characterized by ≥3 unformed stools/day and positive C. difficile toxin assay. Those patients received rifaximin 400 mg three times daily for 10 days. Resolution of symptoms, repeat assay 10 days after treatment, and followup for recurrence were assessed. Results. Eight patients completed the study, and all reported symptom resolution during treatment. Mean time to last unformed stool was 132 h ± 42.5 h. Seven patients had no relapse by week 2 and in longer followup (median 162 days. One patient had recurrent CDAD during a repeat hospitalization. Conclusions. Rifaximin was effective and safe as first-line treatment for CDAD and did not result in recurrence in most patients.

  20. The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

    Directory of Open Access Journals (Sweden)

    Fresan Ana

    2005-05-01

    Full Text Available Abstract Background The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D2/D3-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. Method Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. Results The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d was well-tolerated without treatment-emergent extrapyramidal side-effects. Conclusion Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia.

  1. Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Berman R

    2011-05-01

    Full Text Available Robert M Berman1, Michael E Thase2, Madhukar H Trivedi3, James A Hazel4, Sabrina Vogel Marler5, Robert D McQuade6, William Carson7, Ross A Baker8, Ronald N Marcus91Neuroscience Global Clinical Research Bristol-Myers Squibb, Wallingford, CT, USA; 2Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 3Division of Mood Disorders Research Program and Clinic, University of Texas Southwestern Medical School, Dallas, TX, USA; 4Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USA; 5Global Biometric Sciences, Bristol-Myers Squibb, Wallingford, CT, USA; 6Global Medical Affairs at Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 7Global Clinical Development, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, NJ, USA; 8Neuroscience Medical Strategy, Bristol-Myers Squibb Company, Plainsboro, NJ, USA; 9Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USABackground: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting.Patients and methods: Patients (n = 706 completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296 nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received open-label aripiprazole for up to 52 weeks.Results: Open-label treatment was completed by 323 patients (32.2%. At endpoint (n = 987, the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients spontaneously reported adverse events were akathisia (26.2%, fatigue (18.0%, and weight gain (17.1%. The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%; all resolved within 45 days of drug

  2. Topical tretinoin 0.1% for pregnancy-related abdominal striae: an open-label, multicenter, prospective study.

    Science.gov (United States)

    Rangel, O; Arias, I; García, E; Lopez-Padilla, S

    2001-01-01

    In an open-label, multicenter, prospective study, 20 women applied tretinoin (retinoic acid) cream 0.1% daily for 3 months to pregnancy-related stretch marks in the abdominal area. Efficacy was evaluated by analysis of one preselected target lesion, which was rated on a six-point scale (-1 = worse to 4 = cleared). At week 12, significant global improvement was noted from baseline in all stretch marks, and the target lesion decreased in length by 20% (P = .01). Erythema and scaling, the most common adverse events, occurred in 11 patients, decreased in severity after the first month of treatment, and were controlled with continued application of tretinoin and petroleum jelly ointment. In this small study, topical application of tretinoin significantly improved the clinical appearance of pregnancy-related stretch marks.

  3. Daily subcutaneous parecoxib injection for cancer pain: an open label pilot study.

    Science.gov (United States)

    Kenner, David J; Bhagat, Sandeep; Fullerton, Sonia L

    2015-04-01

    Nonsteroidal anti-inflammatory analgesics (NSAIDs) are useful in cancer pain but the specific use of subcutaneous parecoxib has not been previously reported. This pilot study aimed to establish the efficacy and side effect profile of short-term sequential single daily dose subcutaneous parecoxib sodium in patients with severe cancer bone pain. Nineteen hospitalized patients with advanced cancer and uncontrolled malignant bone pain (9 males, 10 females) received 24 courses of one, two, or three days sequential therapy with 'off-label' daily subcutaneous parecoxib. All patients were receiving opioid therapy; the median baseline daily oral equivalent dose (OED) of morphine was 180 mg. Pain was assessed at baseline, 24 hours, 48 hours, and 72 hours. Pain scores as assessed on an 11-point numeric pain rating scale (NPRS), any side effects including subcutaneous site reactions, as well as patient satisfaction rating with analgesia were recorded. A clinically significant decrease in pain scores was defined as a reduction of two or more points on the NPRS. Median pain score of all patient treatments decreased from 7 to 4.5 at 24 hours (pSubcutaneous site reactions occurred in 2 (8%) treatments and were mild and self limiting. Short-term daily subcutaneous parecoxib injection was effective for malignant bone pain when added to existing analgesic therapy and was well tolerated. Further research is warranted into the short-term use of parecoxib in hospitalized patients with intractable malignant bone pain.

  4. Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

    Science.gov (United States)

    Stryjer, Rafael; Dambinsky, Yael; Timinsky, Igor; Green, Tamar; Kotler, Moshe; Weizman, Abraham; Spivak, Baruch

    2013-03-01

    The current data suggest that up to 50% of patients with schizophrenia have obsessive-compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive-compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks' duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21-61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

  5. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

    NARCIS (Netherlands)

    Boeree, M.J.; Heinrich, N.; Aarnoutse, R.; Diacon, A.H.; Dawson, R.; Rehal, S.; Kibiki, G.S.; Churchyard, G.; Sanne, I.; Ntinginya, N.E.; Minja, L.T.; Hunt, R.D.; Charalambous, S.; Hanekom, M.; Semvua, H.H.; Mpagama, S.G.; Manyama, C.; Mtafya, B.; Reither, K.; Wallis, R.S.; Venter, A.; Narunsky, K.; Mekota, A.; Henne, S.; Colbers, A.; Balen, G.P. van; Gillespie, S.H.; Phillips, P.P.; Hoelscher, M.

    2017-01-01

    BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South A

  6. Efficacy and tolerability of urate-lowering drugs in gout : a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

    NARCIS (Netherlands)

    Reinders, Mattheus; van Roon, E.N.; Jansen, T.L.; Delsing, J.; Griep, E.N.; Hoekstra, M.; van de Laar, M.F.; Brouwers, J.R.

    Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised

  7. Efficacy and tolerability of urate-lowering drugs in gout : a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

    NARCIS (Netherlands)

    Reinders, Mattheus; van Roon, E.N.; Jansen, T.L.; Delsing, J.; Griep, E.N.; Hoekstra, M.; van de Laar, M.F.; Brouwers, J.R.

    2009-01-01

    Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised

  8. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study.

    Science.gov (United States)

    Weinreb, Robert N; Ong, Tuyen; Scassellati Sforzolini, Baldo; Vittitow, Jason L; Singh, Kuldev; Kaufman, Paul L

    2015-06-01

    To assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension. Randomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28. Of the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%-0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments. LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated. NCT01223378. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. An open-label trial of risperidone and fluoxetine in children with autistic disorder

    Directory of Open Access Journals (Sweden)

    Desousa Avinash

    2010-01-01

    Full Text Available Objective: Various studies have shown the effectiveness of risperidone and fluoxetine in the management of behavioral problems in autism. Aim: The purpose of this study was to compare these two drugs in the management of behavioral problems in autism. Materials and Methods: Forty children with autism were divided into 2 groups in a 16-week open trial that compared these two drugs. Parents rated the children using the Aberrant Behavior Checklist (ABC and the Conners′ Parent Rating Scale - Revised (CPRS-R. The author rated the children using the Children′s Psychiatric Rating Scale and Clinical Global Impression (CGI Scale. Results: The risperidone group showed significant improvement in areas like irritability and hyperactivity, while the fluoxetine group showed significant improvement in speech deviance, social withdrawal and stereotypy. When the two drugs were compared, fluoxetine showed greater improvement in stereotypy, while both drugs showed improvement on the general autism scale; and on anger, hyperactivity and irritability scales. Conclusions : In this open trial, both drugs were well tolerated and appeared to be beneficial in the treatment of common behavioral problems in children with autism. Further controlled and double-blind studies in larger samples are warranted.

  10. A 12-Week Exercise Program for Pregnant Women with Obesity to Improve Physical Activity Levels: An Open Randomised Preliminary Study.

    Directory of Open Access Journals (Sweden)

    Michèle Bisson

    Full Text Available To evaluate whether a 12-week supervised exercise program promotes an active lifestyle throughout pregnancy in pregnant women with obesity.In this preliminary randomised trial, pregnant women (body mass index ≥ 30 kg/m2 were allocated to either standard care or supervised training, from 15 to 27 weeks of gestation. Physical activity was measured by accelerometry at 14, 28 and 36 weeks, while fitness (oxygen consumption (VO2 at the anaerobic threshold, nutrition (caloric intake and macronutrients percentage and anthropometry were assessed at 14 and 28 weeks of gestation. Analyses were performed using repeated measures ANOVA.A total of fifty (50 women were randomised, 25 in each group. There was no time-group interaction for time spent at moderate and vigorous activity (pinteraction = 0.064, but the exercise group's levels were higher than controls' at all times (pgroup effect = 0.014. A significant time-group interaction was found for daily physical activity (p = 0.023; similar at baseline ((22.0 ± 6.7 vs 21.8 ± 7.3 x 10(4 counts/day the exercise group had higher levels than the control group following the intervention ((22.8 ± 8.3 vs 19.2 ± 4.5 x 10(4 counts/day, p = 0.020 and at 36 weeks of gestation ((19.2 ± 1.5 vs 14.9 ± 1.5 x 10(4 counts/day, p = 0.034. Exercisers also gained less weight than controls during the intervention period despite similar nutritional intakes (difference in weight change = -0.1 kg/week, 95% CI -0.2; -0.02, p = 0.016 and improved cardiorespiratory fitness (difference in fitness change = 8.1%, 95% CI 0.7; 9.5, p = 0.041.Compared with standard care, a supervised exercise program allows pregnant women with obesity to maintain fitness, limit weight gain and attenuate the decrease in physical activity levels observed in late pregnancy.ClinicalTrials.gov NCT01610323.

  11. Long-term safety, tolerability and efficacy of fesoterodine in subjects with overactive bladder symptoms stratified by age: pooled analysis of two open-label extension studies.

    Science.gov (United States)

    Sand, Peter K; Heesakkers, John; Kraus, Stephen R; Carlsson, Martin; Guan, Zhonghong; Berriman, Sandra

    2012-02-01

    Previous work has demonstrated the efficacy and safety of fesoterodine in older and younger subjects with overactive bladder (OAB) symptoms. The effect of long-term fesoterodine treatment in different age groups has not been assessed. The aim was to determine the impact of age on the safety, tolerability and efficacy of long-term treatment with fesoterodine 8 mg in subjects with OAB syndrome. This was a pooled analysis of two identically designed open-label extensions of 12-week, randomized, double-blind, placebo-controlled studies. The setting was urology and general practice offices. Subjects who participated in the 12-week, double-blind studies and opted to continue long-term, open-label treatment with fesoterodine were included. Subjects were initiated on fesoterodine 8 mg/day at open-label baseline. After 1 month, subjects could elect dose reduction to 4 mg/day and subsequent re-escalation to 8 mg; each was permitted once annually. Maximal duration of open-label treatment ranged from 24 to 36 months. Discontinuations, subject-reported treatment tolerance, and efficacy (3-day diaries) were assessed at open-label baseline and months 1, 4, 8, 12 and 24. A total of 890 subjects were treated (age fesoterodine 8 mg throughout treatment; this rate was highest among subjects aged ≥75 years (age fesoterodine 8 mg at each visit after open-label baseline up to 36 months. No new or unexpected safety signals were observed in any age group. Most subjects reported 'good' or 'excellent' treatment tolerance throughout the study (age fesoterodine (administered primarily as 8 mg) was well tolerated and associated with sustained improvements in OAB symptoms, irrespective of age.

  12. Robotic and Open Radical Prostatectomy: The First Prospective Randomised Controlled Trial Fuels Debate Rather than Closing the Question.

    Science.gov (United States)

    Fossati, Nicola; Wiklund, Peter; Rochat, Charles-Henry; Montorsi, Francesco; Dasgupta, Prokar; Sanchez-Salas, Rafael; Canda, Abdullah E; Piechaud, Thierry; Artibani, Walter; Mottrie, Alexandre

    2017-03-01

    Despite the finally acquired level 1 evidence, the urologic debate on open versus robotic prostatectomy still persists. This trial from Brisbane will encourage future studies that will better inform this debate and define what robotic surgery offers.

  13. The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

    LENUS (Irish Health Repository)

    Neary, Peter M

    2012-01-01

    Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours.

  14. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.

    Science.gov (United States)

    Vermeulen, Ruud C W; Scholte, Hans R

    2004-01-01

    We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome (CFS). In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later. Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement. Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

  15. Ringer’s lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial

    OpenAIRE

    Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert

    2015-01-01

    Background: The infusion of large amounts of Ringers lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringers lactate exerts these adverse effects when the surgery is performed by laparoscopy. Methods: Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid trea...

  16. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Chow TW

    2011-07-01

    Full Text Available Tiffany W Chow1–6, Ariel Graff-Guerrero4,6, Nicolaas PLG Verhoeff2–4,7, Malcolm A Binns3,8, David F Tang-Wai5,9, Morris Freedman1,3,5, Mario Masellis5,10, Sandra E Black3,5,10, Alan A Wilson4,6, Sylvain Houle4,6, Bruce G Pollock4,61Division of Neurology, 2Department of Psychiatry, 3Rotman Research Institute, Baycrest; 4Departments of Psychiatry, 5Medicine, Division of Neurology, University of Toronto; 6Centre for Addiction and Mental Health PET Centre; 7Kunin-Lunenfeld Applied Research Unit, Baycrest; 8Dalla Lana School of Public Health, University of Toronto; 9University Health Network Memory Clinic; 10LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaBackground: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD, and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.Results: Voxel-wise parametric image analysis of positron emission tomography (PET data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG normalized

  17. Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.

    Science.gov (United States)

    Keefe, John R; Mao, Jun J; Soeller, Irene; Li, Qing S; Amsterdam, Jay D

    2016-12-15

    Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile. We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined. Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred. Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and

  18. An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder.

    Science.gov (United States)

    Brunette, Mary F; Akerman, Sarah C; Dawson, Ree; O'Keefe, Christopher D; Green, Alan I

    2016-06-01

    Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent α2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted.

  19. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

    Directory of Open Access Journals (Sweden)

    Sasaki T

    2014-01-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

  20. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

    NARCIS (Netherlands)

    Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

    2015-01-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled pr

  1. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  2. Sustained improvement in patient-reported outcomes during long-term fesoterodine treatment for overactive bladder symptoms: pooled analysis of two open-label extension studies.

    Science.gov (United States)

    Kelleher, Con J; Dmochowski, Roger R; Berriman, Sandra; Kopp, Zoe S; Carlsson, Martin

    2012-08-01

    • To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects. • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24. • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  3. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial

    NARCIS (Netherlands)

    Pressler, Ronit M.; Boylan, Geraldine B.; Marlow, Neil; Blennow, Mats; Chiron, Catherine; Cross, J. Helen; de Vries, Linda S.; Hallberg, Boubou; Hellstrom-Westas, Lena; Jullien, Vincent; Livingstone, Vicki; Mangum, Barry; Murphy, Brendan; Murray, Deirdre; Pons, Gerard; Rennie, Janet; Swarte, Renate; Toet, Mona C.; Vanhatalo, Sampsa; Zohar, Sarah

    Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding,

  4. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

    Science.gov (United States)

    Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

  5. Long-term tolerability of tolterodine extended release in children 5-11 years of age : Results from a 12-month, open-label study

    NARCIS (Netherlands)

    Nijman, Rien J. M.; Borgstein, Niels G.; Ellsworth, Pamela; Siggaard, Charlotte

    2007-01-01

    Objective: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). Methods: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI sugg

  6. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  7. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial

    NARCIS (Netherlands)

    Pressler, Ronit M.; Boylan, Geraldine B.; Marlow, Neil; Blennow, Mats; Chiron, Catherine; Cross, J. Helen; de Vries, Linda S.; Hallberg, Boubou; Hellstrom-Westas, Lena; Jullien, Vincent; Livingstone, Vicki; Mangum, Barry; Murphy, Brendan; Murray, Deirdre; Pons, Gerard; Rennie, Janet; Swarte, Renate; Toet, Mona C.; Vanhatalo, Sampsa; Zohar, Sarah

    2015-01-01

    Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, an

  8. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  9. Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease : an open-label single-center study

    NARCIS (Netherlands)

    de Vries, Juna M.; van der Beek, Nadine A. M. E.; Hop, Wim C. J.; Karstens, Francois P. J.; Wokke, John H.; de Visser, Marianne; van Engelen, Baziel G. M.; Kuks, Jan B. M.; van der Kooi, Anneke J.; Notermans, Nicolette C.; Faber, Catharina G.; Verschuuren, Jan J. G. M.; Kruijshaar, Michelle E.; Reuser, Arnold J. J.; van Doorn, Pieter A.; van der Ploeg, Ans T.

    2012-01-01

    Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods: Patients in this open-label

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

    National Research Council Canada - National Science Library

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

    2016-01-01

    ...) with augmentation by blonanserin in schizophrenic patients. aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study...

  11. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  12. Comparison of the effects of ranitidine effervescent tablets and magnesium hydroxide-aluminium oxide on intragastric acidity. A single-centre, randomised, open cross-over study.

    Science.gov (United States)

    Propst, A; Propst, T; Judmaier, G

    1996-06-01

    In previous studies measuring intragastric pH in healthy volunteers it was shown that there was a faster onset of action with ranitidine (CAS 66357-35-5) 300 mg effervescent tablets (Zantac) compared to standard tablets. In a single-centre, randomised, open cross-over study the pH-values obtained over 6 h following the administration of one ranitidine 150 mg effervescent tablet were compared with those after aluminium oxide-magnesium hydroxide (algeldrate, CAS 1330-44-5, Al-Mg-hydroxide) 10 ml and placebo in healthy volunteers. 24 healthy male subjects between 19 and 32 years of age entered the study, 19 subjects were available for all three measurements. After an overnight fast, intragastric pH was monitored for 7 h using a glass electrode and a digital data recorder. The time in % during which the pH was > or = 3.5 and the area under the curve of the obtained pH-curves were compared. There was a highly statistically significant difference between ranitidine effervescent tablets versus Al-Mg-hydroxide and placebo whereas there was no such difference between Al-Mg-hydroxide and placebo. The onset of action of ranitidine effervescent tablets was almost immediate. It is concluded that there was a clear superiority of ranitidine effervescent tablets in healthy volunteers and it is suggested that pH-metry in patients with acidity-related diseases should be investigated for a better understanding of the function of effervescent tablets.

  13. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

  14. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Caihong Sun

    2016-06-01

    Full Text Available Autism spectrum disorders (ASD are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily for a period of three months during their structured teaching (intervention group, while the remaining 22 children were not given any supplement for the duration of the study (control group. The Autism Treatment Evaluation Checklist (ATEC and Psychoeducational Profile-third edition (PEP-3 were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group. The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  15. Effects of risperidone on core symptoms of autistic disorder based on childhood autism rating scale: An open label study

    Directory of Open Access Journals (Sweden)

    Padideh Ghaeli

    2014-01-01

    Full Text Available Background: The aim of the present study was to evaluate the effect of risperidone in patients afflicted by autistic disorder especially with regards to its three core symptoms, including "relating to others", "communication skills", and "stereotyped behaviors" based on Childhood Autism Rating Scale (CARS. Materials and Methods: An 8-week open-label study of risperidone for treatment of autistic disorder in children 4-17 years old was designed. Risperidone dose titration was as follow: 0.02 mg/kg/day at the first week, 0.04 mg/kg/day at the second week, and 0.06 mg/kg/day at the third week and thereafter. The outcome measures were scores obtained by CARS, Aberrant Behavior Checklist (ABC, and Clinical Global Impression-Improvement (CGI-I scale. Results: Fifteen patients completed this study. After 8 weeks, CARS total score decreased significantly, (P=0.001. At the end of the study, social interactions and verbal communication skills of the patients were significantly improved (P<0.001, P=0.03, respectively. However, stereotypic behaviors did not show any significant change in this study. Increase in appetite and somnolence were the most reported side effects. Conclusion: This study suggests that risperidone may be an effective treatment for the management of core symptoms of autistic disorder.

  16. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    Science.gov (United States)

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  17. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    DEFF Research Database (Denmark)

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo;

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

  18. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

    Science.gov (United States)

    Kepha, Stella; Nuwaha, Fred; Nikolay, Birgit; Gichuki, Paul; Mwandawiro, Charles S; Mwinzi, Pauline N; Odiere, Maurice R; Edwards, Tansy; Allen, Elizabeth; Brooker, Simon J

    2016-01-15

    School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. NCT01658774. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Cermak, Jan; Kozeny, Jiri; Höschl, Cyril

    2013-02-01

    This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

  20. An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

    Science.gov (United States)

    Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

    2011-01-01

    Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

  1. Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study

    Science.gov (United States)

    Wyndaele, J-J; Goldfischer, E R; Morrow, J D; Gong, J; Tseng, L-J; Guan, Z; Choo, M-S

    2009-01-01

    Aims: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. Methods: This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. Results: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all pfesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy. PMID:19348029

  2. Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial.

    Science.gov (United States)

    Gathwala, Geeta; Marwah, Ashish; Gahlaut, Veena; Marwah, Poonam

    2011-08-01

    To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. Open label, Randomized controlled trial. Neonatal intensive care unit of a tertiary care teaching hospital. 72 full term inborn neonates with severe birth asphyxia. Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40 mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. Phenobarbital (40 mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life.

  3. Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two-month open label pilot study.

    Science.gov (United States)

    von Arnim, Christine A F; Dismar, Stephanie; Ott-Renzer, Cornelia S; Noeth, Nathalie; Ludolph, Albert C; Biesalski, Hans K

    2013-11-15

    Malnutrition is a widespread problem in elderly people and is associated with cognitive decline. However, interventional studies have produced ambiguous results. For this reason, we wanted to determine the effect of micronutrient supplementation on blood and tissue levels and on general nutritional status in persons with mild or moderate cognitive impairment. We performed a 2-month, open-label trial, administering a daily micronutrient supplement to 42 memory clinic patients with mild cognitive deficits. Blood levels of antioxidants, zinc, and B vitamins were determined before and after supplementation. In addition, we assessed metabolic markers for B vitamins and intracellular (buccal mucosa cell [BMC]) antioxidant levels. Nutritional status was assessed by using the Mini Nutritional Assessment (MNA). Blood levels of B vitamins, folic acid, lutein, β-carotene, α-carotene, and α-tocopherol increased significantly. Decreases in homocysteine levels and the thiamine pyrophosphate effect and an increase in holotranscobalamin were observed. We found no increase in intracellular antioxidant levels of BMC. The MNA score in subjects at risk for malnutrition increased significantly, mainly owing to better perception of nutritional and overall health status. Micronutrient supplementation improved serum micronutrient status, with improved metabolic markers for B vitamins but not for intracellular antioxidant status, and was associated with improved self-perception of general health status. Our data underline the necessity of determining micronutrient status and support the use of additional assessments for general health and quality of life in nutritional supplementation trials.

  4. A multicenter, open-label, 52-week study of 2% rebamipide (OPC-12759) ophthalmic suspension in patients with dry eye.

    Science.gov (United States)

    Kinoshita, Shigeru; Awamura, Saki; Nakamichi, Norihiro; Suzuki, Hiroyuki; Oshiden, Kazuhide; Yokoi, Norihiko

    2014-03-01

    To investigate the efficacy and safety of 2% rebamipide ophthalmic suspension administered 4 times daily for 52 weeks in patients with dry eye. Multicenter (17 sites), open-label, single-arm study. A total of 154 patients with dry eye were enrolled in this study. After a 2-week screening period, patients received 2% rebamipide, instilled as 1 drop in each eye, 4 times daily for 52 weeks. The signs and symptoms measures were assessed at baseline, at weeks 2 and 4, and at every 4 weeks thereafter. The objective signs were fluorescein corneal staining score, lissamine green conjunctival staining score, and tear film break-up time, while subjective symptoms were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision). The safety variable was the occurrence of adverse events. For all objective signs and subjective symptoms, the scores significantly improved at week 2 compared with baseline (P rebamipide is effective in improving both the objective signs and subjective symptoms of dry eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well tolerated. Copyright © 2014. Published by Elsevier Inc.

  5. Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study.

    Science.gov (United States)

    Jung, Kyung Eun; Woo, Yu Ri; Lee, Joong Sun; Shin, Jong Ho; Jeong, Jin Uk; Koo, Dae Won; Bang, Ki Tae

    2015-08-01

    Chronic kidney disease-associated pruritus (CKD-aP) is a troublesome symptom in patients with end-stage renal disease (ESRD). Recently, vitamin D deficiency has been known to be one of the possible etiologic factors in CKD-aP. However, limited data is available on whether topical vitamin D treatment is effective for relieving CKD-aP. Therefore, the purpose of this study is to evaluate the effectiveness of topically vitamin D for CKD-aP. Twenty-three patients with CKD-aP were enrolled in a single center, open-label study. Patients were instructed to apply a topical vitamin D (calcipotriol) agent (Daivonex solution; LEO Pharma) or vehicle solution twice daily for a month. We assessed the efficacy and safety of topical vitamin D on CKD-aP using clinical and dermoscopic photographs, and questionnaires including the validated modified pruritus assessment score (VMPAS) and visual analog scale (VAS) every 2 weeks. Dry dermoscopic findings showed significant improvement of scale (dryness) on the skin of topical vitamin D-treated patients compared with those of the vehicle group. Both VMPAS and VAS were significantly decreased after 2 and 4 weeks of the topical vitamin D treatment compared with the vehicle, respectively (P < 0.05). No significant side-effects were observed. Topical vitamin D may be one of the safe and effective therapeutic candidates for CKD-aP.

  6. Treprostinil sodium (Remodulin), a prostacyclin analog, in the treatment of critical limb ischemia: open-label study.

    Science.gov (United States)

    Berman, Scott; Quick, Rhonda; Yoder, Pam; Voigt, Sonia; Strootman, Deborah; Wade, Michael

    2006-01-01

    The purpose of this study was to assess the safety of continuous subcutaneous therapy with treprostinil sodium (Remodulin), a prostacyclin analog, and its effect on ischemic rest pain and ischemic wound healing in subjects with critical limb ischemia (CLI) and no planned revascularization procedure. This was a 12-week, open-label, single-center pilot study enrolling 10 subjects (mean age 82.4 years) with Fontaine stage III to IV (Rutherford class 4-6) peripheral arterial disease and ankle brachial indices less than 0.55. The primary end point was safety, and the secondary end points were the effects of treatment on ischemic rest pain, limb salvage, and wound healing. There was a 62% reduction in mean worst rest pain and a 57% reduction in mean average rest pain at week 12, with most subjects using less pain medication. Three subjects experienced complete healing of their wounds. No subject developed a new wound during the trial. Treprostinil was generally well tolerated. Subcutaneous infusion-site pain was the most frequently reported side effect, with one subject withdrawing from the study as a result. Jaw pain was reported by two subjects. One subject experienced two serious adverse events considered unrelated to treprostinil (cholecystitis and congestive heart failure). This study demonstrates that chronic, continuous subcutaneous treprostinil is safe and can be useful in the treatment of ischemic pain and wounds in subjects with CLI. Future controlled studies are needed to evaluate these effects and determine appropriate patient selection.

  7. An Open Label, Phase 2 Study of MABp1 Monotherapy for the Treatment of Acne Vulgaris and Psychiatric Comorbidity.

    Science.gov (United States)

    Carrasco, Daniel; Stecher, Michael; Lefebvre, Gigi Claire; Logan, Alan C; Moy, Ronald

    2015-06-01

    Acne vulgaris is a common inflammatory skin disorder. There remain few rapid, safe, and effective therapy options for patients with moderate to severe acne vulgaris that also address psychological comorbidities such as anxiety. To assess the efficacy of interleukin 1 alpha blockade in patients with moderate to severe acne vulgaris using the true human monoclonal antibody MABp1. Eleven patients were administered open-label, subcutaneous injections of MABp1 over a six-week period. Objectives were assessment of safety, change in inflammatory lesion count and change in psychosocial functioning using two validated questionnaires. There were no serious adverse events, or adverse events greater than grade I. Median inflammatory lesion counts decreased 36% (IQR -44% to 1%). Anxiety scores improved (from median 6 to 1) as well as self-image assessment (2.3±0.9 to 2.1±0.1) as measured by the Hospital Anxiety and Depression Scale and the modified Body Image Disturbance Questionnaire. Patients had rapid improvement of skin lesions, as well as psychosocial functioning and anxiety. MABp1 may provide a safe and effective means for treating inflammatory acne lesions and. Further studies using this antibody are warranted in this patient population.

  8. Pharmacokinetics, safety, and tolerability of a depot formulation of naltrexone in alcoholics: an open-label trial

    Directory of Open Access Journals (Sweden)

    Koch Monika

    2005-04-01

    Full Text Available Abstract Background Naltrexone is an effective medication for treatment of alcohol dependence, but its efficacy is limited by lack of adherence to the oral dosage form. A long-acting depot formulation of naltrexone may increase adherence. Methods A single site, 6-week open label study was conducted with 16 alcohol dependent subjects each receiving 300 mg of Naltrexone Depot by intramuscular injection. The main outcomes were safety and tolerability of the Naltrexone Depot formulation, blood levels of naltrexone and its main metabolite 6-beta naltrexol, and self-reported alcohol use. All subjects received weekly individual counseling sessions. Results The medication was well tolerated with 88% of subjects completing the 6-week trial. The most common side effect experienced was injection site complications. There were no serious adverse events. Subjects had naltrexone and 6-beta-naltrexol concentrations throughout the trial with mean values ranging from 0.58 ng/mL to 2.04 ng/mL and 1.51 ng/mL to 5.52 ng/mL, respectively, at each sampling time following administration. Compared to baseline, subjects had significantly reduced number of drinks per day, heavy drinking days and proportion of drinking days. Conclusion Naltrexone Depot is safe and well tolerated in alcoholics and these findings support the further investigation of its utility in larger double-blind placebo controlled trials.

  9. 4-WEEK OPEN-LABEL CONTROLLED RANDOMIZED COMPARATIVE STUDY OF THE INJECTABLE AND TABLETTED FORMULATIONS OF METHOTREXATE IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Yu. V. Muravyev

    2011-01-01

    Full Text Available Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT (Methoject (MTJ in rheumatoid arthritis (RA in clinical practice. Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions. Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group. Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently. 

  10. Pharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: a randomized, multicenter, open-label, phase I study.

    Science.gov (United States)

    Petersenn, Stephan; Bollerslev, Jens; Arafat, Ayman M; Schopohl, Jochen; Serri, Omar; Katznelson, Laurence; Lasher, Janet; Hughes, Gareth; Hu, Ke; Shen, George; Reséndiz, Karina Hermosillo; Giannone, Vanessa; Beckers, Albert

    2014-11-01

    Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and IGF-1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF-1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly.

  11. A randomised controlled trial of absorbable versus non-absorbable sutures for skin closure after open carpal tunnel release.

    LENUS (Irish Health Repository)

    Theopold, C

    2012-05-01

    We compared the aesthetic outcome of scars after closure of open carpal tunnel incisions with either absorbable 4-0 Vicryl Rapide or non-absorbable 4-0 Novafil. Patients were recruited in a randomized controlled trial and scars were scored at 6 weeks using a modified Patient and Observer Scar Assessment Scale. Scores demonstrated differences only for pain, vascularity and cross-hatching between both groups, though none of these were statistically significant. The dissolving and falling out of Vicryl Rapide was significantly more comfortable than removal of 4-0 Novafil sutures, assessed on a numerical analogue scale. There was no difference in infection rate between both study groups, supporting overall the use of Vicryl Rapide for the closure of palmar hand incisions, in light of the convenience and cost savings associated with absorbable sutures.

  12. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout

    NARCIS (Netherlands)

    Reinders, M. K.; Haagsma, C.; Jansen, T. L. Th A.; van Roon, E. N.; Delsing, J.; de Laar, M. A. F. J. van; Brouwers, J. R. B. J.

    Objectives: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) (0.30 mmol/l (5 mg/dl). Methods: A randomised, controlled, open-label, multi-centre trial in gout patients with renal

  13. A high rate of non-compliance confounds the study of whole grains and weight maintenance in a randomised intervention trial - the case for greater use of dietary biomarkers in nutrition intervention studies

    DEFF Research Database (Denmark)

    Kristensen, Mette Bredal; Pelletier, Xavier; Ross, Alastair B.

    2017-01-01

    Observational studies consistently find an inverse relationship between whole-grain intake and weight gain. We aimed to confirm this in an open-label researcher-blinded parallel design randomised trial. A total of 179 overweight/obese women with a habitually low whole-grain intake (<16 g/day) wer...

  14. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout

    NARCIS (Netherlands)

    Reinders, M. K.; Haagsma, C.; Jansen, T. L. Th A.; van Roon, E. N.; Delsing, J.; de Laar, M. A. F. J. van; Brouwers, J. R. B. J.

    2009-01-01

    Objectives: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) (0.30 mmol/l (5 mg/dl). Methods: A randomised, controlled, open-label, multi-centre trial in gout patients with renal functio

  15. Multicenter, prospective, open-label, observational study of bimatoprost 0.01% in patients with primary open-angle glaucoma or ocular hypertension

    Directory of Open Access Journals (Sweden)

    Laube T

    2012-05-01

    Full Text Available Stefan Pfennigsdorf,1 Osman Ramez,2 Gerrit von Kistowski,3 Birgit Mäder,4 Peter Eschstruth,5 Michael Froböse,6 Ulrich Thelen,7 Christoph Spraul,8 Dietmar Schnober,9 Hazel Cooper,10 Thomas Laube111Polch Ophthalmology Practice, Polch, 2Buxtehude Ophthalmology Practice, Buxtehude, 3Nürnberg Ophthalmology Practice, Nürnberg, 4Weißwasser Ophthalmology Practice, Weißwasser, 5Ophthalmology Practice, Kiel, 6Ophthalmology Practice, Bielefeld, 7Group Practice, Münster, 8Group Practice, Ulm, 9Ophthalmology Practice, Werdohl, Germany; 10Allergan, Marlow, UK, 11Group Practice, Düsseldorf, GermanyBackground: Bimatoprost 0.01% was developed for improved tolerability over bimatoprost 0.03%, while maintaining efficacy in lowering intraocular pressure (IOP. This multicenter, prospective, open-label, observational study was designed to investigate the efficacy and tolerability of bimatoprost 0.01% in routine clinical practice.Methods: Data were collected from 10,337 patients with primary open-angle glaucoma or ocular hypertension attending 1334 centers in Germany. The primary efficacy outcome was mean change in IOP in each eye from baseline to 10–14 weeks after initiation of bimatoprost 0.01%. Target IOP, prior therapies, additional treatments, and adverse events were also assessed. All treatment decisions were at the physicians’ discretion.Results: Bimatoprost 0.01% significantly lowered mean IOP from baseline by –4.1 mmHg (P < 0.0001 in all patients after a mean of 10.45 weeks. In patients without previous treatment, bimatoprost 0.01% reduced mean IOP from baseline by –6.5 mmHg (P < 0.0001. Bimatoprost 0.01% also significantly reduced IOP in patients previously treated with monotherapy of β-blockers, prostaglandin analogs, carbonic anhydrase inhibitors or bimatoprost 0.03%. No adverse events were reported by 93.9% of patients during treatment with bimatoprost 0.01%; the most commonly reported adverse events were eye irritation (2.0%, ocular

  16. An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Hirano J

    2013-10-01

    Full Text Available Jinichi Hirano,1,2 Koichiro Watanabe,3 Takefumi Suzuki,1,4 Hiroyuki Uchida,1 Ryosuke Den,5 Taishiro Kishimoto,1 Takashi Nagasawa,5 Yusuke Tomita,4 Koichiro Hara,6 Hiromi Ochi,7 Yoshimi Kobayashi,1 Mutsuko Ishii,1 Akane Fujita,1 Yoshihiko Kanai,1 Megumi Goto,1 Hiromi Hayashi,1 Kanako Inamura,1 Fumiko Ooshima,1 Mariko Sumida,1 Tomoko Ozawa,1 Kayoko Sekigawa,1 Maki Nagaoka,1 Kae Yoshimura,1 Mika Konishi,1 Ataru Inagaki,1 Takuya Saito,8 Nobutaka Motohashi,9 Masaru Mimura,1 Yoshiro Okubo,8 Motoichiro Kato,11Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2Ohizumi Hospital, Tokyo, Japan; 3Department of Psychiatry School of Medicine, Kyorin University, Tokyo, Japan; 4Inokashira Hospital, Tokyo, Japan; 5Komagino Hospital, Tokyo, Japan; 6Asai Hospital, Chiba, Japan; 7Kurumegaoka Hospital, Tokyo, Japan; 8Department of Psychiatry School of Medicine, Nippon Medical School, Tokyo, Japan; 9Department of Psychiatry, School of Medicine, University of Yamanashi, Yamanashi, JapanObjective: The use of an algorithm may facilitate measurement-based treatment and result in more rational therapy. We conducted a 1-year, open-label study to compare various outcomes of algorithm-based treatment (ALGO for schizophrenia versus treatment-as-usual (TAU, for which evidence has been very scarce.Methods: In ALGO, patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition were treated with an algorithm consisting of a series of antipsychotic monotherapies that was guided by the total scores in the positive and negative syndrome scale (PANSS. When posttreatment PANSS total scores were above 70% of those at baseline in the first and second stages, or above 80% in the 3rd stage, patients proceeded to the next treatment stage with different antipsychotics. In contrast, TAU represented the best clinical judgment by treating psychiatrists.Results: Forty-two patients (21 females, 39.0 ± 10.9 years

  17. Open-label atomoxetine for attention-deficit/ hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders.

    Science.gov (United States)

    Posey, David J; Wiegand, Ryan E; Wilkerson, Jennifer; Maynard, Melissa; Stigler, Kimberly A; McDougle, Christopher J

    2006-10-01

    The aim of this study was to conduct an initial evaluation of the efficacy of atomoxetine for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with pervasive developmental disorders (PDDs). Children with PDDs and a nonverbal IQ of >or=70 received atomoxetine (target dose 1.2-1.4 mg/kg/day) during the course of an 8-week, open-label, prospective study. Standardized assessments of efficacy and tolerability were collected at regular intervals during the trial. Sixteen children and adolescents (mean age 7.7 +/- 2.2 years, age range 6-14 years) with autistic disorder (n = 7), Asperger's disorder (n = 7), or PDD not otherwise specified (n = 2) received atomoxetine (mean dose 1.2 +/- 0.3 mg/kg/day). Twelve participants (75%) were rated as "much" or "very much improved" on the Clinical Global Impressions-Improvement scale. The most significant improvement was seen in the area of ADHD symptoms as measured by the SNAP-IV and Aberrant Behavior Checklist (effect size = 1.0-1.9). Improvements of lesser magnitude (effect size = 0.4-1.1) were seen in irritability, social withdrawal, stereotypy, and repetitive speech. There were no significant changes on the Conners' Continuous Performance Test. Atomoxetine was well tolerated with the exception of 2 participants (13 %) who stopped medication due to irritability. Weight decreased by a mean of 0.8 kg during the 8-week trial. Placebo-controlled studies are indicated to determine atomoxetine's efficacy for ADHD symptoms in PDDs.

  18. Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

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    Rickard Kristen

    2011-03-01

    Full Text Available Abstract Background Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth. Methods We used a prospective, randomized, open-label, blinded-endpoint (PROBE study design. Pregnant women presenting at Candida were randomized to 6-days of clotrimazole vaginal pessaries (100mg or usual care (screening result is not revealed, no treatment. The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth Results Of 779 women approached, 500 (64% participated in candidiasis screening, and 98 (19.6% had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03. Conclusions A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12609001052224

  19. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

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    Li, Hao; Zhang, Zheng-Yun; Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-05-03

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

  20. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.

    Science.gov (United States)

    Nucci, Marcio; Colombo, Arnaldo L; Petti, Marco; Magana, Martin; Abreu, Paula; Schlamm, Haran T; Sanchez, Sonia P

    2014-01-01

    Incidence and mortality of candidaemia/invasive candidiasis (C/IC) is relatively high in Latin America versus North America and Europe. To assess efficacy and safety of intravenous (IV) anidulafungin in Latin American adults with documented C/IC. All patients in this open-label study received initial IV anidulafungin with optional step-down to oral voriconazole after 5 days; total treatment duration was 14-42 days. The primary endpoint was global response (clinical + microbiological response) at end of treatment (EOT); missing/indeterminate responses were failures. The study enrolled 54 patients; 44 had confirmed C/IC within 96 h before study entry and comprised the modified intent-to-treat population. Global response at EOT was 59.1% (95% CI: 44.6, 73.6), with 13 missing/indeterminate assessments. Thirty-day all-cause mortality was 43.1%. Fourteen patients (31.8%) were able to step-down to oral voriconazole; these patients had lower baseline acute physiological assessment and chronic health evaluation (APACHE) II scores and were less likely to have solid tumours or previous abdominal surgery. Anidulafungin was generally well tolerated with few treatment-related adverse events. Anidulafungin was associated with relatively low response rates influenced by a high rate of missing/indeterminate assessments and mortality comparable to other recent candidaemia studies in Latin America. In a subset of patients with lower APACHE II scores, short-course anidulafungin followed by oral voriconazole was successful.

  1. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

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    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  2. The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

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    van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

    2017-03-07

    North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified

  3. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis

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    Gupta, Vikas; Mesa, Ruben A.; Deininger, Michael W.N.; Rivera, Candido E.; Sirhan, Shireen; Brachmann, Carrie Baker; Collins, Helen; Kawashima, Jun; Xin, Yan; Verstovsek, Srdan

    2017-01-01

    Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post–polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058). PMID:27634203

  4. Sertraline and rapid eye movement sleep without atonia: an 8-week, open-label study of depressed patients.

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    Zhang, Bin; Hao, Yanli; Jia, Fujun; Tang, Yi; Li, Xueli; Liu, Wuhan; Arnulf, Isabelle

    2013-12-02

    Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) may induce or exacerbate rapid eye movement (REM) sleep without atonia (RSWA) and increase the risk of developing REM sleep behavior disorder (RBD). However, most of these studies are retrospective and cross-sectional and employed small sample sizes and a mixture of SSRIs. In this 8-week open-label trial of sertraline in depressed patients (n = 31), depressed patients were administered 50mg sertraline at 8 am on the 1st day and subsequently titrated up to a maximum of 200mg/day. All patients underwent repeated video-polysomnography (vPSG) (baseline, 1st day, 14th day, 28th day, and 56th day). Both tonic (submental) and phasic (submental and anterior tibialis) RSWA events were visually counted. Tonic RSWA increased from 3.2 ± 1.8% at baseline to 5.1 ± 2.3% on the 1st day and 10.4 ± 2.7% on the 14th day; after that, measurements were stable until the 56th day. A similar profile was observed for phasic RSWA. The increases in tonic RSWA (r = 0.56, P = 0.004) and phasic RSWA (submental: r = -0.51, P = 0.02; anterior tibialis: r = 0.41, P = 0.04) were correlated with the degree of the prolonging of REM latency. All of RSWAs were not correlated with patients' demographic and clinical characteristics. Sertraline may induce or exacerbate RSWA. In contrast to idiopathic RBD, sertraline-related RSWA had the specific characteristics of being correlated with the degree of the prolonging of REM latency and no predominance of male sex and elder age, suggesting different pathophysiological mechanisms. The antidepressant-related RSWA should be a potential public health problem in the depressed patients.

  5. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors.

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    Annunziata, Christina M; Kohn, Elise C; LoRusso, Patricia; Houston, Nicole D; Coleman, Robert L; Buzoianu, Manuela; Robbie, Gabriel; Lechleider, Robert

    2013-02-01

    Targeting the cell-surface receptor EphA2, which is highly expressed in some solid tumors, is a novel approach for cancer therapy. We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed/refractory to standard therapy. In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08 mg/kg) every 3 weeks. Six patients received 0.08 mg/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, ~70% by 3 days post-dose. No accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a second dose 3 weeks following dose 1. The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors.

  6. Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women with osteoporosis: an open-label randomized controlled study.

    Science.gov (United States)

    Saito, Kimio; Miyakoshi, Naohisa; Matsunaga, Toshiki; Hongo, Michio; Kasukawa, Yuji; Shimada, Yoichi

    2016-09-01

    The antifracture efficacy of vitamin D in osteoporosis is due to its direct action on bones and indirect extraskeletal effects to prevent falls. Eldecalcitol is an analog of active vitamin D3 that improves bone mineral density and reduces the risk of osteoporotic fractures. However, the effects of eldecalcitol on muscle strength and static and dynamic postural balance are unclear. In this open-label randomized controlled study, we assessed the effects of eldecalcitol on muscle strength and static and dynamic postural balance in 50 postmenopausal women (mean age 74 years) with osteoporosis treated with bisphosphonate. Participants were randomly divided into a bisphosphonate group (alendronate at 35 mg/week; n = 25) or an eldecalcitol group (eldecalcitol at 0.75 μg/day and alendronate at 35 mg/week; n = 25) and were followed up for 6 months. Trunk muscle strength, including back extensor strength and iliopsoas muscle strength, was measured. Static standing balance was evaluated and the one leg standing test was performed to assess static postural balance. Dynamic sitting balance was evaluated and the 10-m walk test, functional reach test, and timed up and go test were performed to assess dynamic postural balance. At 6 months, there were no significant changes in any measure of muscle strength or balance in the bisphosphonate group, whereas eldecalcitol significantly increased back extensor strength (p = 0.012) and iliopsoas muscle strength (p = 0.035). Eldecalcitol also significantly improved findings on the timed up and go test (p = 0.001) and dynamic sitting balance (p = 0.015) at 6 months. These results with eldecalcitol may have an impact on prevention of falls.

  7. Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

    Science.gov (United States)

    Akpınar, Esma; Cerit, Cem; Talas, Anıl; Tural, Ümit

    2016-01-01

    Objective In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline Methods The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. Results The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. Conclusion Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline. PMID:27776387

  8. An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients

    Directory of Open Access Journals (Sweden)

    Hardoy Maria

    2006-08-01

    Full Text Available Abstract Background Atypical antipsychotics are widely used in the treatment of bipolar disorders. Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia, major depressive disorder and, more recently, acute mania. At the moment, however, no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders. The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with standard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing standard therapies. Methods The study enrolled fourteen bipolar I outpatients, not responding to ongoing standard therapy. Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before (range 3–24 months and 5.2 ± 2.7 months after the introduction of amisulpride (range 3–9 months. Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version (CGI-BP score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization. Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride. The relative risk of relapse in the absence of amisulpride therapy was 3.1 (χ2 = 4.2, P Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses. Large, randomized, double-blind, placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to standard therapies for bipolar disorder.

  9. Aquatic therapy versus conventional land-based therapy for Parkinson's disease: an open-label pilot study.

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    Vivas, Jamile; Arias, Pablo; Cudeiro, Javier

    2011-08-01

    To assess and compare 2 different protocols of physiotherapy (land or water therapy) for people with Parkinson's disease (PD) focused on postural stability and self-movement, and to provide methodological information regarding progression within the program for a future larger trial. Randomized, controlled, open-label pilot trial. Outpatients, Parkinson's disease Center of Ferrol-Galicia (Spain). Individuals (N=11) with idiopathic PD in stages 2 or 3 according to the Hoehn and Yahr Scale completed the investigation (intervention period plus follow-up). After baseline evaluations, participants were randomly assigned to a land-based therapy (active control group) or a water-based therapy (experimental group). Participants underwent individual sessions for 4 weeks, twice a week, for 45 minutes per session. Both interventions were matched in terms of exercise features, which were structured in stages with clear objectives and progression criteria to pass to the next phase. Participants underwent a first baseline assessment, a posttest immediately after 4 weeks of intervention, and a follow-up assessment after 17 days. Evaluations were performed OFF-dose after withholding medication for 12 hours. Functional assessments included the Functional Reach Test (FRT), the Berg Balance Scale (BBS), the UPDRS, the 5-m walk test, and the Timed Up and Go test. A main effect of both therapies was seen for the FRT. Only the aquatic therapy group improved in the BBS and the UPDRS. In this pilot study, physiotherapy protocols produced improvement in postural stability in PD that was significantly larger after aquatic therapy. The intervention protocols are shown to be feasible and seem to be of value in amelioration of postural stability-related impairments in PD. Some of the methodological aspects detailed here can be used to design larger controlled trials. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.

    Science.gov (United States)

    Flechner, Stuart M; Gurkan, Alihan; Hartmann, Anders; Legendre, Christophe M; Russ, Graeme R; Campistol, Josep M; Schena, Francesco P; Hahn, Carolyn M; Li, Huihua; Korth-Bradley, Joan M; Tai, Sandi See; Schulman, Seth L

    2013-05-27

    Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors (CNIs) in transplant recipients, nephrotoxicity associated with long-term CNI use remains an important issue. This study evaluated whether a CNI-free regimen, including sirolimus, mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, results in improved long-term renal function. This open-label, randomized, parallel group, comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm. Enrollment was stopped after ≈12 months, with 475 transplanted patients randomized (2:1) to sirolimus (n=314) or cyclosporine A (CsA) treatment (n=161). Mean length of follow-up after transplantation was 190 days; this article focuses on available data through 6 months. Mean±SD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus (69.1±18.7 mL/min) and CsA (66.0±15.2 mL/min) treatment groups. Occurrence and length of delayed graft function was not significantly different between groups. Patients in the sirolimus group experienced numerically lower survival rates (96.9% vs. 99.4%; P=0.14), with nine deaths reported with sirolimus and one with CsA; higher rates of biopsy-confirmed acute rejection (21.4% vs. 6.1%; P<0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001). A sirolimus-based, CNI-free immunosuppressive regimen, when used with mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.

  11. Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

    Directory of Open Access Journals (Sweden)

    Sparavigna A

    2014-10-01

    Full Text Available Adele Sparavigna, Beatrice Tenconi, Ileana De Ponti Derming Srl, Monza, Italy Background: Rosacea is a common, incurable skin barrier disorder characterized by relapses and remissions. Purpose: To evaluate the efficacy of Farmaka Rosacea Cream (FRC, a novel topical formulation for rosacea. Methods: This single-center, open-label pilot study comprised a single-dose substudy in 20 healthy subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2-hour, controlled, single-dose substudy assessed the soothing and reepithelialization properties of FRC after stripping-induced erythema based on the erythema index, transepidermal water loss, skin hydration, and clinical assessments of erythema. In the long-term substudy, subjects applied FRC twice daily for 8 weeks. Clinical assessments included vascular and pigmentary homogeneity and erythema and hemoglobin indices. Subjects completed questionnaires to assess FRC efficacy and cosmetic acceptability. Results: Greater reductions were seen in FRC-treated areas compared with untreated areas for the erythema index (-16% versus -8%; P<0.001 and mean transepidermal water loss (-35.8% versus -10.1%; P<0.001 30 minutes after stripping. Significant improvements over untreated areas were maintained 2 hours after stripping. Skin hydration and clinical erythema assessments also indicated that FRC soothed rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin indices were significantly reduced from baseline after 4 and 8 weeks of treatment. Clinically assessed parameters were significantly improved following FRC application. Subjects assessed FRC positively. Conclusion: Improvement of rosacea symptoms was noted with FRC application. The main film-forming ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids, combined with other soothing and calming ingredients and ultraviolet filters, could explain its efficacy. Keywords: rosacea, erythema, skin

  12. Effect of probiotic yoghurt on animal-based diet-induced change in gut microbiota: an open, randomised, parallel-group study.

    Science.gov (United States)

    Odamaki, T; Kato, K; Sugahara, H; Xiao, J Z; Abe, F; Benno, Y

    2016-09-01

    Diet has a significant influence on the intestinal environment. In this study, we assessed changes in the faecal microbiota induced by an animal-based diet and the effect of the ingestion of yoghurt supplemented with a probiotic strain on these changes. In total, 33 subjects were enrolled in an open, randomised, parallel-group study. After a seven-day pre-observation period, the subjects were allocated into three groups (11 subjects in each group). All of the subjects were provided with an animal-based diet for five days, followed by a balanced diet for 14 days. Subjects in the first group ingested dairy in the form of 200 g of yoghurt supplemented with Bifidobacterium longum during both the animal-based and balanced diet periods (YAB group). Subjects in the second group ingested yoghurt only during the balanced diet period (YB group). Subjects who did not ingest yoghurt throughout the intervention were used as the control (CTR) group. Faecal samples were collected before and after the animal-based diet was provided and after the balanced diet was provided, followed by analysis by high-throughput sequencing of amplicons derived from the V3-V4 region of the 16S rRNA gene. In the YB and CTR groups, the animal-based diet caused a significant increase in the relative abundance of Bilophila, Odoribacter, Dorea and Ruminococcus (belonging to Lachnospiraceae) and a significant decrease in the level of Bifidobacterium after five days of intake. With the exception of Ruminococcus, these changes were not observed in the YAB group. No significant effect was induced by yoghurt supplementation following an animal-based diet (YB group vs CTR group). These results suggest that the intake of yoghurt supplemented with bifidobacteria played a role in maintaining a normal microbiota composition during the ingestion of a meat-based diet. This study protocol was registered in the University Hospital Medical Information Network: UMIN000014164.

  13. An innovative solid oral nutritional supplement to fight weight loss and anorexia: open, randomised controlled trial of efficacy in institutionalised, malnourished older adults.

    Science.gov (United States)

    Pouyssegur, Valerie; Brocker, Patrice; Schneider, Stéphane M; Philip, Jean Luc; Barat, Philippe; Reichert, Ewa; Breugnon, Frederic; Brunet, Didier; Civalleri, Bruno; Solere, Jean Paul; Bensussan, Line; Lupi-Pegurier, Laurence

    2015-03-01

    To evaluate the impact of a solid nutritional supplement on the weight gain of institutionalised older adults>70 years with protein-energy malnutrition. The innovation of these high-protein and high-energy cookies was the texture adapted to edentulous patients (Protibis®, Solidages, France). An open, multicentre, randomised controlled trial. Seven nursing homes. One hundred and seventy-five malnourished older adults, aged 86±8 years. All participants received the standard institutional diet. In addition, Intervention group participants received eight cookies daily (11.5 g protein; 244 kcal) for 6 weeks (w0-w6). Five visits (w-4, w0, w6, w10 and w18). Percentage of weight gain from w0 to w6 (body mass in kg). Appetite, rated using a numerical scale (0: no appetite to 10: extremely good appetite); current episodes of pressure ulcers and diarrhea. Average weight increased in Intervention group (n=88) compared with Control group (n=87) without cookies supplementation (+1.6 versus -0.7%, P=0.038). Weight gain persisted 1 month (+3.0 versus -0.2%, P=0.025) and 3 months after the end of cookies consumption (+3.9 versus -0.9%, P=0.003), with diarrhea reduction (P=0.027). There was a synergistic effect with liquid/creamy dietary supplements. Subgroup analysis confirmed the positive impact of cookies supplementation alone on weight increase (P=0.024), appetite increase (P=0.009) and pressure ulcers reduction (P=0.031). The trial suggested that, to fight against anorexia, the stimulation of touch (finger food; chewing, even on edentulous gums) and hearing (intra-oral sounds) could be valuable alternatives to sight, smell and taste alterations. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    Science.gov (United States)

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

  15. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

    Science.gov (United States)

    Remington, Ruth; Lortie, Jevin J; Hoffmann, Heather; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2015-01-01

    Thirty-four individuals with mild cognitive impairment were randomized for 6 months to a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo, followed by a 6-month open-label extension in which all individuals received NF. The NF cohort improved in the Dementia Rating Scale (DRS; effect size >0.7) and maintained baseline performance in CLOX-1. The placebo cohort did not improve in DRS and declined in CLOX-1, but during the open-label extension improved in DRS and ceased declining in CLOX-1. These findings extend prior studies of NF efficacy for individuals without cognitive impairment and with Alzheimer's disease.

  16. Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results

    OpenAIRE

    Stengel, Fernando M; Petri, Valeria [UNIFESP; Campbell, Gladys AM; Dorantes, Gladys Leon; López, Magdalina; Ricardo L. Galimberti; Valdez, Raúl P; de Arruda, Lucia F; Guerra, Mario Amaya; Chouela, Edgardo N; Licu, Daiana; ,

    2009-01-01

    Introduction Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. Methods We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18–75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/k...

  17. A Prospective, Open Label, Observational Study to Assess the Safety and Efficacy of Herbal Cough Syrup Mykoff® in Patients Suffering from Cough of Varied Aetiologies

    OpenAIRE

    Mangesh Bhalerao; Pradip Awale; Abhijeet Sawle; Dhananjay Sangle; Devendra B Sonawane; Vilas Chavan

    2013-01-01

    A prospective, open label, observational study was conducted at general outpatient clinic to assess the safety and efficacy of herbal cough syrup Mykoff® in patients suffering from cough of varied aetiologies. The patients of either sex, age > 3yrs, suffering from cough due to common cold, mild to moderate upper respiratory tract infections, allergic cough and smoker’s cough were enrolled. The safety was evaluated by means of an analysis of adverse events. In addition, efficacy and tolerabili...

  18. A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients

    OpenAIRE

    Bhandari, Sunil; Kalra, Philip A.; Kothari, Jatin; Ambühl, Patrice M.; Christensen, Jeppe H.; Essaian, Ashot M.; Thomsen, Lars L.; Macdougall, Iain C.; Coyne, Daniel W.

    2015-01-01

    Background Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. Methods This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2 : 1 to either iron isomaltoside 1000 (Group A) or...

  19. Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study

    OpenAIRE

    Mesejo, Alfonso; Montejo-González, Juan Carlos; Vaquerizo-Alonso, Clara; Lobo-Tamer, Gabriela; Zabarte-Martinez, Mercedes; Herrero-Meseguer, Jose Ignacio; Acosta-Escribano, Jose; Blesa-Malpica, Antonio; Martinez-Lozano, Fátima

    2015-01-01

    Introduction Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). Methods This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ...

  20. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    OpenAIRE

    2015-01-01

    Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycem...

  1. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

    OpenAIRE

    Vichinsky, Elliott; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Eckman, James; Lane, Peter; Files, Beatrice; Hassell, Kathryn; Kelly, Patrick; Wilson, Felicia; Bernaudin, Françoise; Forni, Gian Luca; Okpala, Iheanyi; Ressayre-Djaffer, Catherine; Alberti, Daniele

    2007-01-01

    Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change i...

  2. Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation

    OpenAIRE

    Merry, Alan F.; Craig S. Webster; HANNAM Jacqueline; Mitchell, Simon J.; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G

    2011-01-01

    Objective To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Design Prospective randomised open label clinical trial. Setting Five designated operating theatres in a major tertiary referral hospital. Participants Eighty nine consenting anaesthetists managing 1075 cases in which there were 10 764 drug administrations. Intervention Use of the new system (which includes customised drug trays ...

  3. An Open-Label Study of an Herbal Topical Medication (QoolSkin for Patients with Chronic Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Arnon D. Cohen

    2007-01-01

    Full Text Available QoolSkin is novel herbal topical medication indicated for the treatment of patients with psoriasis and we endeavored to determine the efficacy of QoolSkin in patients with chronic plaque psoriasis. In an open-label, parallel-group study conducted at four sites in Israel, patients with chronic plaque psoriasis were treated by application of QoolSkin two to three times per day, for a period of 16 weeks. Clinical assessment was performed using the Psoriasis Area and Severity Index (PASI and the Beer-Sheva Psoriasis Severity Score (BPSS. The study included 100 patients (48 men, 52 women; age 18–65 years. QoolSkin was well tolerated and there were no local or systemic side effects. There was a 19% reduction in PASI, from a mean of 9.8 ± 9.5 before treatment to 8.0 ± 9.6 after treatment (p = 0.09. There was a 20% reduction in BPSS, from a mean of 16.1 ± 9.8 before treatment to 12.8 ± 10.6 after treatment (p = 0.01. The reduction in PASI and BPSS was pronounced in women (32 and 31%, respectively as compared to men (9 and 11%, respectively. The reduction in PASI and BPSS was parallel to the length of time the patients were treated by QoolSkin. In patients treated by one of the investigators, who applied QoolSkin three times per day and for a long period of time (mean 101.1 days, the reduction in PASI was 32.0% and the reduction in BPSS was 37.8%. In patients with chronic plaque psoriasis, QoolSkin treatment was well tolerated. Application of QoolSkin was associated with a decrease in disease severity, as assessed by the patients and physicians. Application of QoolSkin three times per day for long period is associated with a better response to treatment.

  4. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

    Science.gov (United States)

    Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

    2017-01-01

    Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration

  5. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

    Directory of Open Access Journals (Sweden)

    Kasper S

    2017-03-01

    Full Text Available Siegfried Kasper,1 Angelika Dienel2 1Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien, Wien, Austria; 2Dr Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group.Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to

  6. Patient-optimized doses of fesoterodine improve bladder symptoms in an open-label, flexible-dose study.

    Science.gov (United States)

    Wyndaele, Jean-Jacques; Goldfischer, Evan R; Morrow, Jon D; Gong, Jason; Tseng, Li-Jung; Choo, Myung-Soo

    2011-02-01

    To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to

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

    Science.gov (United States)

    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.

  8. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

    Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

  9. AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.

    Science.gov (United States)

    Lakatos, Peter; Bajnok, Laszlo; Lagast, Hjalmar; Valkusz, Zsuzsanna

    2016-05-01

    Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

  10. An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Shang, Chi-Yung; Pan, Yi-Lei; Lin, Hsiang-Yuan; Huang, Lin-Wan; Gau, Susan Shur-Fen

    2015-09-01

    The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported

  11. Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-02-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

  12. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  13. Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

    Science.gov (United States)

    Vourvahis, Manoli; Plotka, Anna; Mendes da Costa, Laure; Fang, Annie; Heera, Jayvant

    2013-12-01

    This open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r) in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1 subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at 700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects received FPV/r at 1,400/100 mg QD alone on days 1 to 10 and then FPV/r at 1,400/100 mg QD plus MVC at 300 mg QD on days 11 to 20. Pharmacokinetic parameters, assessed on day 5 of period 1 and on days 10 and 20 of period 2, included the maximum plasma concentration (Cmax), the concentration at end of dosing interval (Cτ), and the area under the curve over dosing interval (AUCτ). Safety and tolerability were also assessed. MVC geometric mean AUCτ, Cmax, and Cτ were increased by 149, 52, and 374%, respectively, after BID dosing with FPV/r, and by 126, 45, and 80%, respectively, after QD dosing. Amprenavir (the active form of the prodrug fosamprenavir) and ritonavir exposures were decreased in the presence of MVC with amprenavir AUCτ, Cmax, and Cτ decreased by 34 to 36% in the presence of FPV/r plus maraviroc BID and by 15 to 30% with FPV/r plus MVC QD both compared to FPV/r alone. The overall all-causality adverse-event (AE) incidence rate was 96.4%; all AEs were of mild or moderate severity. Commonly reported treatment-related AEs (>20% of patients overall) included diarrhea, fatigue, abdominal discomfort, headache, and nausea. No serious AEs or deaths occurred. In summary, maraviroc exposure increased in the presence of FPV/r, whereas MVC coadministration decreased amprenavir and ritonavir exposures. MVC dosed at 300 mg BID with FPV/r is not recommended due to concerns of lower amprenavir exposures; however, no dose adjustment is warranted with MVC at 150 mg BID in combination with FPV/r based on

  14. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

    Science.gov (United States)

    Kasper, Siegfried; Dienel, Angelika

    2017-01-01

    Purpose This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. Methods The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. Discussion The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout

  15. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial.

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Sierra Romero

    2017-06-01

    Full Text Available There is insufficient evidence to support visceral leishmaniasis (VL treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option.A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i amphotericin B deoxycholate (AmphoB (1 mg/kg/day for 14 days, (ii liposomal amphotericin B (LAMB (3 mg/kg/day for 7 days and (iii a combination of LAMB (10 mg/kg single dose plus meglumine antimoniate (MA (20 mg Sb+5/kg/day for 10 days, compared to (iv standard treatment with MA (20 mg Sb+5/kg/day for 20 days. Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption.378 patients were randomized to the four treatment arms: MA (n = 112, AmphoB (n = 45, LAMB (n = 109, or LAMB plus MA (n = 112. A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222. LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE (p = 0.045, proportion of patients presenting at least one severe AE (p = 0.029, and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003.Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738.ClinicalTrials.gov NCT01310738.

  16. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms.

    Science.gov (United States)

    Kasper, Siegfried; Dienel, Angelika

    2017-01-01

    This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS(®) 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with R

  17. Prospective, open-label study to validate proper use of the Versacloz™ (clozapine oral suspension kit by people with schizophrenia

    Directory of Open Access Journals (Sweden)

    Andre AD

    2015-05-01

    Full Text Available Anthony D Andre Interface Analysis Associates, Saratoga, CA, USA Purpose: This study was designed to validate that people with schizophrenia can correctly, safely, and effectively prepare doses of Versacloz™ using the Versacloz oral suspension kit and instructions for use (IFU.Materials and methods: This was a prospective, open-label, simulated-use validation study of 61 people with schizophrenia who were stabilized on clozapine or were clozapine-naive and stabilized on another antipsychotic treatment. Participants were randomized to one of two groups: untrained (n=46 and trained (n=15. Participants were asked to select the proper syringe and prepare two test doses of 1, 3.5, or 5 mL, as randomly assigned. Participants in the untrained group did not receive any training on using the kit, but had access to kit materials, including packaging and the IFU; both test dose preparations were unaided. Participants in the trained group received brief training from the moderator, and then prepared one test dose during training and one unaided test dose during the study period. Prepared placebo doses were not ingested. Performance and behavior were assessed in 14 critical tasks identified in the user failure mode and effects analysis. Test dose failures or dose errors (threshold ±0.1 mL were assessed. Subjective participant assessments of usability were captured in interviews and IFU comprehension was probed.Results: A total of 107 test doses were prepared: 92 and 15 by the untrained and trained groups, respectively. Overall success for unassisted dose preparation was 87.9%; all test failures (failure to shake the bottle or failure to obtain the correct test dose occurred in the untrained group. All participants selected the correct syringe for their assigned dose.Conclusion: This study shows that the Versacloz oral suspension kit and IFU can be correctly, safely, and effectively used to prepare doses by people with schizophrenia, with few instances of

  18. Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE

    Science.gov (United States)

    Vaccher, S; Grulich, A; McAllister, J; Templeton, D J; Bloch, M; McNulty, A; Holden, J; Poynten, I M; Prestage, G; Zablotska, I

    2016-01-01

    Introduction Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. Methods and analysis PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants—mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. Ethics and dissemination The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete. Trial registration number NCT02206555; Pre-results. PMID:27324719

  19. Open-label treatment with desvenlafaxine in postmenopausal women with major depressive disorder not responding to acute treatment with desvenlafaxine or escitalopram.

    Science.gov (United States)

    Soares, Claudio N; Thase, Michael E; Clayton, Anita; Guico-Pabia, Christine J; Focht, Kristen; Jiang, Qin; Kornstein, Susan G; Ninan, Phillip T; Kane, Cecelia P

    2011-03-01

    Preliminary clinical evidence indicates that menopausal status might impact on the efficacy of certain classes of antidepressants. The aim of this study was to evaluate open-label desvenlafaxine treatment (administered as desvenlafaxine succinate) in postmenopausal women who did not achieve clinical response to acute, double-blind treatment with desvenlafaxine or escitalopram. This phase IIIb, multicentre study included a 6-month open-label extension phase of patients who did not respond in the initial 8-week, randomized, double-blind acute phase. Postmenopausal women aged 40-70 years with a primary diagnosis of major depressive disorder were recruited. PRIMARY INTERVENTION: Non-responders to acute treatment with double-blind desvenlafaxine or escitalopram received flexible-dose, open-label desvenlafaxine 100-200 mg/day for the 6-month extension phase. The primary efficacy assessment was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score. Secondary efficacy outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and -Severity scales, Hamilton Rating Scale for Anxiety, Quick Inventory of Depressive Symptomatology-Self-Report, Visual Analogue Scale-Pain Intensity and the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary health assessments were the Changes in Sexual Functioning Questionnaire, 5-Dimension EuroQoL Index, Health State Today, Menopause Rating Scale, Sheehan Disability Scale, treatment response (≥ 50% decrease in total HAM-D(17) and MADRS score from acute-phase baseline and CGI-I total score ≤ 2), HAM-D(17) remission (total score ≤ 7) and safety. Descriptive statistics were used to summarize outcomes. The efficacy analysis included 123 patients (desvenlafaxine/desvenlafaxine = 64; escitalopram/desvenlafaxine = 59). At final evaluation of the open-label extension phase, mean reductions from acute-phase baseline in HAM-D(17) total scores were -11.33 for the desvenlafaxine

  20. Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS® programme (ORANGE II - Trial): Study protocol for a randomised controlled trial

    NARCIS (Netherlands)

    R. van Dam (Ronald); E.M. Wong-Lun-Hing (Edgar); G.J.P. van Breukelen (Gerard); J.H.M.B. Stoot (Jan); J.R. van der Vorst (Joost); W.J. Bemelmans (Wanda); S.W.M.O. Damink (Steven WM O.); K. Lassen (Kristoffer); C.H. Dejong (Cees); O.R.C. Busch (Olivier); P.J. Tanis (Pieter); L.T. Hoekstra; R. van Hillegersberg (Richard); I.Q. Molenaar (I. Quintus); C. Verhoef (Cornelis); T. Terkivatan (Türkan); J. de Jonge (Jeroen); G.D. Slooter (Gerrit); R.M.H. Roumen (Rudi); J.M. Klaase (Joost); E.B. van Duyn; K. Boscha; R.J. Porte (Robert); M.T. de Boer (Marieke); J.W. Haveman; J.H.W. de Wilt (Johannes); O.R. Buyne; P. van Duijvendijk (Peter); U. Neumann; M. Schmeding; G. Ferla; L.A. Aldrighetti (L.); F. Ferla; J.N. Primrose; M. Abu Hilal; N.W. Pearce; I. Dagher; A. Laurent; B. Topal (B.); R.I. Troisi; B. Edwin

    2012-01-01

    textabstractBackground: The use of lLaparoscopic liver resection in terms of time to functional recovery, length of hospital stay (LOS), long-term abdominal wall hernias, costs and quality of life (QOL) has never been studied in a randomised controlled trial. Therefore, this is the subject of the in

  1. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

    Directory of Open Access Journals (Sweden)

    Stephen P Myers

    2010-02-01

    Full Text Available Stephen P Myers1,2, Joan O’Connor1,2, J Helen Fitton3, Lyndon Brooks4, Margaret Rolfe4, Paul Connellan5, Hans Wohlmuth2,5,6, Phil A Cheras1,2, Carol Morris51NatMed-Research, 2Centre for Health and Wellbeing, 4Graduate Research College, 5Centre for Phytochemistry and Pharmacology, 6Medicinal Plant Herbarium, Southern Cross University, Lismore, NSW, Australia; 3Marinova Pty Ltd, Hobart, Tasmania, AustraliaBackground: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects.Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years] with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5 or 1000 mg (n = 7 of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w, Macrocystis pyrifera (10% w/w and Laminaria japonica (5% w/w plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded.Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect

  2. An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan.

    Science.gov (United States)

    Landy, Stephen H; Tepper, Stewart J; Wein, Theodore; Schweizer, Edward; Ramos, Elodie

    2013-01-01

    To assess the ability of patients, during an acute migraine attack, to successfully self-inject a single dose of sumatriptan using a novel sumatriptan auto-injector (Alsuma(®)), and to evaluate the safety, tolerability, and effectiveness of this sumatriptan auto-injector during an acute migraine attack. This sumatriptan auto-injector is a single-use system for the rapid subcutaneous delivery of 6 mg of sumatriptan succinate in the acute management of migraine pain. This auto-injector was developed to address the clinical need for an easy-to-use and rapid-to-administer system that did not require any assembly during the time of an ongoing attack. This was an open-label, phase 3 trial conducted at 10 sites in the USA. Male or female adults, ages 18-60 years old, were eligible for study entry if they met International Headache Society criteria for migraine with or without aura, with at least 2 attacks per month, and if they reported use of subcutaneous injectable sumatriptan on at least 2 occasions within the previous 2 months. During the onset of a migraine attack of moderate-to-severe intensity, patients were asked to administer a 6-mg subcutaneous dose of sumatriptan using the auto-injector. Patients returned to the study site within 72 hours of the migraine for the post-treatment assessment visit. A total of 63 patients met entry criteria and received a dose of study medication (the intent-to-treat sample). Sixty-one patients (96.8%) reported injection in the thigh, and 2 patients (3.2%) reported injection in the arm. On the patient questionnaire, 100% of patients (95% confidence interval [CI] 94.3-100%) "agreed" or "agreed strongly" that the written instructions for the auto-injector were clear and easy to follow (30.2% "agreed"; 69.8% "agreed strongly"); 95.2% of patients (95% CI 86.7-99.0%) found that the auto-injector was easy to use (36.5% "agreed"; 58.7% "agreed strongly"), and 65.1% of patients (95% CI 52.0-76.7%) stated that they preferred the new auto

  3. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin;

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  4. Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

    Science.gov (United States)

    Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

    2007-01-01

    Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

  5. Rotigotine transdermal system for long-term treatment of patients with advanced Parkinson's disease: results of two open-label extension studies, CLEOPATRA-PD and PREFER.

    Science.gov (United States)

    LeWitt, Peter A; Boroojerdi, Babak; Surmann, Erwin; Poewe, Werner

    2013-07-01

    Open-label extensions [studies SP516 (NCT00501969) and SP715 (NCT00594386)] of the CLEOPATRA-PD and PREFER studies were conducted to evaluate the safety, tolerability and efficacy of the dopaminergic agonist, rotigotine, over several years of follow-up in patients with advanced Parkinson's disease (PD). Eligible subjects completing the double-blind trials received open-label adjunctive rotigotine (≤16 mg/24 h) for up to 4 and 6 years in Studies SP516 and SP715, respectively. Safety and tolerability were assessed using adverse events, vital signs and laboratory parameters, and efficacy assessed using the unified Parkinson's disease rating scale (UPDRS). Of the 395 and 258 patients enrolled in the SP516 and SP715 studies, 48 and 45 % completed, respectively. Adverse events were typically dopaminergic effects [e.g., somnolence (18-25 %/patient-year), insomnia (5-7 %/patient-year), dyskinesias (4-8 %/patient-year) and hallucinations (4-8 %/patient-year)], or related to the transdermal application of a patch (application site reactions: 14-15 %/patient-year). There were no clinically relevant changes in vital signs or laboratory parameters in either study. Mean UPDRS part II (activities of daily living) and part III (motor function) total scores improved from double-blind baseline during dose titration, then gradually declined over the maintenance period. In study SP516, mean UPDRS part II and III total scores were 0.8 points above and 2.8 points below double-blind baseline, respectively, at end of treatment. In study SP715, mean UPDRS part II and III total scores were 4.1 points above and 0.2 points below baseline, respectively, at end of treatment. In these open-label studies, adjunctive rotigotine was efficacious with an acceptable safety and tolerability profile in patients with advanced PD for up to 6 years.

  6. Clinical Efficacy Comparison of Saccharomyces boulardii and Yogurt Fluid in Acute Non-Bloody Diarrhea in Children: A Randomized, Controlled, Open Label Study

    OpenAIRE

    Makbule EREN; Dinleyici, Ener C; Vandenplas,Yvan

    2010-01-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 ± 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, a...

  7. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  8. Safety and efficacy of re-treatments with pyronaridine-artesunate in African patients with malaria: a substudy of the WANECAM randomised trial

    OpenAIRE

    Sagara, Issaka; Beavogui, Abdoul Habib; Zongo, Issaka; Soulama, Issiaka; Borghini-Fuhrer, Isabelle; Fofana, Bakary; Camara, Daouda; Somé, Anyirékun F; Coulibaly, Aboubacar S; Traore, Oumar B; Dara, Niawanlou; Kabore, Moïse J T; Thera, Ismaila; Compaore, Yves D; Sylla, Malick Minkael

    2016-01-01

    Summary Background Sparse data on the safety of pyronaridine-artesunate after repeated treatment of malaria episodes restrict its clinical use. We therefore compared the safety of pyronaridine-artesunate after treatment of the first episode of malaria versus re-treatment in a substudy analysis. Methods This planned substudy analysis of the randomised, open-label West African Network for Clinical Trials of Antimalarial Drugs (WANECAM) phase 3b/4 trial was done at six health facilities in Mali,...

  9. Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

    Science.gov (United States)

    Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

    2014-12-01

    Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.

  10. Comparison of the effectiveness and safety of cefpodoxime and ciprofloxacin in acute exacerbation of chronic suppurative otitis media: A randomized, open-labeled, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Arijit Ghosh

    2012-01-01

    Full Text Available Objective : To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM. Materials and Methods : Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079 was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs. Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results : The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion : The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM.

  11. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.

    Science.gov (United States)

    Ng, Yu-Tze; Conry, Joan; Paolicchi, Juliann; Kernitsky, Lydia; Mitchell, Wendy; Drummond, Rebecca; Isojarvi, Jouko; Lee, Deborah; Owen, Randall

    2012-12-01

    In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2.0 mg/kg/day (≤80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ≥12 months, 128 for ≥18 months, and 94 for ≥24 months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had received clobazam for ≥1 year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazam's adverse event profile was consistent with its profile in controlled trials.

  12. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

    NARCIS (Netherlands)

    Mulenga, V.; Musiime, V.; Kekitiinwa, A.; Cook, A.D.; Abongomera, G.; Kenny, J.; Chabala, C.; Mirembe, G.; Asiimwe, A.; Owen-Powell, E.; Burger, D.M.; McIlleron, H.; Klein, N.; Chintu, C.; Thomason, M.J.; Kityo, C.; Walker, A.S.; Gibb, D.M.

    2016-01-01

    BACKGROUND: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed t

  13. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT) : a multicentre, open-label randomised controlled trial

    NARCIS (Netherlands)

    Koopmans, C.M.; Bijlenga, D.; Groen, H.; Vijgen, S.M.C.; Aarnoudse, J.G.; Bekedam, D; van den Berg, P.P.; de Boer, K.; Burggraaff, Jan; Bloemenkamp, K.W.M.; Drogtrop, A.P.; Franx, A.; de Groot, C.J.M.; Huisjes, A.J.M.; Kwee, A.; van Loon, A.J.; Lub, A.; Papatsonis, D.N.M.; van der Post, J.A.M.; Roumen, F.J.M.E.; Scheepers, H.C.J.; Willekes, C.; Mol, B.W.J.; van Pampus, Maria

    2009-01-01

    Background Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. Methods

  14. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

    NARCIS (Netherlands)

    Mulenga, V.; Musiime, V.; Kekitiinwa, A.; Cook, A.D.; Abongomera, G.; Kenny, J.; Chabala, C.; Mirembe, G.; Asiimwe, A.; Owen-Powell, E.; Burger, D.M.; McIlleron, H.; Klein, N.; Chintu, C.; Thomason, M.J.; Kityo, C.; Walker, A.S.; Gibb, D.M.

    2016-01-01

    BACKGROUND: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed

  15. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study

    NARCIS (Netherlands)

    Baumert, Brigitta G; Hegi, Monika E; van den Bent, Martin J; von Deimling, Andreas; Gorlia, Thierry; Hoang-Xuan, Khê; Brandes, Alba A; Kantor, Guy; Taphoorn, Martin J B; Hassel, Mohamed Ben; Hartmann, Christian; Ryan, Gail; Capper, David; Kros, Johan M; Kurscheid, Sebastian; Wick, Wolfgang; Enting, Roelien; Reni, Michele; Thiessen, Brian; Dhermain, Frederic; Bromberg, Jacoline E; Feuvret, Loic; Reijneveld, Jaap C; Chinot, Olivier; Gijtenbeek, Johanna M M; Rossiter, John P; Dif, Nicolas; Balana, Carmen; Bravo-Marques, Jose; Clement, Paul M; Marosi, Christine; Tzuk-Shina, Tzahala; Nordal, Robert A; Rees, Jeremy; Lacombe, Denis; Mason, Warren P; Stupp, Roger

    2016-01-01

    BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and asses

  16. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

    DEFF Research Database (Denmark)

    de Bono, Johann Sebastian; Oudard, Stephane; Ozguroglu, Mustafa;

    2010-01-01

    Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer...

  17. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients : a randomised, controlled, open-label trial

    NARCIS (Netherlands)

    de Jong, Evelien; van Oers, Jos A; Beishuizen, Albertus; Vos, Piet; Vermeijden, Wytze J; Haas, Lenneke E; Loef, Bert G; Dormans, Tom; van Melsen, Gertrude C; Kluiters, Yvette C; Kemperman, Hans; van den Elsen, Maarten J; Schouten, Jeroen A; Streefkerk, Jörn O; Krabbe, Hans G; Kieft, Hans; Kluge, Georg H; van Dam, Veerle C; van Pelt, Joost; Bormans, Laura; Otten, Martine Bokelman; Reidinga, Auke C; Endeman, Henrik; Twisk, Jos W; van de Garde, Ewoudt M W; de Smet, Anne Marie G A; Kesecioglu, Jozef; Girbes, Armand R; Nijsten, Maarten W; de Lange, Dylan W

    2016-01-01

    BACKGROUND: In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduct

  18. Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II) : An open-label, randomised controlled trial

    NARCIS (Netherlands)

    Broekhuijsen, Kim; Van Baaren, Gert Jan; Van Pampus, Maria G.; Ganzevoort, Wessel; Sikkema, J. Marko; Woiski, Mallory D.; Oudijk, Martijn A.|info:eu-repo/dai/nl/246958898; Bloemenkamp, Kitty W M; Scheepers, Hubertina C J; Bremer, Henk A.; Rijnders, Robbert J P; Van Loon, Aren J.; Perquin, Denise A M; Sporken, Jan M J; Papatsonis, Dimitri N M; Van Huizen, Marloes E.; Vredevoogd, Corla B.; Brons, Jozien T J; Kaplan, Mesrure; Van Kaam, Anton H.; Groen, Henk; Porath, Martina M.; Van Den Berg, Paul P.; Mol, Ben W J; Franssen, Maureen T M; Langenveld, Josje

    2015-01-01

    Patients with hypertensive disorders of pregnancy usually have the 2 treatment options, either immediate delivery or continuing the pregnancy. Although immediately delivery of the placenta is seen as the more definitive of the 2 treatments, it does carry the potentially higher risks of an earlier bi

  19. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial

    NARCIS (Netherlands)

    Camenzind, E.; Wijns, W.; Mauri, L.; Kurowski, V.; Parikh, K.; Gao, R.; Bode, C.; Greenwood, J.P.; Boersma, E.; Vranckx, P.; McFadden, E.; Serruys, P.W.; O'Neil, W.W.; Jorissen, B.; Leeuwen, F van; Steg, P.G.; Verheugt, F.W.

    2012-01-01

    BACKGROUND: We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. METHODS

  20. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

    DEFF Research Database (Denmark)

    Bousser, M.G.; Bouthier, J.; Buller, H.R.;

    2008-01-01

    BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this random...

  1. Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial) : an open-label, randomised controlled trial

    NARCIS (Netherlands)

    Jozwiak, Marta; Rengerink, Katrien Oude; Benthem, Marjan; van Beek, Erik; Dijksterhuis, Marja G. K.; de Graaf, Irene M.; van Huizen, Marloes E.; Oudijk, Martijn A.; Papatsonis, Dimitri N. M.; Perquin, Denise A. M.; Porath, Martina; van der Post, Joris A. M.; Rijnders, Robbert J. P.; Scheepers, Hubertina C. J.; Spaanderman, Marc E. A.; van Pampus, Maria G.; de Leeuw, Jan Willem; Mol, Ben W. J.; Bloemenkamp, Kitty W. M.

    2011-01-01

    Background Induction of labour is a common obstetric procedure. Both mechanical (eg, Foley catheters) and pharmacological methods (eg, prostaglandins) are used for induction of labour in women with an unfavourable cervix. We aimed to compare the effectiveness and safety of induction of labour with a

  2. Fluoxetine for the Treatment of Childhood Anxiety Disorders: Open-Label, Long-Term Extension to a Controlled Trial

    Science.gov (United States)

    Clark, Duncan B.; Birmaher, Boris; Axelson, David; Monk, Kelly; Kalas, Catherine; Ehmann, Mary; Bridge, Jeffrey; Wood, D. Scott; Muthen, Bengt; Brent, David

    2005-01-01

    Objective: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. Method: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they…

  3. Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE).

    Science.gov (United States)

    McElvaney, Noel G; Burdon, Jonathan; Holmes, Mark; Glanville, Allan; Wark, Peter A B; Thompson, Philip J; Hernandez, Paul; Chlumsky, Jan; Teschler, Helmut; Ficker, Joachim H; Seersholm, Niels; Altraja, Alan; Mäkitaro, Riitta; Chorostowska-Wynimko, Joanna; Sanak, Marek; Stoicescu, Paul I; Piitulainen, Eeva; Vit, Oliver; Wencker, Marion; Tortorici, Michael A; Fries, Michael; Edelman, Jonathan M; Chapman, Kenneth R

    2017-01-01

    Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. RAPID-OLE supports the continued efficacy of A1PI in slowing disease

  4. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2011-10-01

    Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

  5. Post-Operative Benefits of Animal-Assisted Therapy in Pediatric Surgery: A Randomised Study

    OpenAIRE

    Valeria Calcaterra; Pierangelo Veggiotti; Clara Palestrini; Valentina De Giorgis; Roberto Raschetti; Massimiliano Tumminelli; Simonetta Mencherini; Francesca Papotti; Catherine Klersy; Riccardo Albertini; Selene Ostuni; Gloria Pelizzo

    2015-01-01

    Background Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period. Patients and Methods Forty children (3–17 years) were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underw...

  6. Endoscopic versus open radial artery harvest and mammario-radial versus aorto-radial grafting in patients undergoing coronary artery bypass surgery: protocol for the 2 × 2 factorial designed randomised NEO trial.

    Science.gov (United States)

    Carranza, Christian L; Ballegaard, Martin; Werner, Mads U; Hasbak, Philip; Kjær, Andreas; Kofoed, Klaus F; Lindschou, Jane; Jakobsen, Janus Christian; Gluud, Christian; Olsen, Peter Skov; Steinbrüchel, Daniel A

    2014-04-23

    Coronary artery bypass grafting using the radial artery has, since the 1990s, gone through a revival. Observational studies have indicated better long-term patency when using radial arteries. Therefore, radial artery might be preferred especially in younger patients where long time patency is important. During the last 10 years different endoscopic techniques to harvest the radial artery have evolved. Endoscopic radial artery harvest only requires a small incision near the wrist in contrast to open harvest, which requires an incision from the elbow to the wrist. However, it is unknown whether the endoscopic technique results in fewer complications or a graft patency comparable to open harvest. When the radial artery has been harvested, there are two ways to use the radial artery as a graft. One way is sewing it onto the aorta and another is sewing it onto the mammary artery. It is unknown which technique is the superior revascularisation technique. The NEO Trial is a randomised clinical trial with a 2 × 2 factorial design. We plan to randomise 300 participants into four intervention groups: (1) mammario-radial endoscopic group; (2) aorto-radial endoscopic group; (3) mammario-radial open surgery group; and (4) aorto-radial open surgery group.The hand function will be assessed by a questionnaire, a clinical examination, the change in cutaneous sensibility, and the measurement of both sensory and motor nerve conduction velocity at 3 months postoperatively. All the postoperative complications will be registered, and we will evaluate muscular function, scar appearance, vascular supply to the hand, and the graft patency including the patency of the central radial artery anastomosis. A patency evaluation by multi-slice computer tomography will be done at one year postoperatively.We expect the nerve conduction studies and the standardised neurological examinations to be able to discriminate differences in hand function comparing endoscopic to open harvest of the

  7. An open-label pilot study to assess the effectiveness of krill oil with added vitamins and phytonutrients in the relief of symptoms of PMS

    Directory of Open Access Journals (Sweden)

    Wakeman MP

    2013-09-01

    Full Text Available Michael P Wakeman School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, West Midlands, UK Abstract: An open-label pilot study over 4 months to evaluate the effectiveness of a compound formulation of ingredients, which individually have been demonstrated to be implicated in the pathogenesis of premenstrual syndrome to ameliorate the most troublesome symptoms of the condition. The supplement provided thiamine, riboflavin, pyridoxine, vitamin D, soy isoflavones, rosemary extract, and krill oil and was taken each day for the 3 months of the trial. Statistically significant effect was reported by the 29 women who completed the study in relief of anxiety, bloating, mood swings, breast tenderness, skin outbreaks, food cravings, fatigue, forgetfulness, insomnia, and headache after 3 months of treatment compared with baseline. This pilot study indicates the formulation to be effective, and a larger placebo-controlled trial is now planned. Keywords: thiamine, riboflavin, pyridoxine, vitamin D, soy isoflavones, rosemary extract, premenstrual syndrome

  8. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    OBJECTIVES: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  9. Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

    Full Text Available Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine. Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine, parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF, mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.

  10. Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study.

    Science.gov (United States)

    Remington, Ruth; Bechtel, Cynthia; Larsen, David; Samar, Annemarie; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2016-01-01

    Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

  11. LFQProfiler and RNP(xl): Open-Source Tools for Label-Free Quantification and Protein-RNA Cross-Linking Integrated into Proteome Discoverer.

    Science.gov (United States)

    Veit, Johannes; Sachsenberg, Timo; Chernev, Aleksandar; Aicheler, Fabian; Urlaub, Henning; Kohlbacher, Oliver

    2016-09-02

    Modern mass spectrometry setups used in today's proteomics studies generate vast amounts of raw data, calling for highly efficient data processing and analysis tools. Software for analyzing these data is either monolithic (easy to use, but sometimes too rigid) or workflow-driven (easy to customize, but sometimes complex). Thermo Proteome Discoverer (PD) is a powerful software for workflow-driven data analysis in proteomics which, in our eyes, achieves a good trade-off between flexibility and usability. Here, we present two open-source plugins for PD providing additional functionality: LFQProfiler for label-free quantification of peptides and proteins, and RNP(xl) for UV-induced peptide-RNA cross-linking data analysis. LFQProfiler interacts with existing PD nodes for peptide identification and validation and takes care of the entire quantitative part of the workflow. We show that it performs at least on par with other state-of-the-art software solutions for label-free quantification in a recently published benchmark ( Ramus, C.; J. Proteomics 2016 , 132 , 51 - 62 ). The second workflow, RNP(xl), represents the first software solution to date for identification of peptide-RNA cross-links including automatic localization of the cross-links at amino acid resolution and localization scoring. It comes with a customized integrated cross-link fragment spectrum viewer for convenient manual inspection and validation of the results.

  12. Duloxetine for the long-term treatment of Major Depressive Disorder in patients aged 65 and older: an open-label study

    Directory of Open Access Journals (Sweden)

    Watkin John G

    2004-12-01

    Full Text Available Abstract Background Late-life depression is a common, chronic and recurring disorder for which guidelines recommend long-term therapy. The safety and efficacy of duloxetine for the treatment of major depressive disorder (MDD were evaluated using data from elderly patients (age ≥ 65 years; n = 101 who participated in a large, multinational, open-label study. Methods Patients meeting DSM-IV criteria for MDD received duloxetine 80 mg/d (40 mg twice daily (BID to 120 mg/d (60 mg BID for up to 52 weeks. Efficacy measures included the Clinical Global Impression of Severity (CGI-S scale, the 17-item Hamilton Rating Scale for Depression (HAMD17, the Beck Depression Inventory-II (BDI-II, the Patient Global Impression of Improvement (PGI-I scale, and the Sheehan Disability Scale (SDS. Safety and tolerability were evaluated using discontinuation rates, spontaneously reported adverse events, and changes in vital signs, ECG, and laboratory analytes. Results Mean changes in HAMD17 total score at Weeks 6, 28, and 52 were -13.0, -17.4 and -17.5 (all p-values 10% of patients included dizziness, nausea, constipation, somnolence, insomnia, dry mouth, and diarrhea. Most events occurred early in the study. Mean changes at endpoint in blood pressure and body weight were less than 2.0 mm Hg, and -0.1 kg, respectively. Conclusions In this open-label study, duloxetine was effective, safe, and well tolerated in the long-term treatment of MDD in patients aged 65 and older.

  13. Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

    Science.gov (United States)

    O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

    2013-03-01

    Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

  14. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome.

    Science.gov (United States)

    Miller, Jennifer L; Angulo, Moris

    2014-02-01

    Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11-q13) that results in a host of behavioral characteristics including excessive interest in food, skin picking, difficulty with a change in routine, and obsessive and compulsive behaviors. Skin-picking can result in serious and potentially life-threatening infections. Recent evidence suggests that the excitatory neurotransmitter glutamate is dysregulated in obsessive-compulsive behaviors, and modulation of the glutaminergic pathway may decrease compulsive behaviors, such as recurrent hair pulling or skin-picking behaviors. N-acetylcysteine (NAC), a derivative of the amino acid cysteine, is thought to act either via modulation of NMDA glutamate receptors or by increasing glutathione in pilot studies. Thirty-five individuals with confirmed PWS (ages 5-39 years, 23 females/12 males) and skin-picking behavior for more than 1 year were treated with N-acetylcysteine (Pharma-NAC®) at a dose of 450-1,200 mg/day. Skin-picking symptoms and open lesions were assessed after 12 weeks of treatment by counting and measuring lesions before and after the medication. All 35 individuals had improvement in skin-picking behaviors. Ten (29%) individuals (six males and four females) did not have complete resolution of skin-picking behavior, but had significant reduction in the number of active lesions. Longer-term, placebo-controlled trials are needed to further assess the potential benefit of this treatment.

  15. Omega-3 fatty acids decreased irritability of patients with bipolar disorder in an add-on, open label study

    Directory of Open Access Journals (Sweden)

    Baldassano Claudia F

    2005-02-01

    Full Text Available Abstract This is a report on a 37-patient continuation study of the open ended, Omega-3 Fatty Acid (O-3FA add-on study. Subjects consisted of the original 19 patients, along with 18 new patients recruited and followed in the same fashion as the first nineteen. Subjects carried a DSM-IV-TR diagnosis of Bipolar Disorder and were visiting a Mood Disorder Clinic regularly through the length of the study. At each visit, patients' clinical status was monitored using the Clinical Monitoring Form. Subjects reported on the frequency and severity of irritability experienced during the preceding ten days; frequency was measured by way of percentage of days in which subjects experienced irritability, while severity of that irritability was rated on a Likert scale of 1 – 4 (if present. The irritability component of Young Mania Rating Scale (YMRS was also recorded quarterly on 13 of the 39 patients consistently. Patients had persistent irritability despite their ongoing pharmacologic and psychotherapy. Omega-3 Fatty Acid intake helped with the irritability component of patients suffering from bipolar disorder with a significant presenting sign of irritability. Low dose (1 to 2 grams per day, add-on O-3FA may also help with the irritability component of different clinical conditions, such as schizophrenia, borderline personality disorder and other psychiatric conditions with a common presenting sign of irritability.

  16. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.

    Science.gov (United States)

    Hofmeijer, Jeannette; Kappelle, L Jaap; Algra, Ale; Amelink, G Johan; van Gijn, Jan; van der Worp, H Bart

    2009-04-01

    Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset

  17. Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Ashwinikumar Raut

    2013-01-01

    Full Text Available Background: AmrutBhallatak (ABFN02, a ′rasayana′ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA and compare it with Glucosamine sulphate (GS Materials and Methods: This was a r andomized open comparative study. Ambulant OPD patients of OA knees (n = 112 were enrolled for 24 weeks. Tablets (750mg each of GS and ABFN02 were matched. Three groups of patients: (A GS, one tablet × twice/day × 24 weeks. (B ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks, two such cycles of drug and non-drug phases alternately for six weeks each (C ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ, paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has significant activity in OA; the formulation needs further investigation.

  18. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2017-05-25

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  19. Evaluation of safety and efficacy of zonisamide in adult patients with partial, generalized, and combined seizures: an open labeled, noncomparative, observational Indian study

    Directory of Open Access Journals (Sweden)

    Dash A

    2016-02-01

    Full Text Available Amitabh Dash,1 Sangeeta Ravat,2 Avathvadi Venkatesan Srinivasan,3 Ashutosh Shetty,4 Vivek Kumar,5 Renu Achtani,6 Vivek Narain Mathur,7 Boby Varkey Maramattom,8 Veeresh Bajpai,9 Nanjappa C Manjunath,10 Randhi Venkata Narayana,11 Suyog Mehta12 1Eisai Co. Ltd., 2Department of Neurology, Seth GS Medical College & KEM Hospital, Mumbai, 3Department of Neurology, Trinity Acute Care Hospital, Chennai, 4Department of Neurology, Criticare Multispeciality Hospital & Research Centre, Mumbai, 5Department of Neurology, Metro Multispeciality Hospital, Noida, 6Department of Neurology, Mata Chanan Devi Hospital, New Delhi, 7Department of Neurology, Vivekananda Hospital, Hyderabad, 8Department of Neurology, Lourdes Hospital, Kochi, 9Department of Neurology, Sai Neurology Clinic, Lucknow, 10Department of Neurology, Brain and Nerve Care, Bangalore, 11Department of Neurology, Seven Hills Hospital, Visakhapatnam, 12Department of Pharmacology & Therapeutics,Government Medical College, Solapur, India Abstract: A prospective, multicentric, noncomparative open-label observational study was conducted to evaluate the safety and efficacy zonisamide in Indian adult patients for the treatment of partial, generalized, or combined seizures. A total of 655 adult patients with partial, generalized, or combined seizures from 30 centers across India were recruited after initial screening. Patients received 100 mg zonisamide as initiating dose as monotherapy/adjunctive therapy for 24 weeks, with titration of 100 mg every 2 weeks if required. Adverse events, responder rates, and seizure freedom were observed every 4 weeks. Efficacy and safety were also assessed using Clinicians Global Assessment of Response to Therapy and Patients Global Assessment of Tolerability to Therapy, respectively. Follow-up was conducted for a period of 24 weeks after treatment initiation. A total of 655 patients were enrolled and received the treatment and 563 completed the evaluation phase. A total of 20

  20. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

    2011-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8%children received an OROS-MPH modal dose of 18 mg,3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3%)) reported AEs,and the majority of the events reported were mild (68.2

  1. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

    DEFF Research Database (Denmark)

    Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

    2015-01-01

    (diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis vaccine). METHODS: This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5mL dose of 9vHPV vaccine...

  2. Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

    NARCIS (Netherlands)

    van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

    2004-01-01

    Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

  3. A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

    Science.gov (United States)

    Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

    2013-01-01

    The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

  4. The Ankle Injury Management (AIM) trial: a pragmatic, multicentre, equivalence randomised controlled trial and economic evaluation comparing close contact casting with open surgical reduction and internal fixation in the treatment of unstable ankle fractures in patients aged over 60 years.

    Science.gov (United States)

    Keene, David J; Mistry, Dipesh; Nam, Julian; Tutton, Elizabeth; Handley, Robert; Morgan, Lesley; Roberts, Emma; Gray, Bridget; Briggs, Andrew; Lall, Ranjit; Chesser, Tim Js; Pallister, Ian; Lamb, Sarah E; Willett, Keith

    2016-01-01

    BACKGROUND Close contact casting (CCC) may offer an alternative to open reduction and internal fixation (ORIF) surgery for unstable ankle fractures in older adults. OBJECTIVES We aimed to (1) determine if CCC for unstable ankle fractures in adults aged over 60 years resulted in equivalent clinical outcome compared with ORIF, (2) estimate cost-effectiveness to the NHS and society and (3) explore participant experiences. DESIGN A pragmatic, multicentre, equivalence randomised controlled trial incorporating health economic evaluation and qualitative study. SETTING Trauma and orthopaedic departments of 24 NHS hospitals. PARTICIPANTS Adults aged over 60 years with unstable ankle fracture. Those with serious limb or concomitant disease or substantial cognitive impairment were excluded. INTERVENTIONS CCC was conducted under anaesthetic in theatre by surgeons who attended training. ORIF was as per local practice. Participants were randomised in 1 : 1 allocation via remote telephone randomisation. Sequence generation was by random block size, with stratification by centre and fracture pattern. MAIN OUTCOME MEASURES Follow-up was conducted at 6 weeks and, by blinded outcome assessors, at 6 months after randomisation. The primary outcome was the Olerud-Molander Ankle Score (OMAS), a patient-reported assessment of ankle function, at 6 months. Secondary outcomes were quality of life (as measured by the European Quality of Life 5-Dimensions, Short Form questionnaire-12 items), pain, ankle range of motion and mobility (as measured by the timed up and go test), patient satisfaction and radiological measures. In accordance with equivalence trial US Food and Drug Administration guidance, primary analysis was per protocol. RESULTS We recruited 620 participants, 95 from the pilot and 525 from the multicentre phase, between June 2010 and November 2013. The majority of participants, 579 out of 620 (93%), received the allocated treatment; 52 out of 275 (19%) who received CCC later

  5. [Long-term opioid therapy in chronic noncancer pain. A systematic review and meta-analysis of efficacy, tolerability and safety in open-label extension trials with study duration of at least 26 weeks].

    Science.gov (United States)

    Häuser, W; Bernardy, K; Maier, C

    2015-02-01

    The efficacy and safety of long-term (≥ 6 months) opioid therapy (LtOT) in chronic noncancer pain (CNCP) is under debate. A systematic review with meta-analysis of the efficacy and harms of opioids in open-label extension studies of randomized controlled trials (RCTs) has not been conducted until now. We screened MEDLINE and clinicaltrials.gov (through to December 2013), as well as reference sections of systematic reviews of long-term RCTs of opioids in CNCP. We included open-label extension trials with a study duration ≥ 26 weeks of RCTs of ≥ 2 weeks duration. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables were calculated. We included 11 open-label extension studies with 2445 participants with nociceptive (low back, osteoarthritis) and neuropathic (radicular, polyneuropathy) pain. Median study duration was 26 (range 26-108) weeks. Four studies tested oxycodone, two studies tramadol and buprenorphine; hydromorphone, morphine, oxymorphone and tapentadol were each tested in one study. Of the patients randomized at baseline, 28.5 % (95 % confidence interval, CI, 17.9-39.2 %) finished the open-label period; 53.5 % (95 % CI 38.1-68.2 %) of patients entering the open-label period finished the open-label period. In sum, the total loss was 71.5 % (95 % CI 60.9-83.1 %) of all patients primarily included into the RCT. A total of 4.9 % (95 % CI 2.9-8.2 %) of patients dropped out due lack of efficacy; 16.8 % (95 % CI 11.0-24.8 %) dropped out to due adverse events (AE) in the open-label period and 0.08 % (95 % CI 0.001-0.05 %) of patients died during the open-label period. Only one study systematically assessed aberrant drug behavior of the patients: 5.7 % (95 % CI 3.4-9.6 %) showed aberrant drug behavior in the opinion of the investigators and 2.6 % (95 % CI 1.2-5.8 %) were judged to show

  6. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Patricia L Hibberd

    Full Text Available BACKGROUND: Although Lactobacillus rhamnosus GG ATCC 53103 (LGG has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly. OBJECTIVES: The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines. METHODS: Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions. RESULTS: There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer, 39 (83% of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70% of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea, 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038 while there was no difference in other pro- or anti-inflammatory plasma cytokines. CONCLUSIONS: Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01274598.

  7. Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter, open-label, phase III study

    Institute of Scientific and Technical Information of China (English)

    Meng-Su Zeng; Hui-Yi Ye; Liang Guo; Wei-Jun Peng; Jian-Ping Lu; Gao-Jun Teng; Yi Huan; Ping Li; Jian-Rong Xu

    2013-01-01

    BACKGROUND: Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. METHODS: This  was  a  single-arm,  open-label,  multicenter study  in  patients  with  known  or  suspected  focal  liver  lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were  evaluated  by  clinical  study  investigators  and  three independent,  blinded  radiologists.  The  primary  efficacy endpoint was sensitivity in lesion detection. RESULTS: Gd-EOB-DTPA  improved  sensitivity  in  lesion detection  by  9.46%  compared  with  pre-contrast  imaging  for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA  vs  pre-contrast,  respectively).  Improvements in  detection  were  more  pronounced  in  lesions  less  than  1 cm.  Gd-EOB-DTPA  improved  diagnostic  accuracy  in  lesion classification. CONCLUSIONS: This  open-label  study  demonstrated  that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly  in  those  smaller  than  1  cm.  Gd-EOB-DTPA  also significantly  improves  the  diagnostic  accuracy  in  lesion classification,  and  furthermore,  Gd-EOB-DTPA  is  safe  in Chinese patients with liver lesions.

  8. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Tournigand, Christophe; de Larauze, Marine Hug; de Gramont, Armand; Laurent-Puig, Pierre; Paget, Jérôme; Hadengue, Alexandra; Notelet, Dominique; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-07-04

    The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013

  9. Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results

    Science.gov (United States)

    Stengel, Fernando M; Petri, Valeria; Campbell, Gladys AM; Dorantes, Gladys Leon; López, Magdalina; Galimberti, Ricardo L; Valdez, Raúl P; de Arruda, Lucia F; Guerra, Mario Amaya; Chouela, Edgardo N; Licu, Daiana

    2009-01-01

    Introduction Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. Methods We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18–75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/kg/wk). The primary endpoint was the proportion of patients achieving a Physician Global Assessment (PGA) rating of “excellent” or “cleared” at Week 24. Safety outcomes were adverse events (AEs), serious AEs (SAEs) and abnormalities on laboratory tests. Results Of 189 patients included in the intent-to-treat and safety populations, 104 (55.0%) were of Hispanic or Latino ethnicity. At Week 24, 92/189 (48.7%) patients achieved or maintained a PGA rating of “excellent” or “cleared”. AEs were reported by 161/189 (85.2%) patients, SAEs by 21/189 (11.1%). One patient died during the study (meningoencephalitis). Laboratory findings were consistent with previous experience. Conclusions Efalizumab demonstrated sustained control of psoriasis up to 24 weeks in patients from Latin America, confirming results seen in Phase III studies conducted in North America and Europe. PMID:20098510

  10. The Effect of a Phaseolus vulgaris and Dietary Fiber Based Supplement on Advanced Glycation End Products: An Open-label Trial

    Directory of Open Access Journals (Sweden)

    Brett J. West

    2015-07-01

    Full Text Available Elevated Advanced Glycation End product (AGE levels are associated with certain impaired health states. As these are disruptive to the function of healthy tissues, due to their protein cross-linking ability, AGEs are significant contributors to the aging process. In fact, population studies have revealed that AGE levels tend to increase as we get older. Certain lifestyle and dietary factors may accelerate AGE accumulation. Therefore, strategies intended to modify these factors, or mitigate their effects, may be useful in controlling the aging process. In an 11 week open-label clinical trial, 30 adult volunteers consumed daily a commercially available combination of white kidney bean extract, dietary fibers, &beta-carotene and noni (Morinda citrifolia fruit pulp, in combination with calorie restriction and exercise. During the course of the trial, participants experienced significant weekly declines in average body weight and fat mass. The average AGE score, as measured by skin auto-fluorescence, had also decreased significantly. In terms of AGE associated years, the change in AGE scores corresponded to an average decrease of 8.83 years. The results indicate that the intervention contributed to improved health and exhibited anti-aging properties.

  11. Quality-of-life assessment in patients with hyperhidrosis before and after treatment with botulinum toxin: results of an open-label study.

    Science.gov (United States)

    Campanati, Anna; Penna, Luca; Guzzo, Teresa; Menotta, Lucia; Silvestri, Barbara; Lagalla, Giovanni; Gesuita, Rosaria; Offidani, Annamaria

    2003-01-01

    Patients with hyperhidrosis, a disorder characterized by increased sweat production, experience substantial functional and emotional problems. Botulinum toxin type A (BTX-A) has been shown to be useful in the treatment of hyperhidrosis; however, few studies have considered the effects of treatment on patients' quality of life (QOL). The objectives of this study were to assess QOL in patients with focal hyperhidrosis; to investigate whether the impairment in QOL in these patients is related to the type of hyperhidrosis or the number of sites involved; and to compare the changes in QOL and the response to BTX-A treatment in patients with axillary and palmar hyperhidrosis. Patients with focal primary hyperhidrosis of the axillae, palms, and soles who had experienced decreased QOL and whose condition had not responded to conventional topical and physical therapies were included in this open-label study. Patients completed a self-administered Dermatology Life Quality Index (DLQI) questionnaire before and 2 weeks after treatment with BTX-A. All 41 patients had experienced a decrease in QOL as measured by the DLQI. The impairement in QOL was not dependent on the number or types of sites involved. Treatment with BTX-A led to improvement in QOL in all patients, with the median DLQI score decreasing (ie, improving) significantly from pretreatment level (P BTX-A; however, preliminary data from the present study suggest that BTX-A improves QOL in patients with focal hyperhidrosis, independent of the presenting clinical picture.

  12. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study.

    Science.gov (United States)

    Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

    2015-01-01

    Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

  13. Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study.

    Science.gov (United States)

    Sato, Kenji; Fukumori, Satoshi; Matsusaki, Takashi; Maruo, Tomoko; Ishikawa, Shinichi; Nishie, Hiroyuki; Takata, Ken; Mizuhara, Hiroaki; Mizobuchi, Satoshi; Nakatsuka, Hideki; Matsumi, Masaki; Gofuku, Akio; Yokoyama, Masataka; Morita, Kiyoshi

    2010-04-01

    Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.

  14. International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia.

    Science.gov (United States)

    Ostrosky-Zeichner, L; Kontoyiannis, D; Raffalli, J; Mullane, K M; Vazquez, J; Anaissie, E J; Lipton, J; Jacobs, P; van Rensburg, J H Jansen; Rex, J H; Lau, W; Facklam, D; Buell, D N

    2005-10-01

    Candida spp. are the fourth leading cause of bloodstream infections, and non-albicans species are increasing in importance. Micafungin is a new echinocandin antifungal agent with excellent in vitro activity against Candida spp. Pediatric, neonatal, and adult patients with new or refractory candidemia were enrolled into this open-label, noncomparative, international study. The initial dose of micafungin was 50 mg/d (1 mg/kg for patients <40 kg) for infections due to C. albicans and 100 mg/d (2 mg/kg for patients <40 kg) for infections due to other species. Dose escalation was allowed. Maximum length of therapy was 42 days. A total of 126 patients were evaluable (received at least five doses of micafungin). Success (complete or partial response) was seen in 83.3% patients overall. Success rates for treatment of infections caused by the most common Candida spp. were as follows: C. albicans 85.1%, C. glabrata 93.8%, C. parapsilosis 86.4%, and C. tropicalis 83.3%. Serious adverse events related to micafungin were uncommon. Micafungin shows promise as a safe and effective agent for the treatment of newly diagnosed and refractory cases of candidemia. Large-scale, randomized, controlled trials are warranted.

  15. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

    Science.gov (United States)

    Ooi, Y P; Weng, S-J; Jang, L Y; Low, L; Seah, J; Teo, S; Ang, R P; Lim, C G; Liew, A; Fung, D S; Sung, M

    2015-08-01

    The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.

  16. Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

    Directory of Open Access Journals (Sweden)

    Ro Jungsil

    2012-07-01

    Full Text Available Abstract Background To evaluate efficacy in patients with brain metastasis (BM on entry into the lapatinib expanded access program (LEAP. Methods LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily. Results Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88. In patients with BM, brain response was synchronized with systemic responses (P = 0.0001. Overall survival (OS was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23. Multivariable analysis found hormone receptor positivity (P = 0.003 and clinical benefit rate (CBR of combined systemic and brain disease (P  Conclusion Lapatinib plus capecitabine is equally effective in patients with or without BM. Trial registration ClinicalTrials.gov (NCT00338247

  17. Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

    Directory of Open Access Journals (Sweden)

    de Vries Juna M

    2012-09-01

    Full Text Available Abstract Background Enzyme replacement therapy (ERT in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Sixty-nine patients (median age 52.1 years were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y; hand-held dynamometry 4.0 pp/y; both p Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up, ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p Conclusions We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

  18. An Open-Label Uncontrolled, Multicenter Study for the Evaluation of the Efficacy and Safety of the Dermal Filler Princess VOLUME in the Treatment of Nasolabial Folds

    Directory of Open Access Journals (Sweden)

    Daisy Kopera

    2015-01-01

    Full Text Available The dermal filler Princess VOLUME is a highly cross-linked, viscoelastic hyaluronic acid injectable gel implant used for aesthetic treatment. To evaluate the efficacy and safety of Princess VOLUME in the treatment of nasolabial folds, an open-label uncontrolled, multicenter study was conducted. Forty-eight subjects were recruited who had moderate to deep wrinkles, according to the Modified Fitzpatrick Wrinkle Scale (MFWS. Subjects received Princess VOLUME in both nasolabial folds at Day 0. Nasolabial fold severity was evaluated at 30, 90, 180, and 270 days after treatment, using the MFWS and the Global Aesthetic Improvement Scale (GAIS. Adverse events and treatment site reactions were recorded. Among the 48 subjects, 93.8% were female with a median age of 52 years. There were significant improvements (P<0.0001 in the MFWS scores at 30, 180, and 270 days after treatment compared with those at baseline, with a mean decrease of 1.484 (±0.408, 1.309 (±0.373, and 1.223 (±0.401, respectively; hence the primary endpoint was achieved and clinical efficacy demonstrated. Princess VOLUME was well tolerated, and most adverse events were injection site reactions of mild to moderate severity. Subject satisfaction (97.9%, subject recommendation of the treatment (93.6%, and investigators GAIS scores (97.9% improvement were high.

  19. Investigation of a possible interaction between quetiapine and armodafinil in patients with schizophrenia: an open-label, multiple-dose study.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Hellriegel, Edward T; Youakim, James M; Yang, Ronghua; Robertson, Philmore

    2012-09-01

    The wakefulness-promoting medication armodafinil (R-modafinil) is being studied as an adjunctive treatment for patients with schizophrenia receiving antipsychotic therapy. This open-label study in 37 adults with schizophrenia evaluated whether a drug-drug interaction occurs between armodafinil (a moderate CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized by CYP3A4). Patients were required to be on a stable dose of quetiapine ≥300 mg once daily in the evening before enrollment. Steady-state quetiapine pharmacokinetics were determined following daily administration of quetiapine alone in the evening (day 5) and then following concomitant armodafinil administration (titrated to 250 mg) daily in the morning (day 38). In 25 evaluable patients, concomitant armodafinil resulted in a statistically significant decrease in mean AUC(0-24) and C(max) values of quetiapine by 42% and 45%, respectively, versus quetiapine alone. Adverse events occurred more frequently with combination therapy and were consistent with the known profiles of the 2 drugs. No significant changes in mean PANSS negative, positive, and total scores or SANS scores were observed. Although the data do not suggest that the observed decrease in systemic exposure to quetiapine was associated with a change in disease state, patients with schizophrenia should be monitored during combination therapy with quetiapine and armodafinil.

  20. Effects of Qianlie'an(前列安) Suppository in Patients with Chronic Prostatitis Syndrome: A Randomized Open-Labelled Prospective and Controlled Trial

    Institute of Scientific and Technical Information of China (English)

    邢俊平; 陈兴发; 杨志尚; 王明珠; 贺大林

    2003-01-01

    Objective: To evaluate the clinical efficacy of Qianlie'an(前列安,QLA) suppository via anal route administration in treating chronic prostatitis syndrome. Methods: A randomized open-labelled prospective controlled trial was carried out. The total of 120 patients with chronic prostatitis syndrome were randomly divided into 2 groups: 60 patients in the treated group who were treated with QLA suppository combined with ofloxacin, and the other 60 patients in the control group who were given ofloxacin alone. The efficacy was evaluated by WBC count in the expressed prostatic secretion (EPS) and the Chronic Prostatitis Symptom Index (CPSI) made by the National Institute of Health (NIH). The clinical effects were also observed in a 4-week follow-up. Results: All but six cases completed the trial and the follow-up.It showed that in the treated group recovery rate was 17. 2%, markedly effective rate 34. 5%, effective rate 32.8%, total markedly effective rate 51.7%, and total effective rate 84. 5%, all of which were superior to those in the control group (total markedly effective rate 32.1% and total effective rate 66.1%, respectively), P<0.01. Conclusion: Administration of QLA suppository via anal route combined with oral antibiotics is an effective therapy for chronic prostatitis syndrome. It can relieve the symptoms of chronic prostatitis syndrome markedly and rapidly. It is a new choice for treatment of the disease.

  1. Postural and Balance Disorders in Patients with Parkinson’s Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

    Directory of Open Access Journals (Sweden)

    Andrea Santamato

    2015-01-01

    Full Text Available Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson’s disease (PD to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

  2. Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study

    Science.gov (United States)

    Tolahunase, Madhuri; Sagar, Rajesh

    2017-01-01

    This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p < 0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p = 0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population. PMID:28191278

  3. Open-label study assessing the long-term efficacy and safety of triple olmesartan/amlodipine/hydrochlorothiazide combination therapy for hypertension.

    Science.gov (United States)

    Volpe, Massimo; de la Sierra, Alejandro; Ammentorp, Bettina; Laeis, Petra

    2014-05-01

    To reduce cardiovascular risk associated with hypertension, the majority of patients require at least two drugs to control their blood pressure (BP), and many require three or more. An open-label extension of a 10-week double-blind study assessed the long-term efficacy and safety of olmesartan/amlodipine/hydrochlorothiazide (OLM/AML/HCTZ) triple combination treatment in 2,509 patients with Grade 2-3 hypertension. After 8 weeks of single-blind OLM/AML/HCTZ 20/5/12.5 mg treatment, patients at BP goal [seated systolic/diastolic BP (SeSBP/SeDBP) hypertension, but at study end 91.9% had normal/high-normal BP. The incidence of adverse events was similar across the treatment groups. In patients with Grade 2-3 hypertension, long-term treatment with OLM/AML/HCTZ triple combination therapy was well tolerated and effective. A high level of BP control and a substantial reduction in the level of hypertension severity were achieved.

  4. Safety and efficacy of fimasartan in patients with arterial hypertension (Safe-KanArb study): an open-label observational study.

    Science.gov (United States)

    Park, Jeong Bae; Sung, Ki-Chul; Kang, Seok-Min; Cho, Eun Joo

    2013-02-01

    Angiotensin II receptor blockers (ARBs) play a key role in hypertension therapy. Recently, fimasartan, the ninth ARB, was developed, but its safety and efficacy have not been well established. The objective of this study was to determine whether age, sex, concomitant disease, and current antihypertensive medications affect the safety and efficacy of fimasartan in patients with arterial hypertension. This was a large-scale, open-label observational study to determine the safety and efficacy of fimasartan in patients with hypertension. Patients who were treated for more than 2 months with fimasartan (60 or 120 mg, once daily) were recruited, and the data were systematically collected using electronic case report forms. Written informed consent forms were obtained from all patients. A total of 14,151 patients (50.7 % males; mean age 59 ± 12 years) were evaluated, of whom 37.9 % were never treated with fimasartan, 53.5 % were switched to fimasartan, and 8.5 % had fimasartan added to their treatment. Overall, fimasartan reduced systolic blood pressure (SBP) from 145.4 ± 18.1 to 126.8 ± 12.6 mmHg and diastolic blood pressure (DBP) from 88.7 ± 11.8 to 79.0 ± 8.7 mmHg (all p safety, efficacy, and compliance of fimasartan were found to be excellent in a large patient population that included patients potentially at higher risk for adverse events.

  5. Safety and efficacy of aliskiren/amlodipine/hydrochlorothiazide triple combination in patients with moderate to severe hypertension: a 54-week, open-label study.

    Science.gov (United States)

    Murray, Alexander V; Koenig, Wolfgang; Garcia-Puig, Juan; Patel, Samir; Uddin, Alkaz; Zhang, Jack

    2012-12-01

    Combination antihypertensive therapies are recommended to attain blood pressure (BP) targets especially in high-risk patients in whom rapid and pronounced BP control is essential. This 28- to 54-week, open-label, multicenter study evaluated the safety and efficacy of a triple combination, aliskiren with amlodipine and hydrochlorothiazide (HCTZ), in patients with moderate to severe hypertension. Following a washout period of up to 4 weeks, patients received aliskiren/HCTZ 300/12.5 mg for 1 week, followed by add-on amlodipine 5 mg for 1 week. Thereafter, the doses of amlodipine and HCTZ were doubled. The first 206 of 564 patients who completed 28 weeks of study continued for an additional 26 weeks. Safety was assessed by recording all adverse events. Efficacy variables included changes in BP from baseline to endpoint and BP control rate. Of 564 patients, 493 completed the study. Peripheral edema (9.4%), headache (5.7%), nasopharyngitis (4.1%), and bronchitis (3.7%) were reported frequently. Clinically significant reductions in mean sitting systolic BP/mean sitting diastolic BP from baseline (-34.2/-20.3 mm Hg and -37.3/-21.8 mm Hg at weeks 28 and 54, respectively) were observed. Corresponding BP control rates were 69.1% and 77.1%. The aliskiren/amlodipine/HCTZ combination in patients with moderate to severe hypertension was well tolerated and provided clinically significant BP reductions and effective BP control. © 2012 Wiley Periodicals, Inc.

  6. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study

    Directory of Open Access Journals (Sweden)

    Manish V. Patel

    2015-01-01

    Full Text Available Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda. The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA. In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

  7. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    Science.gov (United States)

    Kühne, Ulrich; Esmann, Jørgen; von Heimburg, Dennis; Imhof, Matthias; Weissenberger, Petra; Sattler, Gerhard

    2016-01-01

    Cohesive polydensified matrix (CPM®) hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS). Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0) and after injection (<0.6). Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. PMID:27799807

  8. Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study.

    Science.gov (United States)

    Tolahunase, Madhuri; Sagar, Rajesh; Dada, Rima

    2017-01-01

    This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p < 0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p = 0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population.

  9. Effect of osmotic-release oral system methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder: an open-label study.

    Science.gov (United States)

    Na, Kyoung-Sae; Lee, Soyoung Irene; Hong, Sungdo David; Kim, Ji-Hoon; Shim, Se-Hoon; Choi, Jeewook; Yang, Jaewon; Lee, Moon-Soo; Joung, Yoo-Sook; Kim, Eui-Jung; Park, Joon-Ho

    2013-07-01

    We evaluated the effect of osmotic-release oral system (OROS) methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder (ADHD). In an open-label study, 121 adolescents with ADHD were administered flexible doses of OROS methylphenidate for 12 weeks. The efficacy of methylphenidate on ADHD symptoms was evaluated by ADHD Rating Scale (ARS) and Clinical Global Impression Scale (CGI). Learning Skills Test (LST) was used to measure the learning skills of the participants at the baseline and the endpoint. Continuous performance test, visuospatial and verbal working memory, verbal fluency, and inhibition were evaluated before and after the 12 weeks of treatment. The mean total and subscores of LST were significantly increased after the 12-week treatment with OROS methylphenidate. Executive functions were also improved during the trial, with the exception of inhibition measured by the Stroop Test. To the best of our knowledge, this is the first study to examine the influence of OROS methylphenidate on learning skill. As a result, OROS methylphenidate was effective in enhancing learning skills in adolescents with ADHD.

  10. Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study.

    Science.gov (United States)

    Eren, Makbule; Dinleyici, Ener C; Vandenplas, Yvan

    2010-03-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

  11. A Prospective, Open Label, Observational Study to Assess the Safety and Efficacy of Herbal Cough Syrup Mykoff® in Patients Suffering from Cough of Varied Aetiologies

    Directory of Open Access Journals (Sweden)

    Mangesh Bhalerao

    2013-06-01

    Full Text Available A prospective, open label, observational study was conducted at general outpatient clinic to assess the safety and efficacy of herbal cough syrup Mykoff® in patients suffering from cough of varied aetiologies. The patients of either sex, age > 3yrs, suffering from cough due to common cold, mild to moderate upper respiratory tract infections, allergic cough and smoker’s cough were enrolled. The safety was evaluated by means of an analysis of adverse events. In addition, efficacy and tolerability were analysed from the following grades by patients and confirmed by doctor. Of 50 patients, 63% were diagnosed with cough due to upper respiratory tract infections, 17% common cold, 12% allergic cough and 8% smoker’s cough. Substantial improvement, i.e., excellent to good response, in relief of cough was noted in 42 (84% out of 50 patients and fair response in another 4 (8%. Only 4 out of 50 patients showed no relief in symptoms. Most of the patients (98% accepted the remedy well. Only one adverse event was reported. However, a relation to the medication was classified to be unlikely. The test drug Mykoff® is an effective and safe cough syrup that is highly acceptable for patients with cough of short duration.

  12. Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment.

    Science.gov (United States)

    Santamato, Andrea; Ranieri, Maurizio; Cinone, Nicoletta; Stuppiello, Lucia Anna; Valeno, Giovanni; De Sanctis, Jula Laura; Fortunato, Francesca; Solfrizzi, Vincenzo; Greco, Antonio; Seripa, Davide; Panza, Francesco

    2015-01-01

    Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

  13. An Open-Label, Multicenter Observational Study for Patients with Alzheimer’s Disease Treated with Memantine in the Clinical Practice

    Directory of Open Access Journals (Sweden)

    S.S. Stamouli

    2011-01-01

    Full Text Available Background/Aims: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer’s disease (AD. Methods: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE and the Instrumental Activities of Daily Living (IADL scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs were also recorded to evaluate the safety profile of memantine. Results: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≧1 ADRs, and treatment was discontinued due to ADR in 0.7%. Conclusion: Memantine was well tolerated and had a positive effect on the patient’s cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

  14. High potency fish oil supplement improves omega-3 fatty acid status in healthy adults: an open-label study using a web-based, virtual platform.

    Science.gov (United States)

    Udani, Jay K; Ritz, Barry W

    2013-08-08

    The health benefits of omega-3 fatty acids from fish are well known, and fish oil supplements are used widely in a preventive manner to compensate the low intake in the general population. The aim of this open-label study was to determine if consumption of a high potency fish oil supplement could improve blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and impact SF-12 mental and physical health scores in healthy adults. A novel virtual clinical research organization was used along with the HS-Omega-3 Index, a measure of EPA and DHA in red blood cell membranes expressed as a percentage of total fatty acids that has been shown to correlate with a reduction in cardiovascular and other risk factors. Briefly, adult subjects (mean age 44 years) were recruited from among U.S. health food store employees and supplemented with 1.1 g/d of omega-3 from fish oil (756 mg EPA, 228 mg DHA, Minami Nutrition MorEPA Platinum) for 120 days (n = 157). Omega-3 status and mental health scores increased with supplementation (p virtual, web-based platform shows considerable potential for engaging in clinical research with normal, healthy subjects. A high potency fish oil supplement may further improve omega-3 status in a healthy population regularly consuming an omega-3 supplement.

  15. Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell™ to traditional in vitro incubation in a randomized open-label prospective controlled trial.

    Science.gov (United States)

    Doody, Kevin J; Broome, E Jason; Doody, Kathleen M

    2016-04-01

    The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcell™ (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre-determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates. In this prospective randomized open-label controlled single-center study, 40 women aged culture. IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p = 0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p = 0.09) or live birth rate (60 % IVF, 55 % IVC). IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcell™ is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care.

  16. Augmentation of antipsychotics with glycine may ameliorate depressive and extrapyramidal symptoms in schizophrenic patients – a preliminary 10-week open-label study

    Directory of Open Access Journals (Sweden)

    Strzelecki, Dominik

    2013-07-01

    Full Text Available Aim. The objective of this study was to analyze the changes in depressive and extrapyramidal symptomatology during glycine augmentation of antipsychotic treatment in patients with schizophrenia.Materials and methods. Twenty-nine schizophrenic patients (ICD-10 with predominant negative symptoms in stable mental state participated in a 10-week open-label prospective study. Patients received stable doses of antipsychotic drugs for at least 3 months before glycine application. During the next 6 weeks patients received augmentation of antipsychotic treatment with glycine (up to 60 g per day. The first and last two weeks of observation were used to assess stability of mental state. Symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS, the Positive and Negative Syndrome Scale (PANSS, and the Simpson-Angus Extrapyramidal Symptom Rating Scale (SASResults. In the studied group after 6 weeks of administration of glycine a significant improvement in depressive symptoms (reduced scores by 25.8% in HDRS, p <0.001 and reduced scoring in mood symptoms of PANSS were observed. In SAS a reduction of extrapyramidal symptoms’ severity (p <0.05 was also noted. Two weeks after the glycine augmentation the symptom severity in the HDRS, PANSS, and SAS remained at similar levels.Conclusions. Glycine augmentation of antipsychotic treatment may reduce the severity of depressive and extrapyramidal symptoms. Glycine use was safe and well tolerated.

  17. Suppressive therapy versus episodic therapy with oral valacyclovir for recurrent herpes labialis: efficacy and tolerability in an open-label, crossover study.

    Science.gov (United States)

    Gilbert, Stanley C

    2007-04-01

    Oral valacyclovir's efficacy and tolerability as suppressive therapy versus episodic therapy were compared for recurrent herpes labialis (RHL). Subjects with a history of at least 3 RHL episodes in the past year were randomized to receive 6 months of oral valacyclovir episodic therapy at the first sign of prodrome (two 2-g doses separated by 12 hours) and 6 months of oral valacyclovir suppressive therapy (1 g once daily) for 6 months in open-label, crossover fashion. The mean +/- SE number of recurrences per 120 days of follow-up (primary endpoint) was lower with suppressive therapy (0.30 +/- 0.41) than episodic therapy (0.71 +/- 0.79) (P 180 days) for suppressive therapy (P = 0.021). Data for secondary efficacy endpoints (pain severity score, mean duration of recurrences, maximal total lesion area) showed approximately a 30% to 50% reduction in mean values with suppressive therapy compared with episodic therapy, but results were statistically significantly different between the regimens for pain severity only. The percentage of subjects with at least one adverse event over 6 months of treatment that was considered to be drug related was 3% with suppressive therapy and 6% with episodic therapy. Suppressive therapy with oral valacyclovir was more effective than episodic therapy with oral valacyclovir in reducing the frequency of recurrences of herpes labialis and prolonging the time to first recurrence and was also similarly well-tolerated.

  18. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients

    Science.gov (United States)

    Camardese, Giovanni; Leone, Beniamino; Serrani, Riccardo; Walstra, Coco; Di Nicola, Marco; Della Marca, Giacomo; Bria, Pietro; Janiri, Luigi

    2015-01-01

    Objectives We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients. Methods In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up. Main outcome measures Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith–Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively. Results The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation. Conclusion BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples. PMID:26396517

  19. Clinical effectiveness and safety of escitalopram and desvenlafaxine in patients of depression with anxiety: a randomized, open-label controlled trial.

    Science.gov (United States)

    Maity, Nabakumar; Ghosal, Malay Kumar; Gupta, Anupam; Sil, Amrita; Chakraborty, Sushmita; Chatterjee, Suparna

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant. Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D17) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician. Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs 73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.

  20. Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study

    Science.gov (United States)

    Müller, Daniel J.; Ng, Chee H.; Byron, Keith; Berk, Michael; Singh, Ajeet B.

    2017-01-01

    Background Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. Objective To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. Materials and methods A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Results Among remitters (n=95), there was a strong concordance (Kendall’s τ-b=0.84, P=0.0001; Cohen’s κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Conclusion Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing. PMID:27779571

  1. Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.

    Science.gov (United States)

    Serrao, Mariano; Ranavolo, Alberto; Conte, Carmela; Davassi, Chiara; Mari, Silvia; Fasano, Alfonso; Chini, Giorgia; Coppola, Gianluca; Draicchio, Francesco; Pierelli, Francesco

    2015-11-01

    The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.

  2. Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial

    Directory of Open Access Journals (Sweden)

    Abdul Rehman Arshad

    2014-01-01

    Full Text Available Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; P=0.011 and 24.34 versus 13.66%; P=0.045, whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94% patients treated with atorvastatin and 8 (12.12% patients treated with rosuvastatin (P: 0.432. Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin.

  3. Noninterventional open-label trial investigating the efficacy and safety of ectoine containing nasal spray in comparison with beclomethasone nasal spray in patients with allergic rhinitis.

    Science.gov (United States)

    Sonnemann, Uwe; Möller, Marcus; Bilstein, Andreas

    2014-01-01

    Objectives. The current study aimed to compare the efficacy and safety of a classical anti-inflammatory beclomethasone nasal spray in comparison to a physic-chemical stabilizing ectoine containing nasal spray in the treatment of allergic rhinitis. Design and Methods. This was a noninterventional, open-label, observational trial investigating the effects of beclomethasone or ectoine nasal spray on nasal symptoms and quality of life. Over a period of 14 days, patients were asked to daily document their symptoms. Efficacy and tolerability were assessed by both physicians and patients. Results. Both treatments resulted in a significant decrease of TNSS values. An equivalence test could not confirm the noninferiority of ectoine treatment in comparison with beclomethasone treatment. Although clear symptom reduction was achieved with the ectoine products, the efficacy judgment showed possible advantages for the beclomethasone group. Importantly, tolerability results were comparably good in both groups, and a very low number of adverse events supported this observation. Both treatments resulted in a clear improvement in the quality of life as assessed by a questionnaire answered at the beginning and at the end of the trial. Conclusion. Taken together, it was shown that allergic rhinitis can be safely and successfully treated with beclomethasone and also efficacy and safety were shown for ectoine nasal spray.

  4. Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial.

    Science.gov (United States)

    Li, F; Xu, M; Qin, C; Xia, L; Xiong, Y; Xi, X; Fan, X; Gu, J; Pu, J; Wu, Q; Lu, S; Wang, G

    2016-10-01

    We sought to assess the accuracy and safety of the ESAT6-CFP10 reagent in diagnosing tuberculosis (TB) disease. An open-label, randomized phase 2a trial was conducted in 56 healthy adults and 88 TB patients at one medical centre and one teaching hospital in China. All participants received 0.1, 0.5, 1 or 2 μg ESAT6-CFP10 in their right forearm. Moreover, 56 healthy volunteers and 56 patients were given tuberculin-purified protein derivative (TB-PPD) in their left forearm. The remaining 32 patients were administered placebo. The main outcome measure was induration diameter. An enzyme-linked immunospot (ELISPOT) assay was conducted before the skin test. The ESAT6-CFP10 test caused a higher positivity rate than placebo (81.2% (26/32) vs. 3.1% (1/32); p skin test appears to be a safe and promising tool; further testing will confirm its efficacy in identifying TB disease. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    Science.gov (United States)

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

  6. An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR in Treatment-Naive Patients with Hepatitis C Virus (HCV Genotype 1 (GT1.

    Directory of Open Access Journals (Sweden)

    Tarik Asselah

    Full Text Available Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12 and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA 12-week regimen.Overall SVR12 rate (66% was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.ClinicalTrials.gov NCT01846832.

  7. Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon: An open-label pilot study

    Institute of Scientific and Technical Information of China (English)

    Th Witthoeft; M Fuchs; D Ludwig

    2007-01-01

    AIM: To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C.METHODS: We started, before pegylated (PEG)interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon (CIFN) and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72.RESULTS: More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively,showing a negative qualitative PCR [genotype 1 fourteen patients (56%), genotype 2 five (50%),genotype 3 thirteen (87%), genotype 4 four (50%)].Forty-eight percent of genotype 1 patients showed sustained virological response (SVR) six months after the treatment.CONCLUSION: CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy (EOT) rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GT1 and high viral load or for non-responders after failure of standard therapy.

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

    Science.gov (United States)

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

    2016-07-01

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

  9. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  10. The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.

    Science.gov (United States)

    Mühlbacher, Ferdinand; Neumayer, Hans-Helmut; del Castillo, Domingo; Stefoni, Sergio; Zygmunt, Anthony J; Budde, Klemens

    2014-02-01

    This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open-label, 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post-transplantation, 357 patients were randomized to receive standard-dose cyclosporine (sCsA, n = 179) or reduced-dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy-confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long-term renal allograft outcomes. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

  11. Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Lindahl, L M; Gniadecki, Robert

    2011-01-01

    Background: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphomas (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36 Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited...... due to the cumulative toxicity. Complete response rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. Objectives: To evaluate prospectively the efficacy of low-dose TSEBT (10 Gy) in terms of complete cutaneous response rate, overall response rate...... and response duration in CTCL. Methods: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with 4 fractions of 1 Gy/week TSEB to a total skin dose of 10 Gy. Treatment responses were assessed at 1 and 3 months after treatment and subsequently at least every 6 months...

  12. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Jahan Ara Ainuddin

    2015-01-01

    Full Text Available Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P24 hours in metformin group (P<0.01. Significant reduction in cost of treatment was found in metformin group. Conclusion. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763.

  13. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

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    Jenneke Leentjens

    Full Text Available RATIONALE: To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use. METHODS: We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity. RESULTS: β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan. CONCLUSION: The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01727895.

  14. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

    DEFF Research Database (Denmark)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

    2007-01-01

    suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  15. Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

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    Dunbar Lala M

    2005-05-01

    Full Text Available Abstract Background Community-acquired pneumonia (CAP remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. Methods The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. Results Of 149 microbiologically evaluable patients, 57 (9 bacteremic had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%, Moraxella catarrhalis (100%, Staphylococcus aureus (80%, and Legionella spp. (100%. The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%. In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1% and nausea (5.8%. Conclusion Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.

  16. Noninterventional Open-Label Trial Investigating the Efficacy and Safety of Ectoine Containing Nasal Spray in Comparison with Beclomethasone Nasal Spray in Patients with Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Uwe Sonnemann

    2014-01-01

    Full Text Available Objectives. The current study aimed to compare the efficacy and safety of a classical anti-inflammatory beclomethasone nasal spray in comparison to a physic-chemical stabilizing ectoine containing nasal spray in the treatment of allergic rhinitis. Design and Methods. This was a noninterventional, open-label, observational trial investigating the effects of beclomethasone or ectoine nasal spray on nasal symptoms and quality of life. Over a period of 14 days, patients were asked to daily document their symptoms. Efficacy and tolerability were assessed by both physicians and patients. Results. Both treatments resulted in a significant decrease of TNSS values. An equivalence test could not confirm the noninferiority of ectoine treatment in comparison with beclomethasone treatment. Although clear symptom reduction was achieved with the ectoine products, the efficacy judgment showed possible advantages for the beclomethasone group. Importantly, tolerability results were comparably good in both groups, and a very low number of adverse events supported this observation. Both treatments resulted in a clear improvement in the quality of life as assessed by a questionnaire answered at the beginning and at the end of the trial. Conclusion. Taken together, it was shown that allergic rhinitis can be safely and successfully treated with beclomethasone and also efficacy and safety were shown for ectoine nasal spray.

  17. Cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in the treatment of lumbar disc herniation : A prospective randomised controlled trial [ISRCTN51857546

    NARCIS (Netherlands)

    M.P. Arts (Mark); W.C. Peul (Wilco); R. Brand (René); B.W. Koes (Bart); R.T.W.M. Thomeer (Raph)

    2006-01-01

    textabstractBackground: Open discectomy is the standard surgical procedure in the treatment of patients with long-lasting sciatica caused by lumbar disc herniation. Minimally invasive approaches such as microendoscopic discectomy have gained attention in recent years. Reduced tissue trauma allows ea

  18. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group.

    Science.gov (United States)

    Peyrade, Frédéric; Bologna, Serge; Delwail, Vincent; Emile, Jean François; Pascal, Laurent; Fermé, Christophe; Schiano, Jean-Marc; Coiffier, Bertrand; Corront, Bernadette; Farhat, Hassan; Fruchart, Christophe; Ghesquieres, Herve; Macro, Margaret; Tilly, Hervé; Choufi, Bachra; Delarue, Richard; Fitoussi, Olivier; Gabarre, Jean; Haioun, Corinne; Jardin, Fabrice

    2017-01-01

    In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49-67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day -7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day -7 to day -4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m(2) of intravenous doxorubicin, 400 mg/m(2) of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m(2) of oral prednisone on days 1-5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714. Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2-3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5-30·1). The 2-year overall survival was 64·7% (95% CI 55·3-72·7) and median overall survival was not reached (95% CI 30·2-not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients

  19. Effects of institutional rearing and foster care on psychopathology at age 12 years in Romania: follow-up of an open, randomised controlled trial.

    Science.gov (United States)

    Humphreys, Kathryn L; Gleason, Mary Margaret; Drury, Stacy S; Miron, Devi; Nelson, Charles A; Fox, Nathan A; Zeanah, Charles H

    2015-07-01

    Early social deprivation can negatively affect domains of functioning. We examined psychopathology at age 12 years in a cohort of Romanian children who had been abandoned at birth and placed into institutional care, then assigned either to be placed in foster care or to care as usual. We used follow-up data from the Bucharest Early Intervention Project (BEIP), a randomised controlled trial of abandoned children in all six institutions for young children in Bucharest, Romania. In the initial trial, 136 children, enrolled between ages 6-31 months, were randomly assigned to either care as usual or placement in foster care. In this study we followed up these children at age 12 years to assess psychiatric symptoms using the Diagnostic Interview Schedule for Children (4th edition; DISC-IV). We also recruited Romanian children who had never been placed in an institution from paediatric clinics and schools in Bucharest as a comparator group who had never been placed in an institution. The primary outcome measure was symptom counts assessed through DISC-IV scores for three domains of psychopathology: internalising symptoms, externalising symptoms, and attention-deficit hyperactivity disorder (ADHD). We compared mean DISC-IV scores between trial participants and comparators who had never been placed in an institution, and those assigned to care as usual or foster care. Analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747396. We followed up 110 children from the BEIP trial between Jan 27, 2011, and April 11, 2014, and 49 children as comparators who had never been placed in an institution. The 110 children who had ever been placed in an institution had higher symptom counts for internalising disorders (mean 0·93 [SD 1·68] vs 0·45 [0·84], difference 0·48 [95% CI 0·14-0·82]; p=0·0127), externalising disorders (2·31 [2·86] vs 0·65 [1·33], difference 1·66 [1·06-2·25]; pcare as usual, the 55 children in

  20. Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial.

    Science.gov (United States)

    Lipsman, Nir; Lam, Eileen; Volpini, Matthew; Sutandar, Kalam; Twose, Richelle; Giacobbe, Peter; Sodums, Devin J; Smith, Gwenn S; Woodside, D Blake; Lozano, Andres M

    2017-04-01

    Anorexia nervosa is a life-threatening illness. Brain circuits believed to drive anorexia nervosa symptoms can be accessed with surgical techniques such as deep brain stimulation (DBS). Initial results suggest that DBS of the subcallosal cingulate is safe and associated with improvements in mood and anxiety. Here, we investigated the safety, clinical, and neuroimaging outcomes of DBS of the subcallosal cingulate in a group of patients during 12 months of active stimulation. We did this prospective open-label trial at the Department of Surgery of the University of Toronto (Toronto, ON, Canada). Patients were eligible to participate if they were aged 20-60 years and had a diagnosis of anorexia nervosa (restricting or binge-purging subtype) and a demonstrated history of chronicity or treatment resistance. Following a period of medical stabilisation, patients underwent surgery for DBS and received open-label continuous stimulation for the entire 1 year study duration. The primary outcome was safety and acceptability of the procedure. The secondary outcomes were body-mass index (BMI), mood, anxiety, affective regulation, and anorexia nervosa-specific behaviours at 12 months after surgery, as well as changes in neural circuitry (measured with PET imaging of cerebral glucose metabolism at baseline and at 6 and 12 months after surgery). This trial was registered with ClinicalTrials.gov, number NCT01476540. 16 patients with treatment-refractory anorexia nervosa were enrolled between September, 2011, and January, 2014, and underwent DBS of the subcallosal cingulate between November, 2011, and April, 2014. Patients had a mean age of 34 years (SD 8) and average illness duration of 18 years (SD 6). Two patients requested that their devices be removed or deactivated during the study, although their reasons for doing so were poorly defined. The most common adverse event was pain related to surgical incision or positioning that required oral analgesics for longer than 3-4 days

  1. Long-term health-related quality of life improvements among patients treated with lurasidone: results from the open-label extension of a switch trial in schizophrenia.

    Science.gov (United States)

    Awad, George; Ng-Mak, Daisy; Rajagopalan, Krithika; Hsu, Jay; Pikalov, Andrei; Loebel, Antony

    2016-06-01

    Long-term improvement of health-related quality of life (HRQoL) in schizophrenia may improve adherence and reduce relapse and rehospitalization. This analysis examines long-term changes in HRQoL among patients with schizophrenia switched to lurasidone from other antipsychotics. Patients who completed an open-label 6-week switch study continued on lurasidone for an additional 24-weeks. HRQoL was measured using the self-reported Personal Evaluation of Transitions in Treatment (PETiT) scale and Short-Form 12 (SF-12) questionnaire. The PETiT assessed HRQoL via total and domain scores (adherence-related attitude and psychosocial functioning). The SF-12 assessed patients' mental and physical component summary scores (MCS and PCS). Mean changes from the initial baseline were calculated at extension baseline and extension endpoint using analysis of covariance models. Analyses were further stratified by prior antipsychotic medication and responder status; responders were defined as having a ≥20 % improvement in Positive and Negative Syndrome Scale during the first 6-weeks of treatment. The analysis included 144 patients with PETIT or SF-12 data who received ≥1 dose of lurasidone. Mean (standard deviation) PETiT total score improved significantly from 34.9 (9.3) at baseline to 39.5 (8.9) at extension baseline and 39.1 (9.0) at extension endpoint, representing improvements of 4.5 (7.9) and 5.1 (7.2) points, respectively (both p schizophrenia experienced HRQoL improvements that were sustained for an additional 24 weeks of treatment. Further study is warranted to understand the implications of these improvements in terms of employment, adherence, relapse, and rehospitalization. Clinical trials.gov identifier NCT01143090 (June 10th, 2010).

  2. Open-Label Treatment of Moderate or Marked Melasma with a 4% Hydroquinone Skin Care System Plus 0.05% Tretinoin Cream

    Science.gov (United States)

    Rendon, Marta; Dibernardo, Barry; Bruce, Suzanne; Lucas-Anthony, Chere; Watson, Joanne

    2013-01-01

    Objective: To evaluate treating epidermal melasma using a 4% hydroquinone skin care system plus tretinoin 0.05% cream. Design: Multicenter open-label study with all patients receiving above-mentioned treatment for up to 24 weeks. Setting: Private dermatology and plastic surgery clinics and clinical research facilities. Participants: Thirty-seven adult females with moderate or marked epidermal melasma, melasma pigmentation of mild-to-marked intensity and Fitzpatrick skin type III to VI. Measurements: Melasma severity melasma pigmentation intensity melasma improvement, patient satisfaction, quality-of-life measures, erythema, dryness, peeling, burning/stinging. Results: No patient discontinued due to lack of efficacy or treatment-related adverse events. Treatment was associated with a significant reduction from baseline in melasma severity and melasma pigmentation intensity from Week 4 onward (P≤0.001), and 100 percent of patients showed improvement from Week 8 onward. At Week 24, 100 percent of patients were “satisfied” or “very satisfied” with the overall effectiveness of their treatment. Patients’ quality of life also improved (e.g., the proportion of patients feeling embarrassed or self-conscious about their skin “a lot” or “very much” declined from 78 percent at baseline to four percent at Week 24). Mean and median scores for erythema, dryness, peeling, and burning/stinging did not exceed trace levels. Conclusion: Treating moderate-to-severe melasma using the 4% hydroquinone skin care system plus 0.05% tretinoin can significantly reduce the severity of melasma and the intensity of melasma pigmentation within four weeks. Treatment was generally well tolerated and associated with an improved quality of life and high levels of patient satisfaction. PMID:24307923

  3. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study

    Science.gov (United States)

    Gattorno, Marco; Obici, Laura; Cattalini, Marco; Tormey, Vincent; Abrams, Ken; Davis, Nicole; Speziale, Antonio; Bhansali, Suraj G; Martini, Alberto; Lachmann, Helen J

    2017-01-01

    Objective To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1β antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Twenty patients (aged 7–78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those ≤40 kg) in this open-label, proof-of-concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score ≤1) and full or partial serological remission. Results Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data. Conclusions Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment. Trial registration number NCT01242813; Results. PMID:27269295

  4. Rapid and efficient localization of depth electrodes and cortical labeling using free and open source medical software in epilepsy surgery candidates

    Science.gov (United States)

    Princich, Juan Pablo; Wassermann, Demian; Latini, Facundo; Oddo, Silvia; Blenkmann, Alejandro Omar; Seifer, Gustavo; Kochen, Silvia

    2013-01-01

    Depth intracranial electrodes (IEs) placement is one of the most used procedures to identify the epileptogenic zone (EZ) in surgical treatment of drug resistant epilepsy patients, about 20–30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome. We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients. All IEs were identified in the first 24 H (6–24 H) of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients), 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available. To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 IEs) using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis. PMID:24427112

  5. HEAD - TO - HEAD COMPARISON OF TOLERABILITY AND ACCEPTABILITY OF SINGLE DOSE OF FOUR TOPICAL NSAIDS IN PATIENTS UNDERGOING CATARACT SURGERY : A RANDOMIZED OPEN LABEL PARALLEL GROUP STUDY

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar

    2015-07-01

    Full Text Available INTRODUCTION : Ophthalmic NSAIDs are used to control pain , discomfort and inflammation associated with ocular conditions and also , following ophthalmic cataract surgeries. These drugs can cause ocular discomfort following administration which lasts for a short duration. However , there exist differences in the intensity and duration of burning sensation among the c ommonly used ophthalmic NSAIDs. Hence , we evaluated the tolerability and acceptability of four topical NSAIDS i.e. , 0.3% nepafenac (N , 0.5% ketorolac (K , 0.4% ketorolac (K LS and 0.09% bromfenac (B after instilling a single drop. METHODS: This randomized , open label , parallel group study was conducted in the department of Ophthalmology in Narayana Medical College , Nellore. A total number of 80 patients participated in the study. Randomization list was computer generated in a ratio of 1:1:1:1 of N , K , K L Sand B. Each patient received one drop of the study drug either in right or left eye which was also decidedat random.Patients of either gender above21 years of age , having no ocular surface pathology and eligible for cataract surgery were include d in the study. Outcome variables included ocular burning intensity on VAS (0 - 100 mm at 0 min (immediately , 2 min and 6 min after administration of medications , time to complete pain relief and global medication performance rated by patient as 0 (bad , 1 (fair , 2(good or 3 (severe . RESULTS: The mean age of patients was 52.85±17.46 years. All groups were age matched , however there were more females than males (pN>K LS >K on global medication performance. CONCLUSION: Bromfenac had better tolerability and acceptability as compared to other tested topical NSAIDs , which was in the order of B>N> K LS >K.

  6. Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study.

    Science.gov (United States)

    Yeh, Ming-Lun; Huang, Ching-I; Hsieh, Ming-Yen; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Dai, Chia-Yen; Lin, Zu-Yau; Chen, Shinn-Chern; Yu, Ming-Lung; Chuang, Wan-Long

    2016-11-01

    The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients. Copyright © 2016 Kaohsiung Medical University. Published by Elsevier Taiwan.. All rights reserved.

  7. Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Ming-Lun Yeh

    2016-11-01

    Full Text Available The subsequent maintenance therapy in chronic hepatitis B (CHB patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV DNA after 3 years of entecavir (ETV therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL. A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p < 0.001. However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001. LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(side analogue therapy is mandatory for prevention of viral relapse in CHB patients.

  8. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study.

    Science.gov (United States)

    Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro

    2017-07-06

    We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [P=0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P=0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P=0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.

    Science.gov (United States)

    Santos, Raul D; Duell, P Barton; East, Cara; Guyton, John R; Moriarty, Patrick M; Chin, Wai; Mittleman, Robert S

    2015-03-01

    To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. CLINICALTRIALS.GOV: NCT00694109. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

  10. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

    Science.gov (United States)

    Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

    2005-08-01

    Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

  11. Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid) for the treatment of osteoarthritis of the thumb

    Science.gov (United States)

    Velasco, Eloisa; Ribera, Mª Victoria; Pi, Joan

    2017-01-01

    Introduction Osteoarthritis of the trapeziometacarpal (TMC) joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid) in rhizarthrosis. Patients and methods This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS) pain score ≥4 (scale: 0–10). A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score. Results Thirty-five patients (mean age 60.8 years; 85.7% female) received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was −2.00, a reduction of 27.8% (pKapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP) joint flexion, and pinch (clamp) strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five adverse events (injection site reactions) were reported in four patients (11.4%), and there were no serious or allergic reactions. Conclusion This study suggests that viscosupplementation using NASHA is effective and well tolerated in treating the symptoms of rhizarthrosis. PMID:28392718

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

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

    2014-01-01

    Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to olmesartan. All reported adverse events were recorded. A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  13. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

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    Kühne U

    2016-10-01

    Full Text Available Ulrich Kühne,1 Jørgen Esmann,2 Dennis von Heimburg,3 Matthias Imhof,1 Petra Weissenberger,4 Gerhard Sattler,5 On behalf of the BALIA Study Group 1Aesthetische Dermatologie im Medico Palais, Bad Soden, Germany; 2Jørgen Esmann Aps, Hellerup, Denmark; 3Praxisklinik Kaiserplatz, Frankfurt am Main, Germany; 4Corporate Clinical Research, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 5Rosenparkklinik GmbH, Darmstadt, Germany Abstract: Cohesive polydensified matrix (CPM® hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS. Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0 and after injection (<0.6. Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. Keywords: cohesive polydensified matrix, dermal fillers, Belotero, Esthélis, Fortélis, Modélis

  14. Effect of phenylephrine vs. ephedrine on frontal lobe oxygenation during caesarean section with spinal anesthesia: an open label randomized controlled trial

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    Foss, Visti T.; Christensen, Robin; Rokamp, Kim Z.; Nissen, Peter; Secher, Niels H.; Nielsen, Henning B.

    2014-01-01

    Background: During caesarean section spinal anesthesia may provoke maternal hypotension that we prevent by administration of phenylephrine and/or ephedrine. Phenylephrine is however reported to reduce the near infrared spectroscopy-determined frontal lobe oxygenation (ScO2) but whether that is the case for patients exposed to spinal anesthesia is not known. Objectives: To evaluate the impact of phenylephrine vs. ephedrine on ScO2during caesarean section with spinal anesthesia in a single center, open-label parallel-group study with balanced randomization of 24 women (1:1). Secondary aims were to compare the effect of the two drugs on maternal hemodynamics and fetal heart rate. Intervention: Ephedrine (0.8–3.3 mg/min) vs. phenylephrine infusion (0.02–0.07 mg/min). Results: For the duration of surgery, administration of ephedrine maintained ScO2 (compared to baseline +2.1 ± 2.8%; mean ± SE, while phenylephrine reduced ScO2 (−8.6 ± 2.8%; p = 0.005) with a 10.7% difference in ScO2between groups (p = 0.0106). Also maternal heart rate was maintained with ephedrine (+3 ± 3 bpm) but decreased with phenylephrine (−11 ± 3 bpm); difference 14 bpm (p = 0.0053), but no significant difference in mean arterial pressure (p = 0.1904) or CO (p = 0.0683) was observed between groups. The two drugs also elicited an equal increase in fetal heart rate (by 19 ± 3 vs. 18 ± 3 bpm; p = 0.744). Conclusion: In the choice between phenylephrine and ephedrine for maintenance of blood pressure during caesarean section with spinal anesthesia, ephedrine maintains frontal lobe oxygenation and maternal heart rate with a similar increase in fetal heart rate as elicited by phenylephrine. Trial registration: Clinical trials NCT 01509521 and EudraCT 2001 006103 35. PMID:24624090

  15. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

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    Harmatz, Paul R; Mengel, Eugen; Geberhiwot, Tarekegn; Muschol, Nicole; Hendriksz, Christian J; Burton, Barbara K; Jameson, Elisabeth; Berger, Kenneth I; Jester, Andrea; Treadwell, Marsha; Sisic, Zlatko; Decker, Celeste

    2017-02-01

    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  16. Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

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    Mascarenhas, John O.; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M.; Savona, Michael R.; Paquette, Ronald; Turner, A. Robert; Coughlin, Paul; Winton, Elliott; Burn, Timothy C.; O’Neill, Peter; Clark, Jason; Hunter, Deborah; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan

    2017-01-01

    Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×109/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1–24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression. PMID:27789678

  17. Comparative randomized open-label trial on efficacy and safety of Persen® and Persen® Night herbal extracts in patients with short-term insomnia

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    A. P. Rachin

    2016-01-01

    Full Text Available Herbal sedatives serve an alternative to antipsychotics and hypnotics aimed to alleviate symptoms of anxious disorders and insomnia. Valeriana officinalis L., Mentha piperita L. and Melissa officinalis are most widely used in neurology as sedatives of herbal origin. We present the results of a randomized open-label trial on efficiency and safety of Persen® and Persen® Night containing extracts of the above mentioned plants in patients with short-term insomnia. The study consisted of 60 subjects of 18–65 y.o. (mean 42.4 ± 6.9 y.o. with short-term insomnia due to adjustment disorder or mixed anxiety-depressive disorders: 30 of them got Persen® 2 tablets a day and 30 – Persen® Night, 1 capsule 30–60 min before sleep during 4 weeks. The majority (76.5 % of patients referred the onset of insomnia with psychosocial traumatic stressor. Persen® Night’s main action was found on superficial sleep, number of night awakenings, sleep onset rate. At the end of the therapy with this substance 39.7 % of patients fell asleep in 10–15 min, and 92.2 % – in 30 min, accordingly, while for Persen® at 17.4 and 80.3 % accordingly (р < 0.05. In the meantime Persen® decreased the bad sleep perception at awakening and day somnolence, mostly attributed to the mood improvement and decrease of anxiety. Levels of efficacy and safety for both substances were significant, allowing to regard them as potential phytotherapeutic agent in the treatment of insomnia and mixed anxiety-depressive disorders.

  18. Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators

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    Frank Samuel

    2009-12-01

    Full Text Available Abstract Background Tetrabenazine (TBZ selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (Neurology 2006;66:366-372. The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD. Methods Subjects who completed the 13-week, double blind protocol were invited to participate in this open label extension study for up to 80 weeks. Subjects were titrated to the best individual dose or a maximum of 200 mg/day. Chorea was assessed using the Total Maximal Chorea (TMC score from the Unified Huntington Disease Rating Scale. Results Of the 75 participants, 45 subjects completed 80 weeks. Three participants terminated due to adverse events (AEs including depression, delusions with associated previous suicidal behavior, and vocal tics. One subject died due to breast cancer. The other 26 subjects chose not to continue on with each ensuing extension for various reasons. When mild and unrelated AEs were excluded, the most commonly reported AEs (number of subjects were sedation/somnolence (18, depressed mood (17, anxiety (13, insomnia (10, and akathisia (9. Parkinsonism and dysphagia scores were significantly increased at week 80 compared to baseline. At week 80, chorea had significantly improved from baseline with a mean reduction in the TMC score of 4.6 (SD 5.5 units. The mean dosage at week 80 was 63.4 mg (range 12.5-175 mg. Conclusions TBZ effectively suppresses HD-related chorea for up to 80 weeks. Patients treated chronically with TBZ should be monitored for parkinsonism, dysphagia and other side effects including sleep disturbance, depression, anxiety, and akathisia. Trial Registration Clinicaltrials.gov registration number (initial study: NCT00219804

  19. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

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    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  20. Improvement of executive functions in boys with attention deficit hyperactivity disorder: an open-label follow-up study with once-daily atomoxetine.

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    Gau, Susan Shur-Fen; Shang, Chi-Yung

    2010-03-01

    Atomoxetine is efficacious in reducing symptoms of attention deficit hyperactivity disorder (ADHD) but its effect on executive functions needs more investigation. We examined the effect of atomoxetine on a wide range of non-verbal executive functions among 30 drug-naive male patients with DSM-IV ADHD, aged 8-16 yr, in an open-label 12-wk atomoxetine treatment trial. Before administration of atomoxetine, the participants were assessed by psychiatric interviews, the WISC-III, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Rapid Visual Information Processing (RVIP), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC); and reassessed at weeks 4 and 12. All the raw scores of the CANTAB were transformed to z scores based on a normative sample of 180 children aged 8-16 yr. Results showed significant improvement in executive functions after treatment with atomoxetine for 4 wk or 12 wk including improved shifting and flexibility of attention in the IED; improved spatial short-term memory in the SSP; improved sustained attention and increased response inhibition in the RVIP; improved spatial working memory in the SWM; and improved spatial planning and problem solving in the SOC. Our findings suggested that atomoxetine was associated with significant improvement in various non-verbal executive functions among boys with ADHD, in addition to its well-known efficacy in ADHD-related symptom reductions. However, owing to lack of a placebo-controlled trial design, the findings should be interpreted with caution that changes in performance may be due to practice effects.

  1. INFLUENCE OF GRADED AEROBIC EXERCISE ON QUALITY OF LIFE IN POST SURGICAL MITRAL VALVE DISEASE INDIVIDUAL A PROSPECTIVE RANDOMIZED OPEN LABEL STUDY

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    Shanthi C

    2016-10-01

    Full Text Available Background: Post surgical mitral valve disease individual focus their cardiac rehabilitation training on two major goal that is to improve cardiac output response exercises and place an important role in determining exercise tolerance and to improve quality of life. Cardiac rehabilitation programs involve prescribed exercise and education however various other method are being used to improve quality of life. But our study to find out the effectiveness of graded aerobic exercise protocol on ejection fraction and quality of life in post surgical mitral valve disease individuals. Methods: The study design was open label studies total of 100 post surgical mitral valve disease individuals patients from the age group of 20-60 years were recruited from SVIMS hospital. They were randomly divided into two groups. Group I underwent a twelve week structured graded individually tailored exercises. The group II received only none graded (not individualized exercise training. The ejection fraction and quality of life was measured before and after 12 weeks of exercise training for two groups. Results: Repeated measures ANOVA was used to compare mean values of continuous variables between baseline and at the time of discharge and three months after surgery for each parameter. Comparison of means between groups was done by the unpaired student t test. Mean age of the subjects was 40.18±10.29. There was a significant increase in the ejection fraction in the group I(61.34±2.49 to 64.4±3.31 compared to with the group II (61.06±2.51. to 61.62 ±2.37. QOL had improved in group I than group II at p<0.05. Conclusion: A 12 week structured graded aerobic exercise training significantly improved ejection fraction and quality of life in post surgical mitral valve disease individuals.

  2. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

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    Ayuso Carmen

    2010-05-01

    Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

  3. Classic high lateral tension and triangular resection methods to prevent dog ear and elongation scar in patients undergoing abdominoplasty: A comparative open-label clinical trial

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    Hossein Abdali

    2017-01-01

    Full Text Available Background: One of the most common operations in the plastic surgery curse is abdominoplasty. Several methods were recommended for achieving better results. In the present study, efficacy of a new method compared with classical high lateral tension on preventing dog ear and elongation scar was evaluated. Materials and Methods: in an open-label, randomized clinical trial, seventy patients who were candidates for abdominoplasty were selected and randomly divided into two groups. The first group was operated by classic high lateral method and the second group was operated by a new method concentrating on changing incision line and angle. Dog ear prevention, length of scar, improvement, and postoperative complications were compared between the two groups. Results: The mean ± standard deviation (SD length of scar in treated patients with classical and new abdominoplasty surgical methods was 53.68 ± 6.34 and 41.71 ± 1.78 cm, respectively, and the length of scar in the group treated with the new method was significantly shorter (P < 0.001. The mean ± SD distance between two anterior superior iliac spine in group treated by new method was significantly decreased after surgery (31.3 ± 1.3 cm compared to before intervention (36.7 ± 3.9 cm (P < 0.01. Conclusion: The new method is more likely to be successful in patients with high lateral tension abdominoplasty. However, according to the lack of similar studies in this regard and the fact that this method was introduced for the first time, it is recommended that further studies in this area are needed and patients in term of complications after surgery need a longer period of follow-up.

  4. Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: open-label extension of the SOFIA trial.

    Science.gov (United States)

    Wagg, Adrian; Khullar, Vik; Michel, Martin C; Oelke, Matthias; Darekar, Amanda; Bitoun, Caty Ebel

    2014-01-01

    To assess the long-term safety, tolerability, and efficacy of flexible-dose fesoterodine in elderly patients with OAB. Patients aged ≥65 years who completed a 12-week, randomized, double-blind, placebo-controlled trial were eligible for the 12-week, open-label (OL) extension phase. Patients who received double-blind placebo started on fesoterodine 4 mg and could increase to 8 mg after 4 or 8 weeks of OL treatment, while fesoterodine-treated patients continued on their double-blind dose; only one dose escalation or de-escalation was permitted. Discontinuations and adverse events (AEs) were monitored, and patients completed 3-day bladder diaries and patient-reported outcomes at the beginning and end of the 12-week OL phase. Six hundred fifty-four patients entered the 12-week OL extension (mean age 72 years; 52% women). AEs were reported by 30.7% and 48.1% of patients who had received double-blind fesoterodine and placebo, respectively; 1.9% and 9.4%, discontinued due to AEs, respectively. Patients who received double-blind fesoterodine maintained their efficacy response. After 12 weeks of OL treatment, efficacy outcomes in patients who received double-blind placebo were similar to those who had received double-blind fesoterodine. On average, the efficacy response was maintained for the duration of the study. Fesoterodine was well tolerated and improvements in OAB symptoms and quality of life measures were not diminished with longer-term treatment of patients aged ≥65 years. © 2013 Wiley Periodicals, Inc.

  5. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

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    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  6. Polyacrylamide hydrogel injection in the management of human immunodeficiency virus-related facial lipoatrophy: results of the LIPOPHILL open-label study.

    Science.gov (United States)

    Mole, Bernard; Gillaizeau, Florence; Carbonnel, Elisabeth; Pierre, Isabelle; Brazille, Patricia; Grataloup, Christine; Mercier, Sylvie; Duracinsky, Martin; Weiss, Laurence; Piketty, Christophe

    2012-03-01

    Combination antiretroviral therapy (cART) can cause potentially stigmatizing facial lipoatrophy. Encouraging preliminary results have been reported with 2.5% polyacrylamide hydrogel for facial reconstruction. The aim of this multicenter, open-label noncomparative pilot study was to evaluate the efficacy and safety of intradermal facial injections of polyacrylamide hydrogel in HIV-infected patients with severe facial lipoatrophy. The patients received between two and six injections every 4 weeks, according to the aesthetic results. Clinical efficacy was evaluated by means of facial ultrasonography and photography at baseline and months 6, 12, and 24. Adverse events, patient satisfaction, and quality of life were also assessed. One hundred and eleven patients were enrolled and received at least one injection. Mean cheek skin thickness was 9.7 mm [95% CI: 9.1 to 10.2] at baseline. It rose by an average of 4.4 mm [95% CI: 3.9 to 4.9; p<0.001] at month 12 and a further 0.87 mm [95% CI: 0.52 to 1.23; p<0.001] at month 24. The Overall Treatment Satisfaction scale showed an improvement in more than 88% of patients at all visits, based on the appreciations of the patients, their close relatives and physicians, and on independent assessment of facial photographs. Quality of life improved significantly over time, as shown by the lipodystrophy-specific ABCD scale. No severe adverse effects related to the polyacrylamide hydrogel were noted. Polyacrylamide hydrogel injections were well tolerated and significantly improved the aesthetic aspect and quality of life of HIV-infected patients with facial lipoatrophy.

  7. An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

    Science.gov (United States)

    DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

    2015-05-01

    Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

  8. Rapid and efficient localization of depth electrodes and cortical labeling using free and open source medical software in epilepsy surgery candidates.

    Science.gov (United States)

    Princich, Juan Pablo; Wassermann, Demian; Latini, Facundo; Oddo, Silvia; Blenkmann, Alejandro Omar; Seifer, Gustavo; Kochen, Silvia

    2013-01-01

    Depth intracranial electrodes (IEs) placement is one of the most used procedures to identify the epileptogenic zone (EZ) in surgical treatment of drug resistant epilepsy patients, about 20-30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome. We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients. All IEs were identified in the first 24 H (6-24 H) of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients), 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available. To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 IEs) using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis.

  9. Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.

    Science.gov (United States)

    Chopra, Arvind; Chandrashekara, S; Iyer, Rajgopalan; Rajasekhar, Liza; Shetty, Naresh; Veeravalli, Sarathchandra Mouli; Ghosh, Alakendu; Merchant, Mrugank; Oak, Jyotsna; Londhey, Vikram; Barve, Abhijit; Ramakrishnan, M S; Montero, Enrique

    2016-04-01

    The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

  10. Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials.

    Science.gov (United States)

    Lee, Deborah; Kalu, Uwa; Halford, Jonathan J; Biton, Victor; Cloyd, James; Klein, Pavel; Bekersky, Ihor; Peng, Guangbin; Dheerendra, Suresh; Tolbert, Dwain

    2015-06-01

    To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959). Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations. Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥ 5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received oral and IV carbamazepine. IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations. © 2015 Lundbeck LLC. Epilepsia published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

  11. An Open Label Clinical Trial of a Multi-Ingredient Anti-Aging Moisturizer Designed to Improve the Appearance of Facial Skin.

    Science.gov (United States)

    Herndon, James H; Jiang, Lily; Kononov, Tatiana; Fox, Theresa

    2015-07-01

    An open label clinical trial was conducted to determine the effectiveness of a multi-ingredient anti-aging moisturizer designed to improve the appearance of facial skin. Parameters studied included fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, evenness of skin tone (redness), evenness of skin tone (hyperpigmentation) and overall appearance. Thirty-seven female subjects, ages 35-60 years completed the study. Effective ingredients incorporated into the facial anti-aging moisturizer include: Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate) and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer twice daily, once in the morning and once in the evening. Subjects were evaluated at baseline and after 4, 8, and 12 weeks of product usage. Clinical evaluations were conducted at each visit. A self-assessment questionnaire was conducted at week 4, week 8, and week 12. The self-assessment questionnaire included product efficacy inquiries and product aesthetic inquiries. Digital photography was conducted at baseline, week 8, and week 12. After 8 weeks of twice daily use, clinical evaluation results show that the multi-ingredient anti-aging moisturizer produced a statistically significant improvement in the scores of all clinical grading parameters assessed compared to baseline. A greater statistically significant improvement was seen at 12 weeks. At week 12, there was a statistically significant percentage of favorable results versus unfavorable results in all product efficacy and product aesthetic self-assessment questionnaire results. Digital photography supported the clinical grading and self-assessment questionnaire results. Additionally, the multi-ingredient anti-aging moisturizer is judged to be mild and well tolerated. Several tolerability parameters were assessed at all time

  12. Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: an open label trial.

    Science.gov (United States)

    McGirr, Alexander; Van den Eynde, Frederique; Tovar-Perdomo, Santiago; Fleck, Marcelo P A; Berlim, Marcelo T

    2015-03-01

    Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4-6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6, and ≥ 50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial.

    Science.gov (United States)

    Mancías-Guerra, Consuelo; Marroquín-Escamilla, Alma Rosa; González-Llano, Oscar; Villarreal-Martínez, Laura; Jaime-Pérez, José Carlos; García-Rodríguez, Fernando; Valdés-Burnes, Sagrario Lisete; Rodríguez-Romo, Laura Nely; Barrera-Morales, Dinorah Catalina; Sánchez-Hernández, José Javier; Cantú-Rodríguez, Olga Graciela; Gutiérrez-Aguirre, César Homero; Gómez-De León, Andrés; Elizondo-Riojas, Guillermo; Salazar-Riojas, Rosario; Gómez-Almaguer, David

    2014-06-01

    Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion. In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow-derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733). A median of 13.12 × 10(8) TNCs (range, 4.83-53.87) including 10.02 × 10(6) CD34+ cells (range, 1.02-29.9) in a volume of 7 mL (range, 4-10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10(8) TNCs (range, 1.36-17.85), with 3.39 × 10(6) cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found. Subarachnoid placement of autologous bone marrow-derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Rapid and efficient localization of depth electrodes and cortical labeling using free and open source medical software in epilepsy surgery candidates

    Directory of Open Access Journals (Sweden)

    Juan Pablo Princich

    2013-12-01

    Full Text Available Depth intracranial electrodes (IEs placement is one of the most used procedures to identify the epileptogenic zone (EZ in surgical treatment of drug resistant epilepsy patients, about 20-30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome.We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients.All IEs were identified in the first 24 Hs (6-24 Hs of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients, 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available.To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 intracranial electrodes using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis.

  15. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

    Science.gov (United States)

    Valentino, L A; Rusen, L; Elezovic, I; Smith, L M; Korth-Bradley, J M; Rendo, P

    2014-05-01

    Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

  16. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch.

    Science.gov (United States)

    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet(®)) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  17. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Directory of Open Access Journals (Sweden)

    Zhang C

    2017-03-01

    Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

  18. Open-Label, Randomized, 6-Way Crossover, Single-Dose Study to Determine the Pharmacokinetics of Batefenterol (GSK961081) and Fluticasone Furoate When Administered Alone or in Combination.

    Science.gov (United States)

    Ambery, Claire; Riddell, Kylie; Daley-Yates, Peter

    2016-09-01

    To investigate the pharmacokinetics of inhaled batefenterol (BAT) and fluticasone furoate (FF) given alone or in combination via ELLIPTA® dry powder inhaler (DPI-E), and BAT monotherapy via DISKUS® DPI (DPI-D). In this open-label, 6-way crossover study, 48 healthy subjects were randomized to 1 of 6 treatment sequences, comprising 6 single-dose treatment regimens: (1) BAT 1200 μg via DPI-D; (2) BAT 1200 μg via DPI-E without a lactose-filled second strip; (3) BAT 1200 μg via DPI-E with a lactose-filled second strip; (4) BAT/FF 1200/300 μg via DPI-E; (5) FF 300 μg via DPI-E with a lactose-filled second strip; and (6) BAT/FF 900/300 μg via DPI-E. Pharmacokinetic data were analyzed using noncompartmental methods. Plasma BAT area under the curve (AUC) and maximum plasma concentration (Cmax ) were similar for all treatments containing BAT 1200 μg (geometric least-squares means [GLSM] ratio, 0.90-1.06). Plasma FF AUC and Cmax were reduced following BAT/FF 1200/300 μg and 900/300 μg versus FF 300 μg monotherapy (GLSM ratio, 0.62-0.77). BAT 1200 μg administered via DPI-E, alone or in combination with FF, resulted in similar systemic exposure versus BAT administered by DPI-D. FF exposure was reduced when administered in combination with BAT compared with FF alone. © 2016, The American College of Clinical Pharmacology.

  19. Efficacy of a standardized herbal preparation (Roidosanal® in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

    Directory of Open Access Journals (Sweden)

    Kapil Aggrawal

    2014-01-01

    Full Text Available Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal® , in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III were randomly assigned to receive either Roidosanal® (Gr R; n = 37 or Daflon® 500 mg (Gr D; n = 36, for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended.

  20. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    Directory of Open Access Journals (Sweden)

    Mohammad Shafi Kuchay

    2015-01-01

    Full Text Available Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69 or no Vitamin D (n = 68. Fasting plasma glucose (FPG, 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4% in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%. Similarly, FPG (97 ± 7 and 2-h plasma glucose (132 ± 16 were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25 at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels.

  1. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial.

    Directory of Open Access Journals (Sweden)

    Chanthap Lon

    Full Text Available Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline. The first 80 volunteers with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1 to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg piperaquine and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with vivax infection received primaquine at study discharge with six months follow-up.Eighty patients (60 vivax, 15 falciparum, and 5 mixed were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69-94 and 90% for the three-day regimen (95% CI 75-97. PCR-adjusted falciparum efficacy was 75% in both groups with nearly half (45% still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable in vitro piperaquine IC50 levels in all falciparum treatment failures.In the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC50 levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.ClinicalTrials.gov NCT01280162.

  2. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers.

    Science.gov (United States)

    Escudier, Bernard; Faivre, Sandrine; Van Cutsem, Eric; Germann, Nathalie; Pouget, Jean-Christophe; Plummer, Ruth; Vergote, Ignace; Thistlethwaite, Fiona; Bjarnason, Georg A; Jones, Robert; Mackay, Helen; Edeline, Julien; Fartoux, Laetitia; Hirte, Hal; Oza, Amit

    2017-08-10

    Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. NCT01743469.

  3. Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

    Science.gov (United States)

    Kanti, V; Hillmann, K; Kottner, J; Stroux, A; Canfield, D; Blume-Peytavi, U

    2016-07-01

    Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis. © 2015 European Academy of Dermatology and Venereology.

  4. Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study.

    Science.gov (United States)

    Shanshanwal, Sujit J S; Dhurat, Rachita S

    2017-01-01

    Finasteride and dutasteride are inhibitors of the enzyme 5-alpha-reductase which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride inhibits both type I and type II 5-alpha-reductase while finasteride inhibits only the type II enzyme. As both isoenzymes are present in hair follicles, it is likely that dutasteride is more effective than finasteride. To compare the efficacy, safety and tolerability of dutasteride and finasteride in men with androgenetic alopecia. Men with androgenetic alopecia between 18 and 40 years of age were randomized to receive 0.5 mg dutasteride or 1 mg finasteride daily for 24 weeks. The primary efficacy variables were hair counts (thick and thin) in the target area from modified phototrichograms and global photography evaluation by blinded and non-blinded investigators. The secondary efficacy variable was subjective assessment using a preset questionnaire. Patients were assessed monthly for side effects. Ninety men with androgenetic alopecia were recruited. The increase in total hair count per cm[2] representing new growth was significantly higher in dutasteride group (baseline- 223 hair; at 24 weeks- 246 hair) compared to finasteride group (baseline- 227 hair; at 24 weeks- 231 hair). The decrease in thin hair count per cm[2] suggestive of reversal of miniaturization was significantly higher in dutasteride group (baseline- 65 hair; at 24 weeks- 57 hair) compared to finasteride group (baseline- 67 hair; at 24 weeks- 66 hair). Both the groups showed a similar side effect profile with sexual dysfunction being the most common and reversible side effect. Limitations include the short duration of the study (6 months), the small sample size and the fact that it was an open-label study. Dutasteride was shown to be more efficacious than finasteride and the side-effect profiles were comparable.

  5. Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study

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    Karp, Jordan F.; Weiner, Debra K.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F.

    2010-01-01

    Objective: In older adults, major depressive disorder (MDD) and chronic low back pain (CLBP) are common and mutually exacerbating. We predicted that duloxetine pharmacotherapy and Depression and Pain Care Management (DPCM) would result in (1) significant improvement in MDD and CLBP and (2) significant improvements in health-related quality of life, anxiety, disability, self-efficacy, and sleep quality. Design and Intervention: Twelve week open-label study using duloxetine up to 120 mg/day + DPCM. Setting: Outpatient late-life depression research clinic. Patients: Thirty community-dwelling adults >60 years old. Outcome Measures: Montgomery Asberg Depression Rating Scale (MADRS) and McGill Pain Questionnaire-Short Form (MPQ-SF). Results: 46.7% (n = 14) of the sample had a depression remission. All subjects who met criteria for the depression remission also had a pain response. 93.3% (n = 28) had a significant pain response. Of the subjects who met criteria for a low back pain response, 50% (n = 14) also met criteria for the depression remission. The mean time to depression remission was 7.6 (SE = 0.6) weeks. The mean time to pain response was 2.8 (SE = 0.5) weeks. There were significant improvements in mental health-related quality of life, anxiety, sleep quality, somatic complaints, and both self-efficacy for pain management and for coping with symptoms. Physical health-related quality of life, back pain-related disability, and self-efficacy for physical functioning did not improve. Conclusions: Serotonin and norepinephrine reuptake inhibitors like duloxetine delivered with DPCM may be a good choice to treat these linked conditions in older adults. Treatments that target low self-efficacy for physical function and improving disability may further increase response rates. PMID:19750557

  6. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

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    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  7. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

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    Yves Allenbach

    Full Text Available Anti-synthetase syndrome (anti-SS is frequently associated with myositis and interstitial lung disease (ILD. We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants. They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles at M12. Secondary endpoints were normalization of creatine kinase (CK level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point. Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718 to 74.5 IU/L (range, 40-47,857. Corticosteroid doses decreased from 52.5 mg/d (range, 10-70 to 9 mg/d (range, 7-65 and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.Clinicaltrials.gov NCT00774462.

  8. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

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    Salvatore Siena

    Full Text Available This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day and intravenous cetuximab (400 mg/m(2 followed by weekly 250 mg/m(2 in 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.

  9. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study.

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    Martín-Richard, Marta; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Angel; Quindós, Maria; Maisonobe, Pascal

    2013-09-20

    Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

  10. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

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    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet®) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  11. Long-term efficacy and safety of blonanserin in patients with first-episode schizophrenia: a 1-year open-label trial.

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    Ninomiya, Yuriko; Miyamoto, Seiya; Tenjin, Tomomi; Ogino, Shin; Miyake, Nobumi; Kaneda, Yasuhiro; Sumiyoshi, Tomiki; Yamaguchi, Noboru

    2014-12-01

    The purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. Twenty-three antipsychotic-naïve patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24 mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms. Fourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period. Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014

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

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

    2014-01-01

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

  13. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study.

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    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela; Siggaard, Charlotte

    2007-11-01

    To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse events (AEs) and the incidence and reasons for withdrawals. Visits were scheduled at 3, 6, 9, and 12 mo, and investigators were instructed to report all AEs. At 6 and 12 mo, vital signs were recorded and a physical examination was performed. A total of 318 patients were enrolled (double-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection (7%), nasopharyngitis (5%), headache (5%), and abdominal pain (4%); 111 (35%) patients withdrew. The most common reasons for withdrawal were lack of efficacy (12%), symptom improvement (8%), and withdrawn consent (6%). Ten patients (3%) withdrew because of AEs. Long-term treatment with tolterodine ER was well tolerated in children with UUI.

  14. Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings

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    Muriah Dawn Wheelock

    2014-07-01

    Full Text Available Rationale: Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control. Objective: To evaluate the effects of 12 week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC and functional changes within the cognitive control network.Methods: We used single-voxel proton magnetic resonance spectroscopy (1H-MRS in the dACC and functional MRI (fMRI during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design. Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI analysis. Results: We observed a significant decrease in dACC glutamate + glutamine (Glx/Cr levels as well as significant blood oxygen level-dependent signal (BOLD decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.Conclusions: These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD activities between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size, future studies are needed to replicate these findings.

  15. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

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    Takeuchi, Tsutomu; Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki; ,

    2014-01-01

    Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies re...

  16. Food Labels

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    ... Surgery? Choosing the Right Sport for You Shyness Food Labels KidsHealth > For Teens > Food Labels Print A ... have at least 95% organic ingredients. continue Making Food Labels Work for You The first step in ...

  17. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

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    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  18. Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies

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    Turgay Atilla

    2011-05-01

    Full Text Available Abstract Background The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S scales, during up to 1 year of atomoxetine treatment in children with ADHD. Methods Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1 improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2 remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. Results The median time to improvement was 3.7 weeks (~1 month, but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale. The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03 was not statistically significant (p = .33. Conclusions Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study

  19. Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.

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    David A Wohl

    Full Text Available OBJECTIVE: Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r over 24 weeks in a population of virologically suppressed, HIV-1 infected patients. DESIGN: This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV. METHODS: The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs, and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers. RESULTS: After 24 weeks, ABC/3TC+ATV (n = 199 was non-inferior to TDF/FTC+ATV/r (n = 97 by both the primary analysis (87% in both groups and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively, but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30% compared with the ABC/3TC+ATV group (13%. Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment

  20. Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study

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    Blessborn Daniel

    2011-03-01

    Full Text Available Abstract Background Home-management of malaria (HMM strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL, presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs and administered unsupervised by parents or guardians at home. Methods An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5% patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%. The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10 compared with reinfections (205 ng/mL [114-390]; n = 92, or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046. Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home

  1. Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid for the treatment of osteoarthritis of the thumb

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    Velasco E

    2017-03-01

    Full Text Available Eloisa Velasco,1 Mª Victoria Ribera,2 Joan Pi3 1Department of Orthopedic Surgery, Hospital de Sant Joan Despí Moisés Broggi, Barcelona, Spain; 2Department of Anesthesiology, Vall d’Hebron University Hospital, Barcelona, Spain; 3Department of Orthopedics and Traumatology, Parc Taulí University Hospital, Sabadell, Barcelona, Spain Introduction: Osteoarthritis of the trapeziometacarpal (TMC joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid in rhizarthrosis.Patients and methods: This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS pain score ≥4 (scale: 0–10. A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score.Results: Thirty-five patients (mean age 60.8 years; 85.7% female received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was –2.00, a reduction of 27.8% (p<0.001. The reduction in pain exceeded 25% as early as month 1 (26.5%, and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH], Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP joint flexion, and pinch (clamp strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five

  2. Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Son, Hankil; Roh, Hyerang; Lee, Donghwan; Chang, Heechul; Kim, Junku; Yun, Chohee; Park, Kyungsoo

    2013-07-01

    Rosuvastatin, a lipid-lowering agent, has been widely used with olmesartan, a long-acting angiotensin II receptor blocker, indicated for the treatment of dyslipidemia accompanied by hypertension. A fixed-dose combination (FDC) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets. The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg (test formulation) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet (reference formulation) in healthy Korean male volunteers, for the purpose of determining bioequivalence. This single-dose, randomized, open-label, 2-period crossover study enrolled subjects aged 20 to 50 years and within 20% of ideal body weight. Each subject received a single dose of the test and reference formulations orally in a fasted state, with a 7-day washout period between the administrations. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determi