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Sample records for pilot open label

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

    PubMed

    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

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

    PubMed

    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.

  3. A pilot open-label trial of zonisamide in Unverricht-Lundborg disease.

    PubMed

    Italiano, Domenico; Pezzella, Marianna; Coppola, Antonietta; Magaudda, Adriana; Ferlazzo, Edoardo; Bramanti, Placido; Striano, Salvatore; Zara, Federico; Striano, Pasquale

    2011-02-01

    Action myoclonus frequently remains the primary cause of disability in Unverricht-Lundborg disease (EPM1) patients. Pharmacological treatment of myoclonus in these patients continues to be challenging; indeed conventional AEDs may be poorly effective in monotherapy or even in combination. We carried out a pilot, open-label trial of add-on zonisamide (ZNS) in patients with EPM1. Twelve EPM1 patients with epilepsy and action myoclonus were included in the study. Oral ZNS was gradually titrated until the target dose of 6 mg/Kg/day. Unified Myoclonus Rating Scale was obtained in each subject before and after ZNS add-on. A significant reduction of myoclonus severity was reached after ZNS introduction. ZNS was generally well tolerated and only two patients withdrew due to mild adverse effects. Our trial suggests that ZNS may be a valuable therapeutic option in EPM1 patients.

  4. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

    PubMed Central

    Berry-Kravis, E; Hessl, D; Coffey, S; Hervey, C; Schneider, A; Yuhas, J; Hutchison, J; Snape, M; Tranfaglia, M; Nguyen, D V; Hagerman, R

    2009-01-01

    Objective: A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS). Methods: Twelve subjects, recruited from two fragile X clinics, received a single oral dose of 50–150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition. Results: There were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects. Conclusions: Clinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS. PMID:19126569

  5. An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder

    PubMed Central

    Pilkinton, Patricia; Berry, Carlos; Norrholm, Seth; Bartolucci, Al; Birur, Badari; Davis, Lori L.

    2016-01-01

    Objective Selective serotonin reuptake inhibitors (SSRIs) remain the first-line treatment for posttraumatic stress disorder (PTSD). However, adjunctive atypical antipsychotics are often used to target residual or refractory symptoms. Asenapine is a novel atypical antipsychotic that possesses a high serotonin (5-HT2A) to dopamine (D2) affinity ratio and alpha-adrenergic antagonism, which may be advantageous in treating PTSD. This pilot study aimed to identify the therapeutic potential of asenapine as an adjunctive treatment for PTSD. Method Eighteen subjects initiated treatment in this single-site prospective, open-label, 12-week trial of flexibly-dosed asenapine in Veterans with PTSD who had not responded to an adequate course of treatment with an SSRI, venlafaxine, or mirtazapine. Subjects remained on their antidepressant medication and were started on adjunctive asenapine 5 mg sublingual at bedtime, which was gradually titrated to a maximum of 10 mg twice per day, as tolerated. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS) for DSM-IV. Results Fifteen subjects finished at least 4 weeks and eleven completed the 12 week study. There was a significant and clinically meaningful decrease in CAPS from baseline (77.56 ± 14.48) to week 4 (48.7 ± 30.6), and to week 12 (35.3 ± 19.7). Six participants experienced adverse events possibly related to asenapine; however, only three participants discontinued early due to related adverse events. Conclusion This pilot study demonstrated that adjunctive treatment with asenapine may provide additional benefit to some patients experiencing residual PTSD symptoms in spite of optimal antidepressant therapy. A larger efficacy study may be warranted. PMID:27738377

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

    PubMed

    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.

  7. Rotigotine Objectively Improves Sleep in Parkinson's Disease: An Open-Label Pilot Study with Actigraphic Recording

    PubMed Central

    Calandra-Buonaura, Giovanna; Guaraldi, Pietro; Doria, Andrea; Zanigni, Stefano; Nassetti, Stefania; Favoni, Valentina; Cevoli, Sabina; Provini, Federica; Cortelli, Pietro

    2016-01-01

    Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson's disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4–8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021. PMID:26981312

  8. Caffeine in Parkinson's disease: a pilot open-label, dose-escalation study.

    PubMed

    Altman, Robert D; Lang, Anthony E; Postuma, Ronald B

    2011-11-01

    Epidemiologic studies consistently find an inverse association between caffeine use and PD. Numerous explanations exist, but are difficult to evaluate as caffeine's symptomatic effect and tolerability in PD are unknown. We designed an open-label, 6-week dose-escalation study of caffeine to establish dose tolerability and evaluate potential motor/nonmotor benefits. Caffeine was started at 200 mg daily and was increased to a maximum of 1,000 mg. Of 25 subjects, 20 tolerated 200 mg, 17 tolerated 400 mg, 7 tolerated 800 mg, and 3 tolerated 1,000 mg. The most common adverse events were gastrointestinal discomfort, anxiety, and worsening/emerging tremor. At 400 mg daily, we found potential improvements in motor manifestations and somnolence (UPDRS III: -4.5 ± 4.6, P = 0.003; Epworth: -2.0 ± 3.0, P = 0.015). Maximum dose tolerability for caffeine in PD appears to be 100 to 200 mg BID. We found pilot preliminary evidence that caffeine may improve some motor and nonmotor aspects of PD, which must be confirmed in longer term, placebo-controlled, clinical trials. Copyright © 2011 Movement Disorder Society.

  9. Aripiprazole in L-dopa-induced dyskinesias: a one-year open-label pilot study.

    PubMed

    Meco, Giuseppe; Stirpe, Paola; Edito, Fabrizio; Purcaro, Carlo; Valente, Marcella; Bernardi, Silvia; Vanacore, Nicola

    2009-07-01

    Aripiprazole is a novel antipsychotic medication characterized by partial agonism at the D2 and 5-HT1A receptors and by antagonism at the 5-HT2A receptor. The aim of the present study was to evaluate, in an open-label pilot study, the effects and safety of very small doses of aripiprazole on L-dopa-induced dyskinesia of a group of PD patients who did not show a significant clinical benefit by pharmacological treatment with amantadine and mirtazapine. Twelve PD patients with peak-dose LID were enrolled in a period of 1 year. Aripiprazole dosage was of 0.625 mg/day. The ten patients who continued taking aripiprazole displayed a significant decrease in the intensity and frequency of dyskinesias in all parts of the body, particularly in trunk movements (AIMS score T(0) = 14.1 +/- 3.6 vs. final score 2.4. +/- 2.6; P = 0.005). Our study suggests that aripiprazole at very low doses is tolerated and could be efficacy in treating LID.

  10. An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder.

    PubMed

    Kim, Deborah R; Epperson, Neill; Paré, Emmanuelle; Gonzalez, Juan M; Parry, Samuel; Thase, Michael E; Cristancho, Pilar; Sammel, Mary D; O'Reardon, John P

    2011-02-01

    Despite the data that major depressive disorder (MDD) is common during pregnancy and that pregnant women prefer nonmedication treatment options, there is a paucity of research examining alternative treatments for this special population. We present the results of an open label pilot study examining treatment with transcranial magnetic stimulation (TMS) in pregnant women with MDD. Ten women with MDD in the second or third trimester of pregnancy were treated with 20 sessions of 1-Hz TMS at 100% of motor threshold (MT) to the right dorsolateral prefrontal cortex. The total study dose was 6000 pulses. Antenatal monitoring was performed during treatment sessions 1, 10, and 20. Seven of ten (70%) subjects responded (decrease ≥50% in Hamilton Depression Rating Scale [HDRS-17] scores). No adverse pregnancy or fetal outcomes were observed. All infants were admitted to the well baby nursery and were discharged with the mother. Mild headache was the only common adverse event and was reported by 4 of 10 (40%) subjects. TMS appears to be a promising treatment option for pregnant women who do not wish to take antidepressant medications.

  11. An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum.

    PubMed

    Foss, C E; Clark, A R; Inabinet, R; Camacho, F; Jorizzo, J L

    2008-08-01

    Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed. To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG. In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4). By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation. It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown. In this pilot study it appears that alefacept treatment may significantly reduce PG severity

  12. Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study.

    PubMed

    Cobbold, Jeremy F L; Atkinson, Stephen; Marchesi, Julian R; Smith, Ann; Wai, Sann N; Stove, Julie; Shojaee-Moradie, Fariba; Jackson, Nicola; Umpleby, A Margot; Fitzpatrick, Julie; Thomas, E Louise; Bell, Jimmy D; Holmes, Elaine; Taylor-Robinson, Simon D; Goldin, Robert D; Yee, Michael S; Anstee, Quentin M; Thursz, Mark R

    2017-04-20

    Gut microbial dysbiosis is implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy. Patients with biopsy-proven NASH and elevated aminotransferase values were included in this open-label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6-week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic-euglycemic clamp. Fifteen patients (13 men and 2 women) with a median (range) age of 46 (32-63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33-191] vs. 63 [41-218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4-48.3] to 25.5 [17.7-47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3-51.7]% vs. 30.0 [10.8-50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2-46.2]% vs. 24.8 [1.7-59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30-217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment-estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment. These data do not indicate a beneficial effect of rifaximin in patients with NASH. © 2017 The Japan Society of Hepatology.

  13. An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

    PubMed

    Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

    2011-12-01

    To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

  14. An Open-Label Naturalistic Pilot Study of Acamprosate in Youth with Autistic Disorder

    PubMed Central

    Early, Maureen; Stigler, Kimberly A.; Wink, Logan K.; Mullett, Jennifer E.; McDougle, Christopher J.

    2011-01-01

    Abstract To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration–approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects. PMID:22136091

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

    PubMed

    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 (p<0.001) and 4.0 at 48 hours. A response was seen in 17 (71%) of the 24 treatments at 24 hours. There was no difference between median negative change in pain scores in 19 (79%) treatments where pain was either strongly movement related, or in 22 (94%) treatments where local bone tenderness was more pronounced. No major side effects were observed during treatment. One patient died from pulmonary embolism after cessation of concurrent prophylactic low molecular weight heparin prior to staging liver biopsy. Subcutaneous 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

  16. An open-label pilot study of icariin for co-morbid bipolar and alcohol use disorder.

    PubMed

    Xiao, Heather; Wignall, Nicholas; Brown, E Sherwood

    2016-03-01

    Bipolar disorder is associated with a very high prevalence of alcohol-related disorders. However, few studies have examined treatment in this population. Preclinical research suggests a role for the flavonoid icariin in mood and addictive disorders. In this open-label pilot study, we investigated the feasibility and safety of using icariin for persons with bipolar disorder and alcohol abuse or dependence. Ten participants with bipolar I or bipolar II disorders, currently depressed, and with active alcohol abuse or dependence were given open-label icariin of up to 300 mg/day for 8 weeks using a flexible dosing strategy. Participants were assessed using the Hamilton Rating Scale for Depression (HAMD), Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), Hamilton Rating Scale for Anxiety (HAMA), and Young Mania Rating Scale (YMRS). Standard drinks, heavy drinking days, and drinking days were also quantified. Baseline and exit data were analyzed using the Wilcoxon Signed Rank Test. We observed a significant decrease in the HAMD (p = 0.012, d = 0.8), QIDS (p = 0.017, d = 0.7), and HAMA (p = 0.005, d = 1.4) scores. Heavy drinking days (p = 0.034, d = 1.1) and standard drinks (p = 0.038, d = 0.8) also decreased significantly. Icariin was well tolerated and no participants withdrew due to side-effects. Results from this uncontrolled study suggest icariin may decrease depressive symptoms and reduce alcohol consumption in persons with bipolar disorder and alcohol use. Improvement in mood and alcohol use was similar to that observed in an open-label trial of naltrexone in this population. Controlled trials, but at this point not routine clinical use, of icariin seem warranted.

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

    PubMed

    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 < .001). Hours spent shopping per week and money spent shopping both decreased significantly (P < .001). The mean effective dose of memantine was 23.4 ± 8.1 mg/d. Memantine treatment was associated with diminished impulsive 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.

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

    PubMed

    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.

  19. Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

    PubMed

    Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

    2014-10-01

    We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. An open-label pilot study of risperidone in the treatment of methamphetamine dependence.

    PubMed

    Meredith, Charles W; Jaffe, Craig; Yanasak, Elisia; Cherrier, Monique; Saxon, Andrew J

    2007-06-01

    Psychopharmacological treatments for methamphetamine (MA) dependence have questionable efficacy. Open-label risperidone was evaluated in veterans seeking MA dependence treatment. Participants (N = 11) received four weeks of risperidone. They provided weekly self-reports of substance use, urine drug screens, and adverse effects. Neuropsychological assessments and psychiatric symptomatology (Brief Symptom Inventory; BSI) were measured at baseline and follow-up. The eight completers had an average risperidone dose of 3.6 mg/day and decreased days of MA use during the trial from a mean of 13.0 (SD = 6.5) in the 30 days prior to starting risperidone to a mean of 0.125 (SD = 0.4; t = 5.7, p = .001), When measured over time, fine motor function (Grooved Peg Board Dominant Hand) was the only neuropsychological domain to improve significantly. No other domain changed significantly from baseline to follow-up among study completers. BSI data were converted to demographically corrected T-scores utilizing appropriate normative data (mean = 50, SD = 10). BSI somatization T-scores declined from a mean of 59.0 (SD = 8.4) to 51.8 (SD = 8.3; t = 2.7, p <.05), and positive symptom distress declined from a mean of 52.8 (SD =8.0) to 41.7 (SD = 8.6; t= 3.0, p <.05). Risperidone was well tolerated and associated with decreased MA use.

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

    PubMed Central

    Sethi, Priyanka; Sindhi, Sunil; Verma, Ankita; Tulsiani, K. L.

    2015-01-01

    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. PMID:26240542

  2. Effect of Facial Cosmetic Acupuncture on Facial Elasticity: An Open-Label, Single-Arm Pilot Study

    PubMed Central

    Yun, Younghee; Kim, Sehyun; Kim, Minhee; Kim, KyuSeok; Park, Jeong-Su; Choi, Inhwa

    2013-01-01

    Background. The use of acupuncture for cosmetic purposes has gained popularity worldwide. Facial cosmetic acupuncture (FCA) is applied to the head, face, and neck. However, little evidence supports the efficacy and safety of FCA. We hypothesized that FCA affects facial elasticity by restoring resting mimetic muscle tone through the insertion of needles into the muscles of the head, face, and neck. Methods. This open-label, single-arm pilot study was implemented at Kyung Hee University Hospital at Gangdong from August through September 2011. Participants were women aged 40 to 59 years with a Glogau photoaging scale III. Participants received five treatment sessions over three weeks. Participants were measured before and after FCA. The primary outcome was the Moire topography criteria. The secondary outcome was a patient-oriented self-assessment scale of facial elasticity. Results. Among 50 women screened, 28 were eligible and 27 completed the five FCA treatment sessions. A significant improvement after FCA treatment was evident according to mean change in Moire topography criteria (from 1.70 ± 0.724 to 2.26 ± 1.059, P < 0.0001). The most common adverse event was mild bruising at the needle site. Conclusions. In this pilot study, FCA showed promising results as a therapy for facial elasticity. However, further large-scale trials with a controlled design and objective measurements are needed. PMID:23983778

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

    PubMed Central

    Gobbi, Gabriella; Comai, Stefano; Debonnel, Guy

    2014-01-01

    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. PMID:24855361

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

    PubMed

    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 < 0.05 using ANOVA and partial eta squared (η(2)) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett's post hoc testing. Significant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the 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

  5. A pilot open-label trial of minocycline in patients with autism and regressive features

    PubMed Central

    2013-01-01

    Background Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. Methods Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. Results Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and α-2 macroglobulin (α-2 M), was also significantly lower (P = 0.028) while the mature BDNF/α-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-α, CD40L, IL-6, IFN-γ and IL-1β when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. Conclusions Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the

  6. Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study.

    PubMed

    Lundt, Leslie

    2004-08-01

    Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression. This open-label pilot study assessed modafinil, a novel wake-promoting agent, as treatment for seasonal affective disorder/winter depression. Total daily modafinil dose was 100 mg (all patients week 1), and 100 mg or 200 mg split dose (weeks 2-8). Efficacy assessments (weeks 1, 2, 5, and 8) included the Structured Interview Guide for the Hamilton Depression (HAM-D) Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression of Change (CGI-C), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS). Thirteen patients (11 women; mean age, 41 years) were enrolled, 12 were evaluable for efficacy (100 mg dose, five patients; 200 mg dose, seven patients), and nine completed treatment. Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 (P<0.01) through week 8 (P<0.001 weeks 2-8) and MADRS total scores from week 2 through week 8 (P<0.01 for all). At week 8, mean SIGH-SAD total score was 17.1 (versus 37.2 at baseline, P<0.001), and mean MADRS total score was 13.3 (versus 26.9 at baseline, P<0.01). Modafinil significantly improved overall clinical condition at all time points (P<0.001). The response rate was 67% on the SIGH-SAD (29 item), HAM-D (21 item), and MADRS, and 100% on eight atypical SIGH-SAD items. Modafinil significantly reduced fatigue (FSS) and improved wakefulness (ESS) from weeks 2 through 8 (P<0.01). Modafinil was well tolerated. This was an open-label, single site study. Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.

  7. Prospective, Naturalistic, Pilot Study of Open-Label Atomoxetine Treatment in Preschool Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Aman, Michael G.; Ghuman, Harinder S.; Reichenbacher, Thomas; Gelenberg, Alan; Wright, Ron; Rice, Sydney; Fort, Carolyn

    2009-01-01

    Abstract Objective The aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD). Methods Nine boys and 3 girls (mean age = 5.0 ± 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day. Results There was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 ± 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions–Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Children's Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 ± 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to “chest ache.” There were no changes in weight, height, or cardiovascular measures. Conclusion This open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this. PMID:19364293

  8. The effects of QEEG-informed neurofeedback in ADHD: an open-label pilot study.

    PubMed

    Arns, Martijn; Drinkenburg, Wilhelmus; Leon Kenemans, J

    2012-09-01

    In ADHD several EEG biomarkers have been described before, with relevance to treatment outcome to stimulant medication. This pilot-study aimed at personalizing neurofeedback treatment to these specific sub-groups to investigate if such an approach leads to improved clinical outcomes. Furthermore, pre- and post-treatment EEG and ERP changes were investigated in a sub-group to study the neurophysiological effects of neurofeedback. Twenty-one patients with ADHD were treated with QEEG-informed neurofeedback and post-treatment effects on inattention (ATT), hyperactivity/impulsivity (HI) and comorbid depressive symptoms were investigated. There was a significant improvement for both ATT, HI and comorbid depressive complaints after QEEG-informed neurofeedback. The effect size for ATT was 1.78 and for HI was 1.22. Furthermore, anterior individual alpha peak frequency (iAPF) demonstrated a strong relation to improvement on comorbid depressive complaints. Pre- and post-treatment effects for the SMR neurofeedback sub-group exhibited increased N200 and P300 amplitudes and decreased SMR EEG power post-treatment. This pilot study is the first study demonstrating that it is possible to select neurofeedback protocols based on individual EEG biomarkers and suggests this results in improved treatment outcome specifically for ATT, however these results should be replicated in further controlled studies. A slow anterior iAPF at baseline predicts poor treatment response on comorbid depressive complaints in line with studies in depression. The effects of SMR neurofeedback resulted in specific ERP and EEG changes.

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

    PubMed

    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. The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam.

    PubMed

    Allcroft, Peter; Margitanovic, Vera; Greene, Aine; Agar, Meera R; Clark, Katherine; Abernethy, Amy P; Currow, David C

    2013-07-01

    Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid. This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity. Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity. This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.

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

    PubMed Central

    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

  12. An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity.

    PubMed

    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.

  13. Tea tree oil gel for mild to moderate acne; a 12 week uncontrolled, open-label phase II pilot study.

    PubMed

    Malhi, Harsimran Kaur; Tu, Jenny; Riley, Thomas V; Kumarasinghe, Sujith Prasad; Hammer, Katherine A

    2017-08-01

    The efficacy, tolerability and acceptability of a tea tree oil gel (200 mg/g) and face wash (7 mg/g) were evaluated for the treatment of mild to moderate facial acne. In this open-label, uncontrolled phase II pilot study, participants applied tea tree oil products to the face twice daily for 12 weeks and were assessed after 4, 8 and 12 weeks. Efficacy was determined from total numbers of facial acne lesions and the investigator global assessment (IGA) score. Tolerability was evaluated by the frequency of adverse events and the mean tolerability score determined at each visit. Product acceptability was assessed via a questionnaire at the end of the study period. Altogether 18 participants were enrolled, of whom 14 completed the study. Mean total lesion counts were 23.7 at baseline, 17.2 at 4, 15.1 at 8 and 10.7 at 12 weeks. Total lesion counts differed significantly over time by repeated measures anova (P < 0.0001). The mean IGA score was 2.4 at baseline, 2.2 at 4, 2.0 at 8 and 1.9 at 12 weeks, which also differed significantly over time (P = 0.0094). No serious adverse events occurred and minor local tolerability events were limited to peeling, dryness and scaling, all of which resolved without intervention. This study shows that the use of the tea tree oil products significantly improved mild to moderate acne and that the products were well tolerated. © 2016 The Australasian College of Dermatologists.

  14. Pregabalin augmentation of antidepressants in patients with accident-related posttraumatic stress disorder: an open label pilot study.

    PubMed

    Pae, Chi-Un; Marks, David M; Han, Changsu; Masand, Prakash S; Patkar, Ashwin A

    2009-01-01

    This study evaluated the efficacy of pregabalin augmentation of antidepressant treatment in patients with posttraumatic stress disorder (PTSD). Nine patients meeting Diagnostic and Statistical Manual, fourth edition criteria for PTSD who were on stable doses of antidepressants were treated open label with flexibly dosed pregabalin for 6 weeks. All patients were assessed with the Short PTSD Rating Interview, Montgomery-Asberg Depression Rating Scale, Patient Global Impression-severity, Visual Analog Scale-pain, and Sheehan Disability Scale at baseline and weeks 2, 4, and 6. Significant reductions were observed in all effectiveness measures from week 4 to the end of the study. In particular, the numerical improvement of the Visual Analog Scale-pain score was most robust (-53.4%, P=0.007). Pregabalin augmentation was effective and well tolerated during the study. Our findings warrant adequately powered, placebo-controlled clinical trials to confirm the usefulness of pregabalin augmentation of antidepressants in patients with PTSD.

  15. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome.

    PubMed

    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.

  16. Topical imiquimod 5% cream for pediatric plaque morphea: a prospective, multiple-baseline, open-label pilot study.

    PubMed

    Pope, Elena; Doria, Andrea S; Theriault, Marc; Mohanta, Arun; Laxer, Ronald M

    2011-01-01

    Therapeutic options for the treatment of plaque morphea are limited. We explored the efficacy and safety of imiquimod cream in children with plaque morphea. Prospective, open-label, double-baseline study, using imiquimod 5% cream topically for 9 months. The primary outcome measure was improvement in the thickening of morphea plaques using a visual analog scale (VAS) and the DIET score (dyspigmentation/induration/erythema/telangiectasia). Secondary outcome measures were clinicoradiographic correlations and frequency of adverse events. Nine patients, 89% females, with a mean age of 11.33 years (SD = 3.52) were enrolled. At 36 weeks, the mean VAS had decreased from 48.08 (SD = 18.85) to 22.7 (SD = 12.9) (p < 0.0001), and the mean DIET score from 4.38 (SD = 1.2) to 3.06 (SD = 1.39) (p = 0.23). There was very good interrater reliability between DIET score assessments (intraclass correlation coefficient, ICC = 0.75) and VAS (ICC = 0.59) and moderate agreement between parent and investigator VAS (ICC = 0.5). Ultrasonographically measured dermis thickness changed from 1.05 (SD = 0.34) to 0.95 (SD = 0.19) (p = 0.001). One patient experienced ulceration that required temporary discontinuation of intervention. This proof of concept study revealed that imiquimod 5% cream is effective in decreasing the thickening of plaque morphea and safe for pediatric use. Further prospective studies are warranted. Copyright © 2012 S. Karger AG, Basel.

  17. Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a randomized, open-label pilot study.

    PubMed

    Iha, Kosaku; Suzuki, Nao; Yoneda, Masahiro; Takeshita, Toru; Hirofuji, Takao

    2013-10-01

    The aim of the study was to evaluate the effect of mouth cleaning with hinokitiol-containing gel on oral malodor. An open-label, randomized, controlled trial was conducted to assess oral malodor and clinical parameters related to oral malodor before and after mouth cleaning with hinokitiol-containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth cleaning included the teeth, gingiva, and tongue and was carried out 3 times per day for 4 weeks. Organoleptic test (OLT) scores (P = .021), levels of hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of bleeding on probing, average probing pocket depth, and plaque index significantly improved in the group using hinokitiol. In contrast, only the OLT score (P = .031) significantly improved in the control group after the treatment regimen. Mouth cleaning with hinokitiol-containing gel may be effective for reduction of oral malodor. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  19. Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study.

    PubMed

    Osher, Etty; Fattal-Valevski, Aviva; Sagie, Liora; Urshanski, Nataly; Sagiv, Nadav; Peleg, Leah; Lerman-Sagie, Tally; Zimran, Ari; Elstein, Deborah; Navon, Ruth; Valevski, Avi; Stern, Naftali

    2015-04-17

    Late Onset Tay- Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the α subunit (HEXA) of β-hexosaminidase enzyme (HexA). At the present time, no effective treatment exists for LOTS and other neurodegenerative diseases involving the central nerve system (CNS). Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.g., αG269S), but not all LOTS-related mutations. The present study assessed the effect of cyclic, low dose and long term pyrimethamine treatment on HexA in subjects with LOTS. In an open label trial in 4 LOTS patients, PMT was initiated at an average daily dose of ~2.7 mg and administered cyclically guided by blood lymphocyte HexA activity for a mean duration of 82.8 (±22.5; SD) weeks (~1.5 year). HexA activity rose in all subjects, with a mean peak increase of 2.24 folds (±0.52; SD) over baseline activity (range 1.87-3). The mean treatment time required to attain this peak was of 15.7 (±4.8; SD) weeks. Following increase in activity, HexA gradually declined with the continued use of PMT, which was then stopped, resulting in the return of HexA activity to baseline. A second cycle of PMT treatment was then initiated, resulting again in an increase in HexA activity. Three of the patients experienced a measurable neuropsychiatric deterioration whereas one subject remained entirely stable. Cyclic low dose of PMT can increase HexA activity in LOTS patients. However, the observed increase is repeatedly transient and not associated with discernible beneficial neurological or psychiatric effects.

  20. An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain

    PubMed Central

    Harper, Wayne L; Schmidt, William K; Kubat, Nicole J; Isenberg, Richard A

    2015-01-01

    Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale. PMID:25678825

  1. An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain.

    PubMed

    Harper, Wayne L; Schmidt, William K; Kubat, Nicole J; Isenberg, Richard A

    2015-01-01

    Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale.

  2. FDG-PET in Semantic Dementia after 6 Months of Memantine: an Open-Label Pilot Study

    PubMed Central

    Chow, Tiffany W.; Fam, David; Graff-Guerrero, Ariel; Verhoeff, Nicolaas P. G.; Tang-Wai, David F.; Masellis, Mario; Black, Sandra E.; Wilson, Alan A.; Houle, Sylvain; Pollock, Bruce G.

    2012-01-01

    Objectives To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open label study of memantine in frontotemporal dementia (FTD). Methods We repeated fluoro-deoxyglucose positron emission tomography (PET) after 6 months of drug use and subjected the data to an SPM analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI). Results Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia. The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p<0.002) for 5 participants with semantic dementia. The 2–6 month interval revealed a late increase in normalized metabolic activity in the left insula (p<0.013), right insula (p<0.009), and left anterior cingulate (p<0.005). The right anterior cingulate showed both an initial increase and a delayed, further increase (2–6 month, p<0.016). FBI scores worsened by 43.3%. One participant with semantic dementia opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases. Conclusions Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Since one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure. PMID:22674572

  3. Effects of probiotic Lactobacillus brevis KB290 on incidence of influenza infection among schoolchildren: an open-label pilot study

    PubMed Central

    Waki, N; Matsumoto, M; Fukui, Y; Suganuma, H

    2014-01-01

    Abstract We investigated the efficacy of dietary consumption of Lactobacillus brevis KB290 (KB290) against influenza in humans by a preliminary intervention study on elementary schoolchildren, using a commercially available probiotic drink. Subjects were divided into Groups A and B, and an open-label, parallel-group trial was conducted in two 8-week periods at a 1-month interval in winter 2013/2014. Group A was provided with a bottle of the test drink containing KB290 (about 6 billion colony-forming units) every school day in the first period and had no treatment in the second period, and vice versa for Group B. Epidemic influenza was not observed during the first period and only two of 1783 subjects were diagnosed. In the second period, the incidence of influenza in Groups A (no treatment) and B (provided the test drink) was 23·9 and 15·7%, respectively, and the difference was statistically significant (P < 0·001). The reduction in the incidence of influenza by KB290 consumption was especially remarkable in unvaccinated individuals. This is believed to be the first study to show a probiotic food reducing the incidence of influenza in schoolchildren, although further studies are needed to confirm the effectiveness of the probiotic strain KB290. Significance and Impact of the Study We demonstrated a reduction in the incidence of influenza in 1089 schoolchildren by continual intake of a probiotic drink containing Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle ‘Suguki’. The effect was especially evident in subjects not inoculated with influenza vaccine. This is believed to be the first report to show reduced incidence of influenza in schoolchildren taking a probiotic food. Further studies are needed to confirm the effectiveness of the probiotic strain KB290, which may be useful in the development of potential anti-influenza agents derived from common foods. PMID:25294223

  4. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial.

    PubMed

    Urman, B; Ata, B; Yakin, K; Alatas, C; Aksoy, S; Mercan, R; Balaban, B

    2009-07-01

    The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study. One hundred and fifty women with > or =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants. There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33). Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.

  5. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

    PubMed

    Sahlem, Gregory L; Kalivas, Benjamin; Fox, James B; Lamb, Kayla; Roper, Amanda; Williams, Emily N; Williams, Nolan R; Korte, Jeffrey E; Zuschlag, Zachary D; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S; Uhde, Thomas W; George, Mark S; Short, E Baron

    2014-12-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed.

  6. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study.

    PubMed

    Pittock, Sean J; Lennon, Vanda A; McKeon, Andrew; Mandrekar, Jay; Weinshenker, Brian G; Lucchinetti, Claudia F; O'Toole, Orna; Wingerchuk, Dean M

    2013-06-01

    Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in neuromyelitis optica. The aim of this study was to investigate the use of eculizumab--a therapeutic monoclonal IgG that neutralises the complement protein C5--in neuromyelitis optica spectrum disorders. Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a neuromyelitis optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p<0·0001). No patient had worsened disability by any outcome measure. Median score on the expanded disability status scale improved from 4·3 (range 1·0-8·0) before treatment to 3·5 (0-8·0

  7. Open-label, randomized, controlled pilot study of the effects of a glucosamine complex on Low back pain

    PubMed Central

    Tant, Laure; Gillard, Bruno; Appelboom, Thierry

    2005-01-01

    Background: A series of studies has suggested some efficacy of glucosamine in arthrosis of the knee, but virtually no documentation exists regarding its effects on low back pain. Objectives: The primary objective of this study was to examine whether a 12-week course of a glucosamine complex (GC) could benefit patients having low back pain despite a course of noninvasive physical therapy. In addition, we sought to delineate the subgroup of responders. Methods: This open-label, randomized, controlled study was conducted at the Division of Rheumatology and Physical Medicine, Erasme University Hospital, Brussels, Belgium. Male and female outpatients aged 40 to 80 years with low back pain (duration, ≥ 12 weeks; pain score on 10-cm visual analog scale [VAS] [0 = none to 10 = worst imaginable], ≥3 cm) despite noninvasive physical therapy (massage, stretching, heat application, and analgesics for ≥4 weeks) were included. Patients were randomly assigned to receive, in addition to conventional treatment (CT) (physical therapy plus analgesics/antiinflammatories), a GC (enriched with sulfonyl methane, silicon, and a botanical extract of Ribes nigrum) or CT alone (control) for 12 weeks. Pain at rest and on movement (effort) and early morning lumbar stiffness were measured every 4 weeks using the VAS. The primary end point was improvement in VAS score for pain at rest at 12 weeks. Two validated questionnaires were used to assess improvements in quality of life (QOL) (Oswestry Disability Questionnaire [ODQ] [10 items; scale: 0 = no disability to 60 = maximal disability] and Roland-Morris Disability Questionnaire [RMDQ] [24 items; scale: 0 = no disability to 24 = severe disability]). Responders were defined as patients who positively assessed the efficacy of the GC. At each visit, patients were also asked about possible adverse events. Results: Of 36 enrolled patients, 32 completed the study (18 men, 14 women; mean [SE] age, 64 [2] years; 17 in the GC group and 15 in the

  8. Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

    PubMed

    Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

    2015-05-01

    Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

  9. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

    PubMed

    Leentjens, Jenneke; Quintin, Jessica; Gerretsen, Jelle; Kox, Matthijs; Pickkers, Peter; Netea, Mihai G

    2014-01-01

    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. 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. 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. The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. ClinicalTrials.gov NCT01727895.

  10. The Effects of Orally Administered Beta-Glucan on Innate Immune Responses in Humans, a Randomized Open-Label Intervention Pilot-Study

    PubMed Central

    Leentjens, Jenneke; Quintin, Jessica; Gerretsen, Jelle; Kox, Matthijs; Pickkers, Peter; Netea, Mihai G.

    2014-01-01

    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 PMID:25268806

  11. Adding memantine to rivastigmine therapy in patients with mild-to-moderate alzheimer's disease: results of a 12-week, open-label pilot study.

    PubMed

    Riepe, Matthias W; Adler, Georg; Ibach, Bernd; Weinkauf, Birgit; Gunay, Ibrahim; Tracik, Ferenc

    2006-01-01

    At present, inhibition of cholines-terase is the treatment of choice for subjects with mild-to-moderate Alzheimer's disease (AD). Memantine, a noncompetitive antagonist at N-methyl-d-aspartate receptors, is currently used to treat subjects with moderate-to-severe AD. The goal of this multicenter, open-label pilot study was to investigate whether combination therapy with memantine added to rivastigmine is safe and beneficial in subjects with mild-to-moderate AD. Patients with a DSM-IV diagnosis of dementia of the Alzheimer's type (N = 95), who were treated with rivastigmine (6-12 mg/day) for a maximum duration of 24 weeks prior to baseline, received memantine (5-20 mg/day) in combination with rivastigmine for 12 weeks. The primary efficacy variable was the change in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score at the end of 12 weeks compared with baseline. The study was conducted between September 15, 2003, and May 27, 2004. There was a statistically significant difference between baseline and week 12 for the ADAS-cog total score, showing a positive effect of combination therapy. Combination therapy did not evidence any unexpected safety concerns and was well-tolerated by most patients. Memantine in combination with rivastigmine appears to be safe and beneficial in patients with mild-to-moderate AD. Our results need to be confirmed in a large, long-term, randomized, double-blind, placebo-controlled clinical trial.

  12. Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT).

    PubMed

    Reiter, Edward O; Mauras, Nelly; McCormick, Ken; Kulshreshtha, Bindu; Amrhein, James; De Luca, Francesco; O'Brien, Sandra; Armstrong, Jon; Melezinkova, Helena

    2010-10-01

    To evaluate the efficacy, tolerability, and pharmacokinetics of bicalutamide plus anastrozole in young males with testotoxicosis. This was a multicenter, open-label, single-arm, 12-month, Phase II pilot trial in 14 males (2-9 years) with testotoxicosis treated with bicalutamide (12.5, 25, 50, or 100 mg) and anastrozole (0.5 or 1 mg) daily. The primary outcome was change in growth rate. At 1 year, the mean (standard deviation) change from baseline in growth rate was -1.6 (+/- 5.1) cm/year and -0.1 (+/- 1.8) SD units, and in bone maturation was -2.3 (+/- 0.5) years. The bone age/chronological age ratio was reduced from 2.1 (+/- 0.6) at baseline to 1.0 (+/- 0.4) (p = 0.00013). Steady-state trough R-bicalutamide and anastrozole concentrations were attained by Day 21 and 8, respectively. Gynecomastia (42.9%) and breast tenderness (12.5%) were the most common treatment-related adverse events. Treatment of testotoxicosis with bicalutamide plus anastrozole resulted in slower growth rate.

  13. Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

    PubMed

    Levin, Ethan; Debbaneh, Maya; Malakouti, Mona; Brown, Gabrielle; Wang, Eva; Gupta, Rishu; Butler, Daniel; Huynh, Monica; Leon, Argentina; Koo, John Y M

    2015-02-01

    The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of "clear" or "almost clear". Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

  14. Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia

    PubMed Central

    Tegeler, Charles H; Kumar, Sandhya R; Conklin, Dave; Lee, Sung W; Gerdes, Lee; Turner, Dana P; Tegeler, Catherine L; C Fidali, Brian; Houle, Tim T

    2012-01-01

    Effective noninvasive interventions for insomnia are needed. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM™) is a noninvasive, electroencephalography (EEG)-based method to facilitate greater client-unique, autocalibrated improvements of balance and harmony in cortical neural oscillations. This study explores using HIRREM for insomnia. Twenty subjects, with an Insomnia Severity Index (ISI) score of ≥15 (14 women, mean age 45.4, mean ISI 18.6), were enrolled in this randomized, unblinded, wait-list control, crossover, superiority study. Subjects were randomized to receive 8–12 HIRREM sessions over 3 weeks, plus usual care (HUC), or usual care alone (UC). Pre- and post-HIRREM data collection included ISI (primary outcome), and many secondary, exploratory measures (CES-D, SF-36, HR, BP, neurocognitive testing, and VAS scales). The UC group later crossed over to receive HIRREM. ISI was also repeated 4–6 weeks post-HIRREM. All subjects completed the primary intervention period. Analysis for differential change of ISI in the initial intervention period for HUC versus UC showed a drop of 10.3 points (95% CI: −13.7 to −6.9, P < 0.0001, standardized effect size of 2.68). Key secondary outcomes included statistically identical differential change for the crossed-over UC group, and persistence of the effect on the ISI up to > 4 weeks post-HIRREM. Differential change in the HUC group was also statistically significant for CES-D (−8.8, 95% CI: −17.5 to −0.1, P = 0.047), but other exploratory outcomes were not statistically significant. For all receiving HIRREM (n = 19), decreased high-frequency total power was seen in the bilateral temporal lobes. No adverse events were seen. This pilot clinical trial, the first using HIRREM as an intervention, suggests that HIRREM is feasible and effective for individuals having moderate-to-severe insomnia, with clinically relevant, statistically significant benefits based on differential

  15. An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis.

    PubMed

    Brady, C M; DasGupta, R; Dalton, C; Wiseman, O J; Berkley, K J; Fowler, C J

    2004-08-01

    The majority of patients with multiple sclerosis (MS) develop troublesome lower urinary tract symptoms (LUTS). Anecdotal reports suggest that cannabis may alleviate LUTS, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory LUTS. Patients took extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight weeks followed by THC-only (2.5 mg THC per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks. There were few troublesome side effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.

  16. OnabotulinumtoxinA (Botox) nerve blocks provide durable pain relief for men with chronic scrotal pain: a pilot open-label trial.

    PubMed

    Khambati, Aziz; Lau, Susan; Gordon, Allan; Jarvi, Keith A

    2014-12-01

    Chronic scrotal pain (CSP) is a common, often debilitating, condition affecting approximately 4.75% of men. While nerve blocks using local anesthetics usually provide temporary pain relief, there are no publications on the use of longer acting nerve blocks to provide more durable pain relief for men with CSP. The aim of this study was to determine if onabotulinumtoxinA (Botox) cord blocks provide durable pain relief for men with CSP. In this pilot open-label study, men with CSP who had failed medical management but experienced temporary pain relief from a standard cord block underwent a cord block with 100U Botox. The outcomes measured were changes 1, 3, and 6 months post-Botox injection in (i) a 10-point visual analog scale (VAS) pain score; (ii) scrotal tenderness on a three-point scale as rated by physical examination; and (iii) the Chronic Epididymitis Symptom Index (CESI) to measure the severity and impact of scrotal pain on men. Paired t-tests were used to compare groups. Eighteen patients with CSP seen between April and September 2013 had Botox injected as a cord block. At the 1-month follow-up, pain reduction was reported by 72% of patients (mean VAS score: 7.36 vs. 5.61, P < 0.003), while by physical examination 44 and 34% of the men had either complete or partial resolution of scrotal tenderness. In addition, there was also a significant reduction in CESI scores (22.19 vs. 19.25, P < 0.04). At 3 months, 56% had both sustained pain reduction and reduced tenderness based on the VAS score (mean: 7.36 vs. 6.02, P < 0.05) and physical exam. The CESI score continued to be significantly lower. Unfortunately, by 6 months, most men had a return to their baseline levels of pain and tenderness. Our pilot study found that Botox cord blocks provide pain reduction for 3 months or more for most men with CSP. © 2014 International Society for Sexual Medicine.

  17. Open-label pilot study comparing quantitative ultrasound and dual-energy X-ray absorptiometry to assess corticosteroid-induced osteoporosis in patients with chronic kidney disease.

    PubMed

    Grabe, Darren W; Chan, Marcia; Eisele, George

    2006-02-01

    Patients with chronic kidney disease (CKD) might be at high risk for bone disease. Decreased functional kidney mass contributes to renal osteodystrophy, which might be exacerbated by certain drug therapies. Long-term (> or = 6 months) corticosteroid treatment is commonly prescribed in patients with glomerular disease, possibly causing bone loss both indirectly and directly, putting the patient at increased risk for fracture. The dual-energy x-ray absorptiometry (DXA) is the current "gold standard" for measuring osteoporosis-related fractures and works by passing ultrasound waves through bone to determine the structural anisotropy in the heel. This pilot study was designed to determine whether there is a correlation between DXA and quantitative ultrasound (QUS) in detecting corticosteroid-induced osteoporosis. This open-label pilot study was conducted at the Medical Center Nephrology Clinic, Albany Medical College, Albany, New York. Female patients aged > or = 18 years with a diagnosis of CKD and/or a history of kidney transplantation and who were receiving long-term corticosteroid treatment were enrolled. Each patient served as her own control and underwent DXA of the hip and spine (DXA-hip and DXA-spine, respectively) and QUS of the dominant and nondominant heels (QUS-dominant and QUS-nondominant, respectively), within 1 week so that conditions were similar in each patient. Eight patients were included in the study (mean [SD] age, 50.2 [11.2] years). A positive correlation was found between DXA-hip and QUS-nondominant (r2=0.76; P=0.009); however, no correlation was found with DXA-spine. Similarly, a positive correlation was found between DXA-hip and QUS-dominant (r2=0.75; P=0.009), but no correlation with DXA-spine was found (r2=0.22). In this small, selected population, QUS showed a fair correlation with DXA-hip but no correlation with DXA-spine. Further studies are needed to determine the effectiveness in other populations.

  18. An open-label pilot study of aripiprazole for male and female veterans with chronic post-traumatic stress disorder who respond suboptimally to antidepressants.

    PubMed

    Youssef, Nagy A; Marx, Christine E; Bradford, Daniel W; Zinn, Sandra; Hertzberg, Michael A; Kilts, Jason D; Naylor, Jennifer C; Butterfield, Marian I; Strauss, Jennifer L

    2012-07-01

    Emerging data suggest that second-generation antipsychotics such as aripiprazole may be effective in the treatment of post-traumatic stress disorder (PTSD). However, few clinical trials have used aripiprazole in PTSD, and data are limited on its use in Veterans with PTSD. The objective of this pilot trial was to investigate the safety and efficacy of aripiprazole in Veterans with PTSD. Ten individuals (five men and five women) meeting the Diagnostic and statistical manual of mental disorders, 4th ed., PTSD criteria participated in this 12-week, open-label, flexibly dosed monotherapy trial. The dose range of aripiprazole was 5-30 mg/day, titrated to tolerability and clinical response. The primary outcome measure was the Clinician-Administered PTSD Scale. Additional outcomes included the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale (Top-8), the Davidson Trauma Scale, the Positive and Negative Syndrome Scale, the Beck Depression Inventory-Fast Screen, and Clinical Global Impressions-Improvement. Eight participants completed the study, and aripiprazole was generally well tolerated and associated with a significant improvement in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (primary outcome measure) and by the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale, and the Davidson Trauma Scale. An improvement was also observed on all three Positive and Negative Syndrome Scale subscales and the Beck Depression Inventory-Fast Screen, and the average Clinical Global Impressions-Improvement ratings indicated that patients were 'much improved'. These promising initial results merit further investigation in a larger, randomized-controlled trial.

  19. The influence of prophylactic vasoactive treatment on cochlear and facial nerve functions after vestibular schwannoma surgery: a prospective and open-label randomized pilot study.

    PubMed

    Scheller, Christian; Richter, Hans-Peter; Engelhardt, Martin; Köenig, Ralph; Antoniadis, Gregor

    2007-07-01

    Facial nerve paresis and hearing loss are common complications after vestibular schwannoma surgery. Experiments with facial nerves of the rat and retrospectively analyzed clinical studies showed a beneficial effect of vasoactive treatment on the preservation of facial and cochlear nerve functions. This prospective and open-label randomized pilot study is the first study of a prophylactic vasoactive treatment in vestibular schwannoma surgery. Thirty patients were randomized before surgery. One group (n = 14) received a vasoactive prophylaxis consisting of nimodipine and hydroxyethylstarch which was started the day before surgery and was continued until the seventh postoperative day. The other group (n = 16) did not receive preoperative medication. Intraoperative monitoring, including acoustic evoked potentials and continuous facial electromyelograms, was applied to all patients. However, when electrophysiological signs of a deterioration of facial or cochlear nerve function were detected in the group of patients without medication, vasoactive treatment was started immediately. Cochlear and facial nerve function were documented preoperatively, during the first 7 days postoperatively, and again after long-term observation. Despite the limited number of patients, our results were significant using the Fisher's exact test (small no. of patients) for a better outcome after vestibular schwannoma surgery for both hearing (P = 0.041) and facial nerve (P = 0.045) preservation in the group of patients who received a prophylactic vasoactive treatment. Prophylactic vasoactive treatment consisting of nimodipine and hydroxyethylstarch shows significantly better results concerning preservation of the facial and cochlear nerve function in vestibular schwannoma surgery. The prophylactic use is also superior to intraoperative vasoactive treatment.

  20. Safety and Tolerability of Varenicline Tartrate (Champix®/Chantix®) for Smoking Cessation in HIV-Infected Subjects: A Pilot Open-Label Study

    PubMed Central

    Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    Abstract The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix®, Pfizer, Saint-Laurent, QC, Canada or Chantix®, Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p=0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9–12 was 42% (95% confidence interval [CI]: 26–58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline. PMID:22007690

  1. An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study.

    PubMed

    Sardo, Christine L; Kitzmiller, Joseph P; Apseloff, Glen; Harris, Robin B; Roe, Denise J; Stoner, Gary D; Jacobs, Elizabeth T

    2016-01-01

    This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL⁻¹·h⁻¹ compared with 42.4 ± 17.9 pg·mL⁻¹·h⁻¹ for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential.

  2. The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study.

    PubMed

    Sakuraba, Atsushi; Sato, Toshiro; Matsukawa, Hidehiko; Okamoto, Susumu; Takaishi, Hiromasa; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi

    2012-07-01

    Crohn's disease (CD) commonly recurs after surgery, and a number of patients need repeated surgery, especially smokers and those with repeated surgeries or penetrating disease. Whether infliximab prevents postsurgical recurrence in high-risk CD remains unknown. In the present pilot open-labeled study, we investigated the safety and efficacy of scheduled infliximab, which was started early after surgery, in maintaining remission of CD patients who have undergone multiple surgeries due to penetrating disease. Eleven patients (nine male, two female; age range, 26-48 years) who had undergone repeated surgeries (median, 4; range, 2-5) for penetrating disease were enrolled. Two to 4 weeks after surgery, the patients were started on intravenous infliximab (5 mg/kg) at an 8-week interval. The primary end points were the proportion of patients in clinical remission at the end of the study, the rate of endoscopic/radiologic remission at 24 months, and the rate of adverse effects. One patient dropped out due to non-compliance, and ten patients were eligible for analysis. Clinical remission was maintained in six of ten patients (60.0%) at the end of the study. At 24 months, four out of ten patients were in endoscopic or radiological remission (40.0%). Two patients experienced adverse effects (18.2%), one of whom elected to withdraw from the study. The findings of no major safety concern and possible clinical benefit in our study suggest that further investigation of infliximab as a treatment for prevention of postsurgical recurrence in high-risk CD is warranted.

  3. Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial

    PubMed Central

    Chan, Kam Wa; Ip, Tai Pang; Kwong, Alfred Siu Kei; Lui, Sing Leung; Chan, Gary Chi Wang; Cowling, Benjamin John; Yiu, Wai Han; Wong, Dickson Wai Leong; Liu, Yang; Feng, Yibin; Tan, Kathryn Choon Beng; Chan, Loretta Yuk Yee; Leung, Joseph Chi Kam; Lai, Kar Neng; Tang, Sydney Chi Wai

    2016-01-01

    Introduction Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin–angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese–Western medicine protocol for the management of DN. Objective To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2–3 chronic kidney disease and macroalbuminuria. Methods and analysis This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-β1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. Ethics and registration This protocol is approved by the Institutional

  4. A pilot study on the effect of a symbiotic mixture in irritable bowel syndrome: an open-label, partially controlled, 6-month extension of a previously published trial.

    PubMed

    Bucci, C; Tremolaterra, F; Gallotta, S; Fortunato, A; Cappello, C; Ciacci, C; Iovino, P

    2014-04-01

    In recent years, the efficacy of probiotics has received considerable attention in the treatment for irritable bowel syndrome (IBS). In this regard, a symbiotic mixture (Probinul(®)) has shown beneficial effects. The aim of this study was to extend the previously published 4-week randomized, double-blinded, placebo-controlled study of this symbiotic mixture. This is an open-label prospective, partially controlled, 6-month extension period pilot study in which patients continued to receive the symbiotic mixture (Group 1) or were switched from placebo to symbiotic mixture (Group 2) using cyclic administration (last 2 weeks/month). The primary endpoints were the overall satisfactory relief of bloating and flatulence (assessed as proportions of responders). The secondary endpoints were evaluation of the symptom severity scores (bloating, flatulence, pain and urgency) and bowel function scores (frequency, consistency and incomplete evacuation). Twenty-six IBS patients completed the 6-month extension period (13 patients in Group 1 and 13 patients in Group 2). In the per-protocol analysis, the proportions of responders across time were not significantly different in the groups but in Group 2, there was an increased percentage of responders for flatulence (p = 0.07). In addition, the score of flatulence was reduced significantly during the 6-month treatment period in Group 2 (p < 0.05), while no other significant differences were detected. Treatment with this symbiotic mixture was associated with persistence of relief from flatulence or new reduction in flatulence in the present 6-month long extension study. These results need to be more comprehensively assessed in large, long-term, randomized, placebo-controlled studies.

  5. An open-label pilot study evaluating the effectiveness of the heated lidocaine/tetracaine patch for the treatment of pain associated with carpal tunnel syndrome.

    PubMed

    Nalamachu, Srinivas; Nalamasu, Rohit; Jenkins, Julie; Marriott, Thomas

    2014-09-01

    Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve at the wrist that is characterized by pain, paresthesias, weakness, and loss of dexterity. This pilot study was conducted to evaluate the heated lidocaine/tetracaine patch (HLT patch) as a conservative treatment for pain of CTS. Twenty adult patients (mean age = 44 ± 12 years) with pain secondary to unilateral CTS and electrodiagnostic evidence of mild-to-moderate CTS enrolled in this open-label study. Patients were treated with a single HLT patch placed over the junction of forearm and wrist on the palmar aspect of the wrist twice daily (morning and evening at 12-hour intervals) for 2 hours. At baseline and during the 2-week study, patients graded their pain intensity with an 11-point numerical rating scale (0 = no pain, 10 = worst imaginable pain). Pain interference with general activity, work, and sleep was evaluated with a similar 0-to-10-point scale. Fifteen patients completed the 14-day treatment period. Mean average pain intensity score decreased from 5.1 ± 1.5 at baseline to 2.5 ± 1.6 at end of study in the per-protocol population (P < 0.001). Two-thirds of the patients demonstrated clinically meaningful pain relief (≥ 30% reduction in average pain score), with 40% of the patients reaching this threshold by the third treatment day. Similar improvements were observed for pain interference scores. The HLT patch was generally well tolerated. The HLT patch resulted in clinically meaningful reduction in pain intensity in the majority of patients with mild-to-moderate CTS and may represent a targeted nonsurgical treatment for pain associated with CTS. © 2013 World Institute of Pain.

  6. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

    PubMed

    Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

    2013-04-01

    Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

  7. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

    PubMed Central

    Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial

  8. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial.

    PubMed

    Klarmann-Schulz, Ute; Specht, Sabine; Debrah, Alexander Yaw; Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4-6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Clinical

  9. Open-Label Memantine in Fragile X Syndrome

    ERIC Educational Resources Information Center

    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…

  10. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

    PubMed

    McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

    2016-01-02

    Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to

  11. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

    PubMed Central

    McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

    2016-01-01

    Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23

  12. 75 FR 51058 - Web-Distributed Labeling User Acceptance Pilot

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ... AGENCY Web-Distributed Labeling User Acceptance Pilot AGENCY: Environmental Protection Agency (EPA... ``web-distributed labeling'' (web-distributed labeling) that would make the most current version of some... announcing its intention to conduct a web- distributed labeling ``User Acceptance Pilot'' and is soliciting...

  13. Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study.

    PubMed

    Shelef, Assaf; Barak, Yoram; Berger, Uri; Paleacu, Diana; Tadger, Shelly; Plopsky, Igor; Baruch, Yehuda

    2016-01-01

    Tetrahydrocannabinol (THC) is a potential treatment for Alzheimer's disease (AD). To measure efficacy and safety of medical cannabis oil (MCO) containing THC as an add-on to pharmacotherapy, in relieving behavioral and psychological symptoms of dementia (BPSD). Eleven AD patients were recruited to an open label, 4 weeks, prospective trial. Ten patients completed the trial. Significant reduction in CGI severity score (6.5 to 5.7; p <  0.01) and NPI score were recorded (44.4 to 12.8; p <  0.01). NPI domains of significant decrease were: Delusions, agitation/aggression, irritability, apathy, sleep and caregiver distress. Adding MCO to AD patients' pharmacotherapy is safe and a promising treatment option.

  14. Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.

    PubMed

    Roitman, Pablo; Mechoulam, Raphael; Cooper-Kazaz, Rena; Shalev, Arieh

    2014-08-01

    Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ(9)-tetrahydrocannabinol (THC) for chronic PTSD. Ten outpatients with chronic PTSD, on stable medication, received 5 mg of Δ(9)-THC twice a day as add-on treatment. There were mild adverse effects in three patients, none of which led to treatment discontinuation. The intervention caused a statistically significant improvement in global symptom severity, sleep quality, frequency of nightmares, and PTSD hyperarousal symptoms. Orally absorbable Δ(9)-THC was safe and well tolerated by patients with chronic PTSD.

  15. The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

    PubMed

    Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

    2016-04-01

    Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.

    PubMed

    North, James M; Hong, Kyung-Soo J; Rauck, Richard L

    2016-07-01

    We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM). Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS). A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P < 0.0001) on NPRS. Subjects also reported similar magnitude of improvements in FM and its impact on daily life by end of 4 weeks on FIQ (P < 0.0001). Survey of MOS showed our subjects reporting improved sleep quantity (on average, 1.2 hours over baseline) with gradual and statistically significant improvement in quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8. Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group. Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep. © 2015 World Institute of Pain.

  17. Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study.

    PubMed

    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.

  18. Switching outpatients with schizophrenia and related disorders on long-acting injectable antipsychotics to olanzapine: an open-label naturalistic pilot study.

    PubMed

    Labelle, Alain; Bourget, Dominique; Boulay, Luc Jean; Ellis, Jack; Tessier, Pierre

    2002-12-01

    Little is known about the feasibility of switching patients with schizophrenia from long-acting injectable antipsychotics to oral olanzapine. We completed an open-label 14-week study to assess such a transition. This study included 25 stable outpatients (DSM-IV diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder) who were receiving long-acting injectable antipsychotics. Following a screening visit, patients began treatment with olanzapine 10 mg/day, which was initiated the day of their scheduled injection. Clinical assessments included the Clinical Global Impression-Improvement Scale (CGI-I) and the Positive and Negative Syndrome Scale (PANSS). Patient self-reports of adverse events were monitored and the Extrapyramidal Symptoms Rating Scale completed at each visit. In those completing the trial (N = 18), results revealed that a switch from injectable antipsychotics to olanzapine was associated with significant improvements on the CGI-I, negative symptoms, PANSS total scores, and parkinsonism. In considering the whole sample (last observation carried forward, N = 25), significant improvements on the CGI-I, parkinsonism, and dyskinesia were observed. Finally, those who failed to complete the trial (N = 7) did not change significantly from visit 1 to endpoint on any of the efficacy or safety measures. These results should be considered preliminary and require replication using appropriate control groups.

  19. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

    PubMed

    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 < 0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P < 0.05). Blood 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.

  20. Donepezil combined with natural hirudin improves the clinical symptoms of patients with mild-to-moderate Alzheimer's disease: a 20-week open-label pilot study.

    PubMed

    Li, De-qiang; Zhou, Yu-ping; Yang, Han

    2012-01-01

    To evaluate the efficacy and safety of donepezil plus natural hirudin in patients with mild-to-moderate Alzheimer's Disease. In the 20-week, randomized, open-label and controlled study, 84 patients received either donepezil (5 mg/day for the first 4 weeks and 10 mg/day thereafter) or donepezil plus natural hirudin (3 g/day) treatment. Efficacy was reflected by the change of the total scores of Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog), Activities of Daily Life (ADL) and Neuropsychiatric Inventory (NPI). The patients with the donepezil plus natural hirudin treatment showed more significant improvement in the daily activities and the decline of the cognition than those with donepezil treatment. Significant difference was present in the groups since the 8th week. No group difference was found in the NPI change. However, within the hirudin treatment group, more powerful efficacy including NPI assessment was found in the patients with vascular risk factors (VRF) as comparing to with those without VRF. The combination of donepezil and natural hirudin was well tolerated. The dropout rate was greater in the donepezil and natural hirudin (50%) treatment group than in the donepezil (39%) treatment group. Similar result was found in the incidence of adverse events (23.8% vs 19.0%), but there was no statistical difference between the two groups. Adverse events were the most common reason for the dropout. Although hemorrhage and hypersensitiveness were more common in donepezil plus Maixuekang treatment (11.9% and 7.1%) group than in donepezil treatment (2.4% and 2.4%) group, no significant difference was present between the two groups. Economic problem was another important reason for the patients' withdrawal. Compared with the donepezil treatment in the patients with mild-to-moderate AD, our results suggest that donepezil combined with natural hirudin may improve the treatment effects in the ADL, BPSD and cognition of the patients. Furthermore, this

  1. 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

    PubMed Central

    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

  2. Ultrasound-assisted surgical release of carpal tunnel syndrome: Results of a pilot open-label uncontrolled trial conducted outside the operating theatre.

    PubMed

    Lecoq, Bertrand; Hanouz, Nathalie; Morello, Rémy; Jean-Jacques, Pierre-Yves; Dutheil, Jean-Jacques; Hulet, Christophe; Marcelli, Christian

    2015-12-01

    To confirm the feasibility of ultrasound-assisted surgical release of carpal tunnel syndrome in the interventional radiology room. Study involving 39 patients suffering from carpal tunnel syndrome confirmed by electromyogram and unresponsive to medical treatment. The patients were recruited via orthopedic surgery and rheumatology consultations and were operated on in the interventional radiology room under local anesthesia. A single approach was used, at the wrist flexion crease. Patients were monitored over a 90-day period. This is a descriptive open-label uncontrolled study. Fifteen men and 24 women, aged between 21 and 86 years, were included, 23 of whom were in work. The mean surgical procedure time was of 19.0±4.6 minutes; the mean room occupancy time was of 38.0±8.1 minutes and the mean volume of local anesthetic used was of 14.7±2.3 cc. The score for pain, formication and discomfort experienced in the hand was significantly reduced by day 15 (49.1±21.1 vs. 23.5±19.5; P<0.001). Eight patients continued to present with paresthesia on day 15 and only 3 by day 30. Four patients had returned to work by day 15, 10 patients considered that they could have resumed work within an average of 9.9±4.9 days after the procedure. Twenty-five patients estimated that they could resume their daily activities within a mean period of 7±3.9 days. No postoperative complications related to the procedure were observed. According to the results of this study, ultrasound-assisted surgical release of carpal tunnel syndrome performed outside the operating theatre seems to be effective and well-tolerated. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  3. An Open-Label Evaluator Blinded Study of the Efficacy and Safety of a New Nutritional Supplement in Androgenetic Alopecia: A Pilot Study

    PubMed Central

    Nichols, Anna J.; Hughes, Olivia Bosshardt; Canazza, Agnese

    2017-01-01

    Objective: To evaluate the effectiveness of a novel oral supplement, Forti5®, containing green tea extract, omega 3 and 6 fatty acids, cholecalciferol, melatonin, beta-sitosterol, and soy isoflavones, and in the management of subjects with androgenetic alopecia. Design: A prospective case series of 10 subjects. Setting: Open-label, evaluator-blinded, proof-of-concept study. Participants: Ten adult subjects with androgenetic alopecia completed the study. Subjects were not allowed to use oral or topical hair growth products in the 24 weeks preceding the study or during the study. The nutritional supplement was administered at a dosage of two tablets daily for 24 weeks. Measurements: Clinical evaluations were performed at baseline and at 24 weeks. Efficacy was evaluated using hair mass index measured by cross section trichometer, terminal hair count measured with dermoscopy and Investigator Global Photography Assessment. Results: Overall 80 percent of subjects (8/10) were rated as improved after 24 weeks of supplementation (mean change of +1.4 equivalent to slightly-to-moderately increased). Forty percent of subjects (4/10) were rated as moderately improved (2+), and 10 percent (1/10) were rated as greatly improved (3+). There was a significant improvement in terminal hair count (mean increase of 5.9% or 4.2 more terminal hairs in the area examined, p=0.014) and in Hair Mass Index (mean increase of 9.5% or 4.5 higher Hair Mass Index, p=0.003). Conclusion: These preliminary results indicate that Forti5® a novel nutritional supplement that contains cholecalciferol, omega 3 and 6 fatty acids, melatonin, antioxidants, and botanical 5-alpha reductase inhibitors, may be a useful adjunct in the treatment of androgenetic alopecia. PMID:28367262

  4. A comparison of the antihypertensive and anti-inflammatory effects of aliskiren and ramipril add-on therapy in peritoneal dialysis patients--a pilot open label study.

    PubMed

    Makówka, Agnieszka; Olejniczak-Fortak, Magdalena; Nowicki, Michał

    2012-01-01

    Most hypertensive dialysis patients are currently treated with angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Aliskiren, the direct renin inhibitor, has not been specifically studied in peritoneal dialysis patients. The aim of the study was to compare hypotensive effects of aliskiren and ramipril and their influence on serum potassium and inflammatory parameters in hypertensive peritoneal dialysis patients. Eighteen hypertensive patients on chronic peritoneal dialysis were enrolled in an open-label comparative fixed-order study. The patients had been off RAAS blocking drugs for ≥4 weeks prior to an inclusion. At each of 3 study visits (baseline and after each of the treatment periods) blood pressure, serum lipids, potassium, renin, aldosterone, C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1) were measured. After the baseline visit aliskiren was started (150 mg/d) and after 12 weeks replaced with ramipril (5 mg/d) for the next 12 weeks. Blood pressure was 142/88±15/11 mmHg at baseline, 137/84±10/8 mmHg after aliskiren (ns) and 126/81±11/7 mmHg after ramipril (p<0.05 vs baseline and aliskiren). No incidents of hyperkalemia were observed. Plasma renin concentration increased significantly during aliskiren treatment compared to ramipril (227,6±844 vs. 58,3±765 pg/mL). CRP was similar after both therapies (8,8±34 vs. 8,4±32 µg/mL) but MCP-1 concentration was significantly lower after aliskiren than after ramipril (294,0±172,6 vs. 358,9±183,3 pg/mL). Aliskiren 150 mg/day decreases blood pressure less effectively than ramipril 5 mg/day in peritoneal dialysis patients. It does not influence serum potassium. The decrease of MCP-1 concentration after aliskiren treatment may provide an indirect evidence for its blood pressure independent cardioprotective and anti-inflammatory effects. Copyright © 2012 S. Karger AG, Basel.

  5. Lidocaine patch 5% and its positive impact on pain qualities in osteoarthritis: results of a pilot 2-week, open-label study using the Neuropathic Pain Scale.

    PubMed

    Gammaitoni, Arnold R; Galer, Bradley S; Onawola, Roland; Jensen, Mark P; Argoff, Charles E

    2004-01-01

    To determine the impact of the lidocaine patch 5% on distinct pain qualities associated with osteoarthritis (OA) through use of the Neuropathic Pain Scale (NPS), an assessment tool designed to assess intensity of various pain qualities (i.e.sharp, dull). Patients were enrolled in a prospective, open-label, non-randomized, parallel-group, 2-week study involving 8 clinical trial sites in the United States. Eligible patients had radiographic evidence of OA involving one or both knees and reported moderate-to-severe pain (despite prn or stable doses of analgesics) on the NPS at study enrollment. Patients on prn analgesics were discontinued from all analgesic regimens prior to study entry and received lidocaine patch 5% as monotherapy. Those on stable doses of analgesics were continued on their other analgesic regimens with no additions or dose alterations allowed other than the lidocaine patch 5% as add-on therapy. The lidocaine patch 5% was applied to the area of maximal pain, using no more than a total of 4 patches changed every 24 h. Effectiveness was measured by change from baseline to Week 2 in 4 composite measures of the NPS: NPS-10, NPS-4, NPS-8, and NPS-nonallodynia. Safety was assessed by adverse events (AEs), dermal assessment of application site(s), and skin sensory testing. In the combined patient population (n = 100), 2 weeks of treatment with lidocaine patch 5% significantly improved all 4 NPS composite measures (p < 0.001). Separate analyses by subgroups revealed significant improvements in all 4 composite measures for both the monotherapy group (n = 12; p < 0.01) and add-on therapy group (n = 88; p < 0.001). No treatment-related AEs were reported for the monotherapy group. In the add-on therapy group, 5 patients experienced mild-to-moderate treatment-related AEs. In patients with moderate-to-severe OA of the knee, 2 weeks of treatment with the lidocaine patch 5% significantly reduces the intensity of pain qualities as measured by all 4 NPS composite

  6. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders.

    PubMed

    Taliou, Anilia; Zintzaras, Elias; Lykouras, Lefteris; Francis, Kostantinos

    2013-05-01

    Accumulating evidence suggests an association between autism spectrum disorders (ASD) and inflammation in brain regions related to cognitive function. The natural flavonoid luteolin has antioxidant, anti-inflammatory, mast cell-blocking, and neuroprotective effects. It was shown to improve cognitive performance in a mouse model of ASD, but its effect in humans has not been adequately studied. The goal of this study was to assess the effectiveness and tolerability in white children with ASD of a dietary supplement containing 2 flavonoids (>95% pure), luteolin (100 mg/capsule, from chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside rutin (30 mg/capsule) from the Sophora japonica leaf, formulated in olive kernel oil to increase oral absorption. Fifty children (4-10 years old; 42 boys and 8 girls) with ASD were enrolled in a 26-week, prospective, open-label trial at the 2nd University Department of Psychiatry at "Attikon" General Hospital, Athens, Greece. Children were referred for the study by their respective physicians or came from the practice of the senior author. ASD diagnosis by clinical assessment was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, symptom list and corroborated by using the Autism Diagnostic Observation Schedule. The dose of the study formulation used was 1 capsule per 10 kg weight per day with food. The primary outcome measures were the age-equivalent scores in the Vineland Adaptive Behavior Scales domains. Secondary outcomes included the Aberrant Behavior Checklist, the Autism Treatment Evaluation Checklist, and the Clinical Global Impression-Improvement score. Data were measured at baseline, week 18, and week 26. Parents were interviewed for any possible improvements they noticed and instructed to report any unusual adverse events. A total of 40 children completed the protocol. There was a significant improvement in adaptive functioning as measured by using the VABS age

  7. The Effect of Omega-3 Fatty Acids on Psychophysiological Assessment for the Secondary Prevention of Posttraumatic Stress Disorder: An Open-Label Pilot Study

    PubMed Central

    Matsumura, Kenta; Noguchi, Hiroko; Nishi, Daisuke; Matsuoka, Yutaka

    2012-01-01

    Our recent pilot study has shown that the supplementation of omega-3 fatty acids (fish oil) immediately after a traumatic event may be effective toward the secondary prevention of post-traumatic disorder (PTSD). To lay the groundwork for addressing the mechanism by which omega-3 fatty acids can prevent PTSD, we analyzed its psychophysiological data. The psychophysiological data included heart rate, skin conductance, and continuous blood pressure during patient subjection to startling tones and idiographic trauma-related cues. Of the 8 patients, 1 met the diagnostic criteria for PTSD. Compared to the seven patients without PTSD, one patient with PTSD showed relatively large reactivity to the startle tones. In contrast, this patient did not show large reactivity to the trauma-related cue during script-driven imagery. The combination of psychophysiological measurements in our randomized control trial should shed light on the underlying mechanisms by which omega-3 fatty acids can prevent PTSD. PMID:22980098

  8. Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan.

    PubMed

    Kageyama, Shigeru; Ueda, Shinichiro; Mochizuki, Kouichi; Miyakawa, Masaaki; Sugawara, Masahiro; Nakayama, Michio; Ohashi, Yasuo; Saito, Ikuo; Saruta, Takao

    2012-02-01

    There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20 000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90 mm Hg for the elderly and patients with cerebrovascular disease, <130/80 mm Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a β-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures.

  9. Changes in negative symptoms and EEG in schizophrenic patients after repetitive transcranial magnetic stimulation (rTMS): an open-label pilot study.

    PubMed

    Jandl, M; Bittner, R; Sack, A; Weber, B; Günther, T; Pieschl, D; Kaschka, W-P; Maurer, K

    2005-07-01

    The effects of repetitive transcranial magnetic stimulation (rTMS) on schizophrenic negative symptoms (NS) and EEG topography were investigated in this pilot study. 10 patients with predominant NS were treated with 10 Hz rTMS over the left dorsolateral prefrontal cortex for 5 days. For NS ratings, the Scale for the Assessment of Negative Symptoms (SANS) was used. Both ratings and EEG recordings were obtained pre- and post-rTMS. Electrical activity changes were computed by Low Resolution Brain Electromagnetic Tomography. SANS showed an improvement after rTMS, from 49.0 (SD: 10.7) to 44.7 (SD: 11.8) (means). EEG frequency bands were changed fronto-temporally (right) and were mainly decreases in delta- and beta- and increases in alpha1-activity, as well as decreases in beta-activity in the temporal and parieto-occipital regions (left). Although we are aware of the limitations of this study, we assume a slight improvement in NS. The EEG findings refer to a possible neurophysiologic correlate of their improvement after rTMS.

  10. Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

    PubMed

    Beeler, Remo; Schoenenberger, Andreas W; Bauer, Peter; Kobza, Richard; Bergner, Michael; Mueller, Xavier; Schlaepfer, Reinhard; Zuber, Michel; Erne, Susanne; Erne, Paul

    2014-03-01

    Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. NCT00769678. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

  11. Mycophenolate Mofetil for Induction and Maintenance of Remission in Microscopic Polyangiitis with Mild to Moderate Renal Involvement—A Prospective, Open-Label Pilot Trial

    PubMed Central

    Silva, Francisco; Specks, Ulrich; Kalra, Sanjay; Hogan, Marie C.; Leung, Nelson; Sethi, Sanjeev

    2010-01-01

    Background and objectives: Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA), often targeting myeloperoxidase (MPO). Cyclophosphamide (CYC) plus corticosteroids (CS) is considered standard therapy for patients with renal involvement, but treatment response is not satisfactory in all patients and CYC has well recognized toxicity. This prospective pilot trial explored whether mycophenolate mofetil (MMF) represents an effective alternative to CYC for induction and maintenance of remission in MPA with mild to moderate renal involvement. Design, setting, participants, & measurements: Seventeen P-ANCA/MPO-ANCA-positive patients with MPA with mild to moderate renal involvement received MMF (1000 mg orally, twice daily) and CS (intravenous methylprednisolone, 1 to 3 g, followed by oral prednisone at 1 mg/kg per day). Oral CS were discontinued by month 6; MMF was continued through month 18. The primary outcome measure was remission by month 6 and stable renal function. Secondary endpoints included major relapses necessitating a switch to CYC plus CS, minor relapses requiring an increase in CS dosage, and adverse events. Results: Thirteen of 17 patients enrolled achieved the primary outcome, and 4 failed because of insufficient response, relapse, or MMF intolerance. Twelve patients remained in remission through month 18, renal function remained stable, and proteinuria improved. Side effects of MMF were mild, transient, and responsive to dose adjustments in all patients except one. Conclusions: MMF represents an alternative to CYC for induction and maintenance of remission in patients with MPO-ANCA-associated MPA with mild to moderate renal disease. PMID:20093349

  12. Prospective, randomized, open-label, pilot clinical trial comparing the effects of dexamethasone coadministered with diclofenac potassium or acetaminophen and diclofenac potassium monotherapy after third-molar extraction in adults

    PubMed Central

    Bamgbose, Babatunde Olamide; Akinwande, Jelili Adisa; Adeyemo, Wasiu Lanre; Ladeinde, Akinola Ladipo; Arotiba, Godwin Toyin; Ogunlewe, Mobolanle Olugbemiga

    2006-01-01

    Background: Patients who experience pain, swelling, and trismus after third-molar extraction are reported to experience a 3-fold higher rate of adverse effects (AEs) on quality of life compared with those who are asymptomatic after this surgery. Therefore, investigators emphasize the necessity for better control of this triad of sequelae. Steroids can reduce the risk for physiologic processes of inflammation, thereby suppressing the development of inflammation. Objective: The aim of this study was to compare the effects of dexamethasone 8 mg IM and diclofenac potassium (K) 50 mg PO, dexamethasone 8 mg IM and acetaminophen 1000 mg PO, and monotherapy with diclofenac K 50 mg PO on postoperative pain, swelling, and trismus after surgical removal of third molars. Methods: This prospective, randomized, open-label pilot study was conducted at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos, Nigeria. Patients were randomly allocated to 1 of 3 treatment groups: concomitant treatment with dexamethasone 8 mg IM and diclofenac K 50 mg PO or acetaminophen 1000 mg PO, or monotherapy with diclofenac K 50 mg PO. Overall analgesic efficacy of the drug combinations was assessed for 7 days postoperatively using a 4-point categorical pain-intensity rating scale (0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain). Facial swelling was measured in 1 dimension on days 1, 2, and 7 after surgery using a tape measure placed from the tip of the tragus, to gonion, to the tip of the contralateral tragus, and trismus was assessed using interincisal mouth-opening ability, measured using a vernier-calibrated caliper on postoperative days 1, 2, and 7. Tolerability was assessed using direct questioning of the patients at follow-up visits. Results: A total of 150 patients (50 per treatment group) were included in the analysis (76 women, 74 men; mean [SD] age, 26.8 [5.04] years [range, 18–45 years]; 100% Nigerian). The proportion of

  13. An Open Learner Model for Trainee Pilots

    ERIC Educational Resources Information Center

    Gakhal, Inderdip; Bull, Susan

    2008-01-01

    This paper investigates the potential for simple open learner models for highly motivated, independent learners, using the example of trainee pilots. In particular we consider whether such users access their learner model to help them identify their current knowledge level, areas of difficulty and specific misconceptions, to help them plan their…

  14. An Open Learner Model for Trainee Pilots

    ERIC Educational Resources Information Center

    Gakhal, Inderdip; Bull, Susan

    2008-01-01

    This paper investigates the potential for simple open learner models for highly motivated, independent learners, using the example of trainee pilots. In particular we consider whether such users access their learner model to help them identify their current knowledge level, areas of difficulty and specific misconceptions, to help them plan their…

  15. Head-to-Head Comparison of Aripiprazole and Risperidone in the Treatment of ADHD Symptoms in Children with Autistic Spectrum Disorder and ADHD: A Pilot, Open-Label, Randomized Controlled Study.

    PubMed

    Lamberti, Marco; Siracusano, Rosamaria; Italiano, Domenico; Alosi, Norma; Cucinotta, Francesca; Di Rosa, Gabriella; Germanò, Eva; Spina, Edoardo; Gagliano, Antonella

    2016-08-01

    Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently overlapping neurodevelopmental disorders. Individuals in whom the disorders are comorbid show more severe impairment because of deficits in the processing of social situations, adaptive functioning, and executive control than individuals with either disorder alone. This open-label pilot study aimed to evaluate and compare the efficacy and tolerability of risperidone and aripiprazole for treating ADHD symptoms in patients with both ASD and ADHD over the course of 24 weeks of treatment. Patients (n = 44) were randomly assigned to start treatment with risperidone (22 patients) or aripiprazole (22 patients). Children were evaluated before starting treatment (T0), and after 12 weeks (T1) and 24 weeks (T2) of treatment. At each visit, specific psychiatric clinical scales were administered to assess the efficacy of the two drugs. The mean age was 8.4 ± 2.9 years in the aripiprazole group and 7.8 ± 2.3 years in the risperidone group. A total of 37 children (29 boys and 8 girls) completed the study (18 in the aripiprazole group and 19 in the risperidone group). Aripiprazole and risperidone appeared to have similar benefits in terms of efficacy and tolerability, although there were slight differences between the two drugs. Both groups showed a significant improvement in ADHD symptoms after 24 weeks of treatment (ADHD Rating Scale, Conners Parent Rating Scale-Hyperactivity, and Clinical Global Improvement-Severity Scale). No significant difference between the two drugs on any parameters at 24 weeks were found. Prolactin levels were decreased in the aripiprazole group. Both drugs were well tolerated, with no serious adverse events detected. Our study confirms the efficacy of both aripiprazole and risperidone in ameliorating ADHD symptoms of children also presenting with ASD.

  16. Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study.

    PubMed

    Rossetti, Giuseppe; Pizzocri, Samuele; Brasca, Francesco; Pozzi, Marta; Beltrami, Laura M; Bolla, Giovanni B; Famiani, Roberta; Caimi, Barbara; Omboni, Stefano; Magrini, Fabio; Carugo, Stefano

    2008-06-01

    Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure. The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine. This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140-179 mm Hg and diastolic BP of 90-109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets. Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, -10.3/-9.4 vs -16.6/-9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13%]; P < 0.05). In this small sample of treatment

  17. Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety

    PubMed Central

    Boudreau, Guy P; Grosberg, Brian M; McAllister, Peter J; Lipton, Richard B; Buse, Dawn C

    2015-01-01

    Background Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity. OnabotulinumtoxinA (BOTOX®) is effective and well tolerated in the prophylactic treatment of chronic migraine. This study aimed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms. Methods This was a prospective, open-label, multicenter pilot study. Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms, including Patient Health Questionnaire depression module scores of 5–19. Eligible participants received 155 units of onabotulinumtoxinA, according to the PREEMPT protocol, at baseline and week 12. Assessments included headache frequency, the Headache Impact Test™, the Migraine Disability Assessment, the Beck Depression Inventory®-II, the nine-item Patient Health Questionnaire depression module, and the seven-item Generalized Anxiety Disorder questionnaire. Adverse events were also monitored. Results Overall, 32 participants received treatment. At week 24, there were statistically significant mean (standard deviation [SD]) improvements relative to baseline in the number of headache/migraine-free days (+8.2 [5.8]) (P<0.0001) and in the number of headache/migraine days (−8.2 [5.8]) (P<0.0001) per 30-day period. In addition, there were significant improvements in Headache Impact Test scores (−6.3 [6.9]) (P=0.0001) and Migraine Disability Assessment scores (−44.2 [67.5]) (P=0.0058). From baseline to week 24, statistically significant improvements were also seen in Beck Depression Inventory-II (−7.9 [6.0]) (P<0.0001), Patient Health Questionnaire depression module (−4.3 [4.7]) (P<0.0001), and Generalized Anxiety Disorder questionnaire (−3.5 [5.0]) (P=0.0002) scores. No serious adverse events were reported. Adverse events

  18. Effects of efonidipine, an L- and T-Type dual calcium channel blocker, on heart rate and blood pressure in patients with mild to severe hypertension: an uncontrolled, open-label pilot study☆

    PubMed Central

    Shimizu, Mitsuyuki; Ogawa, Kazuhiko; Sasaki, Hideki; Uehara, Yoshiki; Otsuka, Yumi; Okumura, Hiroyuki; Kusaka, Masafumi; Hasuda, Toshio; Yamada, Taku; Mochizuki, Seibu

    2003-01-01

    Background Dihydropyridines (DHPs), a type of calcium channel blocker (CCB), are commonly prescribed for the treatment of hypertension and angina pectoris. DHPs act mainly on L-type calcium channels, essentially causing reflex tachycardia (elevated heart rate [HR]), which negatively affects cardiac function. Because T-type calcium channels in the sinoatrial node attenuate reflex tachycardia, a dual L- and T-type CCB (eg, efonidipine hydrochloride) may favorably affect cardiac pacing, thereby reducing reflex tachycardia. The effect of efonidipine as a DHP on HR deserves special consideration with regard to reflex tachycardia. Objective The aim of this study was to determine whether the L- and T-type CCB efonidipine can decrease the elevated HR induced by prior treatment using traditional DHPs. Methods This uncontrolled, open-label pilot study was conducted at the Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine (Tokyo, Japan). Patients aged 48 to 80 years with mild to severe hypertension and angina pectoris and who were receiving therapy with a DHP other than efonidipine were eligible. During an 8-week observation period, patients continued therapy with their DHP. After those 8 weeks, therapy was switched to oral efonidipine (40-mg tablet once daily) in patients whose blood pressure (BP) was stable and well controlled and whose HR was >80 bpm. BP and HR were monitored every 4 weeks of treatment with efonidipine. Results Eighteen patients (12 men, 6 women; mean [SD] age, 62.6 [12] years) were enrolled. After the switch to efonidipine, mean (SD) HR decreased significantly, from 94 (7) bpm to 86 (11) bpm at 12 weeks (P<0.05). The antihypertensive effect of efonidipine was similar to that of the DHPs used before the switch to efonidipine therapy, and reflex tachycardia was attenuated. Conclusion In this study of a small sample of patients with mild to severe essential hypertension and angina pectoris, efonidipine was as

  19. Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study

    PubMed Central

    Rossetti, Giuseppe; Pizzocri, Samuele; Brasca, Francesco; Pozzi, Marta; Beltrami, Laura M.; Bolla, Giovanni B.; Famiani, Roberta; Caimi, Barbara; Omboni, Stefano; Magrini, Fabio; Carugo, Stefano

    2008-01-01

    Background: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure. Objective: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine. Methods: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140–179 mm Hg and diastolic BP of 90–109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets. Results: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, −10.3/−9.4 vs −16.6/−9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13

  20. The effectiveness of auxiliary prescription labels: a pilot study.

    PubMed

    Wiederholt, J B; Kotzan, J A; Cooper, J W

    1983-03-01

    Affixed auxiliary prescription labels are widely used in the practice of pharmacy because they supposedly provide the patient with pertinent information that is not contained within the prescription signature. Yet, whether the labels are effective is not known, nor is it known whether the label's elements, such as color, form, and logo, affect perception of the written text. Sound scientific analyses of these questions are limited. Therefore, a pilot study involving a series of experiments was designed to determine whether individual perception of pertinent information is affected by the use of affixed auxiliary prescription labels. The second objective of this study was to evaluate how color and logo differences affected perception of the label's written text. Participants were selected for the experiments after being screened for color blindness, corrected vision, and, in some cases, previous pharmacy employment. Subjects viewed labels affixed to prescription vials via a two-channel tachistoscope. The tachistoscopic methodology measured perception, and its accuracy was verified through a forced-choice instrument. Results from the pilot study were threefold: (1) a sound scientific analysis found affixed auxiliary labels to be effective, (2) significant variance could be attributed to both individual and subject differences, and (3) the unique effects of color and logo could not be determined.

  1. The Effects of Levetiracetam on Alcohol Consumption in Alcohol-Dependent Subjects: An Open Label Study

    PubMed Central

    Sarid-Segal, Ofra; Piechniczek-Buczek, Joanna; Knapp, Clifford; Afshar, Maryam; Devine, Eric; Sickles, Laurie; Uwodukunda, Emma; Richambault, Courtney; Koplow, Jillian; Ciraulo, Domenic

    2017-01-01

    The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects. PMID:18584574

  2. Pilot job accounting and auditing in Open Science Grid

    SciTech Connect

    Sfiligoi, Igor; Green, Chris; Quinn, Greg; Thain, Greg; /Wisconsin U., Madison

    2008-06-01

    The Grid accounting and auditing mechanisms were designed under the assumption that users would submit their jobs directly to the Grid gatekeepers. However, many groups are starting to use pilot-based systems, where users submit jobs to a centralized queue and are successively transferred to the Grid resources by the pilot infrastructure. While this approach greatly improves the user experience, it does disrupt the established accounting and auditing procedures. Open Science Grid deploys gLExec on the worker nodes to keep the pilot-related accounting and auditing information and centralizes the accounting collection with GRATIA.

  3. OpenCL based machine learning labeling of biomedical datasets

    NASA Astrophysics Data System (ADS)

    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

  4. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

  5. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

  6. Uncontrolled, open-label, pilot study of tea tree (Melaleuca alternifolia) oil solution in the decolonisation of methicillin-resistant Staphylococcus aureus positive wounds and its influence on wound healing.

    PubMed

    Edmondson, Margaret; Newall, Nelly; Carville, Keryln; Smith, Joanna; Riley, Thomas V; Carson, Christine F

    2011-08-01

    Many complementary and alternative products are used to treat wounds. The essential oil of Melaleuca alternifolia, tea tree oil, has proven antimicrobial and anti-inflammatory properties, may be useful in methicillin-resistant Staphylococcus aureus (MRSA) decolonisation regimens and is reputed to have 'wound-healing' properties, but more data are required to support these indications. The primary aim of this uncontrolled case series was to assess whether a tea tree oil solution used in a wound cleansing procedure could decolonise MRSA from acute and chronic wounds of mixed aetiology. The secondary aim was to determine if the tea tree oil solution influenced wound healing outcomes. Nineteen participants with wounds suspected of being colonised with MRSA were enrolled in a pilot study. Seven were subsequently shown not to have MRSA and were withdrawn from the study. As many as 11 of the remaining 12 participants were treated with a water-miscible tea tree oil (3·3%) solution applied as part of the wound cleansing regimen at each dressing change. Dressing changes were three times per week or daily as deemed necessary by the study nurse following assessment. One participant withdrew from the study before treatment. No participants were MRSA negative after treatment. After treatment had been implemented, 8 of the 11 treated wounds had begun to heal and reduced in size as measured by computer planimetry. Although this formulation and mode of delivery did not achieve the primary aim of the study, tea tree oil did not appear to inhibit healing and the majority of wounds reduced in size after treatment.

  7. Baclofen for binge eating: an open-label trial.

    PubMed

    Broft, Allegra I; Spanos, Alexia; Corwin, Rebecca L; Mayer, Laurel; Steinglass, Joanna; Devlin, Michael J; Attia, Evelyn; Walsh, B Timothy

    2007-12-01

    Baclofen is a GABA-B agonist that may be useful in the treatment of substance use disorders, and also reduces 'binge-like' eating in rodents. We hypothesized that baclofen might be effective in reducing binge eating episodes in binge eating disorder (BED) and bulimia nervosa (BN). Seven women with BED (n = 4) or BN (n = 3) took baclofen (60 mg/day) for 10 weeks. Six out of seven patients completed the full 10-week trial. Five out of seven participants (3 BED; 2 BN) demonstrated 50% or greater reduction of frequency of binge eating from beginning to end of the study. Three out of seven participants (2 BED; 1 BN) were free of binge eating at study end. Four out of seven participants elected to continue baclofen at study end. Baclofen was well tolerated by the participants. In this open-label trial, baclofen was associated with decreased binge eating frequency in patients with BED and BN. (c) 2007 by Wiley Periodicals, Inc.

  8. Ethosuximide for Essential Tremor: An Open-Label Trial

    PubMed Central

    Gironell, Alexandre; Marin-Lahoz, Juan

    2016-01-01

    Background T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Results Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET. PMID:27625899

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

    PubMed

    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 (P<0.05) on measures of skin picking 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.

  10. Effects of a structured 20-session slow-cortical-potential-based neurofeedback program on attentional performance in children and adolescents with attention-deficit hyperactivity disorder: retrospective analysis of an open-label pilot-approach and 6-month follow-up

    PubMed Central

    Albrecht, Johanna S; Bubenzer-Busch, Sarah; Gallien, Anne; Knospe, Eva Lotte; Gaber, Tilman J; Zepf, Florian D

    2017-01-01

    obtained preliminary data are the rather small sample size, the lack of a control group/a placebo condition and the open-label approach because of the clinical setting and retrospective analysis. The value of the current approach lies in providing pilot data for future studies involving larger samples. PMID:28293109

  11. Mirtazapine in Comorbid Major Depression and Alcohol Dependence: An Open-Label Trial

    PubMed Central

    Cornelius, Jack R.; Douaihy, Antoine B.; Clark, Duncan B.; Chung, Tammy; Wood, D. Scott; Daley, Dennis

    2012-01-01

    Objective This was a first pilot study evaluating the acute phase (8-week) efficacy of the antidepressant medication mirtazapine for the treatment of depressive symptoms and drinking of subjects with comorbid major depressive disorder and alcohol dependence (MDD/AD). We hypothesized that mirtazapine would demonstrate within-group efficacy for the treatment of both depressive symptoms and drinking in these subjects. Methods We conducted a first open label study of the second generation antidepressant mirtazapine in 12 adult outpatient subjects with comorbid major depressive disorder/alcohol dependence. The pharmacological profile of that medication is unique among antidepressants, unrelated to tricyclics or selective serotonin reuptake inhibitors. Results Mirtazapine was well tolerated in this treatment population. Self-reported depressive symptoms decreased from 31.8 to 8.3 on the Beck Depression Inventory, a 74.0% decrease (p<0.001), and drinking decreased from 33.9 to 13.3 drinks per week, a 60.8% decrease (p<0.05). None of the subjects were employed full-time at baseline, but 9 of the 12 (75%) were employed full-time at end-of-study. Conclusions These preliminary findings suggest efficacy for mirtazapine for treating both the depressive symptoms and excessive alcohol use of comorbid major depressive disorder and alcohol dependence. Double-blind studies are warranted to further clarify the efficacy of mirtazapine in this population. PMID:23230395

  12. Open-wheel race car driving: energy cost for pilots.

    PubMed

    Beaune, Bruno; Durand, Sylvain; Mariot, Jean-Pierre

    2010-11-01

    The aim of this study was to evaluate the energy cost of speedway open-wheel race car driving using actimetry. Eight pilot students participated in a training session consisting of 5 successive bouts of around 30 minutes driving at steady speed on the Bugatti speedway of Le Mans (France). Energy expenditure (EE, kcal) was determined continuously by the actimetric method using the standard equation. Energy cost was estimated through physical activity ratio (PAR = EE/BMR ratio, Mets) calculation after basal metabolism rate (BMR, kcal·min-1) estimation. A 1-met PAR value was attributed to the individual BMR of each volunteer. Bout durations and EE were not significantly different between driving bouts. Mean speed was 139.94 ± 2.96 km·h-1. Physical activity ratio values ranged 4.92 ± 0.50 to 5.43 ± 0.47 Mets, corresponding to a 5.27 ± 0.47-Mets mean PAR values and a 1.21 ± 0.41 kcal·min-1 mean BMR value. These results suggest that actimetry is a simple and efficient method for EE and PAR measurements in motor sports. However, further studies are needed in the future to accurately evaluate relationships between PAR and driving intensity or between PAR and race car type.

  13. Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders

    PubMed Central

    Gracious, Barbara; Arnold, L. Eugene; Failla, Mark; Chitchumroonchokchai, Chureeporn; Habash, Diane; Fristad, Mary A.

    2013-01-01

    Abstract Objective The purpose of this study was to report the safety, tolerability, and serum micronutrient concentrations and their correlations with mood changes from an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement, EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD). Methods Ten children ages 6–12 received EMP+ escalating from one to four capsules t.i.d., with four children increased to the maximum suggested dose, five capsules t.i.d. Outcome measures were micronutrient concentrations in serum and red blood cells, vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire and 24 hour dietary recall interview), and mood and global functioning ratings. Results Seven children (70%) completed the study. Three (30%) terminated early for tolerability and compliance issues. Adverse effects were mild and transient, and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No differences occurred in BMI (p=0.310) or waist–hip ratio (WHR; p=0.674) pre- to postsupplementation. Four of the tested serum vitamin concentrations increased from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-α-tocopherol; and folate (all p<0.05). The increase in serum 25-OH vitamin D approached significance (p=0.063). No differences were found in dietary intake pre- to postsupplementation, suggesting that blood nutrient level increases were caused by EMP+. Conclusions In this open prospective study, short-term use of EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action, combined with documentation of increased serum concentrations of specific micronutrients. PMID:24138009

  14. An Open-Label Study of Guanfacine Extended Release for Traumatic Stress Related Symptoms in Children and Adolescents

    PubMed Central

    Grasso, Damion J.; Slivinsky, Michelle D.; Pearson, Geraldine S.; Banga, Alok

    2013-01-01

    Abstract Objective The purpose of this open-label pilot study was to investigate the effectiveness and tolerability of guanfacine extended release (GXR) 1–4 mg given in the evening, on the symptoms of traumatic stress (reexperiencing, avoidance, overarousal), generalized anxiety, and functional impairment in children and adolescents with a history of traumatic stress with or without posttraumatic stress disorder (PTSD). As many of our sample had associated attention-deficit/hyperactivity disorder (ADHD) symptoms, we also assessed whether the presence of traumatic stress symptoms impaired the effectiveness of GXR in the treatment of comorbid ADHD symptoms. Methods Participants were 19 children and adolescents 6–18 years of age, with current traumatic stress symptoms. In an 8 week open-label design, each patient's scores on parent-, child-, and clinician-reported symptom rating scales assessing traumatic stress symptoms, generalized anxiety, ADHD symptoms, functional impairment, and global symptom severity and improvement (n=17) were evaluated off and on GXR using χ2 goodness-of-fit tests, paired t tests, and repeated measures analyses of variance (ANOVAs). To examine patterns of change in outcome measures across treatment, MPlus software was used to conduct linear growth curves modeled with individual-varying times of observation (i.e., random slopes). Results Using an average GXR daily dose of 1.19 mg±0.35 mg and an average weight-adjusted daily dose of 0.03 mg/kg±0.01 mg/kg, significant differences were found on all symptom severity measures. Parent reported UCLA Reaction Index scores assessing cluster B (reexperiencing), C (avoidant), and D (overarousal) symptoms significantly improved. In the presence of PTSD symptoms, children with ADHD experienced significantly improved ADHD symptom scores, suggesting that comorbidity does not attenuate an ADHD symptom response to GXR therapy. Medication was generally well tolerated. Conclusions Within the

  15. Pilot Evaluation of an In-Store Nutrition Label Education Program.

    PubMed

    Dukeshire, Steven; Nicks, Emily; Ferguson, Jennifer

    2014-12-01

    To describe and provide recommendations for the implementation of an evaluation for an already existing, in-store Nutrition Label Education Program (NLEP). We describe the development and implementation of an evaluation consisting of a pre- and postsurvey and one month follow-up. The evaluation was designed to assess satisfaction with the NLEP as well as changes in participant nutrition label knowledge, confidence in using nutrition labels, and actual changes in nutrition label use. Nineteen participants took part in the pilot evaluation. The evaluation was successful in demonstrating high levels of satisfaction with the NLEP as well as positive changes in participant confidence and some increased knowledge in using nutrition labels. However, only 3 people participated in the follow-up, limiting the ability to assess behaviour change. Ideally, NLEPs should include ongoing evaluation that extends beyond just assessing participant satisfaction. Recommendations are provided for conducting such evaluations, including the importance of incorporating the evaluation into the program itself, using existing questionnaires when possible, and employing pre- and postsurveys as well as follow-up interviews to assess change.

  16. Open-label extension studies: do they provide meaningful information on the safety of new drugs?

    PubMed

    Day, Richard O; Williams, Kenneth M

    2007-01-01

    The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

  17. Pharmacokinetic properties of pravastatin in Mexicans: An open-label study in healthy adult volunteers

    PubMed Central

    Escobar, Yesenia; Venturelli, Caterina R.; Hoyo-Vadillo, Carlos

    2005-01-01

    Background: The pharmacokinetic properties of pravastatin, particularlyAUC and Cmax, are variable by population. A description of the pharmacokinetic properties of pravastatin in Mexican mestizos was not found in a search of MEDLINE/PubMed (key terms: pravastatin, Mexican, and pharmacokinetics; years: 1966–2005). Because Mexicans and Japanese have common ancestors (Mongoloid group), they also have a common gene pool. This gene pool was modified by genetic “bottlenecks” that occurred when these populations migrated to the Americas and when the Mexican population mixed with the Spanish population during the 16th and 17th centuries. Previous studies in Japanese subjects showed 5 main mutations on the hepatic drug transporter OATP-C, resulting in higher Cmax and AUC values compared with whites. In the Japanese population, the rates of expression of the *1b and *15 alleles were 46% and 15%, respectively. Objective: The aim of this study was to evaluate the pharmacokinetic propertiesof pravastatin in healthy Mexican mestizo volunteers and to compare them with those in white and Japanese populations described in the literature. Methods: This open-label, uncontrolled pilot study of the pharmacokineticproperties of pravastatin was conducted at the Division of Pharmacology, Center for Research and Advanced Studies, Mexico City, Mexico. Healthy, adult, Mexican volunteers received a single dose of pravastatin 10 mg PO (tablet). High-performance liquid chromatography was used to determine plasma pravastatin concentrations between 15 minutes and 12 hours after dosing. Results: Twenty-four subjects (15 women, 9 men; mean age, 30.6 years)participated in the study. The mean (SD) Cmax was 9.5 (2.4) ng/mL; Tmax, 0.8 (0.3) hours; AUC0−∞ 35.7 (19.7) ng/mL - h; t1/2, 2.7 (1.1) hours; and mean residence time, 3.1 (1.1) hours. One volunteer (4%) had an AUC value that differed substantially from the rest of the study population, producing a bimodal distribution of the

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

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    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, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy. PMID:27621644

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

    PubMed Central

    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. PMID:24319427

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

    PubMed

    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.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  5. STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

    ERIC Educational Resources Information Center

    Erickson, Craig A.; Veenstra-Vanderweele, Jeremy M.; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Bear, Mark F.; Wang, Paul P.; King, Bryan H.

    2014-01-01

    STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32…

  6. Open-Label, Prospective Trial of Olanzapine in Adolescents with Subaverage Intelligence and Disruptive Behavioral Disorders

    ERIC Educational Resources Information Center

    Handen, Benjamin L.; Hardan, Antonio Y.

    2006-01-01

    Objective: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. Method: Sixteen…

  7. Open-Label, Prospective Trial of Olanzapine in Adolescents with Subaverage Intelligence and Disruptive Behavioral Disorders

    ERIC Educational Resources Information Center

    Handen, Benjamin L.; Hardan, Antonio Y.

    2006-01-01

    Objective: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. Method: Sixteen…

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

    ERIC Educational Resources Information Center

    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…

  9. STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

    ERIC Educational Resources Information Center

    Erickson, Craig A.; Veenstra-Vanderweele, Jeremy M.; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Bear, Mark F.; Wang, Paul P.; King, Bryan H.

    2014-01-01

    STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32…

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

    ERIC Educational Resources Information Center

    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…

  11. Phase II open label study of valproic acid in spinal muscular atrophy.

    PubMed

    Swoboda, Kathryn J; Scott, Charles B; Reyna, Sandra P; Prior, Thomas W; LaSalle, Bernard; Sorenson, Susan L; Wood, Janine; Acsadi, Gyula; Crawford, Thomas O; Kissel, John T; Krosschell, Kristin J; D'Anjou, Guy; Bromberg, Mark B; Schroth, Mary K; Chan, Gary M; Elsheikh, Bakri; Simard, Louise R

    2009-01-01

    Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (ppilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate

  12. Phase II Open Label Study of Valproic Acid in Spinal Muscular Atrophy

    PubMed Central

    Swoboda, Kathryn J.; Scott, Charles B.; Reyna, Sandra P.; Prior, Thomas W.; LaSalle, Bernard; Sorenson, Susan L.; Wood, Janine; Acsadi, Gyula; Crawford, Thomas O.; Kissel, John T.; Krosschell, Kristin J.; D'Anjou, Guy; Bromberg, Mark B.; Schroth, Mary K.; Chan, Gary M.; Elsheikh, Bakri; Simard, Louise R.

    2009-01-01

    Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2–3 years, 29 SMA type II ages 2–14 years and 11 type III ages 2–31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p≤0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Δ7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p≤0.0036) and maximum ulnar CMAP scores (p≤0.0001) increased significantly. Conclusions While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various

  13. The Influence of Labeling the Vegetable Content of Snack Food on Children's Taste Preferences: A Pilot Study

    ERIC Educational Resources Information Center

    Pope, Lizzy; Wolf, Randi L.

    2012-01-01

    Objective: This pilot study examined whether informing children of the presence of vegetables in select snack food items alters taste preference. Methods: A random sample of 68 elementary and middle school children tasted identical pairs of 3 snack food items containing vegetables. In each pair, 1 sample's label included the food's vegetable (eg,…

  14. The Influence of Labeling the Vegetable Content of Snack Food on Children's Taste Preferences: A Pilot Study

    ERIC Educational Resources Information Center

    Pope, Lizzy; Wolf, Randi L.

    2012-01-01

    Objective: This pilot study examined whether informing children of the presence of vegetables in select snack food items alters taste preference. Methods: A random sample of 68 elementary and middle school children tasted identical pairs of 3 snack food items containing vegetables. In each pair, 1 sample's label included the food's vegetable (eg,…

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

    PubMed Central

    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 (< 1%) had serious AEs that were considered possibly, probably, or definitely related to the study drug during the on-therapy period. No deaths occurred during the study. Conclusions: 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

  16. Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: An open-label trial.

    PubMed

    Salasche, Stuart J; Levine, Norman; Morrison, Lynne

    2002-10-01

    Preliminary studies indicate that topically applied immune response modifiers may be an effective and safe method of treating actinic keratoses (AKs). Our aim was to study the potential efficacy of topical 5% imiquimod cream in the treatment of facial or scalp AKs and improve the safety profile by using a novel "cycle" dosing regimen. This pilot study is an open-label trial that included 25 patients who had between 5 and 20 discrete AKs within a cosmetic unit of the forehead, scalp, or cheek. Treatment consisted of once-daily application of 5% imiquimod cream, 3 times a week for 4 weeks. to the entire cosmetic unit, followed by a rest period of 4 weeks. The cycle was repeated if any AKs remained after a complete 8-week cycle. A maximum of 3 cycles was permitted (24 weeks). Thirty-three sites in 25 patients were evaluated. Compliance was excellent with a very tolerable safety profile. Complete clearing of all AKs was noted in 82% (27/33) of anatomic sites in 25 study subjects. Almost half the sites (15/33) were clear at the end of the first cycle. A "therapeutic interval" was noted during the rest period wherein clinical inflammation subsided but AKs continued to clear. An added effect was the uncovering and clinical appearance and subsequent eradication of incipient (subclinical) AKs in the treatment area. There was excellent compliance with the cycle therapy regimen. The observations and hypotheses made in this pilot study will be tested in controlled, randomized trials with larger study populations. The identification of a therapeutic interval may prove to be beneficial in formulating individualized dosing regimens.

  17. [Off-label and unlicensed drug use: Results from a pilot study in a pediatric intensive care unit].

    PubMed

    García-López, Isabel; Fuentes-Ríos, Javier Ezequiel; Manrique-Rodríguez, Silvia; M Fernández-Llamazares, Cecilia

    2017-01-01

    To analyze the prevalence of use of off-label and unlicensed drugs in a pediatric intensive care unit of a University Hospital. An observational, descriptive, prospective six week pilot study in a Pediatric Intensive Care Unit. Hospitalized patients aged between 0 and 18 years were included. Each prescribed drug was evaluated taking into account indication and condition of use, according to the information available on the Summary of Product Characteristics established by the European Medicines Agency. A sequential algorithm was defined allowing drug classification in unlicensed, off-label or approved. Forty-two patients were included. A total of 696 prescriptions, involving 102 different drugs, were analyzed. All patients had at least one off-label prescription, and a median of 8.9 off-label prescriptions was obtained. Of the total prescriptions, 8.6% were unlicensed and 53.9% corresponded to off-label use. The main reason for off-label use was by indication, followed by age and dose. A lineal tendency between off-label drug use and patient age was observed, where off-label use increased as patient age decreased. The drugs most commonly used off-label were: atropine, etomidate, dipyrone and ranitidine, and unlicensed drugs: spironolactone, sildenafil, acetazolamide and hydrochlorothiazide. Pediatric Intensive Care Units are characterized by a high ratio of off-label and unlicensed prescriptions. The scarce number of studies performed in this specific and complex sub-population added inconveniency to the current lack of data on safety and efficacy for drugs in paediatrics. Performing studies with these characteristics allows us to document practice on paediatric drug utilisation are required. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Role of ranitidine in negative symptoms of schizophrenia--an open label study.

    PubMed

    Mehta, Varun S; Ram, Daya

    2014-12-01

    In this open label study, 75 patients with a diagnosis of schizophrenia were randomized to three groups of 25 each, receiving 150mg/day ranitidine, 300mg/day ranitidine and receiving only olanzapine. They were rated on PANSS at baseline, 4 and 8 weeks. There was a significant reduction in the scores of negative scale in patients receiving 300mg/day ranitidine in comparison to patients not receiving ranitidine at the end of 4 weeks but was not seen again when assessed at the end of 8 weeks. Though effective in reducing the negative symptoms, the effect was not sustained due to the tolerance to the actions of ranitidine.

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

    PubMed

    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. © 2016 John Wiley & Sons Ltd.

  20. ARE OPEN-LABEL PLACEBOS ETHICAL? INFORMED CONSENT AND ETHICAL EQUIVOCATIONS

    PubMed Central

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

    2016-01-01

    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 forebearers 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 DISTIINCTION BETWEEN AUTONOMY AND BENEFICIENCE. In this paper 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. PMID:26840547

  1. An Open-Labeled Trial of Ramelteon in Idiopathic Rapid Eye Movement Sleep Behavior Disorder

    PubMed Central

    Esaki, Yuichi; Kitajima, Tsuyoshi; Koike, Shigefumi; Fujishiro, Hiroshige; Iwata, Yasuyo; Tsuchiya, Akiko; Hirose, Marina; Iwata, Nakao

    2016-01-01

    Study Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia and elaborate motor activity in association with dream mentation. The melatonin receptor agonist ramelteon has been documented as being effective in two patients with secondary RBD. However, there are no reports on ramelteon treatment for idiopathic RBD. Methods: In an open-labeled trial, we treated 12 consecutive patients with idiopathic RBD for at least 4 w with 8 mg ramelteon given within 30 min before bedtime. Results: Ramelteon treatment did not have a clear effect on REM sleep without atonia or an RBD severity scale measured by video-supported polysomnography. However, clinical assessment using a visual analog scale showed a trend toward significance and there were also definitely positive changes in some individual cases. Ramelteon was well tolerated in most patients, with minor side effects. Conclusions: Considering that ramelteon is associated with few side effects, further study may ascertain whether patients with RBD could be effectively treated by ramelteon, especially when clonazepam may not be suitable due to its side effects. Commentary: A commentary on this article appears in this issue on page 643. Citation: Esaki Y, Kitajima T, Koike S, Fujishiro H, Iwata Y, Tsuchiya A, Hirose M, Iwata N. An open-labeled trial of ramelteon in idiopathic rapid eye movement sleep behavior disorder. J Clin Sleep Med 2016;12(5):689–693. PMID:26857053

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

    PubMed

    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.

  3. Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study.

    PubMed

    Thonnard, Marie; Gosseries, Olivia; Demertzi, Athena; Lugo, Zulay; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Chatelle, Camille; Thibaut, Aurore; Charland-Verville, Vanessa; Habbal, Dina; Schnakers, Caroline; Laureys, Steven

    2013-01-01

    Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study diagnosis) in any of the 60 studied chronic DOC patients.

  4. Bupropion treatment of olanzapine-associated weight gain: an open-label, prospective trial.

    PubMed

    Gadde, Kishore M; Zhang, Wei; Foust, Mariko S

    2006-08-01

    To examine the effectiveness of bupropion in reducing bodyweight gained during treatment with olanzapine. Eight subjects, who received olanzapine for an average duration of 26 months and had gained an average of 13.3 kg bodyweight, participated in a 24-week study in which they received open-label bupropion 150-300 mg/d while continuing olanzapine. The subjects were also provided low-key nutritional counseling. Change in bodyweight was the primary outcome of interest. Changes in fasting blood glucose and lipids were also examined in addition to changes in body composition and bone mineral density. Seven subjects completed the full 24-week study treatment. In the intent-to-treat sample, mean [SE] bodyweight decreased significantly over time (99.6 [5.9] kg to 96.2 [5.8] kg; F = 4.0; P < 0.001); average weight change for the eight subjects was -3.4 kg. Four of eight subjects lost > or =3% bodyweight. There was a significant reduction in total cholesterol. Weight loss did not have a negative effect on bone mineral density. Side effects were generally mild. Bupropion combined with a low-key dietary intervention appeared to be beneficial in reducing olanzapine-associated weight gain in some subjects in this open-label study.

  5. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study.

    PubMed

    Osher, Yamima; Bersudsky, Yuly; Belmaker, R H

    2005-06-01

    Epidemiologic studies have suggested that consumption of cold water fish oils may have some protective function against depression. This proposition is supported by a series of biochemical and pharmacologic studies that have suggested that fatty acids may modulate neurotransmitter metabolism and cell signal trans-duction in humans and that abnormalities in fatty acid and eicosanoid metabolism may play a causal role in depression. Aware of the critical need for antidepression treatments that might not carry the risk of precipitating a manic episode in bipolar patients, we decided to conduct an open-label add-on trial of eicosapentaenoic acid (EPA) in bipolar depression. Twelve bipolar I outpatients with depressive symptoms diagnosed by DSM-IV were treated with 1.5 to 2 g/day of the omega-3 fatty acid EPA for up to 6 months. The study was conducted between September 2001 and January 2003. Eight of the 10 patients who completed at least 1 month of follow-up achieved a 50% or greater reduction in Hamilton Rating Scale for Depression scores within 1 month. No patients developed hypomania or manic symptoms. No significant side effects were reported. This study is limited both by the open-label design and by the small sample size. As in all previous reported studies, patients in this study were treated in an outpatient setting, so that the most severely depressed bipolar patients (requiring hospitalization) are not represented. Although the ultimate utility of omega-3 fatty acids in bipolar depression is still an open question, we believe that these initial results are encouraging, especially for mild to moderate bipolar depression, and justify the continuing exploration of its use.

  6. Efficacy and Tolerability of Asenapine Compared with Olanzapine in Borderline Personality Disorder: An Open-Label Randomized Controlled Trial.

    PubMed

    Bozzatello, Paola; Rocca, Paola; Uscinska, Maria; Bellino, Silvio

    2017-07-24

    Asenapine is a new second-generation antipsychotic that is understudied in borderline personality disorder (BPD). Only one study investigating the use of the drug in this indication (an open-label pilot study) has been conducted to date. The present open-label, randomized, controlled trial aimed to evaluate the efficacy and tolerability of asenapine in comparison with olanzapine, the most broadly studied antipsychotic in BPD. A total of 51 outpatients aged between 18 and 50 years with a diagnosis of BPD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were assigned for 12 weeks to asenapine (5-10 mg/day) or olanzapine (5-10 mg/day). Participants were assessed at baseline and after 12 weeks with the following instruments: the Clinical Global Impression Scale, Severity item (CGI-S), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Social Occupational Functioning Assessment Scale (SOFAS), Borderline Personality Disorder Severity Index (BPDSI), Barratt Impulsiveness Scale, version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI), and Dosage Record and Treatment Emergent Symptom Scale (DOTES). Analysis of variance repeated measures was performed. Intention-to-treat analysis with last observation carried forward was conducted. There were 11 drop-outs (21.57%): six patients taking asenapine and five patients receiving olanzapine. Two patients who received asenapine stopped the drug, one due to oral hypoesthesia and the other due to moderate anxiety. Two patients receiving olanzapine discontinued the treatment because of significant weight gain (≥3 kg). The remaining seven drop-outs resulted from the lack of compliance with the trial prescription. Forty out of the 51 patients (78%) completed the trial: 19 patients received asenapine, while 21 patients received olanzapine. We found a significant within-subject effect (trial duration) for all rating scales

  7. An open access pilot freely sharing cancer genomic data from participants in Texas

    PubMed Central

    Becnel, Lauren B.; Pereira, Stacey; Drummond, Jennifer A.; Gingras, Marie-Claude; Covington, Kyle R.; Kovar, Christie L.; Doddapaneni, Harsha Vardhan; Hu, Jianhong; Muzny, Donna; McGuire, Amy L.; Wheeler, David A.; Gibbs, Richard A.

    2016-01-01

    Genomic data sharing in cancer has been restricted to aggregate or controlled-access initiatives to protect the privacy of research participants. By limiting access to these data, it has been argued that the autonomy of individuals who decide to participate in data sharing efforts has been superseded and the utility of the data as research and educational tools reduced. In a pilot Open Access (OA) project from the CPRIT-funded Texas Cancer Research Biobank, many Texas cancer patients were willing to openly share genomic data from tumor and normal matched pair specimens. For the first time, genetic data from 7 human cancer cases with matched normal are freely available without requirement for data use agreements nor any major restriction except that end users cannot attempt to re-identify the participants (http://txcrb.org/open.html). PMID:26882539

  8. An open access pilot freely sharing cancer genomic data from participants in Texas.

    PubMed

    Becnel, Lauren B; Pereira, Stacey; Drummond, Jennifer A; Gingras, Marie-Claude; Covington, Kyle R; Kovar, Christie L; Doddapaneni, Harsha Vardhan; Hu, Jianhong; Muzny, Donna; McGuire, Amy L; Wheeler, David A; Gibbs, Richard A

    2016-02-16

    Genomic data sharing in cancer has been restricted to aggregate or controlled-access initiatives to protect the privacy of research participants. By limiting access to these data, it has been argued that the autonomy of individuals who decide to participate in data sharing efforts has been superseded and the utility of the data as research and educational tools reduced. In a pilot Open Access (OA) project from the CPRIT-funded Texas Cancer Research Biobank, many Texas cancer patients were willing to openly share genomic data from tumor and normal matched pair specimens. For the first time, genetic data from 7 human cancer cases with matched normal are freely available without requirement for data use agreements nor any major restriction except that end users cannot attempt to re-identify the participants (http://txcrb.org/open.html).

  9. Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy.

    PubMed

    Sanger, Terence D; Bastian, Amy; Brunstrom, Jan; Damiano, Diane; Delgado, Mauricio; Dure, Leon; Gaebler-Spira, Deborah; Hoon, Alec; Mink, Jonathan W; Sherman-Levine, Sara; Welty, Leah J

    2007-05-01

    Although trihexyphenidyl is used clinically to treat both primary and secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in dystonia secondary to disorders such as cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose trihexyphenidyl was conducted in 23 children aged 4 to 15 years with cerebral palsy judged to have secondary dystonia impairing function in the dominant upper extremity. All children were given trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d. Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (chorea, drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (P = .045) but not at 9 weeks (P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic dystonia (excess involuntary movements) worsened at 9 weeks (P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of trihexyphenidyl in cerebral palsy remains equivocal. Trihexyphenidyl may be a safe and effective for treatment for arm dystonia in some children with cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of movement disorder suggested that children with hyperkinetic forms of dystonia may worsen. A larger, randomized

  10. A prospective, open-label study of milnacipran in the prevention of headache in patients with episodic or chronic migraine.

    PubMed

    Engel, Emily Rubenstein; Kudrow, David; Rapoport, Alan M

    2014-03-01

    Migraine is a highly prevalent episodic and chronic neurological disorder that impacts otherwise healthy men and women in their most productive years. An anecdotal survey in our clinical practices suggested that milnacipran, a drug indicated for the treatment of fibromyalgia, reduced the incidence of headache in patients with migraine. In this 3-month, open-label, pilot study, 38 patients diagnosed with episodic migraine and 7 patients with chronic migraine maintained headache diaries to assess the effectiveness and tolerability of milnacipran in headache prevention. After a 1-month period to obtain baseline data, milnacipran treatment was initiated and doses were titrated up to 100 mg/day over 1 month. Maintenance therapy continued for an additional 3 months. The primary efficacy end point was change from baseline in the number of all headache days during the last 28 days of maintenance therapy analyzed, using last observation carried forward (LOCF). Change from baseline in migraine days during the last month of the maintenance period using LOCF was a secondary end point. Milnacipran 100 mg daily was associated with a significant reduction in headache (-4.2 days; P < 0.001) and migraine frequency (-2.2 days; P < 0.003). The adverse event profile was consistent with prior reports of milnacipran for the treatment of other conditions. However, compared with the recommended protocol, a more gradual increase in milnacipran dose was required to improve tolerability for some patients. The robust efficacy signal found in this study strongly suggests that a double-blind, placebo-controlled trial of milnacipran in migraine and chronic headache is warranted.

  11. Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study.

    PubMed

    Jacobi, Arnd; Braeutigam, Matthias; Mahler, Vera; Schultz, Erwin; Hertl, Michael

    2008-01-01

    Facial psoriasis requires a treatment approach other than topical corticosteroids which bear the risk of skin atrophy. Topical pimecrolimus has been shown to be effective in atopic eczema and recently in psoriasis. The aim of this open-label single-center investigator-initiated study was to evaluate the efficacy and safety of pimecrolimus 1% cream in patients with facial psoriasis. 20 adults with facial psoriasis were enrolled. Pimecrolimus 1% cream was applied twice daily to psoriatic lesions of the face over an 8-week period. An 8-week follow-up was added. All clinical parameters showed a significant improvement after 8 and 16 weeks compared to baseline. Pimecrolimus 1% cream was effective and well tolerated. This is the first clinical study with a larger patient cohort reporting a relevant therapeutic effect and favorable safety profile of pimecrolimus 1% cream in facial psoriasis. (c) 2008 S. Karger AG, Basel.

  12. Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial.

    PubMed

    Alajbeg, Ivan; Falcão, Denise P; Tran, Simon D; Martín-Granizo, Rafael; Lafaurie, Gloria I; Matranga, Domenica; Pejda, Slavica; Vuletić, Lea; Mantilla, Rubén; Leal, Soraya C; Bezerra, Ana C Barreto; Ménard, Henri A; Kimoto, Suguru; Pan, Shaoxia; Maniegas, Lourdes; Krushinski, Cheryl A; Melilli, Dario; Campisi, Giuseppina; Paderni, Carlo; Mendoza, Gloria R Bautista; Yepes, Juan F; Lindh, Liselott; Koray, Meltem; Mumcu, Gonca; Elad, Sharon; Zeevi, Itai; Barrios, Beatriz C Aldape; López Sánchez, Rodrigo M; Lassauzay, Claire; Fromentin, Olivier; Beiski, Ben Z; Strietzel, Frank P; Konttinen, Yrjö T; Wolff, Andy; Zunt, Susan L

    2012-06-01

    A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Laserlight cues for gait freezing in Parkinson's disease: an open-label study.

    PubMed

    Donovan, S; Lim, C; Diaz, N; Browner, N; Rose, P; Sudarsky, L R; Tarsy, D; Fahn, S; Simon, D K

    2011-05-01

    Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    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

  15. Design, objectives, execution and reporting of published open-label extension studies.

    PubMed

    Megan, Bowers; Pickering, Ruth M; Weatherall, Mark

    2012-04-01

    Open-label extension (OLE) studies following blinded randomized controlled trials (RCTs) of pharmaceuticals are increasingly being carried out but do not conform to regulatory standards and questions surround the validity of their evidence. OLE studies are usually discussed as a homogenous group, yet substantial differences in study design still meet the definition of an OLE. We describe published papers reporting OLE studies focussing on stated objectives, design, conduct and reporting. A search of Embase and Medline databases for 1996 to July 2008 revealed 268 papers reporting OLE studies that met our eligibility criteria. A random sample of 50 was selected for detailed review. Over 80% of the studies had efficacy stated as an objective. The most common methods of allocation at the start of the OLE were for all RCT participants to switch to one active treatment or for only participants on the new drug to continue, but in three studies all participants were re-randomized at the start of the OLE. Eligibility criteria and other selection factors resulted in on average of 74% of participants in the preceding RCT(s) enrolling in the OLE and only 57% completed it. Published OLE studies do not form a homogenous group with respect to design or retention of participants, and thus the validity of evidence from an OLE should be judged on an individual basis. The term 'open label' suggests bias through lack of blinding, but slippage in relation to the sample randomized in the preceding RCT may be the more important threat to validity. © 2010 Blackwell Publishing Ltd.

  16. Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial.

    PubMed

    Kacmarek, Robert M; Villar, Jesús; Sulemanji, Demet; Montiel, Raquel; Ferrando, Carlos; Blanco, Jesús; Koh, Younsuck; Soler, Juan Alfonso; Martínez, Domingo; Hernández, Marianela; Tucci, Mauro; Borges, Joao Batista; Lubillo, Santiago; Santos, Arnoldo; Araujo, Juan B; Amato, Marcelo B P; Suárez-Sipmann, Fernando

    2016-01-01

    The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. A prospective, multicenter, pilot, randomized controlled trial. A network of 20 multidisciplinary ICUs. Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients

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

    PubMed

    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.

  18. Antioxidant intervention in rheumatoid arthritis: results of an open pilot study.

    PubMed

    van Vugt, Richard M; Rijken, Philip J; Rietveld, Anton G; van Vugt, Arno C; Dijkmans, Ben A C

    2008-06-01

    There is evidence that reactive oxygen species play a causal role in auto-immune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. To determine the potential beneficial effects of an antioxidant intervention on clinical parameters for RA, an open pilot study was designed. Eight non-smoking female patients with rheumatoid factor + RA and a Disease Activity Score (DAS 28) higher than 2.5 were enrolled in the study. Patients had to be receiving stable non-steroidal anti-inflammatory drug treatment and/or 'second line' medication for at least 3 months. The pilot group consumed 20 g of antioxidant-enriched spread daily during a period of 10 weeks. The intervention was stopped after 10 weeks and was followed by a 'wash-out' period of 4 weeks. At t = 0, t = 10 weeks and t = 14 weeks, patients' condition was assessed by means of DAS. In addition, standard laboratory analyses were performed, and blood-samples for antioxidants were taken. The antioxidant-enriched spread was well tolerated. All laboratory measures of inflammatory activity and oxidative modification were generally unchanged. However, the number of swollen and painful joints were significantly decreased and general health significantly increased, as reflected by a significantly improved (1.6) DAS at t = 10 weeks. The antioxidant effect was considered beneficial as, compared to the scores at t = 0, the DAS significantly reduced at t = 10 weeks. Increase of the DAS (0.7) after the "wash-out period" at t = 14 confirmed a causal relation between changes in clinical condition and antioxidants. This open pilot study aimed to assess the clinical relevance of an antioxidant intervention as a first step in assessing potential beneficial effects of antioxidants on rheumatoid arthritis. These conclusions need to be validated in a larger

  19. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study.

    PubMed

    Ashina, Messoud; Dodick, David; Goadsby, Peter J; Reuter, Uwe; Silberstein, Stephen; Zhang, Feng; Gage, Julia R; Cheng, Sunfa; Mikol, Daniel D; Lenz, Robert A

    2017-09-19

    To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM). Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data. Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28-822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo. One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM. NCT01952574. This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life. © 2017 American Academy of Neurology.

  20. Risperidone in children and adolescents with conduct disorder: a single-center, open-label study.

    PubMed

    Ercan, Eyüp Sabri; Kutlu, Ayşe; Cıkoğlu, Sibel; Veznedaroğlu, Baybars; Erermiş, Serpil; Varan, Azmi

    2003-01-01

    Risperidone is one of the most commonly used atypical antipsychotic drugs in the treatment of children and adolescents. However, the data about its use in children and adolescents with conduct disorder (CD) are limited. The aim of this study was to investigate the effectiveness and tolerability of risperidone in controlling major symptoms of CD in children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and severe CD. Children and adolescents were eligible for this single-center, open-label study if they met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for ADHD and ODD and also were diagnosed with severe CD. The patients were treated with risperidone in an open-label fashion for 8 weeks, starting at a daily dosage of 0.25 mg or 0.5 mg (depending on their body weight) in 2 divided doses. The study population comprised 21 children and adolescents (17 boys, 4 girls) with a mean (SD) age of 10.8 (3.6) years. The mean (SD) dosage of risperidone at the end of 8 weeks of treatment was 1.27 (0.42) mg/d (range, 0.75-2.0 mg/d). On the basis of the global improvement subscale of the Clinical Global Impression scale, 16 of 20 patients (80%) were classified as responders. Significant improvements were observed after risperidone treatment in the inattention, hyperactivity/impulsivity, ODD, and CD subscales of the Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (parent and teacher forms). No severe adverse events were reported. The results of this study are consistent with previous findings and suggest that risperidone may be an effective and well-tolerated atypical antipsychotic drug for the treatment of children and adolescents with CD. However, further studies, particularly placebo-controlled and double-blinded, are needed to better define the clinical use of risperidone in children and adolescents with CD.

  1. Armodafinil for fatigue associated with menopause: an open-label trial.

    PubMed

    Meyer, Fremonta; Freeman, Marlene P; Petrillo, Laura; Barsky, Maria; Galvan, Thania; Kim, Semmie; Cohen, Lee; Joffe, Hadine

    2016-02-01

    This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

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

    PubMed Central

    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 < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. Conclusions: Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg

  3. Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

    PubMed

    Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

    2017-10-09

    Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect

  4. An Open-Label Study of Lamotrigine Adjunct or Monotherapy for the Treatment of Adolescents with Bipolar Depression

    ERIC Educational Resources Information Center

    Chang, Kiki; Saxena, Kirti; Howe, Meghan

    2006-01-01

    Objective: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. Method: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages…

  5. An Open-Label Study of Lamotrigine Adjunct or Monotherapy for the Treatment of Adolescents with Bipolar Depression

    ERIC Educational Resources Information Center

    Chang, Kiki; Saxena, Kirti; Howe, Meghan

    2006-01-01

    Objective: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. Method: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages…

  6. ADHD Treatment with Once-Daily OROS Methylphenidate: Final Results from a Long-term Open-Label Study

    ERIC Educational Resources Information Center

    Wilens, Timothy; McBurnett, Keith; Stein, Mark; Lerner, Marc; Spencer, Thomas; Wolraich, Mark

    2005-01-01

    Objective: Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with attention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS[R] MPH. Method: Subjects received OROS…

  7. Six-Week Open-Label Reboxetine Treatment in Children and Adolescents with Attention-Deficit/hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Ratner, Sharon; Laor, Nathaniel; Bronstein, Yifat; Weizman, Abraham; Toren, Paz

    2005-01-01

    Objective: This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) resistant to a previous methylphenidate trial. Method: Thirty-one child and adolescent outpatients, aged 8 to 18 (mean age, 11.7; SD = 2.87)…

  8. Six-Week Open-Label Reboxetine Treatment in Children and Adolescents with Attention-Deficit/hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Ratner, Sharon; Laor, Nathaniel; Bronstein, Yifat; Weizman, Abraham; Toren, Paz

    2005-01-01

    Objective: This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) resistant to a previous methylphenidate trial. Method: Thirty-one child and adolescent outpatients, aged 8 to 18 (mean age, 11.7; SD = 2.87)…

  9. Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: A 1-Year, Open-Label Study of 504 Patients

    ERIC Educational Resources Information Center

    Croonenberghs, Jan; Fegert, Joerg M.; Findling, Robert L.; de Smedt, Goedele; van Dongen, Stefan

    2005-01-01

    Objective: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. Method: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. Results: Seventy-three percent of the 504 patients enrolled completed the study.…

  10. Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: A 1-Year, Open-Label Study of 504 Patients

    ERIC Educational Resources Information Center

    Croonenberghs, Jan; Fegert, Joerg M.; Findling, Robert L.; de Smedt, Goedele; van Dongen, Stefan

    2005-01-01

    Objective: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. Method: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. Results: Seventy-three percent of the 504 patients enrolled completed the study.…

  11. Can serving-size labels reduce the portion-size effect? A pilot study.

    PubMed

    Spanos, Samantha; Kenda, Andree S; Vartanian, Lenny R

    2015-01-01

    Research has shown that the bigger the portion that people are served, the more food they eat; this phenomenon is referred to as the portion-size effect. Providing objective serving-size information on food products has been shown to reduce the influence of external food cues on people's eating behavior. The current study examined whether providing objective serving-size information would also reduce the portion-size effect. 100 female participants were served either a small or large portion of pizza in the context of a taste test. The large portion was either unlabeled, labeled as "Contains 2 servings," or labeled as "Contains 4 servings." Food intake was lower when the large portion was labeled "Contains 4 servings" compared to when it was labeled "Contains 2 servings." Moreover, participants' intake in the large portion/4 servings condition was statistically similar to the intake of participants in the small portion condition. Thus, the standard portion-size effect was observed when the large portion was unlabeled or was labeled as "Contains 2 servings," but not when the large portion was labeled as "Contains 4 servings". These findings suggest that providing serving-size information can reduce the portion-size effect, but that the specific content (and not just the presence) of serving-size information is important in determining food intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Safety and efficacy of infliximab therapy in active behcet's uveitis: an open-label trial.

    PubMed

    Al-Rayes, H; Al-Swailem, R; Al-Balawi, M; Al-Dohayan, N; Al-Zaidi, S; Tariq, M

    2008-11-01

    In this open-label trial, ten male patients with active Behcet's uveitis were enrolled. Initially, two infliximab infusions (5 mg/kg) were given at weeks 0 and 2. The patients continued to receive conventional therapy on recurrence of severe uveitis (RSU) attack. The patients with further attack were regularly given infliximab infusions every 8 weeks. In cases of further RSU attacks, the infusion interval was reduced to 6 weeks. The total follow-up period was 3 years. The patients were monitored for RSU, visual acuity and adverse effects. Reduction in the doses of prednisolone was also monitored. After receiving two infliximab infusions at weeks 0 and 2, three patients remained attack-free and seven patients had another RSU attack between 8th and 47th week. These patients were regularly given infliximab at 8-week intervals. Five out of seven patients remained attack-free. In two patients who had further attack, infusion frequency was increased to 6 weeks. There was a remarkable improvement in visual acuity with no significant adverse reaction except mild respiratory tract infection (two patients), headache (one patient) and mild infusion reaction (one patient). Infliximab is a safe and effective drug for the management of Behcet's uveitis. Selection of optimal dose and frequency of infusion required standardization for individual patient.

  13. Long-term intrathecal ziconotide for chronic pain: an open-label study.

    PubMed

    Webster, Lynn R; Fisher, Robert; Charapata, Steven; Wallace, Mark S

    2009-03-01

    This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated.

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

    PubMed

    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.

  15. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study.

    PubMed

    Aggarwal, Anju; Ghosh, Apurba; Gomber, Sunil; Mitra, Monjori; Parikh, A O

    2011-07-01

    An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever.

  16. Computerized cognitive remediation training for schizophrenia: an open label, multi-site, multinational methodology study.

    PubMed

    Murthy, N V; Mahncke, H; Wexler, B E; Maruff, P; Inamdar, A; Zucchetto, M; Lund, J; Shabbir, S; Shergill, S; Keshavan, M; Kapur, S; Laruelle, M; Alexander, R

    2012-08-01

    A recent single-site study (Fisher et al., 2009. Am J Psychiatry. 166 (7) 805-11) showed that repeated training with the Brain Fitness Program (BFP) improved performance on a battery of neuropsychological tasks. If replicated these data suggest an important non-pharmacological method for ameliorating cognitive impairment in schizophrenia. Our study evaluated the BFP training effects in an open-label, multi-site, multinational clinical trial. Fifty-five stable adult patients with schizophrenia on regular antipsychotic medication completed ≥ 32 BFP training sessions over 8-10 weeks. Training effects on cognitive performance and functional capacity outcome measures were measured using CogState® schizophrenia battery, UCSD Performance based Skills Assessment (UPSA-2) and Cognitive Assessment Interview (CAI). BFP training showed a large and significant treatment effect on a training exercise task (auditory processing speed), however this effect did not generalize to improved performance on independent CogState® assessment. There were no significant effects on UPSA-2 or CAI scores. Our study demonstrated the feasibility of implementing BFP training in a multi-site study. However, BFP training did not show significant treatment effects on cognitive performance or functional capacity outcome measures despite showing large and significant effects on a training exercise. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Zuclopenthixol treatment of behavioral disturbances in mentally retarded children and adolescents: an open-label study.

    PubMed

    Spivak, B; Mozes, T; Mester, R; Kodelik, M; Weizman, A

    2001-01-01

    The present open-label study assessed the efficacy of zuclopenthixol, an thioxanthene neuroleptic with combined dopamine receptors (D1/D2) antagonist activity, in the treatment of severe behavioral disturbances in mentally retarded children and adolescents. A sample of 15 (11 males, 4 females) mentally retarded children and adolescents, ages 5-18 years (12.2 +/- 2.3 [mean +/- SD] years), all exhibiting severe behavioral disturbances, was evaluated. The 12-week zuclopenthixol treatment (up to 26 mg/day) was initiated after a week's washout from previous antipsychotic agents. An assessment of the behavioral disturbances was performed using the 14-item Checklist for Behavior Problems Involving Limited or No Social Awareness (CBP-NSA). The Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale was used to assess the pharmacologic side effects. Results show a significant reduction in total CBP-NSA scores and in individual items such as hyperactivity, aggressive behavior, and temper tantrums (p < 0.001 for each). It seems that zuclopenthixol monotherapy is effective and well tolerated in the treatment of severe behavioral disturbances in mentally retarded children and adolescents. Double-blind, placebo-controlled studies are needed before definitive conclusions can be drawn regarding the efficacy and safety of zuclopenthixol for this population.

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

    PubMed Central

    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

  19. Transcutaneous supraorbital neurostimulation for the prevention of chronic migraine: a prospective, open-label preliminary trial.

    PubMed

    Di Fiore, Paola; Bussone, Gennaro; Galli, Alberto; Didier, Henri; Peccarisi, Cesare; D'Amico, Domenico; Frediani, Fabio

    2017-05-01

    Since chronic migraine is difficult to treat and often associated with medication overuse, non-invasive neurostimulation approaches are worth investigating. Transcutaneous supraorbital neurostimulation using the Cefaly(®) device is promising as a non-invasive preventive treatment for episodic migraine, but no data are available for chronic migraine. Our aim was to perform a preliminary evaluation of the efficacy of the Cefaly(®) device for the prophylaxis of chronic migraine with or without medication overuse. Primary endpoints were 50% reduction in monthly migraine days and 50% reduction in monthly medication use over 4 months. In an open-label study, twenty-three consecutive headache center patients with chronic migraine, diagnosed according to International Headache Society criteria, were recruited prospectively. After informed consent, patients were trained to use Cefaly(®) and instructed to use it for 20 min daily over 4 months. All patients received active neurostimulation. Thirty-five percent of the patients enrolled in the study achieved the study endpoints. Over half the patients had a greater than 50% reduction in acute medication consumption.

  20. Impact of a soy drink on climacteric symptoms: an open-label, crossover, randomized clinical trial

    PubMed Central

    Tranche, Salvador; Brotons, Carlos; Pascual de la Pisa, Beatriz; Macías, Ramón; Hevia, Eduardo; Marzo-Castillejo, Mercè

    2016-01-01

    Abstract Objectives: The objective of this study is to evaluate the effects of a soy drink with a high concentration of isoflavones (ViveSoy®) on climacteric symptoms. Methods: An open-label, controlled, crossover clinical trial was conducted in 147 peri- and postmenopausal women. Eligible women were recruited from 13 Spanish health centers and randomly assigned to one of the two sequence groups (control or ViveSoy®, 500 mL per day, 15 g of protein and 50 mg of isoflavones). Each intervention phase lasted for 12 weeks with a 6-week washout period. Changes on the Menopause Rating Scale and quality of life questionnaires, as well as lipid profile, cardiovascular risk and carbohydrate and bone metabolism were assessed. Statistical analysis was performed using a mixed-effects model. Results: A sample of 147 female volunteers was recruited of which 90 were evaluable. In both sequence groups, adherence to the intervention was high. Regular consumption of ViveSoy® reduced climacteric symptoms by 20.4% (p = 0.001) and symptoms in the urogenital domain by 21.3% (p < 0.05). It also improved health-related quality life by 18.1%, as per the MRS questionnaire (p <0.05). Conclusion: Regular consumption of ViveSoy® improves both the somatic and urogenital domain symptoms of menopause, as well as health-related quality of life in peri- and postmenopausal women. PMID:26806546

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

    PubMed Central

    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

  2. Topiramate in add-on therapy: results from an open-label, observational study.

    PubMed

    Krakow, K; Lengler, U; Rettig, K; Schreiner, A; Schauble, B

    2007-10-01

    An open-label, observational prospective study assessed the effectiveness of topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above with a diagnosis of epilepsy and at least one epileptic seizure during the 12-week retrospective baseline were to be documented. After baseline evaluation, topiramate was added. Ninety-five percent of patients had at least one baseline AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started in monotherapy. Topiramate dose titration and target dose was determined by clinical response and side effect profile. Patients were intended to be followed for a total of 1 year which included 6 visits during which seizure frequency, adverse events, weight as well as clinical global impression were recorded. During the 12 weeks retrospective baseline, a median of 2.8 seizures per month were recorded which reduced significantly to 0.7 per month during the complete treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50% seizure reduction. Ten percent of patients were seizure free during the study. The most commonly reported adverse events were difficulties with memory (4.2%), somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated, and only 5% of patients discontinued treatment due to an adverse event. Retention in the study was higher than previously reported during randomized, dose controlled studies and is likely due to individualized doses as well as slower titration used.

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

    PubMed

    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 (P<.05) on clinician- and self-rated measures of obsessive-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 (P<.05) on primary and secondary study outcome measures. The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-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.

  4. Treatment of seasonal affective disorder with duloxetine: an open-label study.

    PubMed

    Pjrek, E; Willeit, M; Praschak-Rieder, N; Konstantinidis, A; Semlitsch, H V; Kasper, S; Winkler, D

    2008-05-01

    The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder (SAD). 26 SAD patients were treated with open-label duloxetine 60-120 mg per day over 8 weeks. Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD) and the Clinical Global Impression (CGI). To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale (SASS), the Sheehan Disability Scale (SDS), and assessments of days lost due to illness and days with reduction in productivity. Duloxetine led to a significant improvement (p<0.001) of SIGH-SAD, CGI severity, SASS, and SDS scores. Days lost due to illness and days with reduction in productivity were significantly diminished during treatment (p<0.001). Treatment with duloxetine over 8 weeks yielded a response rate (SIGH-SAD<50% of baseline value) of 80.8% and a remission rate (SIGH-SAD<8) of 76.9% in the intention to treat sample. The drop-out rate due to side effects was 15.4%. Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD.

  5. Autologous bone marrow mononuclear cell therapy for autism: an open label proof of concept study.

    PubMed

    Sharma, Alok; Gokulchandran, Nandini; Sane, Hemangi; Nagrajan, Anjana; Paranjape, Amruta; Kulkarni, Pooja; Shetty, Akshata; Mishra, Priti; Kali, Mrudula; Biju, Hema; Badhe, Prerna

    2013-01-01

    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.

  6. An open label trial of C-1073 (mifepristone) for psychotic major depression.

    PubMed

    Belanoff, Joseph K; Rothschild, Anthony J; Cassidy, Frederick; DeBattista, Charles; Baulieu, Etienne-Emile; Schold, Clifford; Schatzberg, Alan F

    2002-09-01

    The rationale for treating patients with psychotic major depression (PMD) with glucocorticosteroid receptor (GR) antagonists is explained. Thirty patients with PMD, with Hamilton Rating Scale for Depression (HAMD-21) scores of 18 or greater, were assigned in an open label trial to receive 50 mg, 600 mg, or 1200 mg of mifepristone for 7 days. All the subjects completed the protocol; there were no dropouts. Side effects were mild and sporadic. Of 19 subjects in the combined 600- and 1200-mg group, 13 had a 30% or greater decline in their Brief Psychiatric Rating Scale (BPRS) scores, compared with 4 of 11 in the 50-mg group. In the 600- and 1200-mg group, 12 of 19 subjects showed a 50% decline in the BPRS positive symptom subscale, a more sensitive index for the symptoms seen in PMD, compared with 3 of 11 in the 50-mg group; 8 of 19 subjects in the 600- and 1200-mg group had a 50% decline in the HAMD-21, compared with 2 of 11 in the 50-mg group. These results suggest that short term use of GR antagonists may be effective in the treatment of psychotic major depression and that further blinded studies are warranted.

  7. Topical pimecrolimus 1% cream for resistant seborrheic dermatitis of the face: an open-label study.

    PubMed

    Ozden, Muge Guler; Tekin, Nilgun Solak; Ilter, Nilsel; Ankarali, Handan

    2010-01-01

    Treatment options for seborrheic dermatitis are numerous, including both topical and systemic agents (e.g. topical corticosteroids, oral antifungals, and psoralen plus UVA). However, long-term use of topical corticosteroids may lead to adverse effects. Pimecrolimus 1% cream is an effective and well tolerated treatment for seborrheic dermatitis. To explore the efficacy of pimecrolimus 1% cream for the treatment of seborrheic dermatitis lesions resistant to conventional treatments. Sixteen patients with resistant seborrheic dermatitis of the face applied pimecrolimus 1% cream twice daily for 2 weeks. The lesions were assessed clinically and the severity of the signs were assessed using a 4-point score. Additionally, the scores of all affected regions (paranasal, forehead, and eyebrows) were evaluated separately to assess whether different results would be obtained in different regions of the face. Also, patients completed self-assessments on a 100 mm Visual Analogue Scale (VAS) at each visit. Statistically significant reductions in the scores of all parameters were observed at day 7 and day 14 of the study. There were no significant differences between the responses on the three regions of the face. No adverse effects were reported except for temporary pruritus immediately after the application of pimecrolimus 1% cream in one patient. Although the interpretation of efficacy was limited by the open-label, non-controlled study design and the small number of patients, this trial suggests that pimecrolimus 1% cream may be a successful treatment choice for patients with resistant seborrheic dermatitis of the face.

  8. Long-term use of oxcarbazepine oral suspension in childhood epilepsy: open-label study.

    PubMed

    Rufo-Campos, Miguel; Casas-Fernández, Carlos; Martínez-Bermejo, Antonio

    2006-06-01

    Studies designed specifically for the pediatric population are needed to assess the tolerability and safety of the new antiepileptic drugs. The purpose of this study was to document the safety, ease of dosing, and acceptance of oxcarbazepine oral suspension in pediatric patients in monotherapy and polytherapy. A prospective, multicenter, open-label study was conducted at the neurology services of three pediatric university hospitals over 12 months. After obtaining signed informed consent, we enrolled a series of 62 patients with epilepsy aged between 2 months and 14 years who began oxcarbazepine treatment in monotherapy or in combination with other antiepileptic drugs to assess the seizure frequency, safety (adverse events), and acceptance of the pharmaceutical form by the patient's family. Fifty patients (80.6%) reduced seizures by at least 50%, 44 (71%) saw a reduction in seizure frequency of over 75%, and 29 (46.8%) were seizure free at the end of the study. The difference in the number of seizures before and after the study was statistically significant, both overall and by type of pathology. Adverse events occurred in four patients (6.4%) and required withdrawal of the drug in two cases (skin rash); three patients (4.8%) withdrew for inefficacy. Five patients (8.1%) withdrew from the treatment. We concluded that, in this series of patients, oxcarbazepine in oral suspension form was seen to help reduce seizure frequency, to have few side effects, and to be accepted by parents and patients.

  9. Vaginal mifepristone for the treatment of symptomatic uterine leiomyomata: an open-label study.

    PubMed

    Yerushalmi, Gil M; Gilboa, Yinon; Jakobson-Setton, Ariella; Tadir, Yona; Goldchmit, Chen; Katz, Danny; Seidman, Daniel S

    2014-02-01

    To evaluate the efficacy and safety of 3 months of vaginal mifepristone treatment on leiomyoma volume and related symptoms. Prospective, open-label, two tertiary centers, phase II clinical trial. Two tertiary medical centers in Israel. Thirty-three enrolled women, ages 30-53 years, diagnosed with symptomatic uterine fibroids. Patients received 10 mg mifepristone vaginally daily for 3 months. Reduction in uterine leiomyoma volume. Improvement in symptoms related to uterine fibroids was assessed with the use of the "Uterine Fibroid Symptoms Quality of Life Questionnaire" (UFS-QoL). The number of bleeding days, safety, and tolerability were secondary measures. Mifepristone treatment significantly reduced leiomyoma volume from 135.3 ± 22.9 cc at enrollment to 101.2 ± 22.4 cc after 3 months of treatment. The UFS-QoL Score significantly decreased from 20.7 ± 0.7 at enrollment to 14.0 ± 0.8 after 3 months of treatment. The number of bleeding days significantly decreased by 3.5 days. Endometrial biopsies showed no evidence of endometrial hyperplasia or cellular atypia. There were no major side effects during the course of the study, and treatment was well tolerated. Vaginal mifepristone may offer an effective treatment option for women with symptomatic uterine leiomyoma and can improve the patients' quality of life. NCT00881140. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. A prospective open-label study of home use of mifepristone for medical abortion in Nepal.

    PubMed

    Conkling, Kathryn; Karki, Chanda; Tuladhar, Heera; Bracken, Hillary; Winikoff, Beverly

    2015-03-01

    To assess the uptake and acceptability of self-administration of mifepristone at home for medical abortion in Nepal. A prospective, comparative, non-randomized, open-label study was conducted at two hospitals in Kathmandu, Nepal, between November 11, 2009, and January 15, 2011. All women in good health and aged 18 years or older who sought medical abortion after fewer than 64 days of pregnancy were enrolled. Participants were offered the choice of taking 200mg mifepristone orally in the clinic or at home; all participants self-administered 400 μg of sublingual misoprostol at home 24-72 hours later. All participants were scheduled to return to the clinic within 14 days of mifepristone administration for follow-up. Among 200 participants, 144 (72.0%) opted to take the mifepristone at home. Medical abortion was successful in 130 (95.6%) of 136 women in the home group who were followed up and 53 (94.6%) of 56 women in the clinic group. Only 4 (2.9%) women in the home group took the mifepristone after the scheduled time. Overall, 133 (97.8%) women in the home group stated that they would recommend home administration of mifepristone if a friend wanted a medical abortion. Self-administration of mifepristone outside the clinic should be offered to all women as part of routine medical abortion services in Nepal. Clinical trials.gov: NCT00994734. Copyright © 2014. Published by Elsevier Ireland Ltd.

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

    PubMed

    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.

  12. Lichen striatus in adults and pimecrolimus: open, off-label clinical study.

    PubMed

    Campanati, Anna; Brandozzi, Giuliano; Giangiacomi, Mirella; Simonetti, Oriana; Marconi, Barbara; Offidani, Anna Maria

    2008-07-01

    Lichen striatus is a well-known, acquired, self-healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side-effects, particularly cutaneous atrophy. To report the results of an open, off-label study on the use of pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen striatus. Three adult patients suffering from relapsing or disseminated and itchy lichen striatus received topical application of pimecrolimus 1% cream (Elidel, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until complete disappearance of the cutaneous lesions. All patients experienced rapid healing of the dermatosis, without any recurrence for at least 14 months. Our preliminary results show that pimecrolimus may represent a useful therapeutic alternative for lichen striatus, although further studies on a larger number of cases are needed to confirm its safety and efficacy in the treatment of this condition.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27730198

  15. Advanced glycation end products dietary restriction effects on bacterial gut microbiota in peritoneal dialysis patients; a randomized open label controlled trial.

    PubMed

    Yacoub, Rabi; Nugent, Melinda; Cai, Weijin; Nadkarni, Girish N; Chaves, Lee D; Abyad, Sham; Honan, Amanda M; Thomas, Shruthi A; Zheng, Wei; Valiyaparambil, Sujith A; Bryniarski, Mark A; Sun, Yijun; Buck, Michael; Genco, Robert J; Quigg, Richard J; He, John C; Uribarri, Jaime

    2017-01-01

    The modern Western diet is rich in advanced glycation end products (AGEs). We have previously shown an association between dietary AGEs and markers of inflammation and oxidative stress in a population of end stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). In the current pilot study we explored the effects of dietary AGEs on the gut bacterial microbiota composition in similar patients. AGEs play an important role in the development and progression of cardiovascular (CVD) disease. Plasma concentrations of different bacterial products have been shown to predict the risk of incident major adverse CVD events independently of traditional CVD risk factors, and experimental animal models indicates a possible role AGEs might have on the gut microbiota population. In this pilot randomized open label controlled trial, twenty PD patients habitually consuming a high AGE diet were recruited and randomized into either continuing the same diet (HAGE, n = 10) or a one-month dietary AGE restriction (LAGE, n = 10). Blood and stool samples were collected at baseline and after intervention. Variable regions V3-V4 of 16s rDNA were sequenced and taxa was identified on the phyla, genus, and species levels. Dietary AGE restriction resulted in a significant decrease in serum Nε-(carboxymethyl) lysine (CML) and methylglyoxal-derivatives (MG). At baseline, our total cohort exhibited a lower relative abundance of Bacteroides and Alistipes genus and a higher abundance of Prevotella genus when compared to the published data of healthy population. Dietary AGE restriction altered the bacterial gut microbiota with a significant reduction in Prevotella copri and Bifidobacterium animalis relative abundance and increased Alistipes indistinctus, Clostridium citroniae, Clostridium hathewayi, and Ruminococcus gauvreauii relative abundance. We show in this pilot study significant microbiota differences in peritoneal dialysis patients' population, as well as the effects of dietary

  16. An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases.

    PubMed

    Forbes, Jessica L; Kim, Regina E Y; Paulsen, Jane S; Johnson, Hans J

    2016-01-01

    The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%.

  17. An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases

    PubMed Central

    Forbes, Jessica L.; Kim, Regina E. Y.; Paulsen, Jane S.; Johnson, Hans J.

    2016-01-01

    The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%. PMID:27536233

  18. Muscular workload of veterinary students during simulated open and laparoscopic surgery: A pilot study.

    PubMed

    Kilkenny, Jessica; Larson, Dennis J; MacCormick, Mathew; Brown, Stephen H M; Singh, Ameet

    2017-08-01

    To compare upper extremity muscle activity and workload between simulated open surgery, multiple port laparoscopic surgery (MLS), and single incision laparoscopic surgery (SLS) techniques in veterinary students. Pilot study. Veterinary students (n = 10) from years 1 to 4. Bipolar skin surface electrodes were fixed bilaterally to the forearm flexor, forearm extensor, biceps brachii, triceps brachii, and upper trapezius muscles. Electromyography data were recorded during one repetition of 2 simulated surgical exercises via open surgery, MLS, and SLS. Participants completed a validated workload survey after each simulated surgical technique. Muscle activity and perceived workload were compared between surgical techniques with 1-way ANOVAs and Fisher's LSD post hoc tests. Muscle activity during peg transfer was higher with MLS and SLS compared to simulated open surgery in the right and left forearm extensors (both P < .0001), right (P < .0001) and left biceps (P = .0005), right triceps (P = .0004), and right upper trapezius muscles (P = .0211). Similar results were found for the right and left forearm extensors (both P < .0001), right (P = .0381) and left (P = .0147) forearm flexors, right biceps (P < .0001), and right triceps (P = .0004) during a simulated suture task. Participants found laparoscopic techniques more mentally demanding, physically demanding, complex, and stressful compared to a simulated open surgical technique. In veterinary students, average muscle activity and perceived workload were highest using MLS and SLS compared to an open surgical technique when performing simulated surgical exercises in a laparoscopic box trainer. © 2017 The American College of Veterinary Surgeons.

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

    PubMed Central

    Myers, Stephen P; O’Connor, Joan; Fitton, J Helen; Brooks, Lyndon; Rolfe, Margaret; Connellan, Paul; Wohlmuth, Hans; Cheras, Phil A; Morris, Carol

    2010-01-01

    Background: 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 seen between the two treatments (P ≤ 0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P ≤ 0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of

  20. Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

    ERIC Educational Resources Information Center

    Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

    2008-01-01

    Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

  1. Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study.

    PubMed

    Kreuzer, Peter M; Landgrebe, Michael; Resch, Markus; Husser, Oliver; Schecklmann, Martin; Geisreiter, Florian; Poeppl, Timm B; Prasser, Sarah J; Hajak, Goeran; Rupprecht, Rainer; Langguth, Berthold

    2014-01-01

    Vagus nerve stimulation represents an established treatment strategy for epilepsy and affective disorders. Recently, positive effects were also shown in animals and humans with tinnitus. Here we report the results of an open pilot study exploring feasibility, safety and efficacy of tVNS in the treatment of chronic tinnitus. Fifty patients with chronic tinnitus underwent tVNS in an open single-armed pilot study which was conducted in two phases applying two different stimulating devices (Cerbomed CM02 and NEMOS). Clinical assessment was based on Tinnitus Questionnaire (TQ), Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), WHO Quality of Life, and various numeric rating scales. Primary outcome was defined as change in TQ (baseline vs. final visit in week 24). The study has been registered with clinicaltrials.gov (NCT01176734). Primary analysis indicated mean TQ reductions of 3.7 points (phase 1) and 2.8 points (phase 2) significant for the first study phase. Secondary analyses indicated a significant BDI reduction for phase 1 (uncorrected for multiple testing), but no further systematic or significant effects. Adverse events included twitching and pressure at electrode placement site. The occurrence of one hospitalization because of palpations and the development of a left bundle branch block were considered as unrelated to the intervention. Cognitive testing revealed no significant changes. Our data demonstrate the feasibility of tVNS over a period of 6 months. There was no clinically relevant improvement of tinnitus complaints. Our data suggest tVNS to be considered safe in patients without a history of cardiac disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study.

    PubMed

    Bradstreet, James Jeffrey; Sych, Nataliia; Antonucci, Nicola; Klunnik, Mariya; Ivankova, Olena; Matyashchuk, Irina; Demchuk, Mariya; Siniscalco, Dario

    2014-01-01

    Autism spectrum disorders (ASDs) are heterogeneous complex neurodevelopmental pathologies defined by behavioral symptoms, but which have well-characterized genetic, immunological, and physiological comorbidities. Despite extensive research efforts, there are presently no agreed upon therapeutic approaches for either the core behaviors or the associated comorbidities. In particular, the known autoimmune disorders associated with autism are appealing targets for potential stem cell therapeutics. Of the various stem cell populations, fetal stem cells (FSCs) offer the potent immunoregulatory functions found in primordial mesenchymal stem cells, while exhibiting rapid expansion capacity and recognized plasticity. These properties enhance their potential for clinical use. Furthermore, FSCs are potent and implantable "biopharmacies" capable of delivering trophic signals to the host, which could influence brain development. This study investigated the safety and efficacy of FSC transplantations in treating children diagnosed with ASDs. Subjects were monitored at pre, and then 6 and 12 months following the transplantations, which consisted of two doses of intravenously and subcutaneously administered FSCs. The Autism Treatment Evaluation Checklist (ATEC) test and Aberrant Behavior Checklist (ABC) scores were performed. Laboratory examinations and clinical assessment of adverse effects were performed in order to evaluate treatment safety. No adverse events of significance were observed in ASD children treated with FSCs, including no transmitted infections or immunological complications. Statistically significant differences (p < 0.05) were shown on ATEC/ABC scores for the domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores when compared to pretreatment values. We recognize that the use of FSCs remains controversial for the present. The results of this study, however, warrant additional investigations into the mechanisms of cell therapies for ASDs, while prompting the exploration of FSCs as "biopharmacies" capable of manufacturing the full array of cell-signaling chemistry. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

  3. Cathodal transcranial direct current stimulation in children with dystonia: a pilot open-label trial.

    PubMed

    Young, Scott J; Bertucco, Matteo; Sheehan-Stross, Rebecca; Sanger, Terence D

    2013-10-01

    Studies suggest that dystonia is associated with increased motor cortex excitability. Cathodal transcranial direct current stimulation can temporarily reduce motor cortex excitability. To test whether stimulation of the motor cortex can reduce dystonic symptoms in children, we measured tracking performance and muscle overflow using an electromyogram tracking task before and after stimulation. Of 10 participants, 3 showed a significant reduction in overflow, and a fourth showed a significant reduction in tracking error. Overflow decreased more when the hand contralateral to the cathode performed the task than when the hand ipsilateral to the cathode performed the task. Averaged over all participants, the results did not reach statistical significance. These results suggest that cathodal stimulation may allow a subset of children to control muscles or reduce involuntary overflow activity. Further testing is needed to confirm these results in a blinded trial and identify the subset of children who are likely to respond.

  4. Metformin monotherapy in melanoma: A pilot, open-label, prospective and multicentric study indicates no benefit.

    PubMed

    Montaudié, Henri; Cerezo, Michael; Bahadoran, Philippe; Roger, Coralie; Passeron, Thierry; Machet, Laurent; Arnault, Jean-Philippe; Verneuil, Laurence; Maubec, Eve; Aubin, François; Granel, Florence; Giacchero, Damien; Hofman, Véronique; Lacour, Jean-Philippe; Maryline, Allegra; Balotti, Robert; Rocchi, Stéphane

    2017-01-25

    Targeted therapies and immunotherapies have significantly improved the prognosis of patients with advanced melanoma (Long et al., 2015; Robert et al., 2015a; Robert et al., 2015b; Ascierto et al., 2015). Unfortunately, treatment failure due to primary and secondary drug resistance are still observed and therefore there is an urgent need to identify new anti-melanoma agents. The oral anti-diabetic drug metformin belongs to the family of biguanides and it is the most widely used antidiabetic drug in the world. This article is protected by copyright. All rights reserved.

  5. Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    PubMed

    2017-10-01

    We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

  6. Major depressive disorder, anhedonia and agomelatine: an open-label study.

    PubMed

    Di Giannantonio, M; Di Iorio, G; Guglielmo, R; De Berardis, D; Conti, C M; Acciavatti, T; Cornelio, M; Martinotti, G

    2011-01-01

    Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.

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

    PubMed

    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.

  8. An open-label trial of risperidone in children and adolescents with severe mood dysregulation.

    PubMed

    Krieger, Fernanda Valle; Pheula, Gabriel Ferreira; Coelho, Roberta; Zeni, Thamis; Tramontina, Silzá; Zeni, Cristian Patrick; Rohde, Luis Augusto

    2011-06-01

    The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD), has been the focus of increasing concern and debate among clinicians and researchers. Our main objective was to assess the effectiveness of risperidone for youths with SMD. An 8-week open label trial with risperidone was conducted. We extensively assessed 97 subjects with semistructured and clinical interviews and enrolled 21 patients in the study. Risperidone was titrated from 0.5 to 3 mg/day in the first 2 weeks. Evaluations were performed at baseline and weeks 2, 4, 6, and 8. Clinical outcome measures were (1) Aberrant Behavior Checklist-Irritability Subscale, (2) Clinical Global Impressions, and (3) severity of co-morbid conditions. We found a significant reduction of the Aberrant Behavior Checklist-Irritability scores during the trial after risperidone use (p < 0.001). The scores at week 2 (mean = 12.03; standard error [SE] = 2.94), week 4 (mean = 15.48; SE = 2.93), week 6 (mean = 12.29; SE = 2.86), and week 8 (mean = 11.28; SE = 3.06) were significantly reduced compared with the baseline mean score (mean = 25.89; SE = 2.76) (p < 0.001). We also found an improvement in attention-deficit/hyperactivity disorder, depression, and global functioning (p < 0.001). Risperidone was effective in reducing irritability in SMD youth. To the best of our knowledge, this is the first psychopharmacological trial in this group of patients with positive results. Further randomized, controlled studies are needed.

  9. Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects

    PubMed Central

    Moore, Kenneth Todd; Byra, William; Vaidyanathan, Seema; Natarajan, Jaya; Ariyawansa, Jay; Salih, Hiba; Turner, Kenneth C

    2015-01-01

    Aims The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives. Methods An open label, non-randomized, sequential two period study. In treatment period 1 (TP1), subjects received rivaroxaban 20 mg once daily (5 days), followed by co-administration with a warfarin loading dose regimen of 5 or 10 mg (for the 10 mg regimen, the dose could be uptitrated to attain target international normalized ratio [INR] ≥2.0) once daily (2–4 days). When trough INR values ≥2.0 were attained, rivaroxaban was discontinued and warfarin treatment continued as monotherapy (INR 2.0–3.0). During treatment period 2, subjects received the same warfarin regimen as in TP1, but without rivaroxaban. Results During co-administration, maximum INR and prothrombin time (PT) values were higher than with rivaroxaban or warfarin monotherapy. The mean maximum effect (Emax) for INR after co-administration was 2.79–4.15 (mean PT Emax 41.0–62.7 s), compared with 1.41–1.74 (mean PT Emax 20.1–25.2 s) for warfarin alone. However, rivaroxaban had the smallest effect on INR at trough rivaroxaban concentrations. Neither rivaroxaban nor warfarin significantly affected maximum plasma concentrations of the other drug. Conclusions The combined pharmacodynamic effects during co-administration of rivaroxaban and warfarin were greater than additive, but the pharmacokinetics of both drugs were unaffected. Co-administration was well tolerated. When transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban concentration to minimize the effect of rivaroxaban on INR. PMID:25475601

  10. Zotepine for behavioural and psychological symptoms in dementia: an open-label study.

    PubMed

    Rainer, Michael K; Mucke, Hermann A M; Krüger-Rainer, Christine; Haushofer, Manfred; Kasper, Sigfried

    2004-01-01

    To provide initial information on the safety and efficacy of the atypical antipsychotic zotepine in the treatment of behavioural and psychological symptoms of dementia (BPSD). This was an open-label, single-centre field study. Twenty-four patients with BPSD associated with Alzheimer's disease (n=12) or other forms of dementia (n=12) were included. During the 8-week observation period, the patients received zotepine (Nipolept) [12.5-150 mg/day] for the psychotic components of BPSD; no other treatment interventions for BPSD were allowed. At baseline, day 28 and day 56, patients were evaluated using the Clinical Global Impressions (CGI) scale; the Mini-Mental State Examination (MMSE), the Syndrome Brief Test (SKT) and the Age Concentration Test (AKT) to assess cognition; and the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfield Agitation Inventory (CMAI) to assess BPSD. General adverse effects and, more specifically, the emergence of extrapyramidal symptoms were also assessed. There was no change from baseline to day 56 in the CGI score and the caregiver burden (as indicated by the caregiver-related section of the NPI). There was also no change in cognition (as assessed by the MMSE, SKT and AKT). The neuropsychiatric symptom score according to part 1 of the NPI (especially key psychotic symptoms, aggression and disinhibition) and the CMAI scores improved by 36% and 15%, respectively, between baseline and the end of the study in a highly statistically significant fashion. No significant differences in treatment response or adverse effect profile were noted between the 12 patients with Alzheimer's disease and the 12 patients with other types of dementia. Zotepine was well tolerated, with tiredness and sedation (five and four cases, respectively) being the most frequent complaints. No clinically significant emergence of extrapyramidal symptoms was seen. Zotepine appears to be well tolerated and effective in treating BPSD, consistent with the performance of other

  11. Metronidazole immediate release formulations: a fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    PubMed

    de Freitas Silva, M; Schramm, S G; Kano, E K; Koono, E E M; Manfio, J L; Porta, V; dos Reis Serra, C H

    2012-10-01

    Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, ke, and t1/2 were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of Cmax, AUC0-t, and AUC0-∞ values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for Cmax (0.92-1.06), AUC0-t (0.97-1.02), and AUC0-∞ (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements. © Georg Thieme Verlag KG Stuttgart · New York.

  12. A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients.

    PubMed

    Diaz-Martinez, A; Benassinni, O; Ontiveros, A; Gonzalez, S; Salin, R; Basquedano, G; Martinez, R A

    1998-01-01

    In this randomized, open-label, 8-week comparative study, the efficacy and safety of venlafaxine and fluoxetine were assessed in outpatients with major depression. One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to improve patient response, the dosage could be increased at the investigator's discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One hundred forty-five patients were evaluated for safety and 110, for efficacy. The mean age was 37 years, and 70% of the patients were female. In both treatment groups, mean scores on the Hamilton Depression Rating Scale decreased significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the Montgomery-Asberg Depression Rating Scale decreased significantly between baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3, venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%), and generalized tremor (20.0%). The results of this study indicate that venlafaxine is effective and well tolerated for the treatment of major depression at doses of 37.5 or 75 mg twice daily and not significantly different from fluoxetine 20 or 40 mg once daily.

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

    PubMed

    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 < 0.001). Muscle spasticity also reduced significantly after transplantation (p-value < 0.001). The therapy was equally effective regardless of sex, age and GMFCS level (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.

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

    PubMed Central

    Fornaro, Michele; McCarthy, Michael J; De Berardis, Domenico; De Pasquale, Concetta; Tabaton, Massimo; Martino, Matteo; Colicchio, Salvatore; Cattaneo, Carlo Ignazio; D’Angelo, Emanuela; Fornaro, Pantaleo

    2013-01-01

    Purpose 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 treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group. Conclusion Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials. PMID:23430979

  15. Liposomal Bladder Instillations for IC/BPS: an Open-Label Clinical Evaluation

    PubMed Central

    Peters, Kenneth M; Hasenau, Deborah; Killinger, Kim A; Chancellor, Michael B; Anthony, Michele; Kaufman, Jonathan

    2015-01-01

    Purpose Intravesical instillation of liposomes is a potentially new therapeutic option for subjects with interstitial cystitis/bladder pain syndrome (IC/BPS). The aim of this study was to explore the safety and clinical outcomes of 4 weekly instillations of sphingomyelin liposomes in an open-label cohort of subjects with IC/BPS. Methods A total of fourteen symptomatic IC/BPS subjects were treated with intravesical liposomes once a week for 4 weeks. Safety measurements included lab specimen collection, vital signs, post void residual (PVR), and assessment of adverse events (AEs). Efficacy measurements included pain visual analog scales (VAS), voiding diaries, global response assessments (GRAs), and O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI and ICPI). Results No treatment-related adverse events (AE) were reported at any time over the course of the study. Urgency VAS scores significantly decreased at 4 weeks (p=0.0029) and 8 weeks (p=0.0112) post-treatment. Pain VAS scores significantly decreased at 4 weeks post-treatment (p=0.0073). Combined ICSI and ICPI scores improved significantly at 4 weeks and 8 weeks (p=0.002 for both time points) post-treatment. Responses to GRA showed improvement at 4 weeks post- instillation. No significant decrease in urinary frequency was found. Conclusion Sphingomyelin liposome instillations were well tolerated in subjects with IC/BPS with no AEs attributed to the test article. Treatment was associated with improvements in pain, urinary urgency, and overall symptom scores. Placebo controlled clinical trials are needed to assess this potential therapy for IC/BPS. PMID:25209396

  16. Phenobarbitone versus phenytoin for treatment of neonatal seizures: an open-label randomized controlled trial.

    PubMed

    Pathak, Garima; Upadhyay, Amit; Pathak, Umesh; Chawla, Deepak; Goel, Sneh P

    2013-08-01

    To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and near-term neonates. Open labeled randomized controlled trial. Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology. To evaluate serum vascular endothelial growth factor (VEGF) levels in children with acute lymphoblastic leukemia (ALL) during the induction phase of chemotherapy.

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

    PubMed

    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.

  18. Lactobacillus GG for treatment of acute childhood diarrhoea: An open labelled, randomized controlled trial

    PubMed Central

    Aggarwal, Sunny; Upadhyay, Amit; Shah, Dheeraj; Teotia, Neeraj; Agarwal, Astha; Jaiswal, Vijay

    2014-01-01

    Background & objectives: Randomized controlled trials in developed countries have reported benefits of Lactobacillus GG (LGG) in the treatment of acute watery diarrhoea, but there is paucity of such data from India. The study was aimed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India. Methods: In this open labelled, randomized controlled trial 200 children with acute watery diarrhoea, aged between 6 months to 5 years visiting outpatient department and emergency room of a teaching hospital in north India were enrolled. The children were randomized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to standard WHO management of diarrhoea. Primary outcomes were duration of diarrhoea and time to change in consistency of stools. Results: Median (inter quartile range) duration of diarrhoea was significantly shorter in children in LGG group [60 (54-72) h vs. 78 (72-90) h; P<0.001]. Also, there was faster improvement in stool consistency in children receiving Lactobacillus GG than control group [36 (30-36) h vs. 42 (36-48) h; P<0.001]. There was significant reduction in average number of stools per day in LGG group (P<0.001) compared to the control group. These benefits were seen irrespective of rotavirus positivity in stool tests. Interpretation & conclusions: Our results showed that the use of Lactobacillus GG in children with acute diarrhoea resulted in shorter duration and faster improvement in stool consistency as compared to the control group. PMID:24820831

  19. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study.

    PubMed

    Cheon, Eun-Jin; Koo, Bon-Hoon; Choi, Joong-Hyun

    2016-03-01

    The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder.

  20. Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia.

    PubMed

    Sutanto, Inge; Tjahjono, Bagus; Basri, Hasan; Taylor, W Robert; Putri, Fauziah A; Meilia, Rizka A; Setiabudy, Rianto; Nurleila, Siti; Ekawati, Lenny L; Elyazar, Iqbal; Farrar, Jeremy; Sudoyo, Herawati; Baird, J Kevin

    2013-03-01

    Radical cure of Plasmodium vivax infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine. However, the safety and efficacy of primaquine against relapse when combined with other drugs have not been demonstrated. This randomized, open-label, and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection. Among 650 soldiers who had returned to their malaria-free base in Java, Indonesia, after 12 months in malarious Papua, Indonesia, 143 with acute P. vivax malaria were eligible for study. One hundred sixteen enrolled subjects were randomized to these treatments: artesunate (200-mg dose followed by 100 mg/day for 6 days), quinine (1.8 g/day for 7 days) plus concurrent primaquine (30 mg/day for 14 days), or dihydroartemisinin (120 mg) plus piperaquine (960 mg) daily for 3 days followed 25 days later by primaquine (30 mg/day for 14 days). Follow-up was for 12 months. One hundred thirteen subjects were analyzable. Relapse occurred in 32 of 41 (78%) subjects administered artesunate alone (2.71 attacks/person-year), 7 of 36 (19%) administered quinine plus primaquine (0.23 attack/person-year), and 2 of 36 (6%) administered dihydroartemisinin-piperaquine plus primaquine (0.06 attack/person-year). The efficacy of primaquine against relapse was 92% (95% confidence interval [CI] = 81% to 96%) for quinine plus primaquine and 98% (95% CI = 91% to 99%) for dihydroartemisinin-piperaquine plus primaquine. Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua, Indonesia.

  1. Istradefylline improves daytime sleepiness in patients with Parkinson's disease: An open-label, 3-month study.

    PubMed

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Uchiyama, Tomoyuki; Watanabe, Yuka; Suzuki, Shiho; Kadowaki, Taro; Fujita, Hiroaki; Matsubara, Takeo; Sakuramoto, Hirotaka; Hirata, Koichi

    2017-09-15

    Istradefylline, a selective adenosine A2A receptor antagonist, has been reported to improve daily "off time" and motor symptoms in patients with Parkinson's disease (PD). However, the effect of istradefylline on sleep problems has not been thoroughly investigated. We evaluated the effect of istradefylline on daytime sleepiness, sleep disturbances, and motor symptoms in 22 PD patients who were affected by the wearing off phenomenon in an open-label, 3-month study. Participants received 20-40mg/day istradefylline once daily (morning) over a 3-month period. The Epworth Sleepiness Scale (ESS), PD sleep scale (PDSS)-2 and PD Questionnaire (PDQ-8) were administered at baseline, 2weeks, 1month, 2months and 3months. At baseline and 3months, patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV. Twenty-one patients (95.5%) completed the study. At 3months, MDS-UPDRS part III (-5.3, p=0.0002) and part IV (-2.5, p=0.001) scores improved and off time decreased significantly (-50.1min, p=0.0004). PDQ-8 scores were unchanged at 3months. ESS scores decreased significantly at 2months and 3months (-2.4 and -3.3, respectively, p<0.0001), but the total PDSS-2 scores did not change. Istradefylline improved daytime sleepiness in PD patients, possibly through its effect on enhancing alertness. In addition, the lack of significant changes in the total PDSS-2 scores over the study period suggests istradefylline had no negative impact on sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Long-term open-label study of pramipexole in patients with primary restless legs syndrome.

    PubMed

    Inoue, Yuichi; Kuroda, Kenji; Hirata, Koichi; Uchimura, Naohisa; Kagimura, Tatsuo; Shimizu, Tetsuo

    2010-07-15

    A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25 mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75 mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3+/-4.7 at baseline to 11.1+/-7.7 at week 8 and 4.9+/-5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by > or =50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9+/-3.1 at baseline to 4.6+/-2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3+/-5.2 to 4.9+/-3.8. Baseline IRLS score < or =20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25-0.75 mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score <20.

  3. A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain

    PubMed Central

    Hagen, N.A.; Lapointe, B.; Ong–Lam, M.; Dubuc, B.; Walde, D.; Gagnon, B.; Love, R.; Goel, R.; Hawley, P.; Ngoc, A. Ho; du Souich, P.

    2011-01-01

    Background Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief. Objectives We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain. Methods In this multicentre open-label longitudinal trial, 30 μg tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. “Responder” was defined as a mean reduction of 30% or more in pain intensity from baseline; and “clinical responder” as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred. Results Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for “responder” [16 patients (36%)] or “clinical responder” [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient–days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance. Conclusions Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted. PMID:21655148

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

    PubMed

    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.

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

    PubMed

    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

  6. Is nail fold capillaroscopy useful in normotensive and primary open angle glaucoma? A pilot study.

    PubMed

    Božić, Marija; Senćanić, Paraskeva-Hentova; Spahić, Goran; Kontić, Dorđe; Marković, Vujica; Marjanović, Ivan; Stojkovic, Milenko; Dorđević-Jocić, Jasmina

    2010-12-01

    Vascular dysregulation is deemed a significant risk factor in glaucoma occurrence and progression. Capillaroscopy of the blood vessels on the finger nail-fold is a method that can provide information regarding the state of the vascular system at the capillary level. The aim of this pilot study was to determine whether there are significant differences in the morphological characteristics of the peripheral blood vessels in normotensive glaucoma and primary open angle glaucoma. An ophthalmological and capillaroscopic examination was conducted on 30 normotensive glaucoma patients and 30 primary open angle glaucoma patients. The capillaroscopic characteristics described were as follows: capillary row density, capillary diameter, number of spirally formed capillaries, permeability of the loop, and loop resistance. Statistically, significantly more intensively spiraled capillaries were found in normotensive glaucoma patients (χ(2) test, p < 0.05). Results confirm the thesis that vascular factors play a significant role in the pathogenesis of the glaucoma, especially in cases where the level of intraocular pressure cannot be deemed responsible for the present damage of the optical nerve. Despite the newer, technologically more developed methods for diagnostics and monitoring glaucoma, it is often not easy to establish the right diagnosis and determine further the course of the illness, since the role the intraocular pressure (IOP) plays compared to the role of vascular factors is unknown; hence, capillaroscopy as a complementary diagnostic procedure can be of help.

  7. Cardiovascular clinical trials in Japan and controversies regarding prospective randomized open-label blinded end-point design.

    PubMed

    Kohro, Takahide; Yamazaki, Tsutomu

    2009-02-01

    Recently, results of several cardiovascular clinical trials conducted in Japan were published. Most of them were designed as prospective randomized open-label blinded end-point (PROBE)-type trials, in which patients were randomly allocated to different regimens and both the patients and doctors are aware of the regimen being administered. Although the PROBE design enables performing trials resembling real-world practices, entails low costs and renders patient recruitment easier, it presents several conditions that have to be satisfied to acquire accurate results, due to its open-label nature. Principally, the so-called hard end points, which are judged by objective criteria, should be used as primary end points in order to prevent biases. In this article, a general description of various designs of clinical studies is provided, followed by a description of the PROBE design, and the precautions to be taken while conducting PROBE-designed trials by comparing trials conducted in Japan and the West.

  8. Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study.

    PubMed

    Ketter, Terence A; Amchin, Jess; Frye, Mark A; Gross, Nicholas

    2016-06-01

    Safe/well-tolerated treatments for bipolar I depression remain limited. We assessed safety/tolerability of adjunctive open-label armodafinil, a wakefulness-promoting agent evaluated in 3 acute, controlled efficacy studies with variable efficacy results. Completers of three 8-week, double-blind, placebo-controlled adjunctive armodafinil studies (150-200 mg/day added to ongoing stable maintenance doses of 1 or 2 protocol-defined mood stabilizers) in bipolar I depression could enter this 6-month, open-label extension study. Objectives included evaluation of safety/tolerability (primary) and efficacy (secondary). 867 patients enrolled; 863 received ≥1 dose of armodafinil and 506 (58%) completed the 6-month study. Headache, insomnia, and anxiety were the most common adverse events (AEs) reported, whereas akathisia, nausea, sedation/somnolence, and weight increase were uncommon. Mean measures assessing emergence of mania, anxiety, insomnia, or suicidality showed no worsening. Discontinuations due to AEs occurred in 57 (7%) patients. Serious AEs occurred in 27 (3%) patients and were considered treatment-related in 8 (1%) patients. Depressive symptoms improved over the 6 months, as did patient functioning. Lack of placebo control. Adjunctive armodafinil was generally safe and well tolerated over 6 months of open-label treatment at 150-200 mg/day when taken with protocol-defined mood stabilizers for bipolar I depression. This 6-month open-label study suggested that armodafinil augmentation of bipolar maintenance therapies may have a favorable risk profile and may improve depressive symptoms in some patients with bipolar I depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Prospective open label study of solifenacin for overactive bladder in children.

    PubMed

    Bolduc, Stéphane; Moore, Katherine; Nadeau, Geneviève; Lebel, Sylvie; Lamontagne, Pascale; Hamel, Micheline

    2010-10-01

    We evaluated the effect of solifenacin for urinary incontinence in children with overactive/neurogenic bladder refractory to oxybutynin or tolterodine. Pediatric patients presenting with refractory overactive bladder with incontinence were offered the opportunity to enter a prospective, open label protocol using adjusted dose regimens of 1.25 to 10 mg solifenacin. Study inclusion criteria were absent correctable neurological anomalies on magnetic resonance imaging, failure of symptoms to improve on intensive behavioral and medical (oxybutynin or tolterodine) therapy, and/or significant side effects of those agents. Followup consisted of a voiding diary, post-void residual urine measurement, urine culture, ultrasound and urodynamics. Families were questioned about continence, side effects, compliance, behavior change and quality of life. The primary end point was efficacy for continence and secondary end points were tolerability and safety. Enrolled in the study were 42 girls and 30 boys. Of the patients 27 with neurogenic bladder, of whom 11 were on clean intermittent catheterization, and 45 with overactive bladder completed a minimum 3-month followup. Patients were on solifenacin a mean of 15.6 months. Mean age at study initiation was 9.0 years. Mean ± SD urodynamic capacity improved from 146 ± 64 to 311 ± 123 ml and uninhibited contractions decreased from 70 ± 29 to 20 ± 19 cm H(2)O (p <0.01). Continence improved in all patients, including 24 who were dry, and 42 and 6 who were significantly and moderately improved, respectively. Of the patients 50 reported no side effects while 15 had mild and 3 had moderate side effects. Four patients withdrew from the protocol due to intolerable side effects. Four patients had significant post-void residual urine (greater than 20 ml). In children with overactive bladder refractory to oxybutynin or tolterodine solifenacin is an effective alternative to improve symptoms. Tolerability was acceptable and the adjusted dose

  10. Foley Catheter for Induction of Labor at Term: An Open-Label, Randomized Controlled Trial

    PubMed Central

    Wang, Zhiqun; Dai, Yimin; Zheng, Mingming; Xu, Biyun; Hu, Yali

    2015-01-01

    Objective This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL) and the maximum time for cervical ripening (12 hours vs. 24 hours) to improve vaginal delivery rate within 24 hours of induction. Methods We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6) were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1) 30-mL balloon for a maximum of 12 hours, (2) 30-mL balloon for a maximum of 24 hours, (3) 80-mL balloon for a maximum of 12 hours, and (4) 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis. Results Five hundred and four women were recruited and randomized (126 women in each group); nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001). Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction. Conclusion For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL) and longer ripening time (24 hours vs. 12 hours) would not shorten induction to delivery interval or reduce cesarean section rate. Trial Registration Chinese Clinical trial registry (ChiCTR-TRC-13003044) PMID:26322635

  11. Open-label observational study of the homeopathic medicine Passiflora Compose for anxiety and sleep disorders.

    PubMed

    Villet, Stéphanie; Vacher, Véronique; Colas, Aurélie; Danno, Karine; Masson, Jean-Louis; Marijnen, Philippe; Bordet, Marie-France

    2016-02-01

    Anxiety and sleep disorders (SDS) are frequently treated with psychotropic drugs. Health authorities in France have been advised to improve access to alternative treatments such as homeopathic medicines. Our aim was to describe the socio-demographic characteristics and clinical progression of patients prescribed homeopathic medicine Passiflora Compose (PC) for anxiety and/or SDS. This was an open-label, observational study. Randomly selected general practitioners (GPs) known to prescribe homeopathic medicines recruited consecutive patients (≥18-years) prescribed PC. The following data were recorded at inclusion by the GP: socio-demographic data and anxiety severity (Hamilton anxiety rating scale or HAM-A); and by the patients: level of anxiety (STAI Spielberger self-assessment questionnaire) and SDS (Jenkins sleep scale or JSS). Anxiety and SDS were reassessed after 4 weeks of treatment using the same scales. A total of 639 patients (mean age: 46.3 ± 17.5 years; 78.6% female) were recruited by 98 GPs. Anxiety was present in 85.4% (HAM-A) and 93.3% (Spielberger State) at inclusion (mean scores: 17.8 ± 8.91 and 54.59 ± 11.69, respectively) and SDS was present in 74.0% (mean score: 15.24 ± 5.28). A total of 401 (62.7%) patients received PC alone and 167 (26.1%) PC + psychotropics. After 4 weeks, mean anxiety scores decreased by more than 7, 12 and 6 points (HAM-A, Spielberger State and Trait respectively), and SDS score by more than 4 points (JSS). Anxiety and/or SDS improved significantly in patients included on this study. PC could be an alternative to the use of psychotropic drugs for first intention treatment of anxiety and SDS. Further studies are needed to confirm those results. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  12. Foley Catheter for Induction of Labor at Term: An Open-Label, Randomized Controlled Trial.

    PubMed

    Gu, Ning; Ru, Tong; Wang, Zhiqun; Dai, Yimin; Zheng, Mingming; Xu, Biyun; Hu, Yali

    2015-01-01

    This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL) and the maximum time for cervical ripening (12 hours vs. 24 hours) to improve vaginal delivery rate within 24 hours of induction. We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6) were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1) 30-mL balloon for a maximum of 12 hours, (2) 30-mL balloon for a maximum of 24 hours, (3) 80-mL balloon for a maximum of 12 hours, and (4) 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis. Five hundred and four women were recruited and randomized (126 women in each group); nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001). Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction. For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL) and longer ripening time (24 hours vs. 12 hours) would not shorten induction to delivery interval or reduce cesarean section rate. Chinese Clinical trial registry (ChiCTR-TRC-13003044).

  13. Evaluation of open-label topiramate as primary or adjunctive therapy in infantile spasms.

    PubMed

    Zou, Li-Ping; Lin, Qing; Qin, Jiong; Cai, Fang-Cheng; Liu, Zhi-Sheng; Mix, Eilhard

    2008-01-01

    A multicenter open-label clinical trial was conducted to evaluate the clinical usefulness of topiramate (TPM) as primary or adjunctive therapy for infantile spasms in the postmarketing period in China. Thirty-four centers participated in the trial. Patients included in the study had 1 or more seizures per day before treatment. One hundred twenty (22.1%) very young patients with an age younger than 6 month and 64.2% of patients were younger than 1 year at start of treatment. All patients received a starting dose of 0.5 to 1 mg kg d TPM twice daily. The dosage was increased by 0.5 to 1 mg kg d every 5 to 7 days up to 3 to 5 mg kg d. The resulting range of the total TPM dosage was 25 to 200 mg d (3.57-20 mg kg d), with a median value of 73.9 mg d. Seizure outcomes were measured by intention-to-treat analysis. Patients were seen by a neurologist, and their data were evaluated at the day of inclusion and after 4, 8, 12, 16, and 20 weeks (from visit 1 to visit 5) of treatment. Five hundred forty-four patients entered the study. After 20 weeks of TPM treatment, 239 patients (43.9%) were seizure-free. A higher proportion of patients in the monotherapy group than in the add-on therapy group showed a seizure rate reduction. An increase in seizure frequency was observed in 8 patients (1.5%) during the 20-week treatment period. Nineteen patients were withdrawn before completing the study, and in 46 cases, some data of the structured data files and questionnaires were missing. No efficacy of TPM treatment was recorded in these cases. Adverse effects occurred in 211 patients (38.8%). Most frequent side effects were anorexia and somnolence. Topiramate proved to be an effective and safe monotherapy and add-on therapy in patients with infantile spasms younger than 1 year.

  14. An Open-Label, Rater-Blinded, Augmentation Study of Aripiprazole in Treatment-Resistant Depression

    PubMed Central

    Patkar, Ashwin A.; Peindl, Kathleen; Mago, Rajnish; Mannelli, Paolo; Masand, Prakash S.

    2006-01-01

    Background: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D2 and serotonin 5-HT1A receptors and antagonism at the 5-HT2 receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. Method: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10–30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. Results: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). Conclusions: The study indicates the potential utility of aripiprazole as an

  15. An open-label, 6-month study of allopurinol safety in gout: The LASSO study.

    PubMed

    Becker, Michael A; Fitz-Patrick, David; Choi, Hyon K; Dalbeth, Nicola; Storgard, Chris; Cravets, Matt; Baumgartner, Scott

    2015-10-01

    Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses. Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency. Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred

  16. Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial

    PubMed Central

    Arjyal, Amit; Basnyat, Buddha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Agrawaal, Krishna Kumar; Shakya, Nikki; Shrestha, Kabina; Sharma, Manish; Lama, Sanju; Shrestha, Kasturi; Khatri, Nely Shrestha; Shrestha, Umesh; Campbell, James I; Baker, Stephen; Farrar, Jeremy; Wolbers, Marcel; Dolecek, Christiane

    2011-01-01

    Summary Background We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults. Methods We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327. Findings 844 patients with a median age of 16 (IQR 9–22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40–1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68–4·68

  17. Label-free identification of antibiotic resistant isolates of living Escherichia coli: Pilot study.

    PubMed

    Cheong, Youjin; Jin Kim, Young; Kang, Heeyoon; Choi, Samjin; Joo Lee, Hee

    2017-02-01

    We introduce a label-free spectroscopic method to classify subtypes of quinolone-nonsusceptible Escherichia coli (E. coli) isolates obtained from human blood cultures. Raman spectroscopy with a 30-nm gold-deposited, surface-enhanced Raman scattering (SERS) substrate was used to evaluate three multilocus sequencing typing (MLST)-predefined groups including E. coli ATCC25922, E. coli ST131:O75, and E. coli ST1193:O25b. Although there was a coffee-ring effect, the ring zone was selected at the ideal position to screen E. coli isolates. Strong Raman peaks were present at 1001-1004 cm(-1) (CC aromatic ring breathing stretching vibrational mode of phenylalanine), 1447-1448 cm(-1) (CH2 scissoring deformation vibrational mode), and 1667 cm(-1) (amide I α-helix). Although the three MLST-predefined E. coli isolates had similar Raman spectral patterns, a support vector machine (SVM) learning algorithm-assisted principal component analysis (PCA) analysis had superior performance in detecting the presence of quinolone-nonsusceptible E. coli isolates as well as classifying similar microbes, such as quinolone-nonsusceptible E. coli ST131:O75 and E. coli ST1193:O25b isolates. Therefore, this label-free and nondestructive technique is likely to be useful for clinically diagnosing quinolone-nonsusceptible E. coli isolates with the MLST method.

  18. Symptomatic or prophylactic treatment of weekend migraine: an open-label, nonrandomized, comparison study of frovatriptan versus naproxen sodium versus no therapy.

    PubMed

    Guidotti, Mario; Barrilà, Caterina; Leva, Serena; De Piazza, Claudio; Omboni, Stefano

    2013-01-01

    Migraine often occurs during weekends. The efficacy of frovatriptan, naproxen sodium, or no therapy for the acute or prophylactic treatment of weekend migraineurs was tested in an open-label, nonrandomized pilot study. Twenty-eight subjects (mean age 36 ± 12 years, including 18 females) suffering from migraine without aura were followed up for six consecutive weekends. No treatment was administered during the first two weekends. On the third and fourth weekends, patients were given frovatriptan 2.5 mg and on the fifth and sixth weekends naproxen sodium 500 mg. Treatment was taken on Saturday and Sunday morning, regardless of the occurrence of migraine. Efficacy was evaluated through a diary, where patients reported the severity of migraine on a scale from 0 (no migraine) to 10 (severe migraine) and use of rescue medication. The migraine severity score was significantly lower with frovatriptan (4.8 [95% confidence interval (CI) 3.8-5.9]) than with naproxen sodium (5.7 [CI 5.1-6.4], P< 0.05 versus frovatriptan) or no therapy (6.6 [6.2-7.0], P< 0.01 versus frovatriptan). The difference in favor of frovatriptan was more striking in patients not taking rescue medication (frovatriptan, 1.9 [1.5-2.3]) versus naproxen sodium 3.6 [3.0-4.2], P< 0.001) and versus no therapy (5.1 [4.4-5.8], P< 0.001) and on the second day of treatment. The rate of use of rescue medication was significantly (P< 0.05) lower on frovatriptan (12.5%) than on naproxen sodium (31.3%) or no therapy (56.3%). This pilot study provides the first evidence of the efficacy of a second-generation triptan as symptomatic or prophylactic treatment for weekend migraine.

  19. Symptomatic or prophylactic treatment of weekend migraine: an open-label, nonrandomized, comparison study of frovatriptan versus naproxen sodium versus no therapy

    PubMed Central

    Guidotti, Mario; Barrilà, Caterina; Leva, Serena; De Piazza, Claudio; Omboni, Stefano

    2013-01-01

    Background Migraine often occurs during weekends. The efficacy of frovatriptan, naproxen sodium, or no therapy for the acute or prophylactic treatment of weekend migraineurs was tested in an open-label, nonrandomized pilot study. Methods Twenty-eight subjects (mean age 36 ± 12 years, including 18 females) suffering from migraine without aura were followed up for six consecutive weekends. No treatment was administered during the first two weekends. On the third and fourth weekends, patients were given frovatriptan 2.5 mg and on the fifth and sixth weekends naproxen sodium 500 mg. Treatment was taken on Saturday and Sunday morning, regardless of the occurrence of migraine. Efficacy was evaluated through a diary, where patients reported the severity of migraine on a scale from 0 (no migraine) to 10 (severe migraine) and use of rescue medication. Results The migraine severity score was significantly lower with frovatriptan (4.8 [95% confidence interval (CI) 3.8–5.9]) than with naproxen sodium (5.7 [CI 5.1–6.4], P< 0.05 versus frovatriptan) or no therapy (6.6 [6.2–7.0], P< 0.01 versus frovatriptan). The difference in favor of frovatriptan was more striking in patients not taking rescue medication (frovatriptan, 1.9 [1.5–2.3]) versus naproxen sodium 3.6 [3.0–4.2], P< 0.001) and versus no therapy (5.1 [4.4–5.8], P< 0.001) and on the second day of treatment. The rate of use of rescue medication was significantly (P< 0.05) lower on frovatriptan (12.5%) than on naproxen sodium (31.3%) or no therapy (56.3%). Conclusion This pilot study provides the first evidence of the efficacy of a second-generation triptan as symptomatic or prophylactic treatment for weekend migraine. PMID:23355779

  20. Determining the frequency of open windows in motor vehicles: a pilot study using a video camera in Houston, Texas during high temperature conditions.

    PubMed

    Long, Tom; Johnson, Ted; Ollison, Will

    2002-05-01

    Researchers have developed a variety of computer-based models to estimate population exposure to air pollution. These models typically estimate exposures by simulating the movement of specific population groups through defined microenvironments. Exposures in the motor vehicle microenvironment are significantly affected by air exchange rate, which in turn is affected by vehicle speed, window position, vent status, and air conditioning use. A pilot study was conducted in Houston, Texas, during September 2000 for a specific set of weather, vehicle speed, and road type conditions to determine whether useful information on the position of windows, sunroofs, and convertible tops could be obtained through the use of video cameras. Monitoring was conducted at three sites (two arterial roads and one interstate highway) on the perimeter of Harris County located in or near areas not subject to mandated Inspection and Maintenance programs. Each site permitted an elevated view of vehicles as they proceeded through a turn, thereby exposing all windows to the stationary video camera. Five videotaping sessions were conducted over a two-day period in which the Heat Index (HI)-a function of temperature and humidity-varied from 80 to 101 degrees F and vehicle speed varied from 30 to 74 mph. The resulting videotapes were processed to create a master database listing vehicle-specific data for site location, date, time, vehicle type (e.g., minivan), color, window configuration (e.g., four windows and sunroof), number of windows in each of three position categories (fully open, partially open, and closed), HI, and speed. Of the 758 vehicles included in the database, 140 (18.5 percent) were labeled as "open," indicating a window, sunroof, or convertible top was fully or partially open. The results of a series of stepwise linear regression analyses indicated that the probability of a vehicle in the master database being "open" was weakly affected by time of day, vehicle type, vehicle color

  1. Substance abuse treatment for HIV infected young people: an open pilot trial.

    PubMed

    Esposito-Smythers, Christianne; Brown, Larry K; Wolff, Jennifer; Xu, Jiahong; Thornton, Sarah; Tidey, Jennifer

    2014-02-01

    The purpose of this study was to test an integrated cognitive behavioral and contingency management (CBT/CM) intervention for young people living with HIV (YPLH) with an alcohol and/or cannabis use disorder in an open pilot trial. Seventeen participants (ages 18-24) were recruited from three HIV community clinics. Assessments were completed at pre-and post-treatment as well as 3 month follow-up. Eighty percent of participants were retained in the study. Results suggest that the CBT/CM intervention was acceptable, feasible, and could be delivered with fidelity. Further, participants reported significant reductions in alcohol use, withdrawal symptoms, dependence symptoms and related problems, as well as co-occurring depressive symptoms and delinquent behavior across assessment periods. A trend was evident for reductions in marijuana use and related problems. Overall, these preliminary results suggest that a substance abuse CBT/CM intervention tailored to YPLH is acceptable, feasible, and holds promise for symptomatic improvement. Further testing of this type of protocol is warranted. © 2013.

  2. Clinical profiles of primary open angle glaucoma versus normal tension glaucoma patients: a pilot study.

    PubMed

    Asrani, Sanjay; Samuels, Brian; Thakur, Mugdha; Santiago, Cecilia; Kuchibhatla, Maragatha

    2011-05-01

    To study the health profiles and behavioral differences between primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. Confidential mail survey of ICD-9 defined POAG (n = 277) and NTG (n = 116) patients was carried out to collect information regarding age, gender, height, weight, waist circumference, blood pressure (BP), medications [prescription (Rx) and over the counter (OTC)], education, and the Short Health Anxiety Inventory (SHAI). NTG patients (59/116) were significantly more likely to respond to the survey than POAG patients (43/277), p = 0.0001, and to have obtained college level education (70% vs. 42%), p = 0.003. Body weight, waist circumference, body mass index, systolic BP, pulse pressure, and ratio of prescription medications to OTC medications were significantly lower in the NTG group (p < 0.0001). The SHAI score, mean age, and diastolic BP were not different between the two groups. A subgroup analysis of college-educated patients in both groups revealed persisting significant differences in waist circumference, systolic BP, and ratio of Rx to OTC medications. NTG patients do not have significantly greater health anxiety than POAG patients. NTG patients are more likely to have lower BMI, systolic BP, and ratio of Rx to OTC medications than POAG patients. The pilot nature of this study limits generalizability of these findings. Larger studies confirming these findings and elucidating the role of refractive error and medical history on such differences are needed.

  3. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    PubMed Central

    Gregersen, Kine; Lind, Ragna A; Valeur, Jørgen; Bjørkkjær, Tormod; Berstad, Arnold; Lied, Gülen Arslan

    2010-01-01

    Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect. PMID:21189836

  4. Substance Abuse Treatment for HIV Infected Young People: An Open Pilot Trial

    PubMed Central

    Esposito-Smythers, Christianne; Brown, Larry K.; Wolff, Jennifer; Xu, Jiahong; Thornton, Sarah; Tidey, Jennifer

    2013-01-01

    The purpose of this study was to test an integrated cognitive behavioral and contingency management (CBT/CM) intervention for young people living with HIV (YPLH) with an alcohol and/or cannabis use disorder in an open pilot trial. Seventeen participants (ages 18–24) were recruited from three HIV community clinics. Assessments were completed at pre-and post-treatment as well as three month follow-up. Eighty percent of participants were retained in the study. Results suggest that the CBT/CM intervention was acceptable, feasible, and could be delivered with fidelity. Further, participants reported significant reductions in alcohol use, withdrawal symptoms, dependence symptoms and related problems, as well as co-occurring depressive symptoms and delinquent behavior across assessment periods. A trend was evident for reductions in marijuana use and related problems. Overall, these preliminary results suggest that a substance abuse CBT/CM intervention tailored to YPLH is acceptable, feasible, and holds promise for symptomatic improvement. Further testing of this type of protocol is warranted. PMID:23988190

  5. Immediate changes in temporomandibular joint opening and pain following vibration therapy: a feasibility pilot study

    PubMed Central

    Muir, Brad; Brown, Courtney; Brown, Tara; Tatlow, Dionne; Buhay, Jeremy

    2014-01-01

    Objective The purpose of this pilot study was to determine the scientific and process feasibility in an effort to direct future larger trials. Methods: Scientific Feasibility: Twelve subjects were randomly allocated to an intervention and a control group. The intervention protocol consisted of intraoral vibration therapy on the muscles of mastication bilaterally for a period of 1 minute per muscle. Process Feasibility: Several feasibility outcomes were examined including recruitment and retention rates and consent. Results: Scientific Feasibility: Large effect sizes were generated for both mouth opening and VAS in favour of the intervention group. Process Feasibility: a recruitment ratio of 2.3 respondents to 1 participant was determined, along with a retention to loss ratio of 13:1 and a consent to loss ratio of 12:0. Conclusion: Scientific Feasibility: The scientific results should be interpreted with caution due to the small sample sizes employed. The study seems to support the scientific feasibility of a future larger single treatment trial. Process Feasibility: Recruitment and retention rates and ratios seem to support future studies. Utilizing the feasibility results of the current study to direct a future larger multiple treatment trial consistent with other comparable TMD studies however is limited. PMID:25550672

  6. Label-free reflectance hyperspectral imaging for tumor margin assessment: a pilot study on surgical specimens of cancer patients

    NASA Astrophysics Data System (ADS)

    Fei, Baowei; Lu, Guolan; Wang, Xu; Zhang, Hongzheng; Little, James V.; Patel, Mihir R.; Griffith, Christopher C.; El-Diery, Mark W.; Chen, Amy Y.

    2017-08-01

    A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.

  7. Lumboperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (SINPHONI-2): an open-label randomised trial.

    PubMed

    Kazui, Hiroaki; Miyajima, Masakazu; Mori, Etsuro; Ishikawa, Masatsune

    2015-06-01

    Lumboperitoneal shunt surgery has the potential to alleviate symptoms of normal pressure hydrocephalus but the benefits of such surgery have not been tested in a randomised trial. The aim of this trial was to determine the safety and efficacy of the lumboperitoneal shunt surgery for this disorder. For the open-label randomised SINPHONI-2 trial, eligible participants (60-85 years of age) with idiopathic normal pressure hydrocephalus, with ventriculomegaly, and tightness of the high-convexity and medial subarachnoid spaces on MRI, were recruited from 20 neurological and neurosurgical centres in Japan. Enrolled participants were randomly assigned in a 1:1 ratio according to a random code generated by the trial statistician, with a permuted block design (using a block size of 4 or 6) within each centre, to receive lumboperitoneal shunt surgery within 1 month after randomisation, or to surgery postponed for 3 months. Patients and assessors were not masked to treatment assignment. The primary endpoint was favourable outcome, defined as an improvement of one point or more on the modified Rankin scale (mRS) at 3 months after randomisation, analysed by intention to treat, and the main secondary endpoint was the same outcome 12 months after surgery, analysed per protocol. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), number UMIN000002730. Between March 1, 2010, and Oct 19, 2011, 93 patients with idiopathic normal pressure hydrocephalus were enrolled and randomly assigned to the immediate treatment group (n=49) or the postponed treatment group (n=44). More patients in the immediate treatment group than in the postponed treatment group had an improvement of one point or more on the mRS at 3 months: 32 (65%) of 49 in the immediate group vs 2 (5%) of 44 in the postponed group (difference 61% [95% CI 42-68]; p<0·0001). The number of patients who had an improvement of one point or more on the mRS at 12

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

    PubMed

    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

  9. Safety and Exploratory Efficacy at 36 Months in Open-HART, an Open-Label Extension Study of Pridopidine in Huntington's Disease.

    PubMed

    McGarry, Andrew; Kieburtz, Karl; Abler, Victor; Grachev, Igor D; Gandhi, Sanjay; Auinger, Peggy; Papapetropoulos, Spyridon; Hayden, Michael

    2017-08-12

    Open-HART is an open-label extension of HART, a randomized, placebo-controlled, dose-ranging, parallel-group study. To evaluate safety and exploratory efficacy of open-label pridopidine over 36 months in subjects with Huntington's disease (HD). Open-HART subjects were treated with pridopidine 45 mg twice daily (BID). After initial evaluation by telephone (Week 1) and in person (Month 1), in-person visits occurred every 3 months, alternating between safety and clinical visits (safety plus Unified Huntington's Disease Rating Scale [UHDRS] assessment). The UHDRS was performed for pre-specified analysis as a secondary outcome measure. Adverse events (AEs), laboratory values, and electrocardiography were monitored throughout. Most subjects (89%) reported at least one AE, with 30% experiencing treatment-related AEs. The most common AEs during the first year were falls (12.7%), anxiety (9.3%), insomnia (8.5%), irritability (6.8%), and depression (5.9%). Ninety-nine percent of subjects took concomitant medications. Two seizures were reported as AEs. No arrhythmias or suicide attempts were reported. Five deaths occurred, all considered treatment unrelated. Secondary exploratory analyses of subjects on pridopidine demonstrated motor deterioration (as measured by the UHDRS total motor score) consistent with HD's natural history, as shown in large observational studies. A post-hoc, exploratory analysis of TFC performance compared to placebo groups from other long-term HD studies demonstrated no significant effect for pridopidine on TFC progression after correction for multiple comparisons. Pridopidine 45 mg BID was generally safe and tolerable in HD subjects over 36 months. TMS declined in a manner consistent with the known natural history of HD.

  10. Improvement of QOL and Immunological Function With Lentinula Edodes Mycelia in Patients Undergoing Cancer Immunotherapy: An Open Pilot Study.

    PubMed

    Tanigawa, Keishi; Itoh, Yusuke; Kobayashi, Yasunobu

    2016-07-01

    Context • Combined treatment with an extract of Lentinula edodes mycelia (LEM) and chemotherapy has been reported to improve quality of life (QOL) and immunological function in cancer patients. However, those effects have not been elucidated for patients receiving cancer immunotherapy. Objective • The present study intended to investigate the effects of oral LEM on QOL and immunological function in cancer patients receiving immunotherapy. Design • The research team designed an open-label, single-armed pilot study. Setting • The study took place at Bio-Thera Clinic, a facility associated with Tokyo Women's Medical University in Tokyo, Japan. Participants • The participants were 10 cancer patients undergoing cancer immunotherapy at Bio-Thera Clinic. Intervention • The participants received either dendritic cell (DC)-based cancer vaccine therapy or CD3-activated T-lymphocyte (CAT) therapy as immunotherapy. They received the immunotherapy only for the first 4 wk of the study, and then oral LEM (1800 mg/d) was added for the next 4 wk. Outcome Measures • Preintervention and at 4 and 8 wk after the start of the study, participants completed a QOL survey, and immunological parameters were measured. Results • Participants' QOL symptom scores increased (ie, worsened) by 5.1 ± 1.7 during the first 4 wk of treatment when they were receiving immunotherapy only, but it decreased (ie, improved) by -2.5 ± 1.6 during the next 4 wk when the immunotherapy was combined with the LEM, P < .05. The measurement of the immunological parameters during the 4 wk of immunotherapy combined with LEM showed that the amount of interferon-γ (IFN-γ) produced in the peripheral blood tended to increase as compared with that during the first 4 wk of immunotherapy only. The rise in IFN-γ was correlated with changes in several regulatory T cells (Tregs) (ie, forkhead box P3 [FOXP3]+/cluster of differentiation 4 [CD4]+ and transforming growth factor beta [TGF-β]). Conclusions • The

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

    PubMed

    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.

  12. An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder

    PubMed Central

    Sharif-Askary, Banafsheh; Harkins, Elizabeth A.; Frank, Heather R.; Brotman, Melissa A.; Penton-Voak, Ian S.; Maoz, Keren; Bar-Haim, Yair; Munafò, Marcus; Pine, Daniel S.; Leibenluft, Ellen

    2016-01-01

    Abstract Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function. Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a “balance point,” the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task. Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex. Conclusions:These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger. PMID:26745832

  13. Early active motion protocol following open reduction internal fixation of the scaphoid: A pilot study.

    PubMed

    Dunn, J-C; Kusnezov, N; Fares, A; Buccino, Z; Esquivel, D; Mitchell, J

    2017-02-01

    Scaphoid fractures are common injuries which traditionally have been treated with long periods of immobilization even after open reduction and internal fixation (ORIF). The purpose of this pilot investigation was two-fold: 1) describe a precise postoperative Early Active Motion (EAM) rehabilitation protocol following ORIF of scaphoid fractures and 2) record the outcomes of the EAM protocol. Eight consecutive patients having undergone ORIF of the scaphoid were enrolled in the EAM and followed for a minimum of 1 year. At 12 weeks, Disabilities of the Arm Shoulder and Hand (DASH) score, Mayo Wrist score, and range of motion values were obtained. At 1 year, a telephone survey was conducted and several data points were obtained including DASH and Mayo Wrist score, number of push-ups, satisfaction with surgery and ability to remain on active duty. All 8 patients were male, on active duty, with an average age of 26 years. Two patients used tobacco products and none had major health problems. All patients completed the EAM protocol and obtained CT; all CT exams demonstrated healing at 8 weeks. At 12 weeks postoperatively, the average DASH score was 8.8±16 (range: 0-47.5), Mayo wrist score was 88±10 (range: 75-100) and range of motion nearly symmetrical. At a mean final follow-up of 15.4 months postoperatively, the average DASH score was 1.1±1.7 (Range: 0-4.5), Mayo wrist score was 97.5±4 (range 90-100), average number of push-ups was 57 (40-70) at the prior Army Physical Fitness Test. All patients were satisfied with surgery and all remained on active duty at 1 year. There were no reported complications. The EAM protocol following scaphoid fracture ORIF is safe and effective. The EAM can reliably return patients back to high demand activity earlier than a traditional protocol.

  14. Efficacy of chess training for the treatment of ADHD: A prospective, open label study.

    PubMed

    Blasco-Fontecilla, Hilario; Gonzalez-Perez, Marisa; Garcia-Lopez, Raquel; Poza-Cano, Belen; Perez-Moreno, Maria Rosario; de Leon-Martinez, Victoria; Otero-Perez, Jose

    2016-01-01

    To examine the effectiveness of playing chess as a treatment option for children with ADHD. Parents of 44 children ages 6 to 17 with a primary diagnosis of ADHD consented to take part in the study. Parents completed the Spanish version of the Swanson, Nolan and Pelham Scale for parents (SNAP-IV) and the Abbreviated Conner's Rating Scales for parents (CPRS-HI) prior to an 11-week chess-training program. We used a paired t-test to compare pre- and post-intervention outcomes, and Cohen-d calculations to measure the magnitude of the effect. The statistical significance was set at P<.05. Children with ADHD improved in both the SNAP-IV (t=6.23; degrees of freedom (df)=41; P<.001) and the CPRS-HI (t=5.39; df=33; P<.001). Our results suggest a large effect in decreasing the severity of ADHD as measured by the SNAP-IV (d=0.85) and the CPRS-HI (d=0.85). Furthermore, we found a correlation between intelligence quotient and SNAP-IV improvement (P<.05). The results of our pilot study should be interpreted with caution. This pilot project highlights the importance of carrying out larger studies with a case-control design. If our results are replicated in better designed studies, playing chess could be included within the multimodal treatment of ADHD. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  15. A preliminary review of a pilot curriculum to teach open surgical skills during general surgery residency with initial feedback.

    PubMed

    Are, Chandrakanth; Lomneth, Carol; Stoddard, Hugh; Azarow, Kenneth; Thompson, Jon S

    2012-07-01

    The aim of this study is to provide a preliminary review of a pilot curriculum to teach open surgical skills during general surgery residency and obtain initial feedback. The general surgery residency program introduced an open surgical skills training curriculum in 2009. The skills sessions are undertaken under the guidance of the faculty. An annual survey was distributed to the residents and faculty to obtain their feedback. A total of 50 sessions were conducted over the last 2 years. Ninety-five percent of the residents perceived this educational activity to be above average to exceptional with nearly 70% rating it as exceptional. Sixty-three percent of the faculty perceived it as above average to exceptional, with nearly 40% rating it as exceptional. The open surgical skills training curriculum was rated as the most educational activity in the program by residents and faculty alike. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Randomized Comparison of Subcuticular Sutures Versus Staples for Skin Closure After Open Abdominal Surgery: a Multicenter Open-Label Randomized Controlled Trial.

    PubMed

    Imamura, Kazuhiro; Adachi, Kensuke; Sasaki, Ritsuko; Monma, Satoko; Shioiri, Sadaaki; Seyama, Yasuji; Miura, Masaru; Morikawa, Yoshihiko; Kaneko, Tetsuji

    2016-12-01

    The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the "suture" and "staple" group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

  17. An oral appliance with or without elastic bands to control mouth opening during sleep-a randomized pilot study.

    PubMed

    Norrhem, Niclas; Marklund, Marie

    2016-09-01

    Oral appliances (OAs) hold the lower jaw forward to reduce obstructive sleep apneas. Some OA designs allow mouth opening, which influences the forward positioning of the lower jaw. The aim of this pilot study was to compare the efficacy of an adjustable, custom-made OA (Narval®) in its original design, which allowed mouth opening, with the same OA with elastic bands that restricted mouth opening. Consecutive patients with an apnea-hypopnea index (AHI) of ≥15 were randomized to start with an OA either with or without elastic bands in a single-blinded, crossover, pilot study. The patients underwent acclimatization and titration. After 3 weeks use of each device, they had renewed sleep apnea recordings and responded to questionnaires. Washout periods took place between the tests. Ten subjects with a median AHI of 19.7 (interquartile range (IQR) 17.3 to 31.8) were included. The AHI decreased to 3.1 (IQR 1.5-14.7) (p < 0.01) with the OA and to 5.1 (IQR 2.4-14.3) (p < 0.01) with the OA with elastic bands, with no difference between them (p = 0.7). The two subjects with severe obstructive sleep apnea (OSA) almost halved their supine AHI with, as compared to without, elastic bands. The majority of the patients preferred to use the elastic bands. This pilot study indicates that elastic bands markedly reduced the supine AHI in two subjects with severe sleep apnea as compared to without elastic bands. The majority of the patients preferred the use of elastic bands, although no significant difference in the AHI was observed with versus without the elastic bands in the whole sample.

  18. Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

    PubMed Central

    Metcalfe, Chris; Avery, Kerry; Berrisford, Richard; Barham, Paul; Noble, Sian M; Fernandez, Aida Moure; Hanna, George; Goldin, Robert; Elliott, Jackie; Wheatley, Timothy; Sanders, Grant; Hollowood, Andrew; Falk, Stephen; Titcomb, Dan; Streets, Christopher; Donovan, Jenny L; Blazeby, Jane M

    2016-01-01

    BACKGROUND Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. OBJECTIVES The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. DESIGN Pilot parallel three-arm randomised controlled trial nested within feasibility work. SETTING Two UK NHS departments of upper gastrointestinal surgery. PARTICIPANTS Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. INTERVENTIONS Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. MAIN OUTCOME MEASURE The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. RESULTS During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the

  19. Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial.

    PubMed

    Arpa, J; Sanz-Gallego, I; Rodríguez-de-Rivera, F J; Domínguez-Melcón, F J; Prefasi, D; Oliva-Navarro, J; Moreno-Yangüela, M

    2014-01-01

    The objective of the study was to test the efficacy, safety and tolerability of triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia (FRDA) patients in a clinical pilot study. Patients included in this study were 10 males and three females, 14-61 years of age (average 30.2 ± 12.1), diagnosed with FRDA with normal ventricular function. Patients were treated with triple therapy with deferiprone at 5-25 mg/kg/day, idebenone at 10-20 mg/kg/day and riboflavin at 10-15 mg/kg/day for 15-45 months. The efficacy of this triple therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA) and by the change from baseline in echocardiogram parameters. Four patients discontinued due to adverse events (AEs) related with deferiprone. The annual worsening rate (AWR) was estimated in this series as 0.96 (CI 95%: 0.462-1.608) SARA score, whereas AWR for our FRDA cohort was estimated as 2.05 ± 1.23 SARA score. LVMI only decreased by 6.5 g/m(2) (6.2%) at the end of the first year of therapy. LVEF remained stable, except in case of three patients. Our results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Sudarshan Kriya yoga improves quality of life in healthy people living with HIV (PLHIV): results from an open label randomized clinical trial

    PubMed Central

    Mawar, N.; Katendra, T.; Bagul, R.; Bembalkar, S.; Vedamurthachar, A.; Tripathy, S.; Srinivas, K.; Mandar, K.; Kumar, N.; Gupte, N.; Paranjape, R.S.

    2015-01-01

    Background & objectives: Improving quality of life (QOL) of healthy people living with HIV (PLHIV) is critical needing home-based, long-term strategy. Sudarshan Kriya yoga (SKY) intervention is acknowledged for its positive impact on health. It is hypothesised that SKY would improve PLHIV's QOL, justifying an evaluation. Methods: In this open label randomized controlled pilot trial, 61 adult PLHIV with CD4 count more than 400 cells/µl and Karnofsky scale score above 70 were enrolled. Those with cardiac disease, jaundice, tuberculosis, or on antiretroviral therapy/yoga intervention were excluded. All were given standard care, randomized to SKY intervention (31: I-SKY) and only standard of care in control (30: O-SOC) arms. The I-SKY participants were trained for six days to prepare for daily practice of SKY at home for 30 min. A validated 31-item WHOQOL-HIVBREF questionnaire was used to document effect in both arms from baseline to three visits at 4 wk interval. Results: Baseline QOL scores, hypertension and CD4 count were similar in both arms. An overall 6 per cent improvement of QOL scores was observed in I-SKY group as compared to O-SOC group, after controlling for baseline variables like age, gender, education and occupation (P =0.016); 12 per cent for physical (P =0.004), 11 per cent psychological (P =0.023) and 9 per cent level of independence (P =0.001) domains. Improvement in I-SKY observed at post-training and in the SKY adherence group showed increase in these two domains. Conclusions: A significant improvement in QOL scores was observed for the three health related QOL domains in SKY intervention arm. This low cost strategy improved physical and psychological state of PLHIV calling for upscaling with effective monitoring for sustainability of quality of life. PMID:25857500

  1. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial

    PubMed Central

    Allenbach, Yves; Guiguet, Marguerite; Rigolet, Aude; Marie, Isabelle; Hachulla, Eric; Drouot, Laurent; Jouen, Fabienne; Jacquot, Serge; Mariampillai, Kuberaka; Musset, Lucile; Grenier, Philippe; Devilliers, Herve; Hij, Adrian; Boyer, Olivier; Herson, Serge; Benveniste, Olivier

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusions 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. Trial Registration Clinicaltrials.gov NCT00774462. PMID:26539981

  2. Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

    PubMed Central

    Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

    2014-01-01

    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. PMID:24948863

  3. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

    PubMed

    Allenbach, Yves; Guiguet, Marguerite; Rigolet, Aude; Marie, Isabelle; Hachulla, Eric; Drouot, Laurent; Jouen, Fabienne; Jacquot, Serge; Mariampillai, Kuberaka; Musset, Lucile; Grenier, Philippe; Devilliers, Herve; Hij, Adrian; Boyer, Olivier; Herson, Serge; Benveniste, Olivier

    2015-01-01

    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.

  4. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease

    PubMed Central

    Friedman, Neil J; Butron, Karla; Robledo, Nora; Loudin, James; Baba, Stephanie N; Chayet, Arturo

    2016-01-01

    Background Dry eye disease (DED), a chronic disorder affecting the tear film and lacrimal functional unit, is a widely prevalent condition associated with significant burden and unmet treatment needs. Since specific neural circuits play an important role in maintaining ocular surface health, microelectrical stimulation of these pathways could present a promising new approach to treating DED. This study evaluated the efficacy and safety of nasal electrical stimulation in patients with DED. Methods This prospective, open-label, single-arm, nonrandomized pilot study included 40 patients with mild to severe DED. After undergoing two screening visits, enrolled subjects were provided with a nasal stimulation device and instructed to use it at home four times daily (or more often as needed). Follow-up assessments were conducted up to day 180. The primary efficacy endpoint was the difference between unstimulated and stimulated tear production quantified by Schirmer scores. Additional efficacy endpoints included change from baseline in corneal and conjunctival staining, symptoms evaluated on a Visual Analog Scale, and Ocular Surface Disease Index scores. Safety parameters included adverse event (AE) rates, visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, and endoscopic nasal examinations. Results Mean stimulated Schirmer scores were significantly higher than the unstimulated scores at all visits, and corneal and conjunctival staining and symptom scores from baseline to day 180 were significantly reduced. No serious device-related AEs and nine nonserious AEs (three device-related) were reported. Intraocular pressure remained stable and most subjects showed little or no change in visual acuity at days 30 and 180. No significant findings from other clinical examinations were noted. Conclusion Neurostimulation of the nasolacrimal pathway is a safe and effective means of increasing tear production and reducing symptoms of dry eye in patients

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

    PubMed Central

    Herrera-Estrella, Miguel; Apiquian, Rogelio; Fresan, Ana; Sanchez-Torres, Isabel

    2005-01-01

    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. PMID:15869707

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

    PubMed

    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.

  7. Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich's ataxia: an open-label trial.

    PubMed

    Arpa, Javier; Sanz-Gallego, Irene; Rodríguez-de-Rivera, Francisco J; Domínguez-Melcón, Francisco J; Prefasi, Daniel; Oliva-Navarro, Javier; Moreno-Yangüela, Mar; Pascual-Pascual, Samuel I

    2013-10-01

    Minimal objective evidence exists regarding management of Friedreich's ataxia (FRDA). Antioxidant and recombinant human erythropoietin therapies have been considered potential treatments to slow progression of FRDA in a small number of studies. The primary objective of the current study was to test the efficacy, safety, and tolerability of triple therapy-darbepoetin alfa, idebenone, and riboflavin-in FRDA in a clinical pilot study. Patients included in this study were nine females, 16 to 45 years of age (average 28 ± 8), diagnosed with FRDA with confirmed GAA repeat expansion mutations in the FXN gene and a GAA repeat ≥400 on the shorter allele. Patients had a baseline score between 8 and 28.5 (average 20.7 ± 8.3) on the scale for the assessment and rating of ataxia and 94.3 ± 27.2 g/m(2) in left ventricular mass index (LVMI). Patients had been treated with triple therapy with 150 μg darbepoetin alfa every 2 or 3 weeks, 10-20 mg/kg/day idebenone, and 10-15 mg/kg/day riboflavin for 32 ± 19.4 months (range of 8-56 months). Triple therapy was tolerated. Although not statistically significant, improvement of ataxia was observed during the first six 4-month periods of the study. Furthermore, a small decrease in disease progression during the first 2 years of treatment was observed. Long-term statistically nonsignificant improvement of LVMI and stability of the echocardiographic parameters could be considered. Triple therapy may slow disease progression of FRDA.

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

    PubMed

    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.

  9. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study.

    PubMed

    Hidese, Shinsuke; Ota, Miho; Wakabayashi, Chisato; Noda, Takamasa; Ozawa, Hayato; Okubo, Tsutomu; Kunugi, Hiroshi

    2017-04-01

    l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

  10. Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial

    PubMed Central

    Malbrán, A; Riedl, M; Ritchie, B; Smith, W B; Yang, W; Banerji, A; Hébert, J; Gleich, G J; Hurewitz, D; Jacobson, K W; Bernstein, J A; Khan, D A; Kirkpatrick, C H; Resnick, D; Li, H; Fernández Romero, D S; Lumry, W

    2014-01-01

    Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1–10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1–10, the median time to onset of primary symptom relief was 1·0–2·0 h. For laryngeal attacks 1–12, patient-assessed median time to initial symptom improvement was 0·3–1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks. PMID:24749847

  11. Ren Shen Yangrong Tang for Fatigue in Cancer Survivors: A Phase I/II Open-Label Study

    PubMed Central

    Xu, Yichen; Chen, Yanzhi

    2015-01-01

    Abstract Objectives: This open-label, prospective, phase I/II trial was performed to establish the safety and efficacy of Traditional Chinese Medicine (TCM) herbal products for treating non–anemia-related fatigue in patients with cancer. Although this practice is widespread in China, it has not been confirmed in a prospective clinical study. Design: Thirty-three patients who had completed cancer treatment, had stable disease and no anemia, and reported moderate to severe fatigue (rated ≥4 on a 0–10 scale) were enrolled in a TCM outpatient clinic. Patients took Ren Shen Yangrong Tang (RSYRT) decoction, a soup containing 12 TCM herbs, twice a day for 6 weeks. RSYRT aims to correct qi deficiency. Fatigue was assessed before and after RSYRT therapy, which all patients completed. Results: No discomfort or toxicity was observed. Before the study, all patients had had fatigue for at least 4 months. Fatigue severity decreased significantly from before therapy to 6 weeks after therapy: from 7.06 to 3.30 on a 0–10 scale (p<0.001). Fatigue category (mild, moderate, severe) shifted significantly (p=0.024): Of 22 patients with severe fatigue (rated ≥7) before therapy, 11 had mild fatigue and 11 had moderate fatigue after TCM treatment. The time-to-fatigue-alleviation was 2–3 weeks. Conclusion: RSYRT therapy was safe and was associated with fatigue improvement in nonanemic cancer survivors, consistent with historical TCM clinical practice experience. Because of a possible placebo effect in this open-label study, decoction RSYRT warrants further study in randomized clinical trials to confirm its effectiveness for managing moderate to severe fatigue. PMID:25918996

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

    PubMed

    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 < 0.01), which further improved between the 8th and 12th weeks (p < 0.01). Concerning overall anxiety scores, a statistically significant improvement was noted between the 2nd and 4th weeks (p < 0.01), which further continued throughout the 8th (p < 0.05) and 12th weeks (p < 0.05). The present study demonstrated a good therapeutic response to pregabalin in patients with depression comorbid with GAD after a 12-week treatment period. Both anxiety and depressive symptomatology significantly improved, and minimal side effects were observed. Copyright © 2012 John Wiley & Sons, Ltd.

  13. Levodopa—carbidopa intestinal gel in advanced Parkinson’s disease open-label study: Interim results

    PubMed Central

    Fernandez, Hubert H.; Vanagunas, Arvydas; Odin, Per; Espay, Alberto J.; Hauser, Robert A.; Standaert, David G.; Chatamra, Krai; Benesh, Janet; Pritchett, Yili; Hass, Steven L.; Lenz, Robert A.

    2013-01-01

    Levodopa–carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson’s disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson’s Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson’s Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean “Off” time was 6.7 h/day. “Off” time was reduced by a mean of 3.9 (±3.2) h/day and “On” time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common. PMID:23287001

  14. The Effect of a Unique Pacifier on Anterior Open Bite and Overjet in the Primary Dentition: A Pilot Study.

    PubMed

    Nowak, Arthur J; Kim, Amy S; Scott, Jo Anna M; Berg, Joel H

    2016-01-01

    Pacifiers are the most common device used by children to satisfy their sucking needs. Because of their design, reports of anterior open bite and increased overjet are common. The purposes of this pilot study were to measure the effects of a unique pacifier in toddlers who have existing open bites and increased overjets; and secondly to determine the feasibility of recruiting and retaining toddlers for a six-month study. Toddlers with existing open bite and increased overjet currently using a conventional pacifier were recruited from a university pediatric dental clinic. Baseline information was obtained. Visual examination and intraoral measurements were obtained. The study pacifier was introduced to replace the existing pacifier. Follow-up data was collected at three and six months post-intervention. Eight of the 11 toddlers (73 percent) completed the study. Recruitment was challenging because of the inclusion criteria and transportation; retaining participants required numerous reminders to parents. There was a significant difference between initial and final open bite and overjet measurements. It is feasible to recruit and retain toddlers but it required significant staff interventions. There was a significant improvement in reducing existing open bite and overjet with the pacifier after six months.

  15. Open-Trial Pilot of "Mind Reading" and in Vivo Rehearsal for Children with HFASD

    ERIC Educational Resources Information Center

    Thomeer, Marcus L.; Rodgers, Jonathan D.; Lopata, Christopher; McDonald, Christin A.; Volker, Martin A.; Toomey, Jennifer A.; Smith, Rachael A.; Gullo, Gaetano

    2011-01-01

    In this pilot study, the authors evaluated a manualized administration of the "Mind Reading" (MR) program with in vivo rehearsal to determine the effects on emotion recognition and autism features of eleven 7- to 12-year-old children with High-Functioning Autism Spectrum Disorders (HFASD), and to determine the overall feasibility of the…

  16. Open-Trial Pilot of "Mind Reading" and in Vivo Rehearsal for Children with HFASD

    ERIC Educational Resources Information Center

    Thomeer, Marcus L.; Rodgers, Jonathan D.; Lopata, Christopher; McDonald, Christin A.; Volker, Martin A.; Toomey, Jennifer A.; Smith, Rachael A.; Gullo, Gaetano

    2011-01-01

    In this pilot study, the authors evaluated a manualized administration of the "Mind Reading" (MR) program with in vivo rehearsal to determine the effects on emotion recognition and autism features of eleven 7- to 12-year-old children with High-Functioning Autism Spectrum Disorders (HFASD), and to determine the overall feasibility of the…

  17. The Co-Worker Training Model: Outcomes of an Open Employment Pilot Project.

    ERIC Educational Resources Information Center

    Farris, Bryan; Stancliffe, Roger J.

    2001-01-01

    A pilot study evaluated the viability of trained co-workers (n=12) providing direct job training and support to 10 individuals with mental retardation. Employment outcomes for consumers with co-worker support were as good as for those with job coach support. Consumers also experienced high levels of involvement with co-workers. (Contains…

  18. A phase I, open-label, single-dose, mass balance study of 14C-labeled abiraterone acetate in healthy male subjects.

    PubMed

    Acharya, Milin; Gonzalez, Martha; Mannens, Geert; De Vries, Ronald; Lopez, Christian; Griffin, Thomas; Tran, NamPhuong

    2013-04-01

    1. Metabolic disposition of (14)C-abiraterone acetate (AA), a prodrug of abiraterone was assessed in a phase I, open-label, single-dose (1000 mg, approximately 100 μCi) study in healthy males (18-55 years, N = 8). Blood, urine, and faecal samples were obtained at specified timepoints for determination of abiraterone concentrations in the plasma, total radioactivity (TR), and the metabolite profile. 2. Most plasma AA concentrations were below the limit of quantification. The mean maximum plasma concentration (Cmax) of abiraterone was 10.4 ng/mL, mean area under the plasma concentration-time curve (AUC) from 0 to the last measurable plasma concentration (AUC0-last) was 74.8 ng·h/mL. The exposures for TR in plasma (Cmax = 3429 ng·eq/mL; AUC0-last = 26,683 ng eq·h/mL) and whole blood (Cmax = 1836 ng·eq/mL; AUC0-last = 12,162 ng·eq·h/mL) were >300-fold higher than abiraterone exposure in plasma. The majority of TR resided in the plasma compartment of blood. 3. Main circulating metabolites were abiraterone sulfate and N-oxide abiraterone sulfate. The main metabolite excreted in urine was N-oxide abiraterone sulfate (4.22% of TR). Major components of TR in faeces were unchanged AA (55.3% of TR) and abiraterone (22.3% of TR). Mean recovery of TR in faeces was 87.9%, indicating faeces as primary route of excretion.

  19. 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).

    PubMed

    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

  20. Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures.

    PubMed

    Petrisor, Bradley; Sun, Xin; Bhandari, Mohit; Guyatt, Gordon; Jeray, Kyle J; Sprague, Sheila; Tanner, Stephanie; Schemitsch, Emil; Sancheti, Parag; Anglen, Jeff; Tornetta, Paul; Bosse, Michael; Liew, Susan; Walter, Stephen

    2011-09-01

    Open fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an important goal in management, and different lavage fluids and irrigation techniques (e.g., high- or low-pressure lavage) have been described for this purpose. However, there are a limited number of randomized trials comparing irrigating solutions or irrigating technique. We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds. We conducted a multicenter, blinded, randomized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage. The primary composite outcome of reoperation, measured at 12 months after initial operative procedure, included infection, wound healing problems, and nonunion. Planned reoperations were not included. Secondary outcomes included all infection, all wound healing problems, and nonunion as well as functional outcomes scores (EuroQol-5 dimensions and short form-12). Eighty-nine patients completed the 1-year follow-up. Among all patients, 13 (23%) in the castile soap group and 13 (24%) in the saline group had a primary outcome event (hazard ratio, 0.91, 95% confidence interval: 0.42-2.00, p = 0.52). Sixteen patients (28%) in the high-pressure group and 10 patients (19%) in the low-pressure group had a primary outcome event (hazard ratio 0.55, 95% confidence interval: 0.24-1.27, p = 0.17). Functional outcome scores showed no significant differences at any time point between groups. The fluid lavage of open wounds pilot randomized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection, wound healing problems, or nonunion. We have

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

    PubMed

    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.

  2. Open label study of the effect of amantadine on weight gain induced by olanzapine.

    PubMed

    Bahk, Won-Myong; Lee, Kyoung-Uk; Chae, Jeong-Ho; Pae, Chi-Un; Jun, Taeyoun; Kim, Kwang-Soo

    2004-04-01

    The purpose of the present paper was to investigate the effects of the dopamine agonist amantadine in those patients with weight gain induced by olanzapine. An open trial was conducted in those patients who gained >3 kg in weight induced by olanzapine use. All subjects were evaluated by weight, body mass index (BMI), the Brief Psychiatric Rating Scale (BPRS), and the Extrapyramidal Symptom Rating Scale (ESRS) before and after the use of amantadine in addition to olanzapine. Twenty-five of 30 enrolled patients completed the present study. Mean bodyweight and BMI was increased by 6.44 +/- 4.42 kg and 5.04 +/- 3.47 kg/m2 significantly with olanzapine alone (P < 0.001). When amantadine and olanzapine were used together, the average weight and BMI decreased by 1.07 +/- 3.19 kg and 0.84 +/- 2.5 kg/m2, but did not have statistical significance. The average values of BPRS showed a significant decrease (P < 0.001). No significant changes were present in ESRS. Amantadine did not have an effect on weight gain induced by olanzapine. Randomized placebo-controlled prospective studies are needed.

  3. Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing's disease: results from an open-ended, open-label extension trial.

    PubMed

    Schopohl, Jochen; Gu, Feng; Rubens, Robert; Van Gaal, Luc; Bertherat, Jérôme; Ligueros-Saylan, Monica; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Boscaro, Marco; Pivonello, Rosario

    2015-10-01

    Report the efficacy and safety of pasireotide sc in patients with Cushing's disease during an open-ended, open-label extension to a randomized, double-blind, 12-month, Phase III study. 162 patients entered the core study. 58 patients who had mean UFC ≤ ULN at month 12 or were benefiting clinically from pasireotide entered the extension. Patients received the same dose of pasireotide as at the end of the core study (300-1,200 μg bid). Dose titration was permitted according to efficacy or drug-related adverse events. 40 patients completed 24 months' treatment. Of the patients who entered the extension, 50.0% (29/58) and 34.5% (20/58) had controlled UFC (UFC ≤ ULN) at months 12 and 24, respectively. The mean percentage decrease in UFC was 57.3% (95% CI 40.7-73.9; n = 52) and 62.1% (50.8-73.5; n = 33) after 12 and 24 months' treatment, respectively. Improvements in clinical signs of Cushing's disease were sustained up to month 24. The most frequent drug-related adverse events in patients who received ≥1 dose of pasireotide (n = 162) from core baseline until the 24-month cut-off were diarrhea (55.6%), nausea (48.1%), hyperglycemia (38.9%), and cholelithiasis (31.5%). No new safety issues were identified during the extension. Reductions in mean UFC and improvements in clinical signs of Cushing's disease were maintained over 24 months of pasireotide treatment. The safety profile of pasireotide is typical for a somatostatin analogue, except for the frequency and degree of hyperglycemia; patients should be monitored for changes in glucose homeostasis. Pasireotide represents the first approved pituitary-targeted treatment for patients with Cushing's disease.

  4. Determining the frequency of open windows in residences: a pilot study in Durham, North Carolina during varying temperature conditions.

    PubMed

    Johnson, Ted; Long, Tom

    2005-07-01

    Air pollution exposures in the residential microenvironment can be significantly affected by air exchange rate (AER). A number of studies have shown that AER in residences is significantly affected by the number and location of open windows and doors. A pilot study was conducted in Durham, North Carolina, to determine whether useful data on open windows and doors could be acquired through a visual survey. The study consisted of 72 2-h survey sessions conducted between October 24, 2001 and March 13, 2003. During the first hour of each session, a technician selected a set of corner residences in one of 48 census tracts and completed a survey form and meteorological measurements for each residence. During the second hour, the technician revisited each residence surveyed during the first hour. The resulting database included data on 2200 "residential visits" (1100 residences times two visits per residence). The technician observed one or more open windows during 20.0 percent of the residential visits. One or more open doors were observed during 13.4 percent of the residential visits; 28.2 percent of the residential visits were associated with at least one open window or door. A series of stepwise linear regression analyses were performed on the data to identify factors associated with open windows and doors. Results of these analyses indicated that the likelihood of one or more windows being opened tended to increase under the following conditions: occupancy at time of visit; session during April, May, or June; high population or housing density; window air conditioning (AC) units; absence of AC; large number of doors; and wind speed above 2 mph. The likelihood of open doors tended to increase under the following conditions: occupancy at time of visit; residence within city limits; session during April, May, or June; detached one-story residence; large number of doors; high housing density; school out; and residence within 10 m of road. Transition probabilities (closed

  5. Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

    PubMed Central

    Kim, Sung-Bae; Lee, Jung Shin; Kim, Heung Tae; Im, Yong Hyuck; Kim, Tae Won; Ryoo, Baek Yeol; Park, Yeon Hee; Park, Joon Oh; Park, Keunchil; Katoh, Hitoshi; Yamamoto, Minoru

    2007-01-01

    Abstract Background: Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan. Objective: The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH. Methods: This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study. Results: Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1–23] and day 6, 5.5 [1–17

  6. Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial.

    PubMed

    Di Iorio, Biagio; Molony, Donald; Bell, Cynthia; Cucciniello, Emanuele; Bellizzi, Vincenzo; Russo, Domenico; Bellasi, Antonio

    2013-10-01

    Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. Open-label randomized controlled trial with parallel groups. 466 incident hemodialysis patients recruited from 18 centers in Italy. Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. Blind event adjudication. At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 [SD] vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 [IQR, 0-30] vs 30 [IQR, 7-180]). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. Open-label design, higher baseline coronary artery calcification burden in calcium carbonate-treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of

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

    PubMed Central

    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

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

    PubMed

    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

  9. Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder.

    PubMed

    Baldwin, David S; Hansen, Thomas; Florea, Ioana

    2012-10-01

    The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder. Patients entered this 52-week, open-label extension study after completing an 8-week lead-in study. Safety and tolerability were evaluated at regular intervals on the basis of spontaneously reported adverse events (AEs), clinical safety laboratory tests, vital signs, ECG and physical examination. Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A total of 535 patients were treated and 61.3% (n = 328) completed the study, resulting in 393 patient years of exposure to vortioxetine. AEs reported by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, six patients had eight AEs related to sexual dysfunction. There were no clinically significant safety findings with respect to mean changes of vital signs, weight, ECG parameters, or clinical laboratory values. Patients entered the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 52 (OC). By the end of the study, the proportion of responders had increased from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a relapse rate (MADRS ≥22) of 9.7%. As with all open-label studies, the conclusions that can be drawn are limited by the lack of a placebo control, making it difficult to assess causality of any changes in outcome measures. However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. This study has the ClinicalTrials.gov identifier: NCT00694304.

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

    ERIC Educational Resources Information Center

    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…

  11. An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

    2007-01-01

    Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

  12. 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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  16. Acceptability of drug detection monitoring among participants in an open-label pre-exposure prophylaxis study.

    PubMed

    Koester, Kimberly A; Liu, Albert; Eden, Christopher; Amico, K Rivet; McMahan, Vanessa; Goicochea, Pedro; Hosek, Sybil; Mayer, Kenneth H; Grant, Robert M

    2015-01-01

    In the world of HIV pre-exposure prophylaxis (PrEP) research, there is emerging interest in providing study participants with pharmacokinetic results from drug level testing to guide adherence counseling. The iPrEx randomized control trial was the first study to produce meaningful results of PrEP in humans. In the iPrEx open-label extension (OLE) study, blood plasma samples collected in the first 12 weeks of study participation were tested for the presence of tenofovir/emtricitabine--the drugs which compromise PrEP. Study clinicians shared results (detectable/undetectable) with participants at their 24-week visit. We evaluated the acceptability of receiving these results among a subset of iPrEx OLE participants. We conducted in-depth interviews (n = 59) with participants (those with and those without drug detected) enrolled in Boston, Chicago, and San Francisco to assess their experiences with receiving drug detection feedback. Incorporating drug detection results into the clinical study visit was well received and no negative reactions were expressed. For about half of participants, receiving their drug detection lab result was useful while for others it was not important. In a few cases, no drug detected results led to increased efforts to take PrEP consistently and in most cases enhanced open discussion of missed doses. Participants reported a desire for greater specificity, particularly quantitative drug levels needed for protection. We recommend exploring strategies to increase the salience of drug level results, including using feedback to target adherence counseling, and reducing the time between specimen collection, testing, and receipt of results. Future studies should evaluate the feasibility and impact of providing more specific quantitative drug levels using biomarkers of longer term PrEP exposure, i.e., hair/dried blood spots.

  17. Adjunctive Lisdexamfetamine Dimesylate Therapy in Adult Outpatients With Predominant Negative Symptoms of Schizophrenia: Open-Label and Randomized-Withdrawal Phases

    PubMed Central

    Lasser, Robert A; Dirks, Bryan; Nasrallah, Henry; Kirsch, Courtney; Gao, Joseph; Pucci, Michael L; Knesevich, Mary A; Lindenmayer, Jean-Pierre

    2013-01-01

    Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20–70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was −12.9 (−15.0, −10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted. PMID:23756608

  18. Bias was reduced in an open-label trial through the removal of subjective elements from the outcome definition.

    PubMed

    Kahan, Brennan C; Doré, Caroline J; Murphy, Michael F; Jairath, Vipul

    2016-09-01

    To determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment. Reanalysis of an open-label trial comparing a restrictive vs. liberal transfusion strategy for gastrointestinal bleeding. The usual definition of the primary outcome, further bleeding, allows subjective clinical symptoms to be used alone for diagnosis, whereas the definition used in the trial required more objective confirmation by endoscopy. We compared treatment effect estimates for these two definitions. Fewer subjective symptom-identified events were confirmed using more objective methods in the restrictive arm (18%) than in the liberal arm (56%), indicating differential assessment between arms. An analysis using all events (both subjective and more objective) led to an odds ratio of 0.83 (95% confidence interval [CI]: 0.50-1.37). When only events confirmed using more objective methods were included, the odds ratio was 0.50 (95% CI: 0.32-0.78). The ratio of the odds ratios was 1.66, indicating that including unconfirmed events in the definition biased the treatment effect upward by 66%. Modifying the outcome definition to exclude subjective elements substantially reduced bias. This may be a useful strategy for reducing bias in trials that cannot blind outcome assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Phase II, Randomized, Open-Label Study of Pegfilgrastim-Supported VDC/IE Chemotherapy in Pediatric Sarcoma Patients

    PubMed Central

    Spunt, Sheri L.; Irving, Helen; Frost, Jami; Sender, Leonard; Guo, Matthew; Yang, Bing-Bing; Dreiling, Lyndah; Santana, Victor M.

    2010-01-01

    Purpose This multicenter, randomized, open-label study evaluated the efficacy, safety, and pharmacokinetics of a single subcutaneous pegfilgrastim injection with daily subcutaneous filgrastim administration in pediatric patients receiving myelosuppressive chemotherapy for sarcoma. Patients and Methods Forty-four patients with previously untreated, biopsy-proven sarcoma stratified into three age groups (0-5, 6-11, and 12-21 years) were randomly assigned in a 6:1 randomization ratio to receive a single pegfilgrastim dose of 100 μg/kg (n = 38) or daily filgrastim doses of 5 μg/kg (n = 6) after chemotherapy (cycles 1 and 3: vincristine-doxorubicin-cyclophosphamide; cycles 2 and 4: ifosfamide-etoposide). The duration of grade 4 neutropenia, time to neutrophil recovery, incidence of febrile neutropenia, and adverse events were recorded. Results Pegfilgrastim and filgrastim were similar for all efficacy and safety end points, and their pharmacokinetic profiles were consistent with those in adults. Younger children experienced more protracted neutropenia and had higher median pegfilgrastim exposure than older children. Conclusion A single dose of pegfilgrastim at 100 μg/kg administered once per chemotherapy cycle is comparable to daily injections of filgrastim at 5 μg/kg for pediatric sarcoma patients receiving myelosuppressive chemotherapy. PMID:20142595

  20. Open-Label Study of Craving in Smokers With Schizophrenia Using Nicotine Nasal Spray Compared to Nicotine Patch

    PubMed Central

    Williams, Jill M.; Gandhi, Kunal K.; Karavidas, Maria Katsamanis; Steinberg, Marc L.; Lu, Shou-En; Foulds, Jonathan

    2009-01-01

    Rationale: Nicotine nasal spray (NNS) may be better for relieving acute cigarette cravings than other nicotine replacement and it may help smokers with schizophrenia because of its rapid onset of action. Objectives: We tested whether NNS was more effective than a nicotine patch (NP; 21 mg) in reducing cue-induced craving during a 3-day abstinence. Methods: Twenty-five smokers with schizophrenia or schizoaffective disorder (SA) were randomized to open-label NNS or NP treatment after baseline measures of craving were assessed. NNS users were instructed to dose at a minimum of 1/hour and up to a maximum of 40/day. Averages from a 4-item visual analogue scale (need, urge, want to smoke, crave a cigarette) measured craving. Results: Five subjects who smoked (4 NP, 1 NNS) were excluded, leaving 21 (11 NP, 10 NNS) for analyses. No differences were detected between groups on baseline craving. On day 3, NNS users reported significantly less craving in response to smoking cues compared to NP users (mean craving scores: NNS, 7.0; NP, 20.3; p = .014). A repeated measure ANCOVA demonstrated significantly reduced craving in the NNS group compared to the NP group from baseline to day 3 (F = 5.09; p = .037). NNS users took an average of 20 doses/day, and NNS was rated as being as easy to use as NP. Conclusions: The potential utility of NNS in smokers with schizophrenia supports the need for placebo-controlled studies. PMID:19763279

  1. A Prospective, Open-Label Study of Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    SciTech Connect

    Kamstrup, Maria R.; Specht, Lena; Skovgaard, Gunhild L.; Gniadecki, Robert

    2008-07-15

    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 fractions over 4 successive days. Results: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated 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 of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control.

  2. [Treatment with venlafaxine extended release for climacteric women with depression or anxiety diagnosis. An open-label study].

    PubMed

    Iglesias, C; Pato, E; Ocio, S; Ortigosa, J C; Santamarina, S; Merino, M J; Alonso, M J; Fernández, L; Alonso, J L; Rodríguez, L

    2009-01-01

    The objective of this observational study was to assess under real clinical practice conditions the effectiveness and safety of venlafaxine extended release in anxiety-depressed and hormone-related symptoms in climacteric women with anxiety or depressive disorders. Observational, prospective, open-label, multicenter, 24-week study, carried out in Spain. A sample of 45 outpatients, adult women between 45 and 55 years of age, diagnosed of depressive disorder, generalized anxiety disorder or social anxiety disorder were analyzed. Venlafaxine extended release was administered for 24 weeks at doses according to the investigator's clinical criteria. Of the total of 45 patients who were included in the study, 43 (95.6%) completed it. The patients' age range was of 47 to 55 years old, median of 50 and mean of 50.82. The clinical condition evolution was assessed with the evaluation scales scores: Blatt-Kuppermann Menopausal Index, Hamilton Depression Rating Scale, Hamilton Anxiety Scale and Clinical Global Impression. During the 24-week period, a significant decrease in the different scales scores showed a clinical improvement. The results achieved show that treatment with venlafaxine extended release significantly improved the clinical condition of climacteric patients with anxiety or depressive disorder. If these results are confirmed with placebo-controlled clinical trials, they will support the utility of Venlafaxine extended release in this kind of patients.

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

    PubMed

    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.

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

    PubMed

    Ghaeli, Padideh; Nikvarz, Naemeh; Alaghband-Rad, Javad; Alimadadi, Abbas; Tehrani-Doost, Mehdi

    2014-01-01

    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). 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. 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. This study suggests that risperidone may be an effective treatment for the management of core symptoms of autistic disorder.

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

    PubMed

    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.

  6. Rapid responders to frovatriptan in acute migraine treatment: results from a long-term, open-label study.

    PubMed

    Spierings, Egilius L H; Keywood, Charlotte

    2009-01-01

    The chronic nature of migraine and the reliance on acute treatment constitute the basis of the present long-term, open-label study. First, assessment of the tolerability and safety of frovatriptan, 2.5-7.5 mg taken orally over 24 hours, for the acute treatment of migraine, repeatedly over a 12-month period. Second, assessment of the efficacy and tolerability of a second, double-blind dose of 2.5-mg frovatriptan, compared with placebo, for nonresponse at 2 hours after treatment of moderate or severe headache with 2.5-mg frovatriptan. With regard to the first attack treated, 173 (36%) of the 486 subjects in the study did not take a second dose at 2 hours for nonresponse. At 2 hours and 4 hours, these "rapid responders" experienced a decrease in headache intensity from moderate or severe to mild or no pain in 84% and 98%, respectively ("headache response"). Six percent of them experienced recurrence of moderate or severe headache within 24 hours following a response at 4 hours and 12% took rescue medication. The response, measured in terms of median time to "complete migraine relief," was maintained over 30 subsequent migraine attacks, treated from attack 2 onwards over the course of 12 months. Frovatriptan provides a remarkably fast and high headache response in a subgroup of more than one-third of migraineurs, with a very low 24-hour headache recurrence and low rescue medication intake.

  7. Mirtazapine versus venlafaxine for the treatment of somatic symptoms associated with major depressive disorder: a randomized, open-labeled trial.

    PubMed

    Kang, Eun-Ho; Lee, In-Soo; Chung, Sang-Keun; Lee, Sang-Yeol; Kim, Eui-Jung; Hong, Jin-Pyo; Oh, Kang-Seob; Woo, Jong-Min; Kim, Seonwoo; Park, Joo-Eon; Yu, Bum-Hee

    2009-09-30

    Somatic symptoms are often important in the treatment of major depressive disorder (MDD). The aim of this open-labeled trial was to examine the efficacy of mirtazapine for the treatment of MDD with clinically significant somatic symptoms, as compared with venlafaxine. A total of 126 patients with MDD (score >/=18 on the Hamilton Rating Scale for Depression-17) were included in both the intent-to-treat (n=73 in the mirtazapine group and n=53 in the venlafaxine group) and completer analysis (n=51 and n=37, respectively). After treatment, both treatment groups showed similar improvements in depressive symptoms. Repeated measures analysis of variance for the intent-to-treat population revealed that there were no significant differences in mean change of the Symptom Check List-90-Revised (SCL-90-R) somatization subscores between the two groups. For completers, there was a significant timextreatment interaction in the SCL-90-R somatization subscores, but the differences between the two groups at endpoint did not reach statistical significance in post-hoc analysis. In conclusion, this study suggests that overall efficacies of mirtazapine and venlafaxine are similar for the treatment of overall symptoms in MDD, and both drugs may be useful for the treatment of somatic symptoms in MDD patients.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27338456

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

    PubMed

    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.

  10. Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study.

    PubMed

    Hamaguchi, Yasuhito; Sumida, Takayuki; Kawaguchi, Yasushi; Ihn, Hironobu; Tanaka, Sumiaki; Asano, Yoshihide; Motegi, Sei-Ichiro; Kuwana, Masataka; Endo, Hirahito; Takehara, Kazuhiko

    2017-01-01

    A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52-week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan.

  11. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.

    PubMed

    Lotan, Itay; Treves, Therese A; Roditi, Yaniv; Djaldetti, Ruth

    2014-01-01

    The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD. Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P < 0.001). Analysis of specific motor symptoms revealed significant improvement after treatment in tremor (P < 0.001), rigidity (P = 0.004), and bradykinesia (P < 0.001). There was also significant improvement of sleep and pain scores. No significant adverse effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.

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

    PubMed Central

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

    2016-01-01

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

  13. Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial

    PubMed Central

    2014-01-01

    Background In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake. The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. Methods Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. Results Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. Conclusions These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated. Trial registration EudraCT 2011-000770-60 PMID:24690227

  14. Testing the validity of the Danish urban myth that alcohol can be absorbed through feet: open labelled self experimental study

    PubMed Central

    Hansen, Christian Stevns; Færch, Louise Holmsgaard

    2010-01-01

    Objective To determine the validity of the Danish urban myth that it is possible to get drunk by submerging feet in alcohol. Design Open labelled, self experimental study, with no control group. Setting Office of a Danish hospital. Participants Three adults, median age 32 (range 31-35), free of chronic skin and liver disease and non-dependent on alcohol and psychoactive drugs. Main outcome measures The primary end point was the concentration of plasma ethanol (detection limit 2.2 mmol/L (10 mg/100 mL)), measured every 30 minutes for three hours while feet were submerged in a washing-up bowl containing the contents of three 700 mL bottles of vodka. The secondary outcome was self assessment of intoxication related symptoms (self confidence, urge to speak, and number of spontaneous hugs), scored on a scale of 0 to 10. Results Plasma ethanol concentrations were below the detection limit of 2.2 mmol/L (10 mg/100 mL) throughout the experiment. No significant changes were observed in the intoxication related symptoms, although self confidence and urge to speak increased slightly at the start of the study, probably due to the setup. Conclusion Our results suggest that feet are impenetrable to the alcohol component of vodka. We therefore conclude that the Danish urban myth of being able to get drunk by submerging feet in alcoholic beverages is just that; a myth. The implications of the study are many though. PMID:21156749

  15. Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial.

    PubMed

    Sepede, Gianna; De Berardis, Domenico; Gambi, Francesco; Campanella, Daniela; La Rovere, Raffaella; D'Amico, Michele; Cicconetti, Alessandra; Penna, Laura; Peca, Silvana; Carano, Alessandro; Mancini, Enrico; Salerno, Rosa Maria; Ferro, Filippo Maria

    2006-02-01

    The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.

  16. Finasteride in the treatment of Taiwanese men with androgenetic alopecia: a 12-month open-label study.

    PubMed

    Lin, Jeng-Hsien; Chen, Wen-Chieh

    2002-08-01

    Finasteride 1 mg/day is effective in the treatment of androgenetic alopecia (AGA). Our open-label study assessed the efficacy and safety of finasteride for the treatment of Taiwanese men with AGA. We enrolled 34 Taiwanese men (aged 18-40 yr) with AGA of modified Norwood/Hamilton scale (MNHS) grade II-V. In investigator assessments at 12 months, five of 21 subjects (23.8%) had two-grade improvement in MNHS grade and 12 of 21 subjects (57.1%) had one-grade improvement; the others remained at the same grade. In global photographic evaluation, five of 31 subjects (15.1%) had observable hair growth at 6 months and 11 of 21 subjects (52.4%) had observable hair growth at 12 months. Patient self-assessment of hair growth was favorable across all questions in the treatment course, more significantly at 12 months than at 6 months; nine of 21 subjects (42.9%) were satisfied with their overall appearance at 12 months. Serum prostate specific antigen levels had decreased by 23.4% at 12 months. Adverse effects, including abnormal liver function (5/34), were minimal, and the causal relationship with finasteride could not be established. Thus, in Taiwanese men with AGA, finasteride 1 mg/day for 1 year slowed the progression of hair loss and increased hair growth.

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

    PubMed

    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.

  18. Fluorouracil cream 0.5% for actinic keratoses on multiple body sites: an 18-month open-label study.

    PubMed

    Stough, Dow; Bucko, Alicia D; Vamvakias, George; Rafal, Elyse S; Davis, Steven A

    2010-05-01

    This prospective 18-month, open-label, multicenter study assessed the long-term safety and efficacy of fluorouracil cream 0.5% in 277 participants with multiple actinic keratoses (AKs) on the face/anterior scalp and other body sites. Two treatment/observation cycles were separated by 12 months. During treatment cycle 1 (TC1), all participants were treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Twelve months later, all participants were assessed for treatment cycle 2 (TC2); participants with face/anterior scalp AKs (N = 98) were re-treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Only 4 participants (7.4%) experienced a treatment-related adverse event (AE) that was not an application site reaction or eye irritation. No unexpected AEs were reported; most were mild or moderate. After TC1 (week 8), the number of AK lesions was significantly reduced on the face/anterior scalp and all other treated body sites (P < .0001). Clearance rates were 30.5% (hands), 39.8% (face/anterior scalp), and 79.1% (lips). After TC2 (week 60), face/anterior scalp AKs were significantly reduced (P < .0001) and the clearance rate was 33.3%. This study indicates that fluorouracil cream 0.5% with a patented microsponge delivery system was well-tolerated and effective in treating and preventing recurrence of AK lesions up to 18 months after initial treatment.

  19. Comparison of Prednisolone, Etoricoxib, and Indomethacin in Treatment of Acute Gouty Arthritis: An Open-Label, Randomized, Controlled Trial

    PubMed Central

    Xu, Lingling; Liu, Shiqun; Guan, Meiping; Xue, Yaoming

    2016-01-01

    Background At present there are several kinds of medicine for treating acute gout arthritis (AGA). This study compared the efficacy and safety of prednisolone, etoricoxib, and indomethacin in the treatment of AGA. Material/Methods This was an open-label, randomized, active-comparator study in patients with AGA. Patients were randomized to 4 days of prednisolone 35 mg qd, etoricoxib 120 mg qd, or indomethacin 50 mg tid. The primary efficacy endpoint was the reduction of self-assessed pain in the index joint from baseline. Secondary endpoints included changes in physician’s assessment of tenderness, erythema, swelling, and joint activity; patient assessment of response to therapy; and safety. Results We analyzed 113 patients. Baseline demographics were comparable among treatment groups. Oral prednisolone, etoricoxib, and indomethacin were similarly effective in improving pain, tenderness, and joint activity over 4 days. For inflammation, oral prednisolone, etoricoxib, and indomethacin were similarly effective in reducing erythema, but prednisolone might be more effective in reducing swelling than indomethacin. The patient response to therapy was similar in the 3 groups. There were more total adverse events with indomethacin compared with the other 2 drugs. Conclusions Efficacy was comparable among prednisolone, etoricoxib, and indomethacin for the treatment of AGA. Prednisolone might be more effective in reducing inflammation and it had a better safety profile. PMID:26965791

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

    PubMed

    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 < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. Rationale and design of Short-Term EXenatide therapy in Acute ischaemic Stroke (STEXAS): a randomised, open-label, parallel-group study

    PubMed Central

    McGrath, Rachel T; Hocking, Samantha L; Priglinger, Miriam; Day, Susan; Herkes, Geoffrey K; Krause, Martin; Fulcher, Gregory R

    2016-01-01

    Introduction Both hyperglycaemia and hypoglycaemia in acute ischaemic stroke (AIS) are associated with increased infarct size and worse functional outcomes. Thus, therapies that can maintain normoglycaemia during stroke are clinically important. Glucagon-like peptide 1 (GLP-1) analogues, including exenatide, are routinely used in the treatment of hyperglycaemia in type 2 diabetes, but data on the usefulness of this class of agents in the management of elevated glucose levels in AIS are limited. Owing to their glucose-dependent mechanism of action, GLP-1 analogues are associated with a low risk of hypoglycaemia, which may give them an advantage over intensive insulin therapy in the acute management of hyperglycaemia in this setting. Methods and analysis The Short-Term EXenatide therapy in Acute ischaemic Stroke study is a randomised, open-label, parallel-group pilot study designed to investigate the efficacy of exenatide at lowering blood glucose levels in patients with hyperglycaemia with AIS. A total of 30 patients presenting with AIS and blood glucose levels >10 mmol/L will be randomised to receive the standard therapy (intravenous insulin) or intravenous exenatide for up to 72 h. Outcomes including blood glucose levels within the target range (5–10 mmol/L), the incidence of hypoglycaemia and the feasibility of administering intravenous exenatide in this patient population will be assessed. A follow-up visit at 3 months will facilitate evaluation of neurological outcomes post-stroke. Ethics and dissemination This study has been approved by the local Institutional Review Board (Northern Sydney Local Health District Human Research Ethics Committee). The study results will be communicated via presentations at scientific conferences and through publication in peer-reviewed journals. Conclusions As GLP-1 analogues require elevated glucose levels to exert their insulin potentiating activity, the use of exenatide in the management of hyperglycaemia in AIS may

  2. B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment

    PubMed Central

    Fluge, Øystein; Risa, Kristin; Lunde, Sigrid; Alme, Kine; Rekeland, Ingrid Gurvin; Sapkota, Dipak; Kristoffersen, Einar Kleboe; Sørland, Kari; Bruland, Ove; Dahl, Olav; Mella, Olav

    2015-01-01

    Background Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS. Methods In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months. Findings Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8–66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity. Conclusion In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed

  3. B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.

    PubMed

    Fluge, Øystein; Risa, Kristin; Lunde, Sigrid; Alme, Kine; Rekeland, Ingrid Gurvin; Sapkota, Dipak; Kristoffersen, Einar Kleboe; Sørland, Kari; Bruland, Ove; Dahl, Olav; Mella, Olav

    2015-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS. In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months. Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity. In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse

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

    PubMed

    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 <45 years, n= 134; 45-64 years, n= 432; 65-74 years, n= 204; ≥75 years, n= 94); most subjects (77%) who continued treatment maintained the 8-mg dose. • Among subjects in the overall population, there were significant improvements in all KHQ domains, ICIQ-SF scores, and bladder-related problems at open-label baseline vs double-blind baseline (P < 0.05); additional significant improvements were observed at months 12 and 24 vs open-label baseline in all outcomes (P < 0.05) except for the KHQ General Health Perception domain. • When data were stratified by gender or age, significant improvements at open-label baseline vs double-blind baseline were further significantly enhanced or sustained at months 12 and 24 for most KHQ domains, and for ICIQ-SF scores and bladder-related problems for all groups. Women had significantly greater

  5. Involving Software Engineering Students in Open Source Software Projects: Experiences from a Pilot Study

    ERIC Educational Resources Information Center

    Sowe, Sulayman K.; Stamelos, Ioannis G.

    2007-01-01

    Anecdotal and research evidences show that the Free and Open Source Software (F/OSS) development model has produced a paradigm shift in the way we develop, support, and distribute software. This shift is not only redefining the software industry but also the way we teach and learn in our software engineering (SE) courses. But for many universities…

  6. Involving Software Engineering Students in Open Source Software Projects: Experiences from a Pilot Study

    ERIC Educational Resources Information Center

    Sowe, Sulayman K.; Stamelos, Ioannis G.

    2007-01-01

    Anecdotal and research evidences show that the Free and Open Source Software (F/OSS) development model has produced a paradigm shift in the way we develop, support, and distribute software. This shift is not only redefining the software industry but also the way we teach and learn in our software engineering (SE) courses. But for many universities…

  7. Effectiveness of omalizumab in patients with inadequately controlled severe persistent allergic asthma: an open-label study.

    PubMed

    Niven, R; Chung, K F; Panahloo, Z; Blogg, M; Ayre, G

    2008-10-01

    In a 1-year, randomized, open-label study in patients with moderate-to-severe allergic (immunoglobulin E (IgE)-mediated) asthma, adding omalizumab to best standard care (BSC) significantly improved efficacy outcomes compared with BSC alone (control). We assessed the efficacy of omalizumab in the subgroup of patients with inadequately controlled severe persistent allergic asthma despite high-dose inhaled corticosteroids (ICS) plus a long-acting beta(2)-agonist (LABA), which reflects the European Union (EU) label population. Efficacy outcomes included annual asthma exacerbation rate, annual asthma deterioration-related incident (ADRI) rate, % predicted forced expiratory volume in 1 s (FEV(1)), asthma symptoms (Wasserfallen score) and quality of life (Mini Asthma Quality of Life Questionnaire (Mini-AQLQ)), which were compared in the omalizumab and control groups. Outcomes were also determined for omalizumab-treated patients judged to have responded to therapy (> or = 0.5-point improvement in Mini-AQLQ overall score at 27 weeks). In total, 164 patients (omalizumab, n=115; control, n=49) were receiving high-dose ICS plus a LABA. Annual asthma exacerbation rate was significantly reduced by 59% in the omalizumab group vs. control (1.26 vs. 3.06; P<0.001). ADRI rate was significantly reduced by 40% in the omalizumab group compared with control (5.61 vs. 9.40; P<0.05). Significant improvements were also seen in % predicted FEV(1) (71% vs. 60%; P<0.001), change from baseline in asthma symptom scores (-6.7 vs. 0.5; P<0.05) and Mini-AQLQ overall score (1.32 vs. 0.17; P<0.001). In omalizumab-treated patients, 71/102 (70%) were judged to have responded to therapy. In these Mini-AQLQ-assessed responders, exacerbation rate was reduced by 64% vs. control (1.12 vs. 3.06; P<0.001), ADRI rate was reduced by 50% vs. control (4.71 vs. 9.40; P<0.01). Percent predicted FEV(1) (73% vs. 60%; P<0.001), change from baseline in asthma symptom scores (-8.1 vs. 0.5; P<0.001) and Mini

  8. Safety profile and tolerability of up to 1 year of pregabalin treatment in 3 open-label extension studies in patients with fibromyalgia.

    PubMed

    Arnold, Lesley M; Emir, Birol; Murphy, T Kevin; Zeiher, Bernhardt G; Pauer, Lynne; Scott, Gayle; Petersel, Danielle

    2012-05-01

    Pain relief and an acceptable safety profile have been reported in randomized controlled trials (RCTs) of pregabalin in the treatment of fibromyalgia (FM) for up to 14 weeks. To evaluate the safety profile and tolerability of pregabalin (75-300 mg BID) treatment for up to 1 year in patients with FM. Twelve-week data were pooled from 3 open-label extension studies of pivotal RCTs. Study 1 was a 1-year extension of a 13-week RCT, and studies 2 and 3 were 12-week extensions of 14-week RCTs. The 1-year data were separately evaluated. The open-label data are summarized using descriptive statistics. Overall, 1206 patients (92.4% female) with a mean (SD) age of 48.8 (10.7) years received open-label extended pregabalin treatment. A total of 119 of 1206 patients (9.9%) permanently discontinued study participation due to treatment-emergent adverse events (all causality) at 12 weeks (pooled data) and 53 of 429 (12.4%) within 1 year. Consistent with previous RCTs, the most commonly reported treatment-emergent adverse events with open-label pregabalin treatment were dizziness, somnolence, headache, peripheral edema, and increased weight. The highest incidence rates in the pooled 12-week data were for dizziness (214 of 1206; 17.7%) and somnolence (96 of 1206; 8.0%). In ratings of severity (mild, moderate, severe), most were reported as mild to moderate. The mean (SD) change in patient-reported visual analog scale pain scores (0-100) from the open-label baseline to the end of treatment was -21 (30.5) in study 1 (1 year), -26.7 (28.8) in study 2 (12 weeks), and -20.1 (26.8) in study 3 (12 weeks). The data from these extension studies suggest that the adverse event safety profile and tolerability of patients with FM treated with open-label pregabalin (75-300 mg BID) for up to 1 year were stable and were consistent with those of previous studies. ClinicalTrials.gov identifiers: NCT00151528 (A0081057 [study 1]), NCT00282997 (A0081078 [study 2]), and NCT00346034 (A0081101 [study 3

  9. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.

    PubMed

    Dondorp, Arjen M; Fanello, Caterina I; Hendriksen, Ilse C E; Gomes, Ermelinda; Seni, Amir; Chhaganlal, Kajal D; Bojang, Kalifa; Olaosebikan, Rasaq; Anunobi, Nkechinyere; Maitland, Kathryn; Kivaya, Esther; Agbenyega, Tsiri; Nguah, Samuel Blay; Evans, Jennifer; Gesase, Samwel; Kahabuka, Catherine; Mtove, George; Nadjm, Behzad; Deen, Jacqueline; Mwanga-Amumpaire, Juliet; Nansumba, Margaret; Karema, Corine; Umulisa, Noella; Uwimana, Aline; Mokuolu, Olugbenga A; Adedoyin, Olanrewaju T; Johnson, Wahab B R; Tshefu, Antoinette K; Onyamboko, Marie A; Sakulthaew, Tharisara; Ngum, Wirichada Pan; Silamut, Kamolrat; Stepniewska, Kasia; Woodrow, Charles J; Bethell, Delia; Wills, Bridget; Oneko, Martina; Peto, Tim E; von Seidlein, Lorenz; Day, Nicholas P J; White, Nicholas J

    2010-11-13

    Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054. 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63-0·90; relative reduction 22·5%, 95% CI 8·1-36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49-0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66-0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64-0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients

  10. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study.

    PubMed

    van Oers, Marinus H J; Kuliczkowski, Kazimierz; Smolej, Lukáš; Petrini, Mario; Offner, Fritz; Grosicki, Sebastian; Levin, Mark-David; Gupta, Ira; Phillips, Jennifer; Williams, Vanessa; Manson, Stephanie; Lisby, Steen; Geisler, Christian

    2015-10-01

    Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia. This open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1:1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737. Between May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (<1%) patient in the ofatumumab group did not receive the

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

    PubMed Central

    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

  12. Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study.

    PubMed

    Krause, Petra; Fuhr, Uwe; Schnitker, Jörg; Albrecht, Uwe; Stein, Raimund; Rubenwolf, Peter

    2013-11-01

    We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10 mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects. Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve

  13. Methylphenidate Transdermal System: A Multisite, Open-Label Study of Dermal Reactions in Pediatric Patients Diagnosed With ADHD

    PubMed Central

    Squires, Liza; Li, Yunfeng; Civil, Richard; Paller, Amy S.

    2010-01-01

    Objective: To characterize dermal reactions and examine methylphenidate (MPH) sensitization in subjects receiving methylphenidate transdermal system (MTS). Method: This multicenter, open-label, dose-optimization study utilized MTS doses of 10, 15, 20, and 30 mg in children aged 6 to 12 years, inclusive (N = 305), with a DSM-IV-TR primary diagnosis of attention-deficit/hyperactivity disorder. The study was conducted between January 8, 2007, and August 23, 2007. Subjects wore MTS on their hips for 9 hours per day, alternating sides daily for a total of 7 weeks. Assessments included the Experience of Discomfort scale, Transdermal System Adherence scale, and Dermal Response Scale (DRS; 0 = no irritation, 7 = strong reaction). On-study reevaluations were conducted to characterize DRS scores ≥ 4. Epicutaneous allergy patch testing was conducted for DRS scores ≥ 6, persistent DRS scores ≥ 4, DRS score increase following an assessment of ≥ 4, or DRS scores of 4 or 5 following elective discontinuation. Results: Approximately half of subjects experienced definite erythema at the patch site that generally dissipated within 24 hours. Four subjects experienced a DRS score of 4 (1%): erythema in 1 subject resolved on study treatment, 2 cases resolved poststudy and subjects tolerated oral MPH, and 1 subject discontinued treatment. The latter subject was referred for patch testing and was diagnosed with allergic contact sensitization to MPH. Conclusions: Few severe dermal effects were seen with MTS treatment. Dermal reactions were characterized as contact dermatitis and dissipated rapidly. On patch testing, 1 subject (0.3%) manifested sensitization to MPH. Trial Registration: clinicaltrials.gov Identifier: NCT00434213 PMID:21494336

  14. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

    PubMed

    Serpell, Michael G; Notcutt, William; Collin, Christine

    2013-01-01

    Sativex is an endocannabinoid system modulator principally containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit.

  15. Switch from oral pramipexole or ropinirole to rotigotine transdermal system in advanced Parkinson's disease: an open-label study.

    PubMed

    Chung, Sun Ju; Kim, Jong-Min; Kim, Jae Woo; Jeon, Beom Seok; Singh, Pritibha; Thierfelder, Stephan; Ikeda, Junji; Bauer, Lars

    2015-05-01

    Investigate safety, feasibility and efficacy of switching therapy in patients with advanced-stage Parkinson's disease (PD) inadequately controlled with pramipexole (≤ 3.5 mg/day) or ropinirole (≤ 14 mg/day) to rotigotine transdermal system (≤ 14 mg/24 h; dose adjustments ≤ 16 mg/24 h permitted). PD0009 (ClinicalTrials.gov: NCT01711866) was an open-label study in patients with advanced-stage PD receiving levodopa, and experiencing sleep disturbance or early-morning motor impairment. Pramipexole/ropinirole was switched to equivalent dose rotigotine overnight or in two stages. During the 4-week treatment period rotigotine dose adjustments were permitted (up to 16 mg/24 h). Primary variable: Clinical Global Impressions (CGI) item 4: side effects (assessing safety) at end of treatment. 79/87 (91%) patients completed the study; 2 (2%) withdrew due to adverse events (AEs). Most (84; 97%) had CGI item 4 score < 3 indicating switch did not interfere with functioning; three experienced drug-related AEs interfering with functioning (score = 3). 62% patients improved on Patient Global Impression of Change, assessing effectiveness. AEs occurring ≥ 5%: application site pruritus (10%), application site erythema (7%), dizziness (7%), dyskinesia (7%), erythema (6%), pruritus (6%). Unified Parkinson's Disease Rating Scale II and III, Parkinson's Disease Sleep Scale-2 and Pittsburgh Sleep Quality Index were unchanged. Numerical improvements in 'off' time, awakenings and nocturias were observed. Switch from pramipexole or ropinirole to rotigotine (up to 14 mg/24 h) was feasible and possibly associated with some benefit.

  16. An open-label tolerability and efficacy study of an aluminum sesquichlorohydrate topical foam in axillary and palmar primary hyperhidrosis.

    PubMed

    Innocenzi, Daniele; Ruggero, Arianna; Francesconi, Lidia; Lacarrubba, Francesco; Nardone, Beatrice; Micali, Giuseppe

    2008-07-01

    Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat gland production that primarily involves the axillae as well as palms and soles. Common first-line topical treatment for PH consists of aluminum salts (AS) that act by physically blocking eccrine sweat gland ducts. However, primary irritant contact dermatitis is a common side effect of AS treatment. Recently, a new low-residue, thermophobic foam formulation containing 20% aluminum sesquichlorohydrate has been developed (Nidrox, Mipharm S.p.A.). To evaluate the local tolerability and efficacy of 20% aluminum sesquichlorohydrate foam in the treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled in a multicenter, open-label study. Local tolerability was evaluated by physicians assessing itching, burning, and skin irritation using a four-point score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified with a visual score. Efficacy was assessed by means of Minor test score using a four-point score (range 0-3). The foam was applied to clean dry skin, every night during the first 2 weeks and three times a week during the following 2 weeks. Clinical evaluations were performed at baseline, at day 14 and at day 28. Patients were monitored throughout the study for adverse events. All 20 subjects completed the study. The foam induced a significant reduction of the Minor score in comparison with baseline values (p = 0.0002) both at day 14 and at day 28. At the end of the 4-week treatment period, the foam reduced eccrine sweating by 61% (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial except for one subject who experienced a mild and transient itching sensation. No other side effects were reported during the study. This new foam appears to be an effective and well-tolerated topical treatment in reducing sweating in patients with axillary and palmar PH.

  17. Randomized, Open-Label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects

    PubMed Central

    Sun, Haiying; Ting, Lillian; Machineni, Surendra; Praestgaard, Jens; Kuemmell, Andreas; Stein, Daniel S.; Sunkara, Gangadhar; Kovacs, Steven J.; Tanaka, S. Ken

    2016-01-01

    Omadacycline is a first-in-class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The bioavailability of a phase 3 tablet formulation relative to that obtained via intravenous (i.v.) administration (and of other oral formulations relative to that of the phase 3 tablet) was investigated in an open-label, randomized, four-period, crossover study with healthy subjects age 18 to 50 years. Subjects received omadacycline at 100 mg i.v., 300 mg orally as two different tablet formulations with different dissolution profiles, and 300 mg as an oral solution. Plasma omadacycline concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Twenty of 24 subjects completed all treatment periods. The two tablet formulations produced equivalent total exposures. The phase 3 tablet produced an exposure equivalent to that of the 100-mg i.v. dose, with a geometric mean ratio (90% confidence intervals [CI]) for area under the concentration-time curve from 0 h to infinity [AUC∞]) of 1.00 (0.93, 1.07). The absolute bioavailability of the tablets was approximately 34.5%. Intersubject variability was consistent among the oral formulations (∼20 to 25%). Single oral and i.v. doses of omadacycline were well tolerated; three subjects experienced mild adverse events (dizziness, nausea, and vomiting) that resolved without intervention. A 300-mg dose of the tablet formulation of omadacycline intended for use in phase 3 studies produced a total exposure equivalent to that of a 100-mg i.v. dose. PMID:27736760

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

    PubMed

    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.

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

    PubMed

    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 < .001, paired t test). Interestingly, further improvements of those scores were observed at every visit up to week 52. No deaths were reported, yet serious adverse events that were not thought to be drug related were observed in 6 patients. The incidence of any of the adverse events did not markedly increase throughout the 52-week treatment period. The results of this study show that 2% 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.

  20. A New Viscous Cysteamine Eye Drops Treatment for Ophthalmic Cystinosis: An Open-Label Randomized Comparative Phase III Pivotal Study.

    PubMed

    Liang, Hong; Labbé, Antoine; Le Mouhaër, Jeannie; Plisson, Céline; Baudouin, Christophe

    2017-04-01

    The purpose of this study was to evaluate the efficacy of new viscous cysteamine hydrochloride (CH) eye drops (vCH 0.55%) compared with standard CH 0.10% drops treatment. This was an open-label, phase III, randomized, two-arm multicenter trial conducted at two centers in France. Cystinosis patients ≥2 years old were randomized 1:1 to receive eye drops, four times per day for 90 days in both eyes. We compared the superiority in reducing corneal cystine crystal density as assessed by in vivo confocal microscopy (IVCM). We also evaluated photophobia, corneal cystine crystal scores (CCCSs), and cystine crystal depth measured by optical coherence tomography. Safety objectives were to assess adverse events (AEs), local adverse drug reactions, and ocular safety parameters. We included 15 patients with vCH 0.55% and 16 patients with CH 0.10% drops for 90 days. The mean absolute change in IVCM total score at day 90 in the vCH 0.55% drops group (-4.6 ± 3.1) was significantly greater than and superior to the mean absolute change in the CH 0.10% drops group (-0.46 ± 3.38; P < 0.0001). Photophobia, CCCS, and corneal cystine crystal depth were significantly more improved in the vCH 0.55% drops group than in the CH 0.10% group. The most frequent local adverse drug reactions in both groups were stinging, burning, redness, and blurred vision. vCH 0.55% was effective in reducing corneal cystine crystal density and superior to treatment with CH 0.10% drops, which offer advantages over hospital pharmacy formulations and is a more preferable and convenient treatment option.

  1. Treatment with paliperidone in children with behavior disorders previously treated with risperidone: an open-label trial.

    PubMed

    Fernández-Mayoralas, Daniel Martín; Fernández-Jaén, Alberto; Muñoz-Jareño, Nuria; Calleja-Pérez, Beatriz; Fernández-Perrone, Ana Laura; Arribas, Sonia López

    2012-01-01

    Paliperidone is the main active metabolite of risperidone, with certain pharmacokinetic and tolerability characteristics that suggest it may be used in special groups, such as children. Our purpose is to document the clinical experience with the use of paliperidone in children with severe behavior problems that were partially refractory to treatment with risperidone and psychological treatment. This is a prospective 16-week open-label study of paliperidone in 18 patients (mean age, 13.4 years) with severe and excessive irritability in the context of generalized developmental disorders or attention-deficit/hyperactivity disorder. Patients who had exhibited an inadequate response to treatment with risperidone (1.5-2 mg/d) over a treatment period of 6 months were treated with paliperidone at 3 mg/d. Symptom severity at the beginning of the study and in response to paliperidone were rated with the Clinical Global Impression (CGI) scale and Overt Aggression Scale. A significant difference was documented between the mean score before treatment and the score after the drug intervention with paliperidone. There was a noticeable clinical improvement in 50% of the cases, as reflected in the CGI. Severity of aggressive behavior, as assessed by the Overt Aggression Scale, decreased significantly after paliperidone treatment: mean (SD), 2.7 (0.92) before treatment versus 1.5 (0.60) after treatment. This compound was safe and well tolerated. Half of the patients clearly responded to paliperidone extended release. Tolerance to this treatment was distinctly better than to risperidone. These preliminary results lay the foundation for further research into the use of paliperidone to treat pediatric disruptive behavior disorders within the context of randomized, double-blind, controlled clinical trials.

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

    PubMed Central

    Lemoine, Patrick; Garfinkel, Doron; Laudon, Moshe; Nir, Tali; Zisapel, Nava

    2011-01-01

    Background 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. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production. PMID:21845053

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

    PubMed

    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

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

    PubMed Central

    2013-01-01

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

  5. High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study.

    PubMed

    Liang, Qian; Li, Nan; Song, Shurong; Zhang, Aihua; Li, Ni; Duan, Ying

    2016-10-01

    The efficacy and safety of two nifuratel dosages for the treatment of aerobic vaginitis (AV) were compared. This was a prospective open-label cohort study of patients diagnosed and treated at the Tianjin Third Central Hospital between January 2012 and December 2013. The co-presence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or/and trichomonal vaginitis (TV; mixed AV) was determined. Patients were randomized to nifuratel-500 (500 mg nifuratel, intravaginal, 10 days) or nifuratel-250 (250 mg nifuratel, intravaginal, 10 days), and followed-up for three to seven days after treatment completion. Primary and secondary outcomes were recovery rate and adverse events, respectively. The study included 142 patients with AV. Age was not significantly different between the groups (n = 71 each), and disease distribution was identical: 29 (40.85%) simple AV and 42 (59.15%) mixed AV (AV + BV, 42.86 %; AV + VVC, 30.95%; AV + TV, 26.19%). In patients with simple AV, the recovery rate did not differ significantly between the nifuratel-500 (26/29, 89.66%) and nifuratel-250 (22/29, 75.86%) groups. In patients with mixed AV, recovery rates were significantly higher in the nifuratel-500 than in the nifuratel-250 group (AV + BV, 88.89% vs 50.00 %; AV + VVC, 76.92 % vs 30.77 %; AV + TV, 90.91 % vs 36.36%; all P < 0.05). Only one patient (nifuratel-500) reported an adverse event (mild anaphylactic reaction). Nifuratel 500 mg showed good clinical efficacy for the treatment of AV, particularly mixed AV, and is superior to the 250 mg dosage in the treatment of mixed AV. © 2016 Japan Society of Obstetrics and Gynecology.

  6. Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol for a multicentre open-label randomised controlled trial

    PubMed Central

    Berkelmans, Gijs H K; Wilts, Bas J W; Kouwenhoven, Ewout A; Kumagai, Koshi; Nilsson, Magnus; Weijs, Teus J; Nieuwenhuijzen, Grard A P; van Det, Marc J; Luyer, Misha D P

    2016-01-01

    Introduction Early start of an oral diet is safe and beneficial in most types of gastrointestinal surgery and is a crucial part of fast track or enhanced recovery protocols. However, the feasibility and safety of oral intake directly following oesophagectomy remain unclear. The aim of this study is to investigate the effects of early versus delayed start of oral intake on postoperative recovery following oesophagectomy. Methods and analysis This is an open-label multicentre randomised controlled trial. Patients undergoing elective minimally invasive or hybrid oesophagectomy for cancer are eligible. Further inclusion criteria are intrathoracic anastomosis, written informed consent and age 18 years or older. Inability for oral intake, inability to place a feeding jejunostomy, inability to provide written consent, swallowing disorder, achalasia, Karnofsky Performance Status <80 and malnutrition are exclusion criteria. Patients will be randomised using online randomisation software. The intervention group (direct oral feeding) will receive a liquid oral diet for 2 weeks with gradually expanding daily maximums. The control group (delayed oral feeding) will receive enteral feeding via a jejunostomy during 5 days and then start the same liquid oral diet. The primary outcome measure is functional recovery. Secondary outcome measures are 30-day surgical complications; nutritional status; need for artificial nutrition; need for additional interventions; health-related quality of life. We aim to recruit 148 patients. Statistical analysis will be performed according to an intention to treat principle. Results are presented as risk ratios with corresponding 95% CIs. A two-tailed p<0.05 is considered statistically significant. Ethics and dissemination Our study protocol has received ethical approval from the Medical research Ethics Committees United (MEC-U). This study is conducted according to the principles of Good Clinical Practice. Verbal and written informed consent is

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

    PubMed Central

    Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-01-01

    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 CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-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). PMID:27058753

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

    PubMed

    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.

  9. Safety and efficacy of Adalimumab in the treatment of moderate to severe palmo-plantar psoriasis: an open label study.

    PubMed

    Richetta, A G; Mattozzi, C; Giancristoforo, S; D'Epiro, S; Cantisani, C; Macaluso, L; Salvi, M; Calvieri, S

    2012-01-01

    Psoriasis of the hands and feet is highly debilitating and difficult to treat. Lesions are very painfull, disabilitating and impair quality of life of patients. Most treatment options have limited efficacy, short duration of response and several adverse events. To investigate the safety and efficacy of Adalimumab in the management of palmo-plantar psoriasis. Adults patients with moderate to severe palmoplantar psoriasis were enrollend in this trial. They received a 6 courses of Adalimumab 40 mg 1 vial every 2 weeks. The study consisted of treatment period of 12 weeks (Weeks 1-12). Safety and efficacy were assessed at weeks 0.6 and 12. PGA (Physician's Global Assesment) and DLQI were used to measure the efficacy. Primary end point of the study was to evaluate patients who achieved a reduction in PGA at week 12. The secondary end point was to evaluate patients who achieved a 50% reduction in PGA at week 12. The tertiary end point evaluated patients who achieved a PGA rating of clear or almost clear. Of 11 patients enrolled 6 showed overall improvement of at least one point of PGA at week 12; 4 of them obtained a PGA of 0 while 5 patient of 11 a ≥ 50% improvement from the beginning of the study. 8 patients showed an increase in quality of life score while receiving the drug at week 12. No serious adverse events were reported during the study. Continuous treatment with Adalimumab for 12 weeks was safe and efficacious in this open-label clinical trial of patients with palmoplantar psoriasis.

  10. Benefits from sustained-release pyridostigmine bromide in myasthenia gravis: results of a prospective multicenter open-label trial.

    PubMed

    Sieb, Jörn Peter; Köhler, Wolfgang

    2010-11-01

    For more than 50 years the acetylcholinesterase inhibitor pyridostigmine bromide has been the drug of choice in the symptomatic therapy for myasthenia gravis. The sustained-release dosage form of pyridostigmine (SR-Pyr) is only available in a limited number of countries (e.g. in the United States and Germany). Astonishingly, the therapeutic usefulness of SR-Pyr has not yet been evaluated. In this non-interventional prospective open-label trial, 72 patients with stable myasthenia gravis were switched from instant-release dosage forms of pyridostigmine bromide to SR-Pyr. The results from the 37 patients younger than 60 years were separately analyzed. The initial daily dose of SR-Pyr was 288.1 ± 171.0mg. The drug switch was unproblematic in all patients. The number of daily doses was significantly reduced from 4.3 to 3.6 (p=0.011). The switch to SR-Pyr ameliorated the total quantified myasthenia gravis (QMG) score from 0.9 ± 0.5 to 0.6 ± 0.4 (p<0.001) in all patients and in the younger subgroup. This was accompanied by a significant improvement in the quality of life parameters. The health status valued by EuroQoL questionnaire improved from 0.626 ± 0.286 to 0.782 ± 0.186 (p<0.001). After switching to SR-Pyr, 28 adverse reactions disappeared and 24 adverse reactions occurred less frequent or weaker, however, 17 new adverse reactions were documented. Our results support the usefulness of SR-Pyr in an individualized therapeutic regimen to improve quality of life regardless of the patient's age in myasthenia gravis. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Phase II open-label study of bevacizumab combined with neoadjuvant anthracycline and taxane therapy for locally advanced breast cancer.

    PubMed

    Clavarezza, Matteo; Turazza, Monica; Aitini, Enrico; Saracchini, Silvana; Garrone, Ornella; Durando, Antonio; De Placido, Sabino; Bisagni, Giancarlo; Levaggi, Alessia; Bighin, Claudia; Restuccia, Eleonora; Scalamogna, Roberto; Galli, Anna; Del Mastro, Lucia

    2013-08-01

    Neoadjuvant anthracycline- and taxane-based chemotherapy is frequently administered in breast cancer. Pathological complete response (pCR) rates vary according to clinical disease stage and biology of breast cancer. The critical role of angiogenesis in the progression of breast cancer, together with significantly improved efficacy when bevacizumab is combined with chemotherapy in the metastatic setting, provides a strong rationale for evaluating the integration of bevacizumab into neoadjuvant chemotherapy regimens. A single-arm, multicentre, phase II, open-label study evaluated four 3-weekly cycles of FEC (5-fluorouracil 600 mg/m(2), epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)) followed by 12 cycles of weekly paclitaxel (80 mg/m(2)) in combination with bevacizumab 10 mg/kg every 2 weeks as neoadjuvant therapy for HER2-negative stage III locally advanced or inflammatory breast carcinoma. The primary endpoint was pCR rate. Planned treatment was completed in 49 of the 56 enrolled patients. In the intent-to-treat population, the pCR rate was 21% and the clinical response rate was 59%. Breast-conserving surgery was achieved in 34% of patients. In the subgroup of 15 patients with triple-negative disease, the pCR rate was 47%. Grade 3 adverse events in ≥5% of patients were neutropenia, leucopenia, asthenia, and rash. One case each of hypertensive retinopathy and post-operative wound complication, both after treatment completion, were considered probably related to bevacizumab. There were no treatment-related deaths and no cardiac function abnormalities. This study indicates that FEC followed by weekly paclitaxel with bevacizumab is an active neoadjuvant regimen for locally advanced breast cancer, with no major safety concerns. NCT00559845. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial.

    PubMed

    Shoeibi, Ali; Olfati, Nahid; Soltani Sabi, Mohsen; Salehi, Maryam; Mali, Sara; Akbari Oryani, Mahsa

    2017-03-01

    Despite the huge health and economic burden of migraine headache, few medications have been approved for its prophylactic treatment, most of which can potentially induce serious adverse effects. Coenzyme Q10 (CoQ10) is a supplement and has shown preliminary benefits in migraine prophylaxis. We aimed to assess this effect in an adult population. This is an open-label, parallel, add-on, match-controlled trial. Eighty patients diagnosed with migraine headache based on International Headache Society criteria were allocated to receiving only their current preventive drugs or their current preventive drugs plus 100 mg CoQ10 daily, matching for their baseline characteristics, and were assessed for frequency and severity of attacks, and ≥50 % reduction in attack frequency per month. Thirty-six and 37 patients were analyzed in CoQ10 and control groups, respectively. Number of attacks per month dropped significantly in the CoQ10 group (mean decrease: 1.6 vs. 0.5 among CoQ10 and control groups, respectively, p < 0.001). A significant reduction was also evident in the severity of headaches (mean decrease: 2.3 vs. 0.6 among CoQ10 and control groups, respectively, p < 0.001). For ≥50 % reduction in the frequency of attacks per month, the number needed to treat was calculated as 1.6. No side effects for CoQ10 were observed. This study suggests that CoQ10 might reduce the frequency of headaches, and may also make them shorter in duration, and less severe, with a favorable safety profile.

  13. Frovatriptan for acute treatment of migraine associated with menstruation: results from an open-label postmarketing surveillance study.

    PubMed

    Newman, Lawrence C; Harper, Samira; Jones, Beverly A; Campbell, John

    2009-08-01

    To examine the effectiveness and tolerability of acute treatment with frovatriptan in women experiencing menstrual migraine (MM) vs. female migraineurs with non-MM. This was an open-label postmarketing surveillance study (n = 7107) conducted in Germany to assess acute treatment with frovatriptan in one to three migraine attacks. This retrospective subanalysis evaluated acute frovatriptan treatment in women who experienced >or=1 MM attack vs. those women with non-MM attacks. Effectiveness and tolerability were graded using a 4-point scale (1 = very good, 2 = good, 3 = satisfactory, 4 = poor). Demographics were similar in MM (n = 1931) and non-MM patients (n = 2080), except that mean age (38.3 vs 45.3 years, respectively) and number of migraine attacks per month were less in the MM group than in the non-MM group (both p < 0.001). Although 98% of women reported that their previous migraines were moderate or severe, only one third in each treatment group previously used triptans. Prestudy medications were rated as good or very good for effectiveness by 20.3% and 19.2% of the MM and non-MM groups, respectively. In contrast, the effectiveness of frovatriptan was rated as very good or good by 92.7% and 90.9% of women in the MM and non-MM groups, respectively. Forty-three percent and 96% of all women rated their previous medication and frovatriptan, respectively, as having good or very good tolerability. Among women rating their previous medication as poor or satisfactory, most (94%) rated frovatriptan as very good or good. Acute frovatriptan treatment improved patient ratings of treatment effectiveness and tolerability in women with migraine associated with menses.

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

    PubMed

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

    2016-10-01

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

  15. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.

    PubMed

    Dalgleish, Angus G; Stebbing, Justin; Adamson, Douglas Ja; Arif, Seema Safia; Bidoli, Paolo; Chang, David; Cheeseman, Sue; Diaz-Beveridge, Robert; Fernandez-Martos, Carlos; Glynne-Jones, Rob; Granetto, Cristina; Massuti, Bartomeu; McAdam, Karen; McDermott, Raymond; Martín, Andrés J Muñoz; Papamichael, Demetris; Pazo-Cid, Roberto; Vieitez, Jose M; Zaniboni, Alberto; Carroll, Kevin J; Wagle, Shama; Gaya, Andrew; Mudan, Satvinder S

    2016-09-27

    Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Patients were randomised (2 : 1) to IMM-101 (10 mg ml(-l) intradermally)+GEM (1000 mg m(-2) intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01). IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.

  16. Effectiveness of agomelatine on anhedonia in depressed patients: an outpatient, open-label, real-world study.

    PubMed

    Gargoloff, Pedro Damian; Corral, Ricardo; Herbst, Luis; Marquez, Miguel; Martinotti, Giovanni; Gargoloff, Pedro Rafael

    2016-11-01

    The aim of this real-world study was to evaluate the effect of agomelatine on anhedonia as primary endpoint in outpatients under treatment of major depressive episodes. The study was an open-label, multicenter, 8-week phase IV trial. Two hundred fifty-seven (257) patients were recruited, and 143 patients were included in the analysis. Agomelatine was administered orally as a 25-mg tablet. The dose could be increased to 50 mg after 2 weeks of treatment. An improvement in the severity of anhedonia (Snaith-Hamilton Pleasure Scale total score) was observed from 8.5 points at baseline to 4.1 at week 8, statistically significant (p < 0.05) from the first week. Significant decreases in scores on the severity of depression (Quick Inventory of Depressive Symptomatology 16-item Self-Report [QIDS-SR-16]), anxiety (Generalized Anxiety Disorder 7-item scale), and in overall clinical status (CGI) were also found over 8 weeks, independently from the presence of a first or recurrence episode. Response (QIDS-SR-16 score ≥ 50% of baseline) at week 8 was observed in 65.7% of the patients, while 49.6% of the patients achieved remission (QIDS-SR-16 score ≤ 5). Agomelatine was shown to be effective on anhedonia, depression, and anxiety in subjects with major depression. The pragmatic design of the study reflects real-world clinical practice providing interesting insights into routine care management. Copyright © 2016 John Wiley & Sons, Ltd.

  17. UNBLOCK: an open-label, dose-finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis.

    PubMed

    O'Brien, S H; Yee, D L; Lira, J; Goldenberg, N A; Young, G

    2015-09-01

    Direct thrombin inhibitors offer potential advantages over unfractionated heparin but have been poorly studied in children. To determine appropriate dosing of bivalirudin in children and adolescents and the relationship between activated partial thromboplastin time (APTT) and plasma bivalirudin concentration. The UNBLOCK (UtilizatioN of BivaLirudin On Clots in Kids) study was an open-label, single-arm, dose-finding, pharmacokinetic, safety and efficacy study of bivalirudin for the acute treatment of deep vein thrombosis (DVT) in children aged 6 months to 18 years. Drug initiation consisted of a bolus dose (0.125 mg kg(-1) ) followed by continuous infusion (0.125 mg kg h(-1) ). Dose adjustments were based on the APTT, targeting a range of 1.5-2.5 times each patient's baseline APTT. Safety was assessed by specific bleeding endpoints and efficacy by repeat imaging at 48-72 h and 25-35 days. Eighteen patients completed the study. Following the bolus dose and the initial infusion rate, most patients' APTT values were within the target range. The infusion rate bivalirudin correlated more closely with drug concentration than the APTT. At 48-72 h, nine (50%) patients had complete or partial thrombus resolution, increasing to 16 (89%) at 25-35 days. No major and one minor bleeding event occurred. Bivalirudin demonstrated reassuring safety and noteworthy efficacy in terms of early clot resolution in children and adolescents with DVT. Although a widely available and familiar monitoring tool, the APTT correlates poorly with plasma bivalirudin concentration, possibly limiting its utility in managing pediatric patients receiving bivalirudin for DVT. © 2015 International Society on Thrombosis and Haemostasis.

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

    PubMed Central

    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

  19. Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial

    PubMed Central

    Rossi, Roberta; Bonanni, Alice; Quinn, Robert R.; Sica, Felice; Bodria, Monica; Pasini, Andrea; Montini, Giovanni; Edefonti, Alberto; Belingheri, Mirco; De Giovanni, Donatella; Barbano, Giancarlo; Degl’Innocenti, Ludovica; Scolari, Francesco; Murer, Luisa; Reiser, Jochen; Fornoni, Alessia; Ghiggeri, Gian Marco

    2015-01-01

    Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1–16 years who had developed SDNS in the previous 6–12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6–13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS. PMID:25592855

  20. Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial.

    PubMed

    Ravani, Pietro; Rossi, Roberta; Bonanni, Alice; Quinn, Robert R; Sica, Felice; Bodria, Monica; Pasini, Andrea; Montini, Giovanni; Edefonti, Alberto; Belingheri, Mirco; De Giovanni, Donatella; Barbano, Giancarlo; Degl'Innocenti, Ludovica; Scolari, Francesco; Murer, Luisa; Reiser, Jochen; Fornoni, Alessia; Ghiggeri, Gian Marco

    2015-09-01

    Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

  1. Open-Label Observational Study for Evaluating the Short-term Benefits of Rabeprazole Medication on Laryngopharyngeal Reflux

    PubMed Central

    Shin, Myung-Hee; Nam, Soon Yuhl; Park, Young-Hak

    2012-01-01

    Objectives The aims of this study were to determine the benefits of short-term empirical proton pump inhibitor (PPI) medication on laryngopharyngeal reflux (LPR) and to determine whether scores on the reflux symptom index (RSI) and the reflux finding score (RFS) could be combined to identify subgroups of patients that will more likely to improve with this medication. Methods Fifty-one Korean Otolaryngology Board-certified specialists joined this prospective, multi-center, and open-label observational study. A total of 1,142 adult patients with LPR was enrolled for 12 weeks of rabeprazol medication. According to pre-treatment scores on RSI and RFS, patients were divided into 4 subgroups. RFS and RSI were measured repeatedly with a month interval along the treatment period. Changes of RSI and RFS were analyzed in an overall study cohort as well as in each subgroup. Results Approximately 40% (n=455) of enrolled patients were followed up until 12 weeks of PPI treatment. Significant improvement in RSI was obtained in 29%, 58%, and 75% of patients after 4, 8, and 12 weeks of PPI medication. RFS was improved in 16%, 42%, and 57% of the patients with 4, 8, and 12 weeks of PPI medication. All subgroups showed improvement regardless of their pre-treatment scores on the RSI and RFS. Conclusion Even though RSI and RFS may be used as a general guideline for LPR management, pre-treatment RSI and RFS are not useful in predicting the patients' response to short-term PPI medication in the usual pattern of practice for LPR, which is mostly based on the physical evaluation and history taking. PMID:22468199

  2. Replacement of warfarin with a novel oral anticoagulant in endoscopic mucosal resection: a multicentre, open-label, randomised controlled trial

    PubMed Central

    Yamada, Takuya; Kada, Akiko; Uraoka, Toshio; Kuwai, Toshio; Watanabe, Noriko; Sasaki, Yoshihiro; Mabe, Katsuhiro; Takahashi, Yasuo; Kagaya, Takashi; Kimura, Toshihisa; Hamada, Hiroshige; Saito, Akiko M; Harada, Naohiko

    2017-01-01

    Introduction This randomised controlled trial aims to compare the efficacy of warfarin replacement with apixaban without postoperative resumption of heparin with that of conventional heparin bridging in patients taking warfarin and scheduled to undergo endoscopic mucosal resection (EMR): specifically, by checking for reduction in proportion of postoperative bleeding following EMR. Methods and analysis The multicentre, open-label randomised parallel-group, controlled intervention study regards patients taking warfarin who are scheduled to undergo colon EMR. Enrolled patients have been taking oral warfarin for non-valvular atrial fibrillation or venous thrombosis on an outpatient basis, and have been found to have a colorectal polyp (including adenoma or early-stage cancer) for which EMR was indicated. They are assigned to one of two groups. The primary endpoint is proportion of postoperative bleeding. The secondary endpoints are hospital stay length, therapeutic endoscopy outcomes such as proportion of en bloc resection, proportion of perforation, proportion of intraoperative bleeding, incidence of cerebral infarction/systemic embolism events, incidence of adverse events and serious adverse events, and proportion of postoperative therapeutic endoscopy. Ethics and dissemination This trial was approved by the National Hospital Organization Central Review Board for Clinical Trials (19 April 2016). Discussion The paucity of reports with high evidence levels was considered problematic when the Japan Gastroenterological Endoscopy Society’s gastroenterological endoscopy guidelines were revised in 2012. The results of this trial will have high medical significance, as its data could serve as the basis for revisions in the next edition of the guidelines. Trial registration number This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) accepted from the International Committee of Medical Journal Editors (ICMJE

  3. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension

    PubMed Central

    Findling, Robert L.; Hardan, Antonio Y.; Hendren, Robert L.; Melmed, Raun D.; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M.; Palmer, Robert H.; Graham, Stephen M.; Gage, Allyson T.; Perhach, James L.; Katz, Ephraim

    2017-01-01

    Abstract Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of

  4. A parallel open-label trial to evaluate microbial cellulose wound dressing in the treatment of diabetic foot ulcers.

    PubMed

    Solway, Douglas R; Clark, William A; Levinson, Dennis J

    2011-02-01

    The purpose of this study was to compare the rate of wound healing in diabetic foot ulcers (DFU) using either a microbial cellulose (MC) wound dressing or Xeroform™ Petrolatum gauze. In a parallel, open-label trial in which the primary outcome was the rate of wound healing and the time to wound closure, 15 ulcers in type II diabetic patients received an MC dressing. Wounds in 19 control patients with type II diabetes were treated with a Xeroform gauze dressing. All wounds were non infected, Wagner stage II or III and received standard care including debridement, non weight bearing limb support and weekly wound evaluation. The mean time to heal in the MC (±SE) treated group was 32 days ± 2.5 and for controls it was 48 days ± 4.7 (P < 0.01). The rate of weekly wound closure (mean ± SE) was 1.7 times faster in the MC-treated group (cellulose treated, -5.04% per week ± 0.38 versus control, -2.93% per week ± 0.19), (P < 0.001). Among covariants tested by univariate regression, only the original wound area correlated with the time to wound closure (P < 0.001). In conclusion, with the provision of current standards of care, the application of an MC dressing to a diabetic ulcer may enhance the rate of wound healing and shorten the time course of epithelisation. © 2010 The Authors. © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  5. Deep brain stimulation for Huntington's disease: long-term results of a prospective open-label study.

    PubMed

    Gonzalez, Victoria; Cif, Laura; Biolsi, Brigitte; Garcia-Ptacek, Sara; Seychelles, Anne; Sanrey, Emily; Descours, Irene; Coubes, Christine; de Moura, Ana-Maria Ribeiro; Corlobe, Astrid; James, Syril; Roujeau, Thomas; Coubes, Philippe

    2014-07-01

    OBJECT.: To date, experience of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Huntington's disease (HD) has been limited to a small number of case reports. The aim of this study was to analyze long-term motor outcome of a cohort of HD patients treated with GPi DBS. Seven patients with pharmacologically resistant chorea and functional impairment were included in a prospective open-label study from 2008 to 2011. The main outcome measure was the motor section of the Unified Huntington's Disease Rating Scale. The primary end point was reduction of chorea. Patients underwent MRI-guided bilateral GPi implantation. The median duration of follow-up was 3 years. A significant reduction of chorea was observed in all patients, with sustained therapeutic effect; the mean improvement on the chorea subscore was 58.34% at the 12-month follow-up visit (p = 0.018) and 59.8% at the 3-year visit (p = 0.040). Bradykinesia and dystonia showed a nonsignificant trend toward progressive worsening related to disease evolution and partly to DBS. The frequency of stimulation was 130 Hz for all patients. DBS-induced bradykinesia was managed by pulse-width reduction or bipolar settings. Levodopa mildly improved bradykinesia in 4 patients. Regular off-stimulation tests confirmed a persistent therapeutic effect of DBS on chorea. GPi DBS may provide sustained chorea improvement in selected HD patients with pharmacologically resistant chorea, with transient benefit in physical aspects of quality of life before progression of behavioral and cognitive disorders. DBS therapy did not improve dystonia or bradykinesia. Further studies including quality of life measures are needed to evaluate the impact of DBS in the long-term outcome of HD.

  6. A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex

    PubMed Central

    Myers, Stephen P; O’Connor, Joan; Fitton, J Helen; Brooks, Lyndon; Rolfe, Margaret; Connellan, Paul; Wohlmuth, Hans; Cheras, Phil A; Morris, Carol

    2011-01-01

    Background: Isolated fucoidans from brown marine algae have been shown to have a range of immune-modulating effects. This exploratory study aimed to determine whether a seaweed nutrient complex containing a blend of extracts from three different species of brown algae plus nutrients is safe to administer and has biological potential as an immune modulator. The study was undertaken as an open-label combined Phase I and II study. Methods: Participants (n = 10) were randomized to receive the study medication at either a 100 mg (n = 5) or 1000 mg (n = 5) dose over 4 weeks. The primary outcome measurement was in vivo changes in lymphocyte subsets. The secondary outcome measures were ex vivo changes in T-lymphocyte (CD4 and CD8) activation, phagocytosis of granulocytes and monocytes, T helper 1/T helper 2 cytokines, and serum oxygen radical absorbance capacity. Results: The preparation was found to be safe over the 4 weeks at both doses tested. There were no clinically relevant changes to blood measurements of hemopoietic, hepatic, or renal function. Immunomodulatory measurements showed no dose response between the two doses. The combined results from the two doses demonstrated a significant increase in cytotoxic T cell numbers and phagocytic capacity in monocytes, and a significant decrease in levels of the inflammatory cytokine interleukin 6. A separate analysis of the 100 mg dose (n = 5) alone showed a significant linear component over time (P < 0.05) for phagocytosis by both granulocytes and monocytes. Conclusion: The seaweed nutrient complex was safe to use when taken orally over 4 weeks. The preparation was demonstrated to have potential as an immune modulator, and this bioactivity deserves further exploration. PMID:21383915

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

    PubMed

    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.

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

    PubMed Central

    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

  9. Gatifloxacin Versus Ofloxacin for the Treatment of Uncomplicated Enteric Fever in Nepal: An Open-Label, Randomized, Controlled Trial

    PubMed Central

    Koirala, Samir; Basnyat, Buddha; Arjyal, Amit; Shilpakar, Olita; Shrestha, Kabina; Shrestha, Rishav; Shrestha, Upendra Man; Agrawal, Krishna; Koirala, Kanika Deshpande; Thapa, Sudeep Dhoj; Karkey, Abhilasha; Dongol, Sabina; Giri, Abhishek; Shakya, Mila; Pathak, Kamal Raj; Campbell, James; Baker, Stephen; Farrar, Jeremy; Wolbers, Marcel; Dolecek, Christiane

    2013-01-01

    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). PMID:24282626

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

    PubMed

    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. © 2013.

  11. Noninvasive diagnosis of hypolactasia with 4-Galactosylxylose (Gaxilose): a multicentre, open-label, phase IIB-III nonrandomized trial.

    PubMed

    Aragón, Juan J; Hermida, Carmen; Martínez-Costa, Oscar H; Sánchez, Valentina; Martín, Igor; Sánchez, José J; Codoceo, Rosa; Cano, José M; Cano, Ana; Crespo, Laura; Torres, Yolanda; García, Francisco J; Fernández-Mayoralas, Alfonso; Solera, Jesús; Martínez, Pilar

    2014-01-01

    Hypolactasia affects over half of the world population. Diagnosis remains problematic as currently available tests, such as the hydrogen breath test, have low reliability and lactose intolerance symptoms are unspecific. We evaluated the diagnostic performance and safety of a new noninvasive diagnostic test based on urine or serum measurement of D-xylose after lactase cleavage of orally administered 4-galactosylxylose (gaxilose). In a multicentre, open-label, nonrandomized, phase IIb-III study, consecutive patients with symptoms suggestive of lactose intolerance sequentially underwent intestinal biopsy for direct measurement of lactase activity (reference standard), hydrogen breath test, and blood glucose test after lactose challenge, 4- and 5-hour urine-based gaxilose test, and blood-based gaxilose test. For the gaxilose tests, 0 to 4 and 4 to 5 hours urine samples were taken after a 0.45 g gaxilose dose, whereas serum samples were taken 90 minutes after a 2.7 g dose for D-xylose determination. Genetic testing of hypolactasia was also assessed. Of the 222 patients enrolled, 203 completed all diagnostic tests; 108 were hypolactasic according to biopsy. The sensitivities and specificities and positive and negative predictive values of the gaxilose tests were all >90% versus 69% to 85% for the hydrogen breath test and the blood glucose test. The area under the ROC curve was significantly higher for the gaxilose tests (>0.9, P≤0.007). These tests also had higher sensitivity than genetic testing for hypolactasia and were well tolerated. The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.

  12. Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial.

    PubMed

    Zhang, Di; Ke, Li; Ni, Zhen; Chen, Yu; Zhang, Lin-Hui; Zhu, Shao-Hua; Li, Chan-Juan; Shang, Lei; Liang, Jie; Shi, Yong-Quan

    2017-08-01

    Due to increasing antimicrobial resistance, a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori (H pylori) eradication. However, different results are varied greatly and the availability of bismuth was limited in some countries. We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication. In a randomized, open-label, non-inferiority, phase IV trial between November 25, 2014, and October 15, 2015, 612 treatment-naive patients were randomly assigned to 14-day berberine-containing (n = 308) or 14-day bismuth-containing (n = 304) quadruple therapy. The primary outcomes were eradication rates determined by the C urea breath test (C-UBT) 28 days after the end of treatment. The secondary outcomes were adverse events and compliance. The baseline demographic data including age, gender, body mass index (BMI), general condition and severity score were not statistically different in both groups. The eradication rates in bismuth and berberine groups were 86.4% (266/308) and 90.1% (274/304) in intention-to-treat (ITT) analysis (P = .149), and 89.6% (266/297) and 91.3% (273/299) in per-protocol (PP) analysis (P = .470), respectively. No statistically significant difference was found in the overall incidence of adverse events between both groups (35.7% vs 28.6%, P = .060). Both regimens achieved the recommended efficacy for H pylori eradication. The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region.

  13. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study.

    PubMed

    Wiebe, Sabrina; Schnell, David; Külzer, Raimund; Gansser, Dietmar; Weber, Anne; Wallenstein, Gudrun; Halabi, Atef; Conrad, Anja; Wind, Sven

    2017-06-01

    Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30-59 mL/min/1.73 m(2) and 15-29 mL/min/1.73 m(2), respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast) and maximum plasma concentration (C max) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUClast and C max, was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUClast for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3-213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28-39 % for moderate impairment, 34-42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.

  14. Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open-label randomized controlled trial.

    PubMed

    Rodda, C P; Benson, J E; Vincent, A J; Whitehead, C L; Polykov, A; Vollenhoven, B

    2015-09-01

    To determine whether maternal vitamin D supplementation, in the vitamin D deficient mother, prevents neonatal vitamin D deficiency. Open-label randomized controlled trial. Metropolitan Melbourne, Australia, tertiary hospital routine antenatal outpatient clinic. Seventy-eight women with singleton pregnancies with vitamin D deficiency/insufficiency (serum 25-OH Vit D < 75 nmol/l) at their first antenatal appointment at 12-16-week gestation were recruited. Participants were randomized to vitamin D supplementation (2000-4000 IU cholecalciferol) orally daily until delivery or no supplementation. The primary outcome was neonatal serum 25-OH vit D concentration at delivery. The secondary outcome was maternal serum 25-OH vit D concentration at delivery. Baseline mean maternal serum 25-OH vit D concentrations were similar (P = 0·9) between treatment (32 nmol/l, 95% confidence interval 26-39 nmol/l) and control groups (33 nmol/l, 95% CI 26-39 nmol/l). Umbilical cord serum 25-OH vit D concentrations at delivery were higher (P < 0·0001) in neonates of treatment group mothers (81 nmol/l, 95% CI; 70-91 nmol/l) compared with neonates of control group mothers (42 nmol/l, 95% CI; 34-50 nmol/l) with a strongly positive correlation between maternal serum 25-OH Vit D and umbilical cord serum 25-OH vit D concentrations at delivery (Spearman rank correlation coefficient 0·88; P < 0·0001). Mean maternal serum 25-OH Vit D concentrations at delivery were higher (P < 0·0001) in the treatment group (71 nmol/l, 95% CI; 62-81 nmol/l) compared with the control group (36 nmol/l, 95% CI; 29-42 nmol/l). Vitamin D supplementation of vitamin D deficient pregnant women prevents neonatal vitamin D deficiency. © 2015 John Wiley & Sons Ltd.

  15. Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study

    PubMed Central

    2011-01-01

    Background Although trazodone is frequently used by fibromyalgia patients, its efficacy on this disease has not been adequately studied. If effective, pregabalin, whose beneficial effects on pain and sleep quality in fibromyalgia have been demonstrated, could complement the antidepressant and anxiolytic effects of trazodone. The aim of the present study was to assess the effectiveness of trazodone alone and in combination with pregabalin in the treatment of fibromyalgia. Methods This was an open-label uncontrolled study. Trazodone, flexibly dosed (50-300 mg/day), was administered to 66 fibromyalgia patients during 12 weeks; 41 patients who completed the treatment accepted to receive pregabalin, also flexibly dosed (75-450 mg/day), added to trazodone treatment for an additional 12-week period. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), the Brief Pain Inventory (BPI), the Short-Form Health Survey (SF-36), and the Patients' Global Improvement scale (PGI). Emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test. Results Treatment with trazodone significantly improved global fibromyalgia severity, sleep quality, and depression, as well as pain interference with daily activities although without showing a direct effect on bodily pain. After pregabalin combination additional and significant improvements were seen on fibromyalgia severity, depression and pain interference with daily activities, and a decrease in bodily pain was also apparent. During the second phase of the study, only two patients dropped out due to side effects. Conclusions Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in association was good. Trial

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

    PubMed

    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. © 2013 Blackwell Verlag GmbH.

  17. Green tea (Camellia sinensis) for patients with knee osteoarthritis: A randomized open-label active-controlled clinical trial.

    PubMed

    Hashempur, Mohammad Hashem; Sadrneshin, Sara; Mosavat, Seyed Hamdollah; Ashraf, Alireza

    2016-12-18

    Green tea is known as a dietary supplement and a novel functional food worldwide. Since there are increasing preclinical evidence about efficacy of green tea for treating osteoarthritis, this study has aimed at assessing its efficacy and safety for patients with knee osteoarthritis. This is a randomized open-label active-controlled clinical trial. As many as fifty adults with osteoarthritis of knee were randomly allocated to receive the green tea extract (in dosage form of tablet) plus diclofenac tablet as "intervention group"; or: diclofenac tablet alone as "control group" for a period of four weeks. Patients were assessed at the beginning of intervention, and then 4 weeks later, in terms of pain score via visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire's total score in addition to its 3 sub-scores. Furthermore, they were asked about any adverse effects during intervention period. Mean differences of VAS pain, total WOMAC, and WOMAC physical function scores in green tea group showed a significant reduction, compared with the control group (P = 0.038, P = 0.006, and P = 0.004, respectively). However, No significant differences between the two groups were observed, regarding mean differences of WOMAC pain and stiffness scores of the enrolled patients (P = 0.163, and P = 0.150, respectively). Additionally, only 1 patient reported gastric upset [in control group]. It seems that green tea extract might well be considered as an adjunctive treatment both for control of pain and for the betterment of knee joint physical function in adults with osteoarthritis. However, further studies of longer duration and larger sample size are needed. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

    PubMed

    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.

  19. Cyclosporine 0.05% Ophthalmic Emulsion for Dry Eye in Korea: A Prospective, Multicenter, Open-Label, Surveillance Study

    PubMed Central

    Byun, Yong-Soo; Rho, Chang Rae; Cho, Kyungjin; Choi, Jin A; Na, Kyung Sun

    2011-01-01

    Purpose To assess the effectiveness and tolerability of cyclosporine ophthalmic emulsion (CsA) 0.05% in patients with moderate to severe dry eye disease in Korea. Methods This was a prospective, multicenter, open-label, surveillance study of 392 Korean patients with moderate to severe dry eye disease who were treated with CsA 0.05% for three months. An assessment of effectiveness was performed at baseline, and after 1, 2, and 3 months. The primary effectiveness outcomes were changes in ocular symptoms and Schirmer score. The secondary effectiveness outcomes were a change in conjunctival staining, use of artificial tears, global evaluation of treatment, and patient satisfaction. The primary safety outcome was the incidence and nature of adverse events. Results A total of 362 patients completed the study. After three months, all ocular symptom scores were significantly reduced compared to the baseline values, while the Schirmer scores were significantly increased relative to baseline (p < 0.0001). After three months, there were significant reductions from baseline in conjunctival staining (p < 0.01) and use of artificial tears (p < 0.0001). According to clinicians' global evaluations, most patients (>50%) experienced at least a 25% to 50% improvement in symptoms from baseline at each follow-up visit. The majority of patients (72.0%) were satisfied with the treatment results, and 57.2% reported having no or mild symptoms after treatment. The most common adverse events were ocular pain (11.0%). Conclusions Our findings indicate that CsA 0.05% is an effective and tolerable treatment for dry eye disease in Korean clinical practice. PMID:22131772

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

    PubMed Central

    Hirano, Jinichi; Watanabe, Koichiro; Suzuki, Takefumi; Uchida, Hiroyuki; Den, Ryosuke; Kishimoto, Taishiro; Nagasawa, Takashi; Tomita, Yusuke; Hara, Koichiro; Ochi, Hiromi; Kobayashi, Yoshimi; Ishii, Mutsuko; Fujita, Akane; Kanai, Yoshihiko; Goto, Megumi; Hayashi, Hiromi; Inamura, Kanako; Ooshima, Fumiko; Sumida, Mariko; Ozawa, Tomoko; Sekigawa, Kayoko; Nagaoka, Maki; Yoshimura, Kae; Konishi, Mika; Inagaki, Ataru; Saito, Takuya; Motohashi, Nobutaka; Mimura, Masaru; Okubo, Yoshiro; Kato, Motoichiro

    2013-01-01

    Objective 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-old) participated in this study. The baseline PANSS total score indicated the presence of severe psychopathology and was significantly higher in the ALGO group (n = 25; 106.9 ± 20.0) than in the TAU group (n = 17; 92.2 ± 18.3) (P = 0.021). As a result of treatment, there were no significant differences in the PANSS reduction rates, premature attrition rates, as well as in a variety of other clinical measures between the groups. Despite an effort to make each group unique in pharmacologic treatment, it was found that pharmacotherapy in the TAU group eventually became similar in quality to that of the ALGO group. Conclusion While the results need to be carefully interpreted in light of a hard-to-distinguish treatment manner between the two groups and more studies are necessary, algorithm-based antipsychotic treatments for schizophrenia compared well to treatment-as-usual in this study. PMID:24143104

  1. Thalidomide induces clinical remission and mucosal healing in adults with active Crohn's disease: a prospective open-label study.

    PubMed

    He, Yao; Mao, Ren; Chen, Fang; Xu, Ping-Ping; Chen, Bai-Li; Wu, Yun; Qiu, Yun; Zhang, Sheng-Hong; Feng, Rui; Zeng, Zhi-Rong; Ben-Horin, Shomron; Chen, Min-Hu

    2017-05-01

    Thalidomide is effective in inducing and maintaining clinical remission in children and adolescents with refractory Crohn's disease (CD). However, little is known about the efficacy and safety of thalidomide for adult patients with CD. We conducted a prospective open-label cohort study between January 2013 and April 2015. A total of 47 adult patients with active CD who were dependent/resistant or intolerant to corticosteroids and/or immunomodulators or biologics received 50-100 mg of thalidomide daily. Primary outcome was clinical remission evaluated at week 8. Endoscopic assessment was performed at week 24 and defined as endoscopic response (decrease in Crohn's Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal healing (MH) (no ulceration). A total of 47 adults with active CD were enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8, but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients included (intention-to-treat analysis). Altogether 32 patients consented and underwent ileocolonoscopy at week 24. The rate of endoscopic response and complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients but necessitated therapy discontinuation in only 5/47 (10.6%) of patients. Low-dose thalidomide was effective and tolerated for inducing and maintaining clinical remission in adult patients with active CD, but the optimal time frame for thalidomide to induce clinical remission may be longer than previously appreciated and is probably optimal at 12 weeks. MH could reasonably be achievable with thalidomide.

  2. Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial.

    PubMed

    Ballou, Sarah; Kaptchuk, Ted J; Hirsch, William; Nee, Judy; Iturrino, Johanna; Hall, Kathryn T; Kelley, John M; Cheng, Vivian; Kirsch, Irving; Jacobson, Eric; Conboy, Lisa; Lembo, Anthony; Davis, Roger B

    2017-05-25

    Placebo medications, by definition, are composed of inactive ingredients that have no physiological effect on symptoms. Nonetheless, administration of placebo in randomized controlled trials (RCTs) and in clinical settings has been demonstrated to have significant impact on many physical and psychological complaints. Until recently, conventional wisdom has suggested that patients must believe that placebo pills actually contain (or, at least, might possibly contain) active medication in order to elicit a response to placebo. However, several recent RCTs, including patients with irritable bowel syndrome (IBS), chronic low back pain, and episodic migraine, have demonstrated that individuals receiving open-label placebo (OLP) can still experience symptomatic improvement and benefit from honestly described placebo treatment. This paper describes an innovative multidisciplinary trial design (n = 280) that attempts to replicate and expand upon an earlier IBS OLP study. The current study will compare OLP to double-blind placebo (DBP) administration which is made possible by including a nested, double-blind RCT comparing DBP and peppermint oil. The study also examines possible genetic and psychological predictors of OLP and seeks to better understand participants' experiences with OLP and DBP through a series of extensive interviews with a randomly selected subgroup. OLP treatment is a novel strategy for ethically harnessing placebo effects. It has potential to re-frame theories of placebo and to influence how physicians can optimize watch-and-wait strategies for common, subjective symptoms. The current study aims to dramatically expand what we know about OLP by comparing, for the first time, OLP and DBP administration. Adopting a unique, multidisciplinary approach, the study also explores genetic, psychological and experiential dimensions of OLP. The paper ends with an extensive discussion of the "culture" of the trial as well as potential mechanisms of OLP and

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

    PubMed

    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.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26743120

  5. Patient-posture and Ileal-intubation during colonoscopy (PIC): a randomized controlled open-label trial.

    PubMed

    Ahammed, Sk Mahiuddin; Das, Kshaunish; Sarkar, R; Dasgupta, J; Bandopadhyay, S; Dhali, G K

    2014-06-01

    Patient's posture change is commonly employed by a colonoscopist to achieve complete examination. We studied whether patient's posture (left-lateral decubitus vs supine) influenced the success rate of ileal intubation. In this prospective open-label randomized study performed in the Endoscopy Suite of a tertiary-care center, all adult outpatients referred for colonoscopy, in whom cecal intubation was achieved and who satisfied predefined inclusion criteria, were randomized to undergo ileal intubation in either of the above two postures. Colonoscopy (EC-201 WL, Fujinon) was performed after overnight poly-ethylene-glycol preparation, under conscious sedation and continuous pulse-oxymetry monitoring. After confirming cecal intubation, patients were randomized for ileal intubation. Success was defined by visualization of ileal mucosa or villi (confirmed by digital photography) and was attempted until limited by pain and/or time of ≥ 6 min. Of 320 eligible patients, 217 patients (150 males) were randomized, 106 to left-lateral decubitus and 111 to supine posture. At baseline, the two groups were evenly matched. Successful ileal intubation was achieved in 145 (66.8 %) patients overall, significantly higher in the supine posture (74.8 % versus 58.5 %; P = 0.014). On multivariate analysis, supine posture (P = 0.02), average/good right-colon preparation (P < 0.01), non-thin-lipped ileocecal (IC) valve (P < 0.001) and younger age (P = 0.02) were independent predictors of success. Positive ileal findings were recorded in 13 (9 %) patients. Ileoscopy is more successful in supine than in left-lateral decubitus posture. Age, bowel preparation and type of IC valve also determine success.

  6. Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children

    ERIC Educational Resources Information Center

    Williams, Olajide; DeSorbo, Alexandra; Sawyer, Vanessa; Apakama, Donald; Shaffer, Michele; Gerin, William; Noble, James

    2016-01-01

    Objectives: We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. Method: We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after…

  7. Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children.

    PubMed

    Williams, Olajide; DeSorbo, Alexandra; Sawyer, Vanessa; Apakama, Donald; Shaffer, Michele; Gerin, William; Noble, James

    2016-02-01

    We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after the intervention (immediate and delayed) in schools. The intervention comprised three 1-hour assembly-style hip-hop-themed multimedia classes. A mean total of 225 children participated in two baseline preintervention sales with and without calorie labels; 149 children participated in immediate postintervention food sales, while 133 children participated in the delayed sales. No significant change in purchased calories was observed in response to labels alone before the intervention. However, a mean decline in purchased calories of 20% (p < .01) and unhealthy foods (p < .01) was seen in immediately following the intervention compared to baseline purchases, and this persisted without significant decay after 7 days and 12 days. A 3-hour culturally targeted calorie label intervention may improve food-purchasing behavior of children. © 2015 Society for Public Health Education.

  8. Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children

    ERIC Educational Resources Information Center

    Williams, Olajide; DeSorbo, Alexandra; Sawyer, Vanessa; Apakama, Donald; Shaffer, Michele; Gerin, William; Noble, James

    2016-01-01

    Objectives: We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. Method: We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after…

  9. 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.

    PubMed

    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 <45 years, n = 140; 45-64 years, n = 444; 65-74 years, n = 208; ≥75 years, n = 98); 49% continued treatment for ≥ 24 months (age <45 years, 43%; 45-64 years, 54%; 65-74 years, 50%; ≥75 years, 37%). Seventy-seven percent of subjects remained on fesoterodine 8 mg throughout treatment; this rate was highest among subjects aged ≥75 years (age <45 years, 72%; 45-64 years, 77%; 65-74 years, 73%; ≥75 years, 87%). Approximately 80% of continuing subjects were receiving 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 <45 years, ≥90%; 45-64 years, ≥93%; 65

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

    PubMed

    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.

  11. Emergency in-flight egress opening for general aviation aircraft. [pilot bailout

    NASA Technical Reports Server (NTRS)

    Bement, L. J.

    1980-01-01

    An emergency in-flight egress system was installed in a light general aviation airplane. The airplane had no provision for egress on the left side. To avoid a major structural redesign for a mechanical door, an add on 11.2 kg (24.6 lb) pyrotechnic-actuated system was developed to create an opening in the existing structure. The skin of the airplane was explosively severed around the side window, across a central stringer, and down to the floor, creating an opening of approximately 76 by 76 cm. The severed panel was jettisoned at an initial velocity of approximately 13.7 m/sec. System development included a total of 68 explosive severance tests on aluminum material using small samples, small and full scale flat panel aircraft structural mockups, and an actual aircraft fuselage. These tests proved explosive sizing/severance margins, explosive initiation, explosive product containment, and system dynamics. This technology is applicable to any aircraft of similar construction.

  12. The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study.

    PubMed

    Ketter, Terence A; Sachs, Gary S; Durgam, Suresh; Lu, Kaifeng; Starace, Anju; Laszlovszky, István; Németh, György

    2017-08-18

    We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania. In this multinational, multicenter study, open-label, flexible-dose, cariprazine 3-12mg/d was administered for up to 16 weeks to patients (18-65 years) with bipolar mania. Safety evaluations included adverse events (AEs), laboratory values, vital signs, and extrapyramidal symptom (EPS) scales. Symptom change was evaluated by Young Mania Rating Scale (YMRS) total score change from baseline using the last observation carried forward approach. Of the 402 patients taking cariprazine, 33% completed the trial; the most frequent reasons for discontinuation were withdrawal of consent (20%), AEs (16%), and protocol violation (14%). Most common AEs leading to discontinuation were akathisia (4.7%) and depression (1.5%). Mean treatment duration was 57.7 days; mean cariprazine dose was 6.2mg/d. The incidence of serious AEs was 7.5% (most common: mania [2.2%], depression [1.2%]); 83.3% had treatment-emergent AEs, including akathisia (32.6%), headache (16.7%), constipation (10.7%), and nausea (10.4%). Mean body weight increased <1kg; 9.3% had ≥7% weight gain; 5.7% had sedation; 3% had somnolence. Mean changes in laboratory values, vital signs, ECGs, and ophthalmology parameters were not clinically significant. Mean YMRS total score decreased by -15.2 at week 16. Uncontrolled, open-label design. Open-label cariprazine 3-12 (mean 6.2) mg/d for up to 16 weeks was generally well tolerated, with low (<10%) rates of sedation and ≥7% weight gain. Although akathisia occurred in 33%, it yielded discontinuation in <5%. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study.

    PubMed

    Cutler, Andrew J; Durgam, Suresh; Wang, Yao; Migliore, Raffaele; Lu, Kaifeng; Laszlovszky, István; Németh, György

    2017-05-08

    Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia. This was a multicenter, open-label, flexible-dose study of cariprazine 3-9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3-9 mg/d) and 4 weeks of safety follow-up. A total of 586 patients received open-label cariprazine treatment, ~39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable. Long-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.

  14. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study.

    PubMed

    Durgam, Suresh; Greenberg, William M; Li, Dayong; Lu, Kaifeng; Laszlovszky, Istvan; Nemeth, Gyorgy; Migliore, Raffaele; Volk, Stephen

    2017-01-01

    Cariprazine, a dopamine D3/D2 receptor partial agonist antipsychotic, demonstrated efficacy and tolerability in 6-week, randomized, placebo-controlled schizophrenia trials. Schizophrenia is a chronic disorder that requires continuous treatment; therefore, the long-term safety and tolerability profile of antipsychotic agents is an important factor in guiding clinician decisions. This single-arm, open-label extension study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia. Patients enrolled in this study completed a 6-week, randomized, placebo- and active-controlled study and had responded (Clinical Global Impressions-Severity [CGI-S] ≤3; ≥20 % reduction in Positive and Negative Syndrome Scale [PANSS] total score) to treatment at the end of the lead-in study. Patients (N = 93) received flexibly dosed, open-label cariprazine (1.5-4.5 mg/day) for up to 48 weeks. Approximately 50 % (46/93) of patients completed the 48 weeks of open-label treatment. The most common adverse events (AEs) were akathisia (14 %), insomnia (14 %), and weight increased (12 %). Serious AEs (SAEs) occurred in 13 % of patients; 11 % discontinued due to AEs. Mean changes in metabolic parameters were generally small and not clinically relevant. Mean body weight increased by 1.9 kg from the start of the lead-in study to the end of the extension study. There were no discontinuations associated with change in metabolic parameters or body weight. Long-term cariprazine treatment was not associated with prolactin elevation or clinically significant changes in cardiovascular parameters. In this 48-week, single-arm trial, open-label cariprazine (1.5-4.5 mg/day) treatment was generally safe and well tolerated with no new safety concerns associated with long-term treatment.

  15. Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials.

    PubMed Central

    Hays, J T; Croghan, I T; Schroeder, D R; Offord, K P; Hurt, R D; Wolter, T D; Nides, M A; Davidson, M

    1999-01-01

    OBJECTIVES: The purpose of this study was to determine the efficacy and safety of the nicotine patch for smoking cessation in an over-the-counter environment. The years of study were 1994 to 1995. METHODS: Parallel 6-week trials were conducted: a placebo-controlled trial of no-cost 22-mg, 24-hour nicotine patch therapy and an open label trial of the same therapy with patches purchased by subjects. Participants (n = 958) were 18 years or older, had smoked at least 15 cigarettes daily for at least 6 months, and were enrolled at 3 study sites. The main outcome measure was self-reported smoking abstinence confirmed by expired carbon monoxide measurements. RESULTS: Smoking cessation rates in the placebo-controlled trial were 16.8% and 9.6% at week 6 and 8.7% and 4.3% at week 24 for the active patch and placebo groups, respectively. Smoking cessation rates in the open label-pay trial were 19.0% and 10.8% at weeks 6 and 24, respectively. A slight increase in adverse cardiovascular events was noted only in the open label-pay group in comparison with the placebo group. CONCLUSIONS: In an over-the-counter environment, the 22-mg, 24-hour nicotine patch is effective and safe for smoking cessation treatment. PMID:10553392

  16. Open source challenges for hospital information system (HIS) in developing countries: a pilot project in Mali

    PubMed Central

    2010-01-01

    Background We are currently witnessing a significant increase in use of Open Source tools in the field of health. Our study aims to research the potential of these software packages for developing countries. Our experiment was conducted at the Centre Hospitalier Mere Enfant in Mali. Methods After reviewing several Open Source tools in the field of hospital information systems, Mediboard software was chosen for our study. To ensure the completeness of Mediboard in relation to the functionality required for a hospital information system, its features were compared to those of a well-defined comprehensive record management tool set up at the University Hospital "La Timone" of Marseilles in France. It was then installed on two Linux servers: a first server for testing and validation of different modules, and a second one for the deployed full implementation. After several months of use, we have evaluated the usability aspects of the system including feedback from end-users through a questionnaire. Results Initial results showed the potential of Open Source in the field of health IT for developing countries like Mali. Five main modules have been fully implemented: patient administrative and medical records management of hospital activities, tracking of practitioners' activities, infrastructure management and the billing system. This last component of the system has been fully developed by the local Mali team. The evaluation showed that the system is broadly accepted by all the users who participated in the study. 77% of the participants found the system useful; 85% found it easy; 100% of them believe the system increases the reliability of data. The same proportion encourages the continuation of the experiment and its expansion throughout the hospital. Conclusions In light of the results, we can conclude that the objective of our study was reached. However, it is important to take into account the recommendations and the challenges discussed here to avoid several

  17. Selective serotonin reuptake inhibitor combined with dengzhanshengmai capsule improves the fatigue symptoms: a 12-week open-label pilot study

    PubMed Central

    Li, De-Qiang; Li, Zhong-Chun; Dai, Zhi-Yuan

    2015-01-01

    Objective: This study was to assess the efficacy and safety of selective serotonin reuptake inhibitor (SSRI) plus Dengzhanshengmai capsule in patients with chronic fatigue syndrome (CFS). Methods: SSRI at a moderate dose plus Dengzhanshengmai (n = 134) with SSRI alone (n = 134) were compared for the efficacy and safety in the treatment of CFS. The therapeutic efficacy and safety were evaluated. Results: As compared to monotherapy group, the efficacy in combined therapy group was better and characterized by the improvement of general fatigue (0.8±0.6 vs. 1.3±0.7), physical fatigue (0.6±0.3 vs. 1.0±0.4) and reduced activity (1.0±0.5 vs. 1.3±0.6) since the 2nd week (P<0.01) and in reduced motivation (2.1±0.8 vs. 2.4±1.0) since the 8th week (P<0.01) and the improvement continued thereafter. The mental fatigue score and HAD score were comparable between two groups (P>0.05). No significant difference was found in the drop-out rate between SSRI group (15.7%) and SSRI plus Dengzhanshengmai group (18.0%). The reasons for drop out were adverse events (7.5% vs. 9.7%), requests of the patients or career requirement (3.7% vs. 4.5%), loss to follow-up and others (2.2% vs. 3.0%) and lack of efficacy (2.2% vs. 0.7%). Although the patients in combined therapy group experienced a higher rate of hypertension than (5.8% vs. 1.5%), no significant difference was observed (P = 0.08). Conclusion: SSRI combined with Dengzhanshengmai capsule may significantly improve the general fatigue, physical fatigue, reduced activity and reduced motivation of CFS patients as compared to monotherapy with SSRI. Furthermore, this combined therapy is safe and tolerable. PMID:26380022

  18. Open-label pilot study of extended-release naltrexone to reduce drinking and driving among repeat offenders.

    PubMed

    Lapham, Sandra C; McMillan, Garnett P

    2011-09-01

    A high proportion of persons convicted of driving while impaired repeat the offense. Many continue drinking and driving, even when faced with long jail terms. Hence, they pose a serious public health threat. This preliminary study evaluated extended-release, injectable naltrexone suspension (XR-NTX) and supportive therapy in reducing (1) drinking and (2) attempts to drive after drinking among repeat driving while impaired offenders with an ignition interlock device installed in their vehicles. Treatment-seeking volunteers received medical management therapy and 3 monthly injections of XR-NTX. We compared data on alcohol consumption, alcohol biomarkers, and interlock information before, during, and after treatment using summary measures and Sign tests. Of 12 consented subjects, 10 received at least 1 injection, and 7 received all 3 injections. All subjects receiving medication reported a decrease in average drinks per day (P < 0.01) and abstinent days (P = 0.02) while on treatment versus pretreatment levels. Average daily drinks decreased by 77%, from 3.0 to 0.69 (P < 0.01), during treatment with XR-NTX. Average drinks per drinking day also declined by 39% during treatment, from 6.6 to 4.0 (P = 0.04). Percent days abstinent increased by 31%, from 56.8 to 81.96 (P = 0.02), which persisted after treatment completion. Biomarkers were consistent with reduced drinking. The percentage of vehicular failures to start due to elevated breath alcohol decreased from 3.1% of tests to 1.29% of tests. A randomized, controlled clinical trial is needed to demonstrate the efficacy of this promising treatment regimen for repeat offenders.

  19. An open-label pilot study of apremilast for the treatment of moderate to severe lichen planus: a case series.

    PubMed

    Paul, Joan; Foss, Clare E; Hirano, Stefanie A; Cunningham, Tina D; Pariser, David M

    2013-02-01

    Current treatments for chronic lichen planus (LP) are often ineffective and may have significant adverse side effects. An alternative safe and effective treatment for recalcitrant LP is needed. We sought to study the safety and efficacy of apremilast in the treatment of moderate to severe LP. Ten patients with biopsy-proven LP received 20 mg of apremilast orally twice daily for 12 weeks with 4 weeks of treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving a 2-grade or more improvement in the Physician Global Assessment (PGA) after 12 weeks of treatment. Three (30%) of the 10 patients achieved a 2-grade or more improvement in the PGA after 12 weeks of treatment; however, all patients demonstrated statistically significant clinical improvement with respect to secondary parameters between baseline and the end of treatment. It may be difficult to generalize the results of this study to a larger patient population with LP because of our small sample size and lack of a control group. In addition, a longer treatment period or higher dose may have been needed for therapeutic efficacy. The safety and efficacy of long-term apremilast therapy is currently unknown. Apremilast may be efficacious in the treatment of LP, but double-blinded, controlled trials are necessary to thoroughly evaluate its safety and efficacy. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study.

    PubMed

    Schmidt, Vanessa; Buckley, Laura M; McEwan, Neil A; Rème, Christophe A; Nuttall, Tim J

    2012-02-01

    This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance(®); Virbac SA) in 10 cats with presumed allergic dermatitis. The cats initially received two sprays/100 cm(2) of skin once daily. Clinical lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm visual analog scale with grade descriptors) and owner assessments of efficacy, tolerance and ease of use (from 1=very poor to 5=excellent) were assessed every 14 days. The frequency of treatment was reduced after day 28 in cats with a >50% reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28 and two at day 42. Intention-to-treat data were analysed. The FeDESI [mean (SD): day 0, 42.2 (15.7) and day 56, 9.9 (11.7); P<0.0001] and pruritus scores [day 0, 61.2 mm (20.1) and day 56, 14.6 mm (16.1); P<0.0001] significantly decreased throughout the trial. The owner scores for tolerance [median (range): day 14, 4 (1-5) and day 56, 4 (3-5); P=0.003] and ease of administration [day 14, 3 (2-5) and day 56, 4 (2-5); P=0.02] significantly increased during the trial, but there was no significant change in efficacy scores [day 14, 4 (3-5) and day 56, 4 (2-5); P=0.5]. There were no adverse effects attributable to the HCA spray, no significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg (1.6); P=0.51] and no significant changes in haematology, biochemistry or urinalysis (n=4). Six cats required every-other-day treatment and four required daily treatment. In conclusion, HCA spray appeared to be effective and safe in these cats, although it is not licensed for use in this species.

  1. Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study

    PubMed Central

    Gervits, Felix; Ash, Sharon; Coslett, H. Branch; Rascovsky, Katya; Grossman, Murray; Hamilton, Roy

    2016-01-01

    Primary progressive aphasia (PPA) is a neurodegenerative condition characterized by gradual deterioration of language function. We investigated whether two weeks of daily transcranial direct current stimulation (tDCS) treatment would improve language abilities in six people with a non-fluent form of PPA. tDCS was applied in an unblinded trial at an intensity of 1.5 mA for 20 min/day over 10 days. At the time of stimulation, patients were engaged in narrating one of several children’s wordless picture stories. A battery of neuropsychological assessments was administered four times: at baseline, immediately following the 2-week stimulation period, and then 6-weeks and 12-weeks following the end of stimulation. We observed improvement in linguistic performance in the domains of speech production and grammatical comprehension. Our encouraging results indicate that larger, sham-controlled studies of tDCS as a potential intervention for PPA are warranted. PMID:27522537

  2. An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

    PubMed

    Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

    2013-12-01

    The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to <45 kg, and 1.75 mg/day for those weighing ≥ 45 kg. The study primarily assessed risperidone's safety; efficacy was assessed as a secondary end-point. Fifty-six (71%) out of 79 enrolled patients completed the OLE; the most common discontinuations were for insufficient response (7 [9%]) or adverse events (AE) (5 [6%]). The most common (≥ 5% frequency in the total group) AEs were increased appetite (11% [n=9]); increased weight and vomiting (9% [n=7] each); sedation, pyrexia, and upper respiratory tract infection (8% [n=6] each); nasopharyngitis (6% [n=5]); and somnolence and fatigue (5% [n=4] each). Extrapyramidal AEs were reported in 6 (8%) patients. Increase in mean weight (11-15%) and body mass index (5-10%) occurred; one patient discontinued because of weight increase. One potentially prolactin-related AE (irregular menstruation) was reported. The risperidone high-dose group had the greatest mean improvement in sleep visual analog scale (24.6). All groups showed additional improvement in efficacy scale scores during the OLE. During this OLE, safety findings with risperidone treatment (maximum weight-based dose of 1.25 mg/day or 1.75 mg/day) were consistent with those observed in the DB phase, and with the current safety information for risperidone in autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

  3. Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia.

    PubMed

    Zhang, Bin; Hao, Yanli; Jia, Fujun; Li, Xueli; Ren, Yanzhen; Zhou, Ping; Liu, Wuhan; Wing, Yun Kwok

    2013-12-01

    Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might induce or exacerbate periodic limb movements during sleep (PLMS). However, most of these studies were retrospective and cross-sectional studies with small sample sizes on a selective SSRI, fluoxetine. Because different SSRIs have different pharmacologic profiles, it was not certain if other SSRIs also might lead to PLMS. Data were taken from an open-label 8-week trial of sertraline in depressive patients with insomnia (n=31). Depressed patients were administered sertraline 50mg at 8:00am on the first day, and the dosage was subsequently titrated up to a maximum of 200mg daily during the 8-week trial. All participants were tested by repeated polysomnography (PSG) (baseline, first day, 14th day, 28th day, and 56th day). Periodic leg movements (PLM) were visually counted and the PLM index (PLMI) was calculated. PLMS was defined as PLMI ⩾5, and significant PLMS was defined as PLMI ⩾15. Compared with baseline (PLMI, 3.6±1.5), all PLMI indices increased on the immediate administration of sertraline on the first day (PLMI, 5.1±3.9). From the 14th day onward, PLMI became stable and significantly higher than baseline and the first day (8.7±3.1 on the 14th day, 8.3±3.7 on the 28th day, and 8.5±3.6 on the 56th day; F[11.81]; P=.003). The clinical responses and PSG characteristics continuously improved during the 8-week trial. The PLMS group (PLMI ⩾5) had a higher arousal index (AI) than the non-PLMS group on the 14th day (9.4±5.5 vs 5.2±3.7; t test, 4.22; P=.03) and the 56th day (8.1±5.5 vs 4.3±3.7; z score, 3.11; P=.04); albeit, there was no significant clinical disturbances in the PLMS group. PLMS were increased during sertraline treatment, but only a few of the PLMS reached the significant level. This effect of sertraline on PLMS might be dosage dependent. Although the sertraline-induced PLMS did not seem to cause significant clinical disturbance, the PLMS group (PLMI

  4. Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.

    PubMed

    Kuwabara, Satoshi; Mori, Masahiro; Misawa, Sonoko; Suzuki, Miki; Nishiyama, Kazutoshi; Mutoh, Tatsuro; Doi, Shizuki; Kokubun, Norito; Kamijo, Mikiko; Yoshikawa, Hiroo; Abe, Koji; Nishida, Yoshihiko; Okada, Kazumasa; Sekiguchi, Kenji; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

    2017-10-01

    Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. ClinicalTrials.gov (NCT01824251). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  5. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh.

    PubMed

    Abedin, Mohammed Joynal; Sayeed, Abdullah Abu; Basher, Ariful; Maude, Richard J; Hoque, Gofranul; Faiz, M A

    2012-06-01

    Severe organophosphate compound (OPC) poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine the best therapy. A study was therefore undertaken to determine the optimal dosing regimen for atropine in the treatment of OPC poisoning. An open-label randomized clinical trial was conducted in Chittagong Medical College Hospital, Chittagong, Bangladesh, on 156 hospitalized individuals with OPC poisoning from June to September 2006. The aim was to compare the efficacy and safety of conventional bolus doses with individualized incremental doses of atropine for atropinization followed by continuous atropine infusion for management of OPC poisoning. Inclusion criteria were patients with a clear history of OPC poisoning with clear clinical signs of toxicity, i.e. features of cholinergic crisis. The patients were observed for at least 96 h. Immediate outcome and complications were recorded. Out of 156 patients, 81 patients received conventional bolus dose atropine (group A) and 75 patients received rapidly incremental doses of atropine followed by infusion (group B). The mortality in group 'A' was 22.5% (18/80) and in group 'B' 8% (6/75) (p < 0.05). The mean duration of atropinization in group 'A' was 151.74 min compared to 23.90 min for group 'B' (p < 0.001). More patients in group A experienced atropine toxicity than in group 'B' (28.4% versus 12.0%, p < 0.05); intermediate syndrome was more common in group 'A' than in group 'B' (13.6% versus 4%, p < 0.05), and respiratory support was required more often for patients in group 'A' than in group 'B' (24.7% versus 8%, p < 0.05). Rapid incremental dose atropinization followed by atropine infusion reduces mortality and morbidity from OPC poisoning and shortens the length of hospital stay and recovery. Incremental atropine and infusion should become the treatment of choice for OPC

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

    PubMed

    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

  7. Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study.

    PubMed

    Aalbers, René; Brusselle, Guy; McIver, Tammy; Grothe, Birgit; Bodzenta-Lukaszyk, Anna

    2012-11-01

    The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta(2)-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments. Adults with mild-to-moderate-severe persistent asthma were randomized to fluticasone/formoterol (100/10 or 250/10 μg twice daily [b.i.d.]) or fluticasone/salmeterol (100/50 or 250/50 μg b.i.d.) for 12 weeks. The onset of bronchodilation (the first post-dose time point at which the forced expiratory volume in 1 second [FEV(1)] was ≥12% greater than the pre-dose value), responder rates (the proportion of patients achieving bronchodilation), and changes in FEV(1) were assessed at days 0 (baseline) and 84. Fluticasone/formoterol (n = 101) provided more rapid onset of bronchodilation than fluticasone/salmeterol (n = 101) over the first 120 min post-dose on days 0 (hazard ratio [HR] = 1.47 [95% CI 1.05-2.05]) and 84 (HR = 1.77 [95% CI 1.14-2.73]). The odds of a patient achieving bronchodilation within 5 min of dosing were almost four-times higher with fluticasone/formoterol than with fluticasone/salmeterol on day 0 (odds ratio [OR] = 3.97 [95% CI 1.96-8.03]) and almost 10-times higher on day 84 (OR = 9.58 [95% CI 2.14-42.90]); the odds of achieving bronchodilation within 120 min post-dose were approximately twofold higher with fluticasone/formoterol on both days. The overall percentage increase in least-squares (LS) mean FEV1 during the 120-min post-dose period was significantly greater with fluticasone/formoterol than fluticasone/salmeterol on days 0 (LS mean treatment difference: 4.70% [95% CI 1.57-7.83]; P = 0.003) and 84 (2.79% [95% CI 0.65-4.93]; P = 0.011). These analyses showed that fluticasone/formoterol provided a faster onset of

  8. An Open-Label Extension Study of the Safety and Efficacy of Risperidone in Children and Adolescents with Autistic Disorder

    PubMed Central

    Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

    2013-01-01

    Abstract Objective: The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. Methods: In this 6 month (26 week) open-label extension (OLE) study, patients (5–17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to <45 kg, and 1.75 mg/day for those weighing ≥45 kg. The study primarily assessed risperidone's safety; efficacy was assessed as a secondary end-point. Results: Fifty-six (71%) out of 79 enrolled patients completed the OLE; the most common discontinuations were for insufficient response (7 [9%]) or adverse events (AE) (5 [6%]). The most common (≥5% frequency in the total group) AEs were increased appetite (11% [n=9]); increased weight and vomiting (9% [n=7] each); sedation, pyrexia, and upper respiratory tract infection (8% [n=6] each); nasopharyngitis (6% [n=5]); and somnolence and fatigue (5% [n=4] each). Extrapyramidal AEs were reported in 6 (8%) patients. Increase in mean weight (11–15%) and body mass index (5–10%) occurred; one patient discontinued because of weight increase. One potentially prolactin-related AE (irregular menstruation) was reported. The risperidone high-dose group had the greatest mean improvement in sleep visual analog scale (24.6). All groups showed additional improvement in efficacy scale scores during the OLE. Conclusions: During this OLE, safety findings with risperidone treatment (maximum weight-based dose of 1.25 mg/day or 1.75 mg/day) were consistent with those observed in the DB phase, and with the current safety information for risperidone in autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. Clinical Trials Registry: This phase-4

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

    PubMed

    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

  10. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

    PubMed

    Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

    2009-05-16

    Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and

  11. Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial.

    PubMed

    Rajan, Arun; Carter, Corey A; Berman, Arlene; Cao, Liang; Kelly, Ronan J; Thomas, Anish; Khozin, Sean; Chavez, Ariel Lopez; Bergagnini, Isabella; Scepura, Barbara; Szabo, Eva; Lee, Min-Jung; Trepel, Jane B; Browne, Sarah K; Rosen, Lindsey B; Yu, Yunkai; Steinberg, Seth M; Chen, Helen X; Riely, Gregory J; Giaccone, Giuseppe

    2014-02-01

    No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy. Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250. 49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3-36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions

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

    PubMed Central

    Dewan, Bhupesh; Chimata, Raghuram

    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 profiles 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 wash-out 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% confidence 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 t½(1.92 ± 0.94 h vs 2.05 ± 1.01 h, P < 0.05). The 90% confidence 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

  13. The shortened infusion time of intravenous ibuprofen, part 2: a multicenter, open-label, surgical surveillance trial to evaluate safety.

    PubMed

    Gan, Tong J; Candiotti, Keith; Turan, Alparslan; Buvanendran, Asokumar; Philip, Beverly K; Viscusi, Eugene R; Soghomonyan, Suren; Bergese, Sergio D

    2015-02-01

    The literature and clinical data support the use of intravenous (IV) infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. According to current guidelines, IV ibuprofen can be administered via a slow IV infusion performed during a 30-minute period. Although recent studies indicate that more rapid infusions may yield additional benefits for patients, the safety of such an approach needs further evaluation. The main purpose of this study was to determine the safety of single and multiple doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction of anesthesia and after the surgical procedure for the treatment of postoperative pain. This was a Phase IV, multicenter, open-label, clinical surveillance study. It was conducted at 21 hospitals in the United States, and 300 adult hospitalized patients undergoing surgery were enrolled. The exclusion criteria for the study were: inadequate IV access; hypersensitivity to any component of IV ibuprofen, aspirin, or related products; and any active, clinically significant bleeding. Also excluded were patients who had taken NSAIDs <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female patients; and patients in the perioperative period of coronary artery bypass graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10 minutes preoperatively. Vital signs, adverse events, and pain scores were assessed. Approximately 22% (65 of 300) of patients reported adverse events (serious and nonserious). The most common adverse event was infusion site pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious adverse events, 8 of which occurred during the first 6 hours. All serious events reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%) discontinued the study drug due to an adverse event (1 patient discontinued the study because of infusion site pain, and 1 patient

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

    PubMed Central

    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 p< 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ≥ 2 points. Significant improvements from baseline (p< 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. Conclusion: Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of

  15. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: A randomized controlled open-label trial

    PubMed Central

    Adenis, A.; Blay, J.-Y.; Bui-Nguyen, B.; Bouché, O.; Bertucci, F.; Isambert, N.; Bompas, E.; Chaigneau, L.; Domont, J.; Ray-Coquard, I.; Blésius, A.; Van Tine, B. A.; Bulusu, V. R.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Le Cesne, A.

    2014-01-01

    Background Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09–0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16–0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6–2.2, P

  16. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

    PubMed

    Kang, Dae-Wook; Adams, James B; Gregory, Ann C; Borody, Thomas; Chittick, Lauren; Fasano, Alessio; Khoruts, Alexander; Geis, Elizabeth; Maldonado, Juan; McDonough-Means, Sharon; Pollard, Elena L; Roux, Simon; Sadowsky, Michael J; Lipson, Karen Schwarzberg; Sullivan, Matthew B; Caporaso, J Gregory; Krajmalnik-Brown, Rosa

    2017-01-23

    Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10(13) bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after

  17. Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson'd Disease: Final 12-Month, Open-Label Results

    PubMed Central

    Fernandez, Hubert H; Standaert, David G; Hauser, Robert A; Lang, Anthony E; Fung, Victor SC; Klostermann, Fabian; Lew, Mark F; Odin, Per; Steiger, Malcolm; Yakupov, Eduard Z; Chouinard, Sylvain; Suchowersky, Oksana; Dubow, Jordan; Hall, Coleen M; Chatamra, Krai; Robieson, Weining Z; Benesh, Janet A; Espay, Alberto J

    2015-01-01

    Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. l-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces l-dopa-plasma–level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day “off” time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, “on” time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks. © 2014 The Authors. Movement Disorders published by Wiley

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

    PubMed

    Romero, Gustavo Adolfo Sierra; 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

    2017-06-01

    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.

  19. Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation.

    PubMed

    Jooste, Edmund H; Hammer, Gregory B; Reyes, Christian R; Katkade, Vaibhav; Szmuk, Peter

    2017-01-01

    Dexmedetomidine (Precedex™) may be used as an alternative sedative in children, maintaining spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on age: patients aged ≥28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1 μg/kg load; 0.05-0.2 μg/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1 μg/kg load; 0.2-2.0 μg/kg/h infusion). Sedation efficacy was assessed and defined as adequate sedation for at least 80% of the time and successful completion of the procedure without the need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level 2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose level 2 discontinued treatment for the following reasons: early completion of diagnostic or therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression (bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for age or relative decrease of 30% from baseline) and hypotension. Four patients received glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension. SpO2 dropped by 10% in

  20. An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis.

    PubMed

    Dolling, David I; Desai, Monica; McOwan, Alan; Gilson, Richard; Clarke, Amanda; Fisher, Martin; Schembri, Gabriel; Sullivan, Ann K; Mackie, Nicola; Reeves, Iain; Portman, Mags; Saunders, John; Fox, Julie; Bayley, Jake; Brady, Michael; Bowman, Christine; Lacey, Charles J; Taylor, Stephen; White, David; Antonucci, Simone; Gafos, Mitzy; McCormack, Sheena; Gill, Owen N; Dunn, David T; Nardone, Anthony

    2016-03-24

    Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in

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

    PubMed

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

    2015-09-01

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

  2. Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.

    PubMed

    Lin, Yumei; Kazlova, Valentina; Ramakrishnan, Shyam; Murray, Mary A; Fast, David; Chandra, Amitabh; Gellenbeck, Kevin W

    2016-01-15

    Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could

  3. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial.

    PubMed

    Adenis, A; Blay, J-Y; Bui-Nguyen, B; Bouché, O; Bertucci, F; Isambert, N; Bompas, E; Chaigneau, L; Domont, J; Ray-Coquard, I; Blésius, A; Van Tine, B A; Bulusu, V R; Dubreuil, P; Mansfield, C D; Acin, Y; Moussy, A; Hermine, O; Le Cesne, A

    2014-09-01

    Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). Primary efficacy analysis ensured

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

    PubMed Central

    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

  5. Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma with Drug Eluting Beads: Results of an Open-Label Study of 62 Patients

    SciTech Connect

    Malagari, Katerina Chatzimichael, Katerina; Alexopoulou, Efthymia; Kelekis, Alexios; Hall, Brenda; Dourakis, Spyridon; Delis, Spyridon; Gouliamos, Athanasios; Kelekis, Dimitrios

    2008-03-15

    The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 {mu}m. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. {alpha}-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10{sup -11}) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, {gamma}-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of

  6. Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma.

    PubMed

    Cheng, Ann-Lii; Thongprasert, Sumitra; Lim, Ho Yeong; Sukeepaisarnjaroen, Wattana; Yang, Tsai-Shen; Wu, Cheng-Chung; Chao, Yee; Chan, Stephen L; Kudo, Masatoshi; Ikeda, Masafumi; Kang, Yoon-Koo; Pan, Hongming; Numata, Kazushi; Han, Guohong; Balsara, Binaifer; Zhang, Yong; Rodriguez, Ana-Marie; Zhang, Yi; Wang, Yongyu; Poon, Ronnie T P

    2016-09-01

    Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and sorafenib, respectively. Common any-cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, respectively [P = 0.0002]). Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for

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

    PubMed

    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 Cl