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Sample records for 52-week multicenter randomized

  1. 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.

  2. Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study.

    PubMed

    Correll, Christoph U; Kohegyi, Eva; Zhao, Cathy; Baker, Ross A; McQuade, Robert; Salzman, Phyllis M; Sanchez, Raymond; Nyilas, Margaretta; Carson, William

    2017-09-01

    To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D2 receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia. This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed. Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline. Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia. Efficacy and Safety Study of Oral Aripiprazole in Adolescents With

  3. Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: A 52-week analysis from phase III open-label multicenter Japanese study.

    PubMed

    Imafuku, Shinichi; Honma, Masaru; Okubo, Yukari; Komine, Mayumi; Ohtsuki, Mamitaro; Morita, Akimichi; Seko, Noriko; Kawashima, Naoko; Ito, Saori; Shima, Tomohiro; Nakagawa, Hidemi

    2016-09-01

    Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and "much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP. © 2016 Japanese Dermatological Association.

  4. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study.

    PubMed

    Marcus, Ronald N; Owen, Randall; Manos, George; Mankoski, Raymond; Kamen, Lisa; McQuade, Robert D; Carson, William H; Findling, Robert L

    2011-09-01

    Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects (6-17 years) with autistic disorder. A 52-week, open-label, flexibly dosed (2-15 mg/d) study of the safety and tolerability of aripiprazole in outpatients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent, 8-week randomized trials or were enrolled de novo (ie, not treated in the randomized trials). Safety and tolerability measures included incidences of adverse events, extrapyramidal symptoms, weight, metabolic measures, vital signs, and other clinical assessments. Subjects were enrolled between September 2006 and June 2009. Three hundred thirty subjects entered the treatment phase: 86 de novo, 174 prior aripiprazole, and 70 prior placebo. A total of 199 (60.3%) subjects completed 52 weeks of treatment. Adverse events were experienced by 286/330 subjects (86.7%). Common adverse events included weight increase, vomiting, nasopharyngitis, increased appetite, pyrexia, upper respiratory tract infection, and insomnia. Discontinuations due to adverse events occurred in 35/330 randomized subjects (10.6%)-most commonly aggression and weight increase. One patient discontinued from the study due to a laboratory-related adverse event (moderately increased alanine transaminase and aspartate transaminase). Nine subjects experienced serious adverse events-most frequently aggression. Extrapyramidal symptoms-related adverse events occurred in 48/330 subjects (14.5%)-most commonly tremor (3.0%), psychomotor hyperactivity (2.7%), akathisia (2.4%), and dyskinesia (not tardive, 2.4%). At > 9 months' aripiprazole exposure (n = 220), mean change in body weight z score was 0.33 and body mass index z score was 0.31. The percentages of subjects with clinically significant fasting metabolic abnormalities at > 9 months were 2% for glucose, 5% for total cholesterol, 7% for low-density lipoprotein cholesterol, 30% for high

  5. Predictors of relapse in patients with major depressive disorder in a 52-week, fixed dose, double blind, randomized trial of selegiline transdermal system (STS).

    PubMed

    Jang, Saeheon; Jung, Sungwon; Pae, Chiun; Kimberly, Blanchard Portland; Craig Nelson, J; Patkar, Ashwin A

    2013-12-01

    We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment. After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥ 14 and a CGI-S score of ≥ 3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse. For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis. While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across

  6. Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study.

    PubMed

    Blom, Dirk J; Djedjos, C Stephen; Monsalvo, Maria Laura; Bridges, Ian; Wasserman, Scott M; Scott, Rob; Roth, Eli

    2015-09-25

    Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. To determine the effects of evolocumab on vitamin E and steroid hormone levels. After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01516879. © 2015 American Heart Association, Inc.

  7. The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males--A Randomized Controlled Trial.

    PubMed

    Andersen, Thomas Rostgaard; Schmidt, Jakob Friis; Pedersen, Mogens Theisen; Krustrup, Peter; Bangsbo, Jens

    2016-01-01

    The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration: ClinicalTrials.gov: NCT01530035.

  8. The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males – A Randomized Controlled Trial

    PubMed Central

    Andersen, Thomas Rostgaard; Schmidt, Jakob Friis; Pedersen, Mogens Theisen; Krustrup, Peter; Bangsbo, Jens

    2016-01-01

    The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration ClinicalTrials.gov: NCT01530035 PMID:26886262

  9. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial.

    PubMed

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c. After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was -0.08% (-0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p < 0.0001) whereas the rate of nocturnal hypoglycemia was 75% lower (p < 0.0001) for IDegAsp versus IGlar. Nocturnal-confirmed hypoglycemia was higher with IGlar whereas overall and diurnal hypoglycemia were higher with IDegAsp dosed at breakfast. These results highlight the importance of administration of IDegAsp with the main meal of the day, tailored to the individual patient's needs. ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext].

  10. Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand*

    PubMed Central

    Lucas, Gregory M.; Young, Alicia; Donnell, Deborah; Richardson, Paul; Aramrattana, Apinun; Shao, Yiming; Ruan, Yuhua; Liu, Wei; Fu, Liping; Ma, Jun; Celentano, David D.; Metzger, David; Jackson, J. Brooks; Burns, David

    2014-01-01

    Background Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. Methods We compared rates of alanine aminotransferase (ALT) elevation ≥ grade 3 (ALT ≥ 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Results Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ≥ grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ≥ grade 2 occurred in 2% of subjects, with no significant difference between arms. Conclusions Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors. PMID:24999060

  11. Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

    PubMed Central

    Raphael, Gordon; Taveras, Herminia; Iverson, Harald; O’Brien, Christopher; Miller, David

    2016-01-01

    Abstract Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma. PMID:26369589

  12. Efficacy of tofacitinib for the treatment of nail psoriasis: Two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis.

    PubMed

    Merola, Joseph F; Elewski, Boni; Tatulych, Svitlana; Lan, Shuping; Tallman, Anna; Kaur, Mandeep

    2017-07-01

    Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated. We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks. In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. This post hoc analysis of patients with existing nail psoriasis assessed the Nail Psoriasis Severity Index (NAPSI) score and proportions of patients achieving ≥50% reduction in NAPSI from baseline (NAPSI50), NAPSI75, or NAPSI100. Baseline mean NAPSI scores for patients treated with tofacitinib 5 mg (N = 487), tofacitinib 10 mg (N = 476), and placebo (N = 233) twice daily were 27.0, 27.3, and 26.9, respectively. At week 16, significantly (all P < .05) more patients receiving tofacitinib 5 mg and tofacitinib 10 mg versus placebo twice daily achieved NAPSI50 (32.8%, 44.2% vs 12.0%), NAPSI75 (16.9%, 28.1% vs 6.8%), and NAPSI100 (10.3%, 18.2% vs 5.1%), respectively. Improvements were sustained to week 52. Limitations include discontinuation of clinical nonresponders at week 28. Tofacitinib treatment resulted in improvements in nail psoriasis versus placebo at week 16; improvements were maintained over 52 weeks [NCT01276639; NCT01309737]. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE).

    PubMed

    Reich, K; Gooderham, M; Green, L; Bewley, A; Zhang, Z; Khanskaya, I; Day, R M; Goncalves, J; Shah, K; Piguet, V; Soung, J

    2017-03-01

    Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons. At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast. Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant

  14. Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489

    PubMed Central

    Curtis, Sean P; Bockow, Barry; Fisher, Chester; Olaleye, Joseph; Compton, Amy; Ko, Amy T; Reicin, Alise S

    2005-01-01

    Background The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA) patients. Methods A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks), patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks); the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study. Results Compared with placebo, the etoricoxib groups displayed significant (p < 0.05), dose-dependent efficacy for all primary endpoints in Part I; efficacy was maintained throughout the 52 weeks of the study. During the 46-week active-comparator controlled period, the etoricoxib groups demonstrated clinical efficacy that was similar to that of diclofenac 150 mg and was generally well tolerated, with a lower incidence of gastrointestinal (GI) nuisance symptoms compared with diclofenac (13.1, 14.7, and 13.5% for etoricoxib 30, 60, and 90 mg, respectively compared with 22.5% for diclofenac). Conclusion In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated. PMID:16321158

  15. Safety and efficacy of the combination of the glucagon-like peptide-1 receptor agonist liraglutide with an oral antidiabetic drug in Japanese patients with type 2 diabetes: post hoc analysis of a randomized, 52-week, open-label, parallel-group trial.

    PubMed

    Kiyosue, Arihiro; Seino, Yutaka; Nishijima, Keiji; Bosch-Traberg, Heidrun; Kaku, Kohei

    2017-10-06

    The aim of this post hoc analysis was to investigate the safety and efficacy of liraglutide in combination with one oral antidiabetic drug (OAD) across different OAD classes. This was a post hoc analysis using data from a 52-week, open-label, parallel-group trial, in which patients with type 2 diabetes inadequately controlled with a single OAD (α-glucosidase inhibitor, glinide, metformin or thiazolidinedione) were randomized to either pre-trial OAD in combination with liraglutide 0.9 mg/day (liraglutide group) or pre-trial OAD in combination with an additional OAD (additional OAD group). The primary outcome investigated in this post hoc analysis was incidence of adverse events (AEs). The proportions of patients experiencing AEs across the different groups of pre-trial OADs were comparable between liraglutide and additional OAD (α-glucosidase inhibitor 74.6% vs 70.0%; glinide 93.1% vs 87.1%; metformin 91.8% vs 87.1%; thiazolidinedione 86.2% vs 96.4%, respectively). Minor hypoglycemia was infrequent (seven episodes in two patients randomized to liraglutide, and two episodes in two patients randomized to additional OAD). Mean reduction in glycated hemoglobin (HbA1c) appeared greater with liraglutide therapy, estimated mean treatment difference (95% confidence interval [CI]) for liraglutide versus additional OAD ranging from -0.14% (-0.48;0.21) [-1.5 mmol/mol (-5.2;2.3)] to -0.44% (-0.79;-0.09) [-4.8 mmol/mol (-8.6;-1.0)]. This analysis suggests that Japanese patients on OAD monotherapy may benefit from a greater improvement in glycemic control, without impacting tolerability, by combining their OAD with liraglutide rather than another OAD, regardless of which OAD monotherapy they are receiving. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study

    PubMed Central

    Jacobsen, Paula L.; Chen, Yinzhong; Serenko, Michael; Mahableshwarkar, Atul R.

    2014-01-01

    Patients with major depressive disorder often experience relapse after responding to treatment; therefore, maintenance therapy with antidepressants is recommended for maintaining response or remission. This multicenter, open-label, flexible-dose, 52-week extension study evaluated the long-term safety, tolerability, and maintenance of efficacy in study participants who had completed one of two randomized, double-blind, placebo-controlled, 8-week dose-ranging vortioxetine trials in study participants with major depressive disorder. At the open-label baseline, all study participants were switched to vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 2.5 to 10 mg/day on the basis of response and tolerability. Treatment with vortioxetine for 52 weeks was well tolerated, with no new safety signals identified. Among the 834 evaluable study participants, treatment-emergent adverse events were reported in 70.6%, with the most common in the combined (all doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to sexual dysfunction was low and weight gain was minimal. Laboratory values, vital signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale results showed no trends of clinical concern. The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set. PMID:24169027

  17. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.

    PubMed

    Alam, Mohammed Y; Jacobsen, Paula L; Chen, Yinzhong; Serenko, Michael; Mahableshwarkar, Atul R

    2014-01-01

    Patients with major depressive disorder often experience relapse after responding to treatment; therefore, maintenance therapy with antidepressants is recommended for maintaining response or remission. This multicenter, open-label, flexible-dose, 52-week extension study evaluated the long-term safety, tolerability, and maintenance of efficacy in study participants who had completed one of two randomized, double-blind, placebo-controlled, 8-week dose-ranging vortioxetine trials in study participants with major depressive disorder. At the open-label baseline, all study participants were switched to vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 2.5 to 10 mg/day on the basis of response and tolerability. Treatment with vortioxetine for 52 weeks was well tolerated, with no new safety signals identified. Among the 834 evaluable study participants, treatment-emergent adverse events were reported in 70.6%, with the most common in the combined (all doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to sexual dysfunction was low and weight gain was minimal. Laboratory values, vital signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale results showed no trends of clinical concern. The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set.

  18. [Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats].

    PubMed

    Ogawa, Yukio; Sekita, Kiyoshi; Umemura, Takashi; Saito, Minoru; Ono, Atsushi; Kawasaki, Yasushi; Uchida, Osayuki; Matsushima, Yuko; Inoue, Tohru; Kanno, Jun

    2004-02-01

    A 52-week study of oral-repeated-dose toxicity for the extraction powder of Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted in both genders of Wistar rats. The rats were administered a graded dose of GS at 0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with the basal powder diet without GS, for 52 weeks. General conditions were recorded daily. Body weights and food consumptions were recorded weekly up to 12 weeks, and thereafter at longer intervals. At 26 weeks, for an intermediate examination, and 52 weeks, for the final examination, animals were subjected to hematology, serum chemistry, and pathological examination. None of the animals died in the period up to 52 weeks. No exposure-related changes in body-weight, in the food consumption, in the hematological examinations, or in the serum biochemical examinations were recognized. No histopathological alterations were seen. Thus, it was concluded that there was no toxic effect in rats treated with GS at up to 1.00% in the diet for 52 weeks. The no-observable-effect level from this study is 1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for female as mean daily intake, for 52 weeks.

  19. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.

    PubMed

    Blom, Dirk J; Hala, Tomas; Bolognese, Michael; Lillestol, Michael J; Toth, Phillip D; Burgess, Lesley; Ceska, Richard; Roth, Eli; Koren, Michael J; Ballantyne, Christie M; Monsalvo, Maria Laura; Tsirtsonis, Kate; Kim, Jae B; Scott, Rob; Wasserman, Scott M; Stein, Evan A

    2014-05-08

    Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. At 52 weeks

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  2. Clinical impact of 8 prospective, randomized, multicenter glaucoma trials.

    PubMed

    Panarelli, Joseph F; Banitt, Michael R; Sidoti, Paul A; Budenz, Donald L; Singh, Kuldev

    2015-01-01

    To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

  3. Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

    PubMed

    Manfredini, Fabio; Mallamaci, Francesca; D'Arrigo, Graziella; Baggetta, Rossella; Bolignano, Davide; Torino, Claudia; Lamberti, Nicola; Bertoli, Silvio; Ciurlino, Daniele; Rocca-Rey, Lisa; Barillà, Antonio; Battaglia, Yuri; Rapanà, Renato Mario; Zuccalà, Alessandro; Bonanno, Graziella; Fatuzzo, Pasquale; Rapisarda, Francesco; Rastelli, Stefania; Fabrizi, Fabrizio; Messa, Piergiorgio; De Paola, Luciano; Lombardi, Luigi; Cupisti, Adamasco; Fuiano, Giorgio; Lucisano, Gaetano; Summaria, Chiara; Felisatti, Michele; Pozzato, Enrico; Malagoni, Anna Maria; Castellino, Pietro; Aucella, Filippo; Abd ElHafeez, Samar; Provenzano, Pasquale Fabio; Tripepi, Giovanni; Catizone, Luigi; Zoccali, Carmine

    2017-04-01

    Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis. Copyright © 2017 by the American Society of Nephrology.

  4. Execution time determines the outcome of the multicenter randomized controlled trials.

    PubMed

    Jiang, Yongjun; Zhai, Qijin; Dai, Zheng; Xu, Xiaomeng; Xu, Xiaohui; Wen, Zhuoyu; Liu, Xinfeng

    2017-03-01

    Multicenter randomized controlled trials are the core of evidence-based medicine. Our study aimed to investigate the key factor which determined the outcome of the multicenter randomized controlled trials. We searched publications in PubMed for multicenter randomized controlled trials reporting primary data on treating and preventing cardiovascular diseases circulation area. The data were extracted from the including trials and used for analysis. A total of 1075 trials for treating and preventing cardiovascular diseases were included, of which 979 were involved in the heart diseases and 96 involved in stroke. The execution time significantly contributed to the outcome of trials with shorter time related to significant outcome. However, the numbers of participated centers and their locations and participants had no effect on the outcome of trials. Moreover, the number of centers showed no significant relationship with execution time. Execution time but not centers or participants contributed to the outcome of multicenter randomized controlled trials. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

  6. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

    PubMed Central

    Forst, T; Guthrie, R; Goldenberg, R; Yee, J; Vijapurkar, U; Meininger, G; Stein, P

    2014-01-01

    Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin. Results Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (−0.89%, −1.03% and −0.26%; p < 0.001); reductions with canagliflozin 100 and 300 mg were maintained at week 52 (−0.92% and −1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (−2.5 and −3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin. Conclusion Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks. PMID:24528605

  7. Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

    PubMed

    Supasyndh, Ouppatham; Sun, Ningling; Kario, Kazuomi; Hafeez, Kudsia; Zhang, Jack

    2016-11-17

    Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.Hypertension Research advance online publication, 17 November 2016; doi:10.1038/hr.2016.151.

  8. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease.

    PubMed

    Yale, J-F; Bakris, G; Cariou, B; Nieto, J; David-Neto, E; Yue, D; Wajs, E; Figueroa, K; Jiang, J; Law, G; Usiskin, K; Meininger, G

    2014-10-01

    This study evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and within a subset of Stage 3 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] ≥ 30 and <50 ml/min/1.73 m(2)). In this 52-week, randomized, double-blind, placebo-controlled study, patients (N = 269; mean eGFR, 39.4 ml/min/1.73 m(2)) received canagliflozin 100 or 300 mg and placebo once daily. Efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and systolic blood pressure (BP); adverse events (AEs) were also recorded. At week 52, canagliflozin 100 and 300 mg reduced HbA1c compared with placebo (-0.19, -0.33 and 0.07%, respectively); placebo-subtracted differences (95% confidence interval) were -0.27% (-0.53, 0.001) and -0.41% (-0.68, -0.14). Canagliflozin also lowered FPG, body weight and BP versus placebo. Overall AE incidence was 85.6, 80.9, and 86.7% with canagliflozin 100 and 300 mg and placebo, respectively. Osmotic diuresis-related AEs were more common with both canagliflozin doses, and incidences of urinary tract infections and volume depletion-related AEs were higher with canagliflozin 300 mg versus placebo. Decreases in eGFR (-2.1, -4.0 and -1.6 ml/min/1.73 m(2)) were seen with canagliflozin 100 and 300 mg compared with placebo. Canagliflozin 100 and 300 mg provided median percent reductions in urine albumin to creatinine ratio versus placebo (-16.4, -28.0 and 19.7%). Canagliflozin improved glycaemic control and was generally well tolerated in patients with T2DM and within a subset of Stage 3 CKD over 52 weeks. © 2014 John Wiley & Sons Ltd.

  9. A randomized prospective multicenter trial of a novel vascular sealant.

    PubMed

    Stone, William M; Cull, David L; Money, Samuel R

    2012-11-01

    Increasing use of anticoagulant medications, particularly antiplatelet therapies, can increase the difficulty in obtaining adequate suture line hemostasis. Multiple vascular sealants have been used as adjuncts to surgical procedures, but none of them have been universally successful. The aim of this study was to evaluate the safety and effectiveness of a new prophylactic vascular sealant in arterial surgery. A randomized prospective multi-institutional trial was undertaken comparing ArterX Vascular Sealant (AVS) with Gelfoam Plus during open arterial reconstruction. Three hundred thirty-one anastomotic sites in 217 patients were randomized. One hundred one of 167 (60.5%) anastomotic sites in the AVS group achieved immediate hemostasis compared with 65 of 164 (39.6%) in the control group (P = 0.001). In anastomoses with polytetrafluoroethylene grafts, 105 of 167 (62.5%) in the AVS group achieved immediate hemostasis compared with 56 of 164 (34.0%) in the control group (P < 0.001). No significant differences were noted in morbidity or mortality. Operative time was significantly less in the AVS group compared with the control group (3.2 vs. 3.8 hours, P < 0.01). Use of AVS results in superior hemostatic effectiveness compared with Gelfoam Plus, with no difference in safety. Although no cost analysis was performed, cost savings likely resulted from significantly decreased operative time. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  10. Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair-A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Part 2-A Pilot Study of Functional Recovery and Structural Outcomes.

    PubMed

    Ide, Junji; Mochizuki, Yu; van Noort, Arthur; Ochi, Hiroshi; Sridharan, Sudhakar; Itoi, Eiji; Greiner, Stefan

    2017-09-01

    The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site. To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein-12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up. Randomized controlled trial; Level of evidence, 2. A total of 20 patients were randomized into 2 groups, rhBMP-12/ACS and standard-of-care (SOC) control, with 16 and 4 patients, respectively. The patients underwent open repair of a rotator cuff tear at least 2 to 4 cm wide; in the rhBMP-12/ACS group, this was augmented with a bioscaffold containing rhBMP-12. Follow-up assessments were conducted with a 100-mm visual analog scale (VAS) for pain and active and passive ranges of motion (ROMs) including forward flexion, elevation in the scapular plane, abduction, and external rotation at 12, 16, 26, 39, and 52 weeks after surgery; isometric strength in scapular abduction and external rotation at 16, 26, 39, and 52 weeks; and magnetic resonance imaging (MRI) at 12 and 52 weeks. The mean VAS score decreased from 37.9 mm preoperatively to 13.8 mm at week 52, and ROM and isometric strength recovered at week 52 in the rhBMP-12/ACS group. The mean VAS score decreased from 48.3 mm preoperatively to 1.5 mm at week 52, and ROM (excluding external rotation) and isometric strength recovered by week 52 in the SOC control group. Of the 16 patients in the rhBMP-12/ACS group, 14 showed an intact repair at week 12; the MRI scans of the other 2 patients could not be evaluated because of artifacts. In the SOC control group, 1 patient showed repair failure. At week 52, 14 repairs in the rhBMP-12/ACS group and 2 repairs with available MRI scans in the SOC control group remained intact. Functional recovery and structural outcomes in patients in whom rhBMP-12/ACS was used

  11. Electroacupuncture for Functional Constipation: A Multicenter, Randomized, Control Trial

    PubMed Central

    Zheng, Cuihong; Ding, Pei; Tian, Man; Wang, Ying; Dong, Haoxu; Zhang, Mingmin; Wang, Wei; Xu, Shabei; Xie, Minjie

    2017-01-01

    Background and Aim. To investigate the efficacy and safety of electroacupuncture (EA) with different current intensities for functional constipation (FC) and to assess whether the effects of EA with different current intensities are superior to the mosapride. Methods. Patients with FC were randomly divided into low current intensity group (LCI), high current intensity group (HCI), and mosapride group (MC). The primary outcome was three or more spontaneous bowel movements (SBMs) per week and an increase of one or more SBMs from baseline during at least 3 of the 4 weeks. Results. The primary outcome was reached by 53.45%, 66.15%, and 52.24% of the patients who received LCI, HCI, and mosapride, respectively. EA can significantly improve the weekly SBMs and stool consistency and reduce straining severity (p < 0.0001, all). HCI improved the quality of life better than mosapride (p < 0.05) and reduced the proportion of severe constipation more than LCI and mosapride (p < 0.05, both). Conclusions. EA is effective and safe at both current intensities for FC; therapeutic effects of LCI and HCI are not superior to mosapride. EA is superior to mosapride in improving patients' life quality and satisfaction level of treatment; EA has fewer adverse events than mosapride. PMID:28250788

  12. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    Students prepare to participate in hands-on science activities at the Logan Heights Library in San Diego, California, during the “52 Weeks of Science” celebration. The Ground Systems Development and Operations (GSDO) Program is participating in the special event with a Journey to Mars display before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  13. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    The Logan Heights Library in San Diego, California is the site of the “52 Weeks of Science” celebration for students. The Ground Systems Development and Operations (GSDO) Program is participating in the special event with a Journey to Mars display. GSDO’s participation before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  14. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    Students visit the displays at the Logan Heights Library in San Diego, California, during the “52 Weeks of Science” celebration. The Ground Systems Development and Operations (GSDO) Program is participating in the special event with a Journey to Mars display before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  15. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    Students and parents visit the displays at the Logan Heights Library in San Diego, California, during the “52 Weeks of Science” celebration. The Ground Systems Development and Operations (GSDO) Program is participating in the special event with a Journey to Mars display before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  16. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    Melissa Jones, center, Ground Systems Development and Operation Program (GSDO) Landing and Recovery director, speaks to a student during the “52 Weeks of Science” celebration at the Logan Heights Library in San Diego, California. GSDO is participating in the special event before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  17. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    A young student visits the displays at the Logan Heights Library in San Diego, California, during the “52 Weeks of Science” celebration. The Ground Systems Development and Operations (GSDO) Program is participating in the special event with a Journey to Mars display before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  18. Orion Underway Recovery Test 5 (URT-5) Trip - "52 Weeks of Scien

    NASA Image and Video Library

    2016-10-19

    A banner celebrating “52 Weeks of Science” is positioned outside of the Logan Heights Library in San Diego, California. The Ground Systems Development and Operations (GSDO) Program is participating in the special event for students with a Journey to Mars display. GSDO’s participation before the start of Underway Recovery Test 5 using a test version of the Orion spacecraft in the Pacific Ocean off the coast of California. The test will allow NASA, Orion manufacturer Lockheed Martin and the U.S. Navy to demonstrate and evaluate the recovery processes, procedures, hardware and personnel necessary for recovery of the Orion crew module on its return from a deep space mission. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities. Orion is scheduled to launch atop NASA’s Space Launch System rocket in 2018. For more information, visit http://www.nasa.gov/orion.

  19. The immunomodulatory nutritional intervention NR100157 reduced CD4+ T-cell decline and immune activation: a 1-year multicenter randomized controlled double-blind trial in HIV-infected persons not receiving antiretroviral therapy (The BITE Study).

    PubMed

    Cahn, P; Ruxrungtham, K; Gazzard, B; Diaz, R S; Gori, A; Kotler, D P; Vriesema, A; Georgiou, N A; Garssen, J; Clerici, M; Lange, J M A

    2013-07-01

    The immunomodulatory nutritional product NR100157 was developed for human immunodeficiency virus (HIV)-infected individuals. We hypothesized that targeting the compromised gastrointestinal tract of HIV-infected individuals would result in systemic immunological benefits. In a multicenter, randomized, controlled, double-blind trial, 340 HIV-1-positive adults not on antiretroviral therapy, with CD4(+) T-cell counts <800/µL, were given either NR100157 or an isocaloric and isonitrogenous control for 52 weeks. Primary outcome was CD4(+) T-cell count. Secondary outcomes included plasma viral load (pVL), safety, and tolerability. In a pilot study (n = 20), levels of CD4(+)CD25(+) and CD8(+)CD38(+) activation were measured (n = 20). The trial is registered at the Dutch Trial Register (NTR886) and ISRCTN81868024. At 52 weeks, CD4(+) T-cell decline showed a 40-cell/µL difference (P = .03) in the intention-to-treat population in favor of the immunomodulatory NR100157 (control vs active, -68 ± 15 vs -28 ± 16 cells/µL/year). The change in pVL from baseline was similar between groups (P = .81). In the pilot study, the percentage of CD4(+)CD25(+) was lower in the active group (P < .05) and correlated with changes in CD4(+) T-cell count (r = -0.55, P < .05). The percentage of CD8(+)CD38(+) levels was unaffected. The specific immunonutritional product NR100157 significantly reduces CD4(+) decline in HIV-1-infected individuals, and this is associated with decreased levels of CD4(+)CD25(+). (This nutritional intervention is likely to affect local gut integrity and gut-associated lymphoid tissue homeostasis, which in turn translates positively to systemic effects.) Clinical Trials Registration. ISRCTN81868024.

  20. Desmopressin after cardiac surgery in bleeding patients. A multicenter randomized trial.

    PubMed

    Bignami, E; Cattaneo, M; Crescenzi, G; Ranucci, M; Guarracino, F; Cariello, C; Baldassarri, R; Isgrò, G; Baryshnikova, E; Fano, G; Franco, A; Gerli, C; Crivellari, M; Zangrillo, A; Landoni, G

    2016-08-01

    Previous studies showed that desmopressin decreases post-operative blood loss in patients undergoing cardiac surgery. These studies were small and never studied the effect of desmopressin in patients with active bleeding. Objective of the study was to determine whether desmopressin reduces red blood cells transfusion requirements in patients with active bleeding after cardiac surgery who had been pre-treated with tranexamic acid. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study randomized elective patients with bleeding after cardiac surgery despite pre-treatment with tranexamic acid, to receive placebo (saline solution) or a single administration of desmopressin (0.3 μg/kg in saline solution). The primary endpoint was the number of patients requiring red blood cells transfusion after randomization and during hospital stay. Secondary end points were: blood loss from chest tubes during the first 24 h after study drug administration, hours of mechanical ventilation, intensive care unit stay, and in-hospital mortality. The study was interrupted after inclusion of 67% of the planned patients for futility. The number of patients requiring red blood cells transfusion after randomization was 37/68 (54%) in desmopressin group and 33/67 (49%) in placebo group (P = 0.34) with no difference in blood loss: 575 (interquartile 422-770) ml in desmopressin group and 590 (476-1013) ml in placebo group (P = 0.42), mechanical ventilation, intensive care unit stay or mortality. This multicenter randomized trial demonstrated that, in patients pre-treated with tranexamic acid, desmopressin should not be expected to improve treatment of patients who experience bleeding after cardiac surgery. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Barbed versus standard sutures for closure in total knee arthroplasty: a multicenter prospective randomized trial.

    PubMed

    Gililland, Jeremy M; Anderson, Lucas A; Barney, Jacob K; Ross, Hunter L; Pelt, Christopher E; Peters, Christopher L

    2014-09-01

    Barbed suture has been associated with improved closure efficiency and safety in TKA in prior studies. We performed a multicenter randomized controlled trial to determine the efficiency and safety of this technology in TKA. We prospectively randomized 411 patients undergoing primary TKA to either barbed running (n=191) or knotted interrupted suture closure (n=203). Closure time was measured intra-operatively. Cost analysis was based on suture and OR time costs. Closure time was shorter with barbed suture (9.8 vs. 14.5 min, p<0.001). Total closure cost was less with barbed suture ($324 vs. $419, p<0.001). Early complications and outcomes were similar between groups. The use of barbed suture in TKA is associated with shorter closure time, lower cost and similar outcomes and complications when compared with standard sutures. Published by Elsevier Inc.

  2. Effects of structured patient education in adults with atopic dermatitis: Multicenter randomized controlled trial.

    PubMed

    Heratizadeh, Annice; Werfel, Thomas; Wollenberg, Andreas; Abraham, Susanne; Plank-Habibi, Sibylle; Schnopp, Christina; Sticherling, Michael; Apfelbacher, Christian; Biedermann, Tilo; Breuer, Kristine; Fell, Isabel; Fölster-Holst, Regina; Heine, Guido; Grimm, Jennifer; Hennighausen, Lars; Kugler, Claudia; Reese, Imke; Ring, Johannes; Schäkel, Knut; Schmitt, Jochen; Seikowski, Kurt; von Stebut, Esther; Wagner, Nicola; Waßmann-Otto, Anja; Wienke-Graul, Ute; Weisshaar, Elke; Worm, Margitta; Gieler, Uwe; Kupfer, Joerg

    2017-09-01

    Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1% to 3% of adults in Western industrialized countries. We sought to investigate the effectiveness of educational training in an outpatient setting on coping with the disease, quality of life, symptoms, and severity in adults with AD. In this German prospective, randomized controlled multicenter study, adult patients with moderate-to-severe AD were educated by referring to a comprehensive 12-hour training manual consented by a multiprofessional study group from different centers (Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene [ARNE]). Patients were randomly allocated to the intervention or waiting control groups. Study visits were performed at baseline and after 1 year (1 year of follow-up). Primary outcomes were defined as a decrease in (1) "catastrophizing cognitions" with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire), (2) "social anxiety" (Marburger Hautfragebogen questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire), and (4) improvement of disease signs and symptoms assessed by using the SCORAD index at 1 year of follow-up. Data were analyzed on an intention-to-treat basis. At 1 year of follow-up, patients from the intervention group (n = 168) showed a significantly better improvement compared with the waiting group (n = 147) in the following defined primary study outcomes: coping behavior with respect to itching (P < .001), quality of life assessed by using the Skindex-29 questionnaire (P < .001), and the SCORAD index (P < .001). This is the first randomized, controlled multicenter study on patient education in adult AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters, as well as AD severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. A 52-Week, Double-Blind Evaluation of the Metabolic Effects of Aripiprazole and Lithium in Bipolar I Disorder

    PubMed Central

    McElroy, Susan L.; Eudicone, James M.; Forbes, Robert A.; Carlson, Berit X.; Baker, Ross A.

    2011-01-01

    Introduction: Metabolic risk factors, termed metabolic syndrome, which include obesity, diabetes, dyslipidemia, and hypertension, are more common in patients with bipolar disorder than in the general population. Moreover, medications used to treat bipolar disorder carry some risk of worsening metabolic parameters. Method: The study was conducted at 46 study centers in the United States, although only 31 study centers enrolled patients in the 40-week extension phase. Patients with acute bipolar I mania, manic or mixed (DSM-IV-TR criteria; Young Mania Rating Scale score ≥ 20), who required hospitalization were randomly assigned to double-blind aripiprazole (15–30 mg/d), lithium (900–1500 mg/d), or placebo for 3 weeks. Patients treated with aripiprazole or lithium continued treatment to week 12, after which they could enter a double-blind 40-week extension phase. Patients were enrolled in the 12-week acute treatment phase between April 2004 and July 2006; the first patient entered extension treatment in October 2004, and the last patient completed treatment in May 2007. Changes in metabolic parameters were compared between patients treated with aripiprazole or lithium for up to 52 weeks using last observation carried forward and analysis of covariance. Analysis stratified by baseline body mass index (BMI) was also conducted. Results: Modest increases in body weight were observed in both groups: +0.97 kg (2.1 lb) for aripiprazole (n = 127) and + 0.74 (1.6 lb) for lithium (n = 136), P = .60. A significant difference in body weight increase was observed only among patients with a BMI < 25: + 2.66 kg (5.9 lb) for aripiprazole (n = 35) and + 0.40 kg (0.9 lb) for lithium (n = 37), P = .02. Mean changes from baseline to week 52 in fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasma glucose, triglycerides, or insulin (last observation carried forward) were small in both aripiprazole and lithium treatment

  4. A multicenter randomized placebo-controlled clinical trial of pramipexole for Tourette's syndrome.

    PubMed

    Kurlan, Roger; Crespi, Giovanna; Coffey, Barbara; Mueller-Vahl, Kirsten; Koval, Stephen; Wunderlich, Glen

    2012-05-01

    Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette's syndrome. There was a multicenter randomized, placebo-controlled, double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette's syndrome. There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole (-7.16) and placebo (-7.17). There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement. In patients with attention deficit hyperactivity disorder, there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo. There was no evidence that pramipexole has efficacy in suppressing tics. Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder. Copyright © 2012 Movement Disorder Society.

  5. Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks

    PubMed Central

    Manns, M P; Wedemeyer, H; Singer, A; Khomutjanskaja, N; Dienes, H P; Roskams, T; Goldin, R; Hehnke, U; Inoue, H

    2012-01-01

    Chronic hepatitis C patients often fail to respond to interferon-based therapies. This phase III study aimed at confirming the efficacy and safety of glycyrrhizin in interferon + ribavirin-based therapy non-responders. A randomised, double-blind, placebo-controlled, comparison of glycyrrhizin, administered intravenously 5×/or 3×/week, and 5×/week placebo for 12 weeks to 379 patients, was followed by a randomised, open comparison of glycyrrhizin i.v. 5×/versus 3×/week for 40 weeks. Primary endpoints were: (1) the proportion of patients with ≥50% ALT (alanine aminotransferase) reduction after 12 weeks double-blind phase, and (2) the proportion of patients with improvement of necro-inflammation after 52 weeks as compared with baseline. The proportion of patients with ALT reduction ≥50% after 12 weeks was significantly higher with 5×/week glycyrrhizin (28.7%, P < 0.0001) and 3×/week glycyrrhizin (29.0%, P < 0.0001) compared with placebo (7.0%). The proportion of patients with improvement in necro-inflammation after 52 weeks was 44.9% with 5×/week and 46.0% with 3×/week, respectively. Glycyrrhizin exhibited a significantly higher ALT reduction compared to placebo after 12 weeks of therapy and an improvement of necro-inflammation and fibrosis after 52-weeks treatment. Generally, glycyrrhizin treatment was well tolerated. PMID:22762137

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

    PubMed Central

    2013-01-01

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

  7. Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial).

    PubMed

    Haverkamp, Leonie; Brenkman, Hylke J F; Seesing, Maarten F J; Gisbertz, Suzanne S; van Berge Henegouwen, Mark I; Luyer, Misha D P; Nieuwenhuijzen, Grard A P; Wijnhoven, Bas P L; van Lanschot, Jan J B; de Steur, Wobbe O; Hartgrink, Henk H; Stoot, Jan H M B; Hulsewé, Karel W E; Spillenaar Bilgen, Ernst J; Rütter, Jeroen E; Kouwenhoven, Ewout A; van Det, Marc J; van der Peet, Donald L; Daams, Freek; Draaisma, Werner A; Broeders, Ivo A M J; van Stel, Henk F; Lacle, Miangela M; Ruurda, Jelle P; van Hillegersberg, Richard

    2015-07-29

    For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Chen, Lifang; Fang, Jianqiao; Ma, Ruijie; Froym, Ronen; Gu, Xudong; Li, Jianhua; Chen, Lina; Xu, Shouyu; Ji, Conghua

    2014-06-08

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

  10. Clinical effectiveness of dermal substitution in burns by topical negative pressure: a multicenter randomized controlled trial.

    PubMed

    Bloemen, Monica C T; van der Wal, Martijn B A; Verhaegen, Pauline D H M; Nieuwenhuis, Marianne K; van Baar, Margriet E; van Zuijlen, Paul P M; Middelkoop, Esther

    2012-01-01

    Previous research has shown clinical effectiveness of dermal substitution; however, in burn wounds, only limited effect has been shown. A problem in burn wounds is the reduced take of the autograft, when the substitute and graft are applied in one procedure. Recently, application of topical negative pressure (TNP) was shown to improve graft take. The aim of this study was to investigate if application of a dermal substitute in combination with TNP improves scar quality after burns. In a four-armed multicenter randomized controlled trial, a split-skin graft with or without a dermal substitute and with or without TNP was compared in patients with deep dermal or full-thickness burns requiring skin transplantation. Graft take and rate of wound epithelialization were evaluated. Three and 12 months postoperatively, scar parameters were measured. The results of 86 patients showed that graft take and epithelialization did not reveal significant differences. Significantly fewer wounds in the TNP group showed postoperative contamination, compared to other groups. Highest elasticity was measured in scars treated with the substitute and TNP, which was significantly better compared to scars treated with the substitute alone. Concluding, this randomized controlled trial shows the effectiveness of dermal substitution combined with TNP in burns, based on extensive wound and scar measurements. © 2012 by the Wound Healing Society.

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

    PubMed

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

    2016-05-13

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

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

    PubMed Central

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

    2016-01-01

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

  13. Laparoscopic versus open adhesiolysis for small bowel obstruction - a multicenter, prospective, randomized, controlled trial

    PubMed Central

    2014-01-01

    Background Laparoscopic adhesiolysis is emerging as an alternative for open surgery in adhesive small bowel obstruction. Retrospective studies suggest that laparoscopic approach shortens hospital stay and reduces complications in these patients. However, no prospective, randomized, controlled trials comparing laparoscopy to open surgery have been published. Methods/Design This is a multicenter, prospective, open label, randomized, controlled trial comparing laparoscopic adhesiolysis to open surgery in patients with computed-tomography diagnosed adhesive small bowel obstruction that is not resolving with conservative management. The primary study endpoint is the length of postoperative hospital stay in days. Sample size was estimated based on preliminary retrospective cohort, which suggested that 102 patients would provide 80% power to detect a difference of 2.5 days in the length of postoperative hospital stay with significance level of 0.05. Secondary endpoints include passage of stool, commencement of enteral nutrition, 30-day mortality, complications, postoperative pain, and the length of sick leave. Tertiary endpoints consist of the rate of ventral hernia and the recurrence of small bowel obstruction during long-term follow-up. Long-term follow-up by letter or telephone interview will take place at 1, 5, and 10 years. Discussion To the best of our knowledge, this trial is the first one aiming to provide level Ib evidence to assess the use of laparoscopy in the treatment of adhesive small bowel obstruction. Trial registration ClinicalTrials.gov identifier: NCT01867528. Date of registration May 26th 2013. PMID:25306234

  14. A multi-center randomized trial of two different intravenous fluids during labor

    PubMed Central

    DAPUZZO-ARGIRIOU, Lisa M.; SMULIAN, John C.; ROCHON, Meredith L.; GALDI, Luisa; KISSLING, Jessika M.; SCHNATZ, Peter F.; RIOS, Angel GONZALEZ; AIROLDI, James; CARRILLO, Mary Anne; MAINES, Jaimie; KUNSELMAN, Allen R.; REPKE, John; LEGRO, Richard S.

    2017-01-01

    Objective To determine if the intrapartum use of a 5% glucose-containing intravenous solution decreases the chance of a cesarean delivery for women presenting in active labor. Methods This was a multi-center, prospective, single (patient) blind, randomized study design implemented at 4 obstetric residency programs in Pennsylvania. Singleton, term, consenting women presenting in active spontaneous labor with a cervical dilation of <6cm were randomized to lactated Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance intravenous fluid. The primary outcome was the cesarean birth rate. Secondary outcomes included labor characteristics, as well as maternal or neonatal complications. Results There were 309 women analyzed. Demographic variables and admitting cervical dilation were similar among study groups. There was no significant difference in the cesarean delivery rate for the D5LR group (23/153 or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95%CI) of 1.32 (0.75, 2.35), P=0.34]. There were no differences in augmentation rates or intrapartum complications. Conclusions The use of intravenous fluid containing 5% dextrose does not lower the chance of cesarean delivery for women admitted in active labor. PMID:25758624

  15. A multi-center randomized trial of two different intravenous fluids during labor.

    PubMed

    Dapuzzo-Argiriou, Lisa M; Smulian, John C; Rochon, Meredith L; Galdi, Luisa; Kissling, Jessika M; Schnatz, Peter F; Gonzalez Rios, Angel; Airoldi, James; Carrillo, Mary Anne; Maines, Jaimie; Kunselman, Allen R; Repke, John; Legro, Richard S

    2016-01-01

    To determine if the intrapartum use of a 5% glucose-containing intravenous solution decreases the chance of a cesarean delivery for women presenting in active labor. This was a multi-center, prospective, single (patient) blind, randomized study design implemented at four obstetric residency programs in Pennsylvania. Singleton, term, consenting women presenting in active spontaneous labor with a cervical dilation of <6 cm were randomized to lactated Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance intravenous fluid. The primary outcome was the cesarean birth rate. Secondary outcomes included labor characteristics, as well as maternal or neonatal complications. There were 309 women analyzed. Demographic variables and admitting cervical dilation were similar among study groups. There was no significant difference in the cesarean delivery rate for the D5LR group (23/153 or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95% CI) of 1.32 (0.75, 2.35), p = 0.34]. There were no differences in augmentation rates or intrapartum complications. The use of intravenous fluid containing 5% dextrose does not lower the chance of cesarean delivery for women admitted in active labor.

  16. Repair or observe moderate ischemic mitral regurgitation during coronary artery bypass grafting? Prospective randomized multicenter data

    PubMed Central

    Gulack, Brian C.; Englum, Brian R.; Castleberry, Anthony W.; Daneshmand, Mani A.; Perrault, Louis P.

    2015-01-01

    Ischemic mitral regurgitation (MR) is a common occurrence following myocardial infarction and its presence is associated with poor outcomes. The optimal treatment of ischemic MR is a matter of debate, especially for patients with moderate MR severity. Some authors advocate for isolated coronary artery bypass grafting (CABG) for patients with moderate MR, maintaining that reverse ventricular remodeling will reduce MR grade and its associated mortality risk, while others argue that a concomitant mitral valve repair (MVR) or replacement is superior. The Cardiothoracic Surgical Trials Network (CTSN) recently published the 1-year results of the Surgical Treatment of Moderate Ischemic Mitral Regurgitation study, a multicenter, randomized, controlled trial investigating the impact of MVR in addition to CABG compared to CABG alone in the treatment of moderate ischemic MR. Here, we have reviewed previous observational and prospective studies investigating moderate ischemic MR treatment as well as the results of the current CTSN randomized trial. Furthermore, we have summarized the current state of the available evidence and preview potential new information that will become available with planned subgroup analyses and further follow-up of enrolled patients in the recently completed CTSN trial. PMID:26309829

  17. Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study.

    PubMed

    Marcus, Ronald N; Owen, Randall; Manos, George; Mankoski, Raymond; Kamen, Lisa; McQuade, Robert D; Carson, William H; Corey-Lisle, Patricia K; Aman, Michael G

    2011-06-01

    To report the long-term efficacy of aripiprazole in the treatment of irritability in children and adolescents (ages 6-17 years) with autistic disorder. This was a 52-week, open-label, flexible-dose (2-15 mg/day) study of aripiprazole for the treatment of children and adolescents with irritability associated with autistic disorder. Eligible subjects were enrolled from two 8-week randomized trials or were enrolled as de novo subjects. "Prior aripiprazole" subjects had received treatment with aripiprazole for 8 weeks before entering this study. Evaluation of efficacy, a secondary objective after evaluation of safety and tolerability in this study, was conducted using the caregiver-rated Aberrant Behavior Checklist-Irritability subscale and the clinician-rated Clinical Global Impression-Improvement score. Three hundred thirty subjects received treatment (de novo, n = 86; prior aripiprazole, n = 174; prior placebo, n = 70) and 199 subjects (60.3%) completed 52 weeks of treatment. At their last study visit, 38.2% of subjects were receiving concomitant central nervous system medications (commonly antidepressants, 13.4%; psychostimulants, 11.5%; antiepileptics, 5.9%). At week 52 (observed cases data set), the mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was -8.0 in de novo subjects and -6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study. At endpoint, the majority of subjects had a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved). Aripiprazole reduced symptoms of irritability associated with autistic disorder in pediatric subjects ages 6-17 years who were studied for up to 1 year.

  18. Aripiprazole once-monthly 400 mg for long-term maintenance treatment of schizophrenia: a 52-week open-label study

    PubMed Central

    Peters-Strickland, Timothy; Baker, Ross A; McQuade, Robert D; Jin, Na; Eramo, Anna; Perry, Pamela; Johnson, Brian R; Duca, Anna; Sanchez, Raymond

    2015-01-01

    Background: Long-term maintenance treatment with an antipsychotic is often required to prevent relapse and mitigate functional deterioration in patients with schizophrenia. Aims: This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia. Methods: This 52-week, open-label study included patients previously enrolled in 1 of 2 AOM 400 randomized controlled trials (RCTs) and de novo patients. Safety endpoints included adverse events (AEs), suicidality, extrapyramidal symptoms, injection-site pain, and clinically relevant changes in clinical and laboratory values. The primary efficacy endpoint was the percentage of stable patients at baseline who remained stable at the last visit of the AOM 400 maintenance phase. All endpoints were assessed with descriptive statistics; there were no formal planned statistical analyses. Results: Of 1,247 patients screened, 1,178 enrolled in the study (194 de novo and 984 patients from the RCTs) and 1,081 received maintenance treatment with AOM 400. The maintenance phase completion rate was 79.4% at 52 weeks. Treatment-emergent AEs in ⩾5% of patients during open-label AOM 400 treatment were headache (7.6%), nasopharyngitis (7.0%), anxiety (6.8%), and insomnia (6.6%). There were no clinically relevant changes in safety parameters of interest. Ninety-five percent of stable patients at baseline remained stable at their last visit during the AOM 400 maintenance phase. Conclusions: The long-term safety and tolerability profile of AOM 400 was comparable to the RCTs, and the long-term therapeutic effect was maintained. PMID:27336044

  19. 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

  20. Baseline findings of the Italian multicenter randomized controlled trial of "once-only sigmoidoscopy"--SCORE.

    PubMed

    Segnan, Nereo; Senore, Carlo; Andreoni, Bruno; Aste, Hugo; Bonelli, Luigina; Crosta, Cristiano; Ferraris, Roberto; Gasperoni, Stefano; Penna, Angelo; Risio, Mauro; Rossini, Francesco Paolo; Sciallero, Stefania; Zappa, Marco; Atkin, Wendy S

    2002-12-04

    A single sigmoidoscopy examination at around age 60 years has been proposed as a cost-effective strategy to prevent colorectal cancer. A multicenter randomized controlled trial, the SCORE trial, is in progress in Italy to estimate the impact of this strategy on colorectal cancer incidence and mortality and the duration of the protective effect. We present the baseline screening outcomes. A questionnaire was mailed to a random sample of 236 568 people aged 55-64 years to assess their eligibility for and interest in screening. Those reporting a history of colorectal cancer, adenomas, inflammatory bowel disease, recent colorectal endoscopy, or two first-degree relatives with colorectal cancer were excluded. Eligible, interested respondents were assigned randomly to the control group (no further contact) or the intervention group (invitation to undergo sigmoidoscopy). Screenees with colorectal cancer, polyps larger than 5 mm, three or more adenomas, adenomas 5 mm or smaller with a villous component of more than 20%, or severe dysplasia were referred for colonoscopy. Of the 56 532 respondents (23.9% of those invited), 34 292 were enrolled and 17 148 were assigned to the screening group. Of those, 9999 attended and 9911 were actually examined by sigmoidoscopy. Distal adenomas were detected in 1070 subjects (10.8%). Proximal adenomas were detected in 116 of 747 (15.5%) subjects without cancer at sigmoidoscopy who then underwent colonoscopy. A total of 54 subjects was found to have colorectal cancer, a rate of 5.4 per 1000 (54% of which were Dukes' A). The procedures were relatively safe, with two perforations (one in 9911 sigmoidoscopy exams and one in 775 colonoscopies) and one hemorrhage requiring hospitalization after polypectomy during colonoscopy. The pain associated with sigmoidoscopy was described as mild or less than expected by 83.3% of the screenees. Sigmoidoscopy screening is generally acceptable to recipients and safe. The high yield of advanced adenomas is

  1. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study.

    PubMed

    Giustina, Andrea; Mazziotti, Gherardo; Cannavò, Salvatore; Castello, Roberto; Arnaldi, Giorgio; Bugari, Giovanna; Cozzi, Renato; Ferone, Diego; Formenti, Anna Maria; Gatti, Enza; Grottoli, Silvia; Maffei, Pietro; Maffezzoni, Filippo; Montini, Marcella; Terzolo, Massimo; Ghigo, Ezio

    2017-07-01

    Increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN-ATG) at high dose (HD) or high frequency (HF) are still scanty. To evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients with active acromegaly. Twenty-four-week prospective, multicenter, randomized, open-label trial. Thirty patients with active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in random growth hormone (GH) values < 1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF and HD LAN-ATG, adverse events. IGF-I decreased significantly (P = 0.007) during the 24-week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08). Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs baseline), without a significant difference between HF and HD groups (P = 0.59). The decrease in serum IGF-I significantly correlated with serum LAN values (P = 0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P = 0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. HF and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRLs therapy.

  2. A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

    PubMed Central

    Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

    2015-01-01

    Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

  3. Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

    PubMed

    Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

    2004-01-01

    The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

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

    PubMed

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

    2012-02-01

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

  5. Limiting loss to follow-up in a multicenter randomized trial in orthopedic surgery.

    PubMed

    Sprague, Sheila; Leece, Pamela; Bhandari, Mohit; Tornetta, Paul; Schemitsch, Emil; Swiontkowski, Marc F

    2003-12-01

    Even the best-designed, randomized controlled trials suffer when patients are lost to follow-up. Incomplete follow-up biases the results of a trial when patients who drop out are different from those who complete follow-up. This is exaggerated further when there are differential dropout rates between study groups. Previous randomized controlled trials in orthopedic trauma have reported up to 28% loss to follow-up. Only by striving to achieve a 0% loss to follow-up rate can we be certain that this type of bias does not affect our results. In our ongoing multicenter, randomized controlled trial comparing reamed and nonreamed intramedullary nailing of tibial shaft fractures, we have implemented several innovative strategies to minimize loss to follow-up. The exclusion criteria and consent process are designed to minimize losses. Study staff are carefully trained in communication and negotiation with patients. Additionally, a central methods center monitors all patient follow-up and aids in finding lost patients. Through these primary, secondary, and tertiary interventions, we have achieved 94% complete 1-year follow-up for the first 440 patients enrolled in the trial. Eleven patients withdrew consent, and we are unable to locate 17 patients. We have successfully minimized the loss to follow-up rate in our trial by incorporating innovative prevention and retention strategies into its design and conduct. Through planning, organization, and committing time and resources to minimizing loss to follow-up, other orthopedic trauma trials can hope to achieve the same high rates of follow-up.

  6. Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial.

    PubMed

    Rainer, Timothy Hudson; Cheng, Chi Hung; Janssens, Hein J E M; Man, Chi Yin; Tam, Lai Shan; Choi, Yu Fai; Yau, Wah Hon; Lee, Ka Hing; Graham, Colin Alexander

    2016-04-05

    Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations. To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout. Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113). Four EDs in Hong Kong. 416 patients aged 18 years or older. Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14. 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P < 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events. Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid. Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is a safe, effective first-line option for treatment of acute gout. Health and Health Services Research Grant Committee of the Hong Kong Government.

  7. Postprescription review improves in-hospital antibiotic use: a multicenter randomized controlled trial.

    PubMed

    Lesprit, P; de Pontfarcy, A; Esposito-Farese, M; Ferrand, H; Mainardi, J L; Lafaurie, M; Parize, P; Rioux, C; Tubach, F; Lucet, J C

    2015-02-01

    Although review of antibiotic therapy is recommended to optimize antibiotic use, physicians do not always perform it. This trial aimed to evaluate the impact of a systematic postprescription review performed by antimicrobial stewardship program (ASP) infectious disease physicians (IDP) on the quality of in-hospital antibiotic use. A multicenter, prospective, randomized, parallel-group trial using the PROBE (Prospective Randomized Open-label Blinded Endpoint) methodology was conducted in eight surgical or medical wards of four hospitals. Two hundred forty-six patients receiving antibiotic therapy prescribed by ward physicians for less than 24 hours were randomized to receive either a systematic review by the ASP IDP at day 1 and days 3 to 4 (intervention group, n = 123) or no systematic review (usual care, n = 123). The primary outcome measure was appropriateness of antimicrobial therapy, a composite score of appropriateness of antibiotic use at days 3 to 4 and appropriate treatment duration, adjudicated by a blinded committee. Analyses were performed on an intention-to-treat basis. In the intervention group, appropriateness of antimicrobial therapy was more frequent (55/123, 44.7% vs. 35/123, 28.5%; odds ratio 2.03, 95% confidence interval 1.20-3.45). Antibiotic treatment duration was lower in the intervention group (median (interquartile range) 7 (3-9) days vs. 10 (7-12) days; p 0.003). ASP IDP counseling to change therapy was more frequent at days 3 to 4 than at day 1 (114/123; 92.7% vs. 24/123; 19.5%, p <0.001). Clinical outcome was similar between groups. This study suggests that a systematic postprescription antibiotic review performed at days 1 and 3 to 4 results in higher quality of antibiotic use and lower antibiotic duration. This trial was registered at ClinicalTrials.gov (NCT01136200).

  8. A 52-week safety study in cynomolgus macaques for genetically modified rice expressing Cry1Ab/1Ac protein.

    PubMed

    Mao, Jie; Sun, Xing; Cheng, Jian-Hua; Shi, Yong-Jie; Wang, Xin-Zheng; Qin, Jun-Jie; Sang, Zhi-Hong; He, Kun; Xia, Qing

    2016-09-01

    A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63.

  9. IMpact of Platelet Rich plasma OVer alternative therapies in patients with lateral Epicondylitis (IMPROVE): protocol for a multicenter randomized controlled study: a multicenter, randomized trial comparing autologous platelet-rich plasma, autologous whole blood, dry needle tendon fenestration, and physical therapy exercises alone on pain and quality of life in patients with lateral epicondylitis.

    PubMed

    Chiavaras, Mary M; Jacobson, Jon A; Carlos, Ruth; Maida, Eugene; Bentley, Todd; Simunovic, Nicole; Swinton, Marilyn; Bhandari, Mohit

    2014-09-01

    Lateral epicondylitis, commonly known as tennis elbow, is the most common cause of lateral elbow pain and the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting. Many therapeutic options, including conservative, surgical, and minimally invasive procedures, have been advocated for the treatment of lateral epicondylitis. Although numerous small studies have been performed to assess the efficacy of various treatments, there are conflicting results with no clear consensus on the optimal treatment. In an economic environment with limited health care resources, it is paramount that optimal cost-effective therapies with favorable patient-important outcomes be identified. This is a protocol paper which outlines a multicenter, multidisciplinary, single-blinded, four-arm randomized controlled trial, comparing platelet-rich plasma (PRP), whole blood injection, dry needle tendon fenestration, and sham injection with physical therapy alone for the treatment of lateral epicondylitis. Patients are screened based on pre-established eligibility criteria and randomized to one of the four study groups using an Internet-based system. The patients are followed at 6-week, 12-week, 24-week, and 52-week time points to assess the primary and secondary outcomes of the study. The primary outcome is pain. Secondary outcomes include health-related quality of life and ultrasound appearance of the common extensor tendon. Two university centers (McMaster University and the University of Michigan) are currently recruiting patients. We have planned a sample size of 100 patients (25 patients per arm) to ensure over 80% power to detect a three-point difference in pain scores at 52 weeks of follow-up. This study has ethics approval from the McMaster University Research Ethics Board (REB# 12-146) and the University of Michigan Institutional Review Board (IRB# HUM00067750). Successful completion of this proposed study will significantly impact

  10. Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial.

    PubMed

    Göke, Burkhard; Gallwitz, Baptist; Eriksson, Johan G; Hellqvist, Åsa; Gause-Nilsson, Ingrid

    2013-04-01

    To compare the long-term safety, tolerability and efficacy of saxagliptin vs. glipizide as add-on therapy to metformin. Adults with glycated haemoglobin (HbA1c) > 6.5-10% (on stable metformin ≥ 1500 mg/day) were randomised to saxagliptin 5 mg/day (n = 428) or glipizide titrated from 5 to 20 mg/day (mean dose 15 mg/day; n = 430) for 52 weeks with a 52-week extension (NCT00575588). Assessment of the long-term safety, tolerability and efficacy of add-on saxagliptin vs. glipizide after 104 weeks was a tertiary objective of the initial 52-week study. Saxagliptin was well tolerated during the 104-week period; 67.1% of patients receiving saxagliptin vs. 72.6% receiving glipizide had ≥ 1 adverse event (AE), and few patients (4.9% vs. 5.6%) discontinued owing to AEs. Fewer patients treated with saxagliptin experienced hypoglycaemia (3.5% vs. 38.4% with glipizide; difference, -34.9%, 95% CI, -39.8 to -30.0) or confirmed hypoglycaemia (0 vs. 9.1% with glipizide). Weight loss was observed with saxagliptin (-1.5 kg) vs. weight gain with glipizide (+1.3 kg; between-group difference, -2.8 kg, 95% CI, -3.32 kg to -2.20 kg). Change from baseline in HbA1c was -0.41 ± 0.04% with saxagliptin and -0.35 ± 0.04% with glipizide (between-group difference, -0.05%, 95% CI, -0.17 to 0.06%). A post hoc analysis showed that the proportion of patients with baseline HbA1c ≥ 7% who achieved HbA1c < 7% (observed data) at week 104 was 23.1% for saxagliptin + metformin and 22.7% for glipizide + metformin. A lower risk of hypoglycaemia and reduced body weight were observed with saxagliptin vs. glipizide. No other clinically significant differences were observed between groups in safety profile. No significant between-group differences were observed for reductions in glycaemic parameters. After week 24, a smaller weekly rise in HbA1c was observed with saxagliptin vs. glipizide as add-on therapy to metformin.

  11. Comparison of mouth guard designs and concussion prevention in contact sports: a multicenter randomized controlled trial.

    PubMed

    Barbic, David; Pater, Joseph; Brison, Robert J

    2005-09-01

    To compare the effectiveness of the WIPSS mouth guard to other currently used mouth guards in the prevention of concussion injuries in athletes participating in varsity football and rugby. : Multicenter, cluster-randomized, controlled trial comparing the WIPSS Brain-Pad mouth guard against the standard use mouth guard of choice. Teams were monitored by their respective athletic therapist, trainer, or sports physician for 1 playing season to diagnose and record incident concussion injuries and dental trauma. Concussion symptoms were also recorded at the time of injury. Five Ontario universities. University male football (394) and university male (129) and female (123) rugby athletes reporting to 2003 fall training camps. The primary end point was the incidence of any diagnosed concussion events during the 2003 playing season as defined by the American Academy of Neurology Concussion Guidelines. Secondary endpoints included the incidence of dental trauma events and observed concussion symptoms. There was no significant difference in the number of concussions observed between the intervention and control arms of this trial (P = 0.79; odds ratio, 1.06, in favor of controls; 95% CI, 0.51, <1.61). No dental trauma events occurred. The 5 most common symptoms experienced by concussed athletes were dizziness, general headache, nausea, loss of visual focus, and personality changes. In this study, concussion rates were not significantly different for varsity football and rugby players who wore the WIPSS Brain-Pad mouth guard compared with other types of mouth guards.

  12. Electrolyte changes after bowel preparation for colonoscopy: A randomized controlled multicenter trial.

    PubMed

    Lee, Kyong Joo; Park, Hong Jun; Kim, Hyun-Soo; Baik, Kwang Ho; Kim, Yeon Soo; Park, Sung Chul; Seo, Hyun Il

    2015-03-14

    To investigate the electrolyte changes between 2-L polyethylene glycol with ascorbic acid 20 g (PEG-Asc) and 4-L PEG solutions. From August 2012 to February 2013, a total of 226 patients were enrolled at four tertiary hospitals. All patients were randomly allocated to a PEG-Asc group or a 4-L PEG. Before colonoscopy, patients completed a questionnaire to assess bowel preparation-related symptoms, satisfaction, and willingness. Endoscopists assessed the bowel preparation using the Boston Bowel Preparation Scale (BBPS). In addition, blood tests, including serum electrolytes, serum osmolarity, and urine osmolarity were evaluated both before and after the procedure. A total of 226 patients were analyzed. BBPS scores were similar and the adequate bowel preparation rate (BBPS ≥ 6) was not different between the two groups (PEG-Asc vs 4-L PEG, 73.2% vs 76.3%, P = 0.760). Bowel preparation-related symptoms also were not different between the two groups. The taste of PEG-Asc was better (41.1% vs 16.7%, P < 0.001), and the willingness to undergo repeated bowel preparation was higher in the PEG-Asc group (73.2% vs 59.3%, P = 0.027) than in 4-L PEG. There were no significant changes in serum electrolytes in either group. In this multicenter trial, bowel preparation with PEG-Asc was better than 4-L PEG in terms of patient satisfaction, with similar degrees of bowel preparation and electrolyte changes.

  13. STAM protocol in dementia: a multicenter, single-blind, randomized, and controlled trial.

    PubMed

    Ceccato, Enrico; Vigato, Giovanna; Bonetto, Chiara; Bevilacqua, Albina; Pizziolo, Paolo; Crociani, Susanna; Zanfretta, Emanuele; Pollini, Lorenza; Caneva, Paolo Alberto; Baldin, Lorella; Frongillo, Cristina; Signorini, Andrea; Demoro, Sara; Barchi, Elisabetta

    2012-08-01

    The Sound Training for Attention and Memory in Dementia (STAM-Dem) is a manualized music-based protocol designed to be used in the rehabilitation of cognitive functions in elderly patients with dementia (PWD). This was a multicenter, single-blind, randomized, and controlled trial that involved 51 PWD. The objective was to test the STAM-Dem efficacy. Patients in the experimental group followed the STAM-Dem for 2 weekly sessions of 45 minutes for 12 weeks (in addition to standard care). Those in the control group continued with the normal "standard care" provided. In the experimental group, the instruments immediate prose memory test (MPI), deferred prose memory test (MPD), attentional matrices, activities of daily living, Music Therapy Activity Scale (SVAM) and Geriatric Music Therapy Profile (GMP) increase significantly from pre to post-test (P < .05). The protocol is feasible and data suggest that there was an effect on attentino (matrices) and prose memory skills (MPI and MPD). The effect size reveals a general improvement in the results of the experimental group.

  14. A Multicenter Randomized Controlled Trial Evaluating a Cx43-Mimetic Peptide in Cutaneous Scarring.

    PubMed

    Grek, Christina L; Montgomery, Jade; Sharma, Meenakshi; Ravi, A; Rajkumar, J S; Moyer, Kurtis E; Gourdie, Robert G; Ghatnekar, Gautam S

    2017-03-01

    The transmembrane protein Cx43 has key roles in fibrogenic processes including inflammatory signaling and extracellular matrix composition. aCT1 is a Cx43 mimetic peptide that in preclinical studies accelerated wound closure, decreased inflammation and granulation tissue area, and normalized mechanical properties after cutaneous injury. We evaluated the efficacy and safety of aCT1 in the reduction of scar formation in human incisional wounds. In a prospective, multicenter, within-participant controlled trial, patients with bilateral incisional wounds (≥10 mm) after laparoscopic surgery were randomized to receive acute treatment (immediately after wounding and 24 hours later) with an aCT1 gel formulation plus conventional standard of care protocols, involving moisture-retentive occlusive dressing, or standard of care alone. The primary efficacy endpoint was average scarring score using visual analog scales evaluating incision appearance and healing progress over 9 months. There was no significant difference in scar appearance between aCT1- or control-treated incisions after 1 month. At month 9, aCT1-treated incisions showed a 47% improvement in scar scores over controls (Vancouver Scar Scale; P = 0.0045), a significantly higher Global Assessment Scale score (P = 0.0009), and improvements in scar pigmentation, thickness, surface roughness, and mechanical suppleness. Adverse events were similar in both groups. aCT1 has potential to improve scarring outcome after surgery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Written pain neuroscience education in fibromyalgia: a multicenter randomized controlled trial.

    PubMed

    van Ittersum, Miriam W; van Wilgen, C Paul; van der Schans, Cees P; Lambrecht, Luc; Groothoff, Johan W; Nijs, Jo

    2014-11-01

    Mounting evidence supports the use of face-to-face pain neuroscience education for the treatment of chronic pain patients. This study aimed at examining whether written education about pain neuroscience improves illness perceptions, catastrophizing, and health status in patients with fibromyalgia. A double-blind, multicenter randomized controlled clinical trial with 6-month follow-up was conducted. Patients with FM (n = 114) that consented to participate were randomly allocated to receive either written pain neuroscience education or written relaxation training. Written pain neuroscience education comprised of a booklet with pain neuroscience education plus a telephone call to clarify any difficulties; the relaxation group received a booklet with relaxation education and a telephone call. The revised illness perception questionnaire, Pain Catastrophizing Scale, and fibromyalgia impact questionnaire were used as outcome measures. Both patients and assessors were blinded. Repeated-measures analyses with last observation carried forward principle were performed. Cohen's d effect sizes (ES) were calculated for all within-group changes and between-group differences. The results reveal that written pain neuroscience education does not change the impact of FM on daily life, catastrophizing, or perceived symptoms of patients with FM. Compared with written relaxation training, written pain neuroscience education improved beliefs in a chronic timeline of FM (P = 0.03; ES = 0.50), but it does not impact upon other domains of illness perceptions. Compared with written relaxation training, written pain neuroscience education slightly improved illness perceptions of patients with FM, but it did not impart clinically meaningful effects on pain, catastrophizing, or the impact of FM on daily life. Face-to-face sessions of pain neuroscience education are required to change inappropriate cognitions and perceived health in patients with FM.

  16. Voriconazole therapeutic drug monitoring: results of a prematurely discontinued randomized multicenter trial

    PubMed Central

    Neofytos, D.; Ostrander, D.; Shoham, S.; Laverdiere, M.; Hiemenz, J.; Nguyen, H.; Clark, W.; Brass, L.; Lu, N.; Marr, K.A.

    2015-01-01

    Background Voriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs). Methods We initiated a prospective, randomized, non-blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician-driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real-time dose adjustments were made to maintain a range between 1–5 μg/mL on the TDM-arm, while levels were assessed retrospectively in the standard arm. Patient questionnaires were administered to assess subjective AEs. Results The study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard-arm, 3 TDM-arm). VOR levels were frequently out of range in the standard-arm (8 tests >5 μg/mL; 9 tests < 1 μg/mL). Three dose changes occurred in the TDM-arm for VOR levels <1 μg/mL. Levels decreased over time in the standard-arm, with mean VOR levels lower at end of therapy compared to TDM (1.3 vs. 4.6 μg/mL, P = 0.008). Conclusions VOR TDM has become widespread clinical practice, based on known variability in drug levels, which impaired accrual in this study. Although comparative conclusions are limited, observations of variability and waning levels over time support TDM. PMID:26346408

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2007-01-01

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

  20. Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial

    PubMed Central

    De Stefano, Carla; Normand, Domitille; Jabre, Patricia; Azoulay, Elie; Kentish-Barnes, Nancy; Lapostolle, Frederic; Baubet, Thierry; Reuter, Paul-Georges; Javaud, Nicolas; Borron, Stephen W.; Vicaut, Eric; Adnet, Frederic

    2016-01-01

    Background The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. Methods and Findings In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members’ experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. Conclusions Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death. PMID:27253993

  1. Efficacy and safety of femtosecond laser-assisted corneal endothelial keratoplasty: a randomized multicenter clinical trial.

    PubMed

    Cheng, Yanny Y Y; Schouten, Jan S A G; Tahzib, Nayyirih G; Wijdh, Robert-Jan; Pels, Elisabeth; van Cleynenbreugel, Hugo; Eggink, Catharina A; Rijneveld, Wilhelmina J; Nuijts, Rudy M M A

    2009-12-15

    To evaluate the efficacy and safety of femtosecond laser-assisted endothelial keratoplasty (FLEK) versus penetrating keratoplasty (PK) in patients with corneal endothelial disease. A randomized multicenter clinical trial of 80 eyes of 80 patients with corneal endothelial disease were randomized to FLEK or PK. Clinical outcomes (astigmatism and visual acuity) and incidence of postoperative complications were compared between the two groups. At 12 months, the percentage of eyes with a refractive astigmatism less than or equal to 3 diopters was higher in the FLEK group in comparison with the PK group (86.2% vs. 51.3%, P=0.004). The mean postoperative best corrected visual acuity was 20/70+/-2 lines in the FLEK group and 20/44+/-2 lines in the PK group (P<0.001), but the gain in the best corrected visual acuity between the two groups was not significantly different. The endothelial cell loss in the FLEK and PK group was 65+/-12% and 23+/-15% (P<0.001). The most common postoperative complication in the FLEK group was graft dislocation (27.8%). Wound healing related problems occurred in six eyes (15%) in the PK group and in none of the FLEK eyes. FLEK effectively reduces postoperative astigmatism and results in an absence of wound healing related problems in patients with endothelial disease. However, visual acuity is lower as compared with conventional PK, and the high level of endothelial cell loss warrants a modification of the insertion technique of the endothelial graft.

  2. Neural correlates of procedural variants in cognitive-behavioral therapy: a randomized, controlled multicenter FMRI study.

    PubMed

    Straube, Benjamin; Lueken, Ulrike; Jansen, Andreas; Konrad, Carsten; Gloster, Andrew T; Gerlach, Alexander L; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Gauggel, Siegfried; Wittchen, Ulrich; Arolt, Volker; Kircher, Tilo

    2014-01-01

    Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PD/AG). It is unknown, how variants of CBT differentially modulate brain networks involved in PD/AG. This study was aimed to evaluate the effects of therapist-guided (T+) versus self-guided (T-) exposure on the neural correlates of fear conditioning in PD/AG. In a randomized, controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before (t1) and after CBT (t2). Quality-controlled fMRI data from 42 patients and 42 healthy subjects (HS) were obtained. Patients were randomized to two variants of CBT (T+, n = 22, and T-, n = 20). The interaction of diagnosis (PD/AG, HS), treatment group (T+, T-), time point (t1, t2) and stimulus type (conditioned stimulus: yes, no) revealed activation in the left hippocampus and the occipitotemporal cortex. The T+ group demonstrated increased activation of the hippocampus at t2 (t2 > t1), which was positively correlated with treatment outcome, and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time (t1 > t2). After T+ exposure, contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus, previously shown to be dysfunctionally activated in PD/AG. Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions. © 2014 S. Karger AG, Basel.

  3. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

    PubMed Central

    Christodoulou, C.; Melville, P.; Scherl, W.F.; Pai, L.-Y.; Muenz, L.R.; He, D.; Benedict, R.H.B.; Goodman, A.; Rizvi, S.; Schwid, S.R.; Weinstock-Guttman, B.; Westervelt, H.J.; Wishart, H.

    2011-01-01

    Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18–59 years, clinically definite multiple sclerosis (MS), and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. Results: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. Conclusions: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. Classification of evidence: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average. PMID:21519001

  4. Internet-Delivered Disease Management for Recurrent Depression: A Multicenter Randomized Controlled Trial.

    PubMed

    Kordy, Hans; Wolf, Markus; Aulich, Kai; Bürgy, Martin; Hegerl, Ulrich; Hüsing, Johannes; Puschner, Bernd; Rummel-Kluge, Christine; Vedder, Helmut; Backenstrass, Matthias

    2016-01-01

    Strategies to improve the life of patients suffering from recurrent major depression have a high relevance. This study examined the efficacy of 2 Internet-delivered augmentation strategies that aim to prolong symptom-free intervals. Efficacy was tested in a 3-arm, multicenter, open-label, evaluator-blind, randomized controlled trial. Upon discharge from inpatient mental health care, 232 adults with 3 or more major depressive episodes were randomized to 1 of 2 intervention groups (SUMMIT or SUMMIT-PERSON) or to treatment as usual (TAU) alone. Over 12 months, participants in both intervention arms received, in addition to TAU, intense monitoring via e-mail or a smartphone, including signaling of upcoming crises, assistance with personal crisis management, and facilitation of early intervention. SUMMIT-PERSON additionally offered regular expert chats. The primary outcome was 'well weeks', i.e. weeks with at most mild symptoms assessed by the Longitudinal Interval Follow-Up Evaluation, during 24 months after the index treatment. SUMMIT compared to TAU reduced the time with an unwell status (OR 0.48; 95% CI 0.23-0.98) through faster transitions from unwell to well (OR 1.44; 95% CI 0.83-2.50) and slower transitions from well to unwell (OR 0.69; 95% CI 0.44-1.09). Contrary to the hypothesis, SUMMIT-PERSON was not superior to either SUMMIT (OR 0.77; 95% CI 0.38-1.56) or TAU (OR 0.62; 95% CI 0.31-1.24). The efficacy of SUMMIT was strongest 8 months after the intervention. The fully automated Internet-delivered augmentation strategy SUMMIT has the potential to improve TAU by reducing the lifelong burden of patients with recurrent depression. The fact that the effects wear off suggests a time-unlimited extension. © 2016 S. Karger AG, Basel.

  5. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Chen, Yuan-Fang; Liu, Jian-Hua; Xu, Neng-Gui; Liang, Zhao-Hui; Xu, Zhen-Hua; Xu, Shu-Jun; Fu, Wen-Bin

    2013-01-03

    More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. The trial was registered in Chinese Clinical Trial Register (ChiCR-TRC-00000481) on 12 August 2009.

  8. Meniett device in meniere disease: Randomized, double-blind, placebo-controlled multicenter trial.

    PubMed

    Russo, Francesca Yoshie; Nguyen, Yann; De Seta, Daniele; Bouccara, Didier; Sterkers, Olivier; Ferrary, Evelyne; Bernardeschi, Daniele

    2017-02-01

    To evaluate the efficacy of portable Meniett low-pressure pulse generator (Medtronic Xomed, Jacksonville, FL) in Meniere disease. Randomized, double-blind, placebo-controlled, multicenter trial carried out in 17 academic medical centers. One hundred twenty-nine adults presenting Meniere disease (American Academy of Otolaryngology-Head and Neck Surgery criteria) not controlled by conventional medical treatment were included. The protocol included three phases: 1) placement of a transtympanic tube and evaluation of its effect (if resolution of symptoms, the patient was excluded); 2) randomization: 6-weeks treatment with Meniett (Medtronic Xomed) or placebo device; 3) removal of the device and 6-week follow-up period. The evaluation criteria were the number of vertigo episodes (at least 20 minutes with a 12-hour free interval) and the impact on daily life as assessed by self-questionnaires. Ninety-seven patients passed to the second phase of the study: 49 and 48 patients received the Meniett (Medtronic Xomed) or the placebo device, respectively. In the placebo group, the number of vertigo episodes decreased from 4.3 ± 0.6 (mean ± standard error of the mean) during the first phase to 2.6 ± 0.5 after 6 weeks of treatment, and to 1.8 ± 0.8 after the removal of the device. Similar results were observed in the Meniett device (Medtronic Xomed) group: 3.2 ± 0.4 episodes during the first phase, 2.5 ± after 6 weeks of Meniett device (Medtronic Xomed) treatment, and 1.5 ± 0.2 after the third phase. An improvement of symptoms was evidenced in all patients, with no difference between the Meniett (Medtronic Xomed) and the placebo device groups. The decrease in the number of vertigo episodes could be explained by an effect of the medical care. 1b. Laryngoscope, 2016 127:470-475, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.

    PubMed

    Muresanu, Dafin F; Heiss, Wolf-Dieter; Hoemberg, Volker; Bajenaru, Ovidiu; Popescu, Cristian Dinu; Vester, Johannes C; Rahlfs, Volker W; Doppler, Edith; Meier, Dieter; Moessler, Herbert; Guekht, Alla

    2016-01-01

    The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo. This study was a prospective, randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Patients were treated with Cerebrolysin (30 mL/d) or a placebo (saline) once daily for 21 days, beginning at 24 to 72 hours after stroke onset. The patients also participated in a standardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset. The primary end point was the Action Research Arm Test score on day 90. The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann-Whitney estimator, 0.71; 95% confidence interval, 0.63-0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann-Whitney estimator, 0.62; 95% confidence interval, 0.58-0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated. Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke. Its safety was comparable with that of the placebo, suggesting a favorable benefit/risk ratio. Because this study was exploratory and had a relatively small sample size, the results should be confirmed in a large-scale, randomized clinical trial. URL: http://www.clinicaltrialsregister.eu. Unique identifier: 2007-000870-21. © 2015 The Authors.

  10. Efficacy and safety of an intraoral electrostimulation device for xerostomia relief: a multicenter, randomized trial.

    PubMed

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

    2011-01-01

    To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex. The device was tested on a sample of patients with xerostomia due to Sjögren's syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage designed to assess the long-term effects of the active device. Improvement in xerostomia severity from baseline was the primary outcome measure. A total of 114 patients were randomized. In stage I, the active device performed better than the sham device for patient-reported xerostomia severity (P<0.002), xerostomia frequency (P<0.05), quality of life impairment (P<0.01), and swallowing difficulty (P<0.02). At the end of stage II, statistically significant improvements were verified for patient-reported xerostomia severity (P<0.0001), xerostomia frequency (P<0.0001), oral discomfort (P<0.001), speech difficulty (P<0.02), sleeping difficulty (P<0.001), and resting salivary flow rate (P<0.01). Our findings indicate that daily use of the device alleviated oral dryness, discomfort, and some complications of xerostomia, such as speech and sleeping difficulties, and increased salivary output. The results show a cumulative positive effect of the device over the period of the study, from baseline to the end of the trial.

  11. A perineal protection device designed to protect the perineum during labor: a multicenter randomized controlled trial.

    PubMed

    Lavesson, Tony; Griph, Inger D; Skärvad, Anna; Karlsson, Ann-Sofi; Nilsson, Helen B; Steinvall, Margareta; Haadem, Knut

    2014-10-01

    The objective of this study was to evaluate the protective effects of a new device for reducing perineal tears during vaginal childbirth. A multicenter open randomized controlled trial (RCT) was performed in Helsingborg, Lund and Malmö, Sweden consisting of 1148 women. Women anticipating a vaginal delivery were either randomized to the intervention group (n=574 in which the perineal protection device was used, or a control group (n=574), in which the perineal protection device was not used. The main outcome measurements were incidence of vaginal and perineal tears (1st to 4th degree tears) and adverse effects on the parturient and newborn. The incidences of first- and second-degree tears of the vagina (p=0.018) and perineum (p=0.005) were significantly reduced in the intervention group compared with the controls. In the intervention- and control group, 184 women (34.9%) and 142 (26.6%) showed no perineal tearing, respectively (p=0.034). Numbers needed to treat to avoid any perianal tearing was 12. The incidence of anal sphincter rupture (ASR) was the same in both groups (n=19; 3.4%). No negative effects on mother or child from using the device were observed. The perineal protective device significantly reduced the incidence of first- and second-degree tears in the vagina and perineum during vaginal birth and also significantly increased the number of parturients with a fully intact posterior commissure. No significant reduction of ASR and no negative effects of the device were observed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks.

    PubMed

    Yamaguchi, Takashi; Gi, Min; Yamano, Shotarou; Fujioka, Masaki; Tatsumi, Kumiko; Kawachi, Satoko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

    2017-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20ppm in their drinking water for 52 weeks. There were no significant differences in the final body weights between the control groups and the treatment groups in male or female rats. In serum biochemistry, in females 20ppm DPAA significantly increased alkaline phosphatase and γ-glitamyl transferase compared to controls, and 10 and 20ppm DPAA significantly increased total cholesterol compared to controls. Absolute and relative liver weights were significantly increased in females treated with 20ppm DPAA compared to the control group. Dilation of the common bile duct outside the papilla of Vater and stenosis of the papilla of Vater was observed in all male and female rats administered 20ppm DPAA. The incidence of intrahepatic bile duct hyperplasia was significantly increased in male and female rats treated with 20ppm DPAA compared to the control groups. These results suggest that DPAA is toxic to the bile duct epithelium in rats. The no-observed adverse effect levels of DPAA were estimated to be 10ppm (0.48mg/kg b.w./day) for males and 5ppm (0.35mg/kg b.w./day) for females under the conditions of this study. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other outcomes over 52 weeks of therapy.

    PubMed

    Mattsson, L-Å; Ipsen, H E; Granqvist, C-J; Kokot-Kierepa, M

    2015-06-01

    Continuous combined hormone replacement therapy (HRT) with 0.5 mg 17β-estradiol (E2) + 0.1 mg norethisterone acetate (NETA) received marketing approval based on 24-week results. The current study collected data up to 52 weeks, including consideration of bleeding, a major reason for stopping HRT. This 52-week (13 lunar-month), non-interventional, prospective study involved 169 women from Norway and Sweden receiving daily oral 0.5 mg E2 + 0.1 mg NETA to treat menopausal symptoms. Incidences and cumulative rates of amenorrhea (no bleeding or spotting) and no bleeding (women could have spotting) were evaluated, together with hot flushes and quality of life. Overall, > 78% and > 90% of subjects were amenorrheic or had no bleeding, respectively, in each of the first 3 lunar months, while > 88% and > 96% were amenorrheic or had no bleeding, respectively, in each of lunar months 10, 11 and 12. Cumulative rates of amenorrhea and no bleeding were 67% and 83%, respectively, in lunar months 1-3, and 84% and 94%, respectively, in lunar months 10-12. The number of hot flushes declined during treatment (means at weeks 1, 12 and 52, respectively: 15.5, 5.0 and 4.1 [mild]; 19.0, 3.0 and 2.3 [moderate]; 10.8, 1.1 and 0.9 [severe]). Improvement in all four domains of the Menopause-Specific Quality of Life-Intervention questionnaire (vasomotor, psychosocial, physical and sexual) was evident by week 26. For women receiving 0.5 mg E2 + 0.1 mg NETA, lack of bleeding-related side-effects, together with beneficial effects on hot flush symptoms and quality of life, may promote treatment continuance.

  14. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy.

    PubMed

    Barnett, Anthony H; Charbonnel, Bernard; Li, Jia; Donovan, Mark; Fleming, Douglas; Iqbal, Nayyar

    2013-10-01

    Achievement of glycemic control is an important objective in the management of type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the safety and efficacy of the dipeptidyl peptidase-4 inhibitor saxagliptin versus placebo as add-on therapy in patients with T2DM inadequately controlled with insulin alone or insulin plus metformin. This was a long-term (28-week) extension of a short-term (24-week), randomized, double-blind, parallel-group trial of saxagliptin 5 mg once daily versus placebo as add-on therapy to open-label insulin or insulin plus metformin therapy totaling 52 weeks of treatment. In contrast with the goal of maintaining a stable insulin dosage during the short-term phase, during the extension phase the insulin dosage was flexible and adjusted as deemed appropriate by the investigator. The study was conducted in a clinical practice setting, including family practice and hospital sites. Patients with T2DM aged 18-78 years with glycated hemoglobin (HbA1c) 7.5-11 % on a stable insulin regimen (30-150 U/day with or without metformin) for ≥8 weeks at screening were included in the study. Patients were stratified by metformin use and randomly assigned 2:1 to oral saxagliptin 5 mg (n = 304) or placebo (n = 151) once daily. All patients who completed the initial 24 weeks of treatment were eligible to participate in the 28-week extension, regardless of whether they had required rescue treatment. The main outcome measure was change in HbA1c from baseline to week 52. In general, the outcomes achieved at week 24 were sustained to week 52. Adjusted mean change from baseline HbA1c at week 52 was greater with saxagliptin (-0.75 %) versus placebo (-0.38 %); the adjusted between-group difference was -0.37 % (95 % CI -0.55 to -0.19); between-group differences were similar in patients treated with metformin (-0.37 % [95 % CI -0.59 to -0.15]) and without metformin (-0.37 % [95 % CI -0.69 to -0.04]). At week 52, a greater proportion of patients

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

    PubMed Central

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

    2010-01-01

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

  16. Music therapy in Huntington's disease: a protocol for a multi-center randomized controlled trial.

    PubMed

    van Bruggen-Rufi, Monique; Vink, Annemieke; Achterberg, Wilco; Roos, Raymund

    2016-07-26

    Huntington's disease is a progressive, neurodegenerative disease with autosomal dominant inheritance, characterized by motor disturbances, cognitive decline and behavioral and psychological symptoms. Since there is no cure, all treatment is aimed at improving quality of life. Music therapy is a non-pharmacological intervention, aiming to improve the quality of life, but its use and efficacy in patients with Huntington's disease has hardly been studied. In this article, a protocol is described to study the effects of music therapy in comparison with a control intervention to improve quality of life through stimulating expressive and communicative skills. By targeting these skills we assume that the social-cognitive functioning will improve, leading to a reduction in behavioral problems, resulting in an overall improvement of the quality of life in patients with Huntington's disease. The study is designed as a multi-center single-blind randomised controlled intervention trial. Sixty patients will be randomised using centre-stratified block-permuted randomisation. Patients will be recruited from four long-term care facilities specialized in Huntington's disease-care in The Netherlands. The outcome measure to assess changes in expressive and communication skills is the Behaviour Observation Scale Huntington and changes in behavior will be assessed by the Problem Behaviour Assesment-short version and by the BOSH. Measurements take place at baseline, then 8, 16 (end of intervention) and 12 weeks after the last intervention (follow-up). This randomized controlled study will provide greater insight into the effectiveness of music therapy on activities of daily living, social-cognitive functioning and behavior problems by improving expressive and communication skills, thus leading to a better quality of life for patients with Huntington's disease. Netherlands Trial Register: NTR4904 , registration date Nov. 15, 2014.

  17. Gastric endoscopic submucosal dissection under steady pressure automatically controlled endoscopy (SPACE); a multicenter randomized preclinical trial.

    PubMed

    Yamada, Takuya; Hirota, Masashi; Tsutsui, Shusaku; Kato, Motohiko; Takahashi, Tsuyoshi; Yasuda, Kazuhiro; Sumiyama, Kazuki; Tsujii, Masahiko; Takehara, Tetsuo; Mori, Masaki; Doki, Yuichiro; Nakajima, Kiyokazu

    2015-09-01

    Steady pressure automatically controlled endoscopy (SPACE) is a new modality that eliminates on-demand insufflation but enables automatic insufflation in the gastrointestinal tract. Though its use in porcine esophageal ESD was reported to be promising, its applicability and potential effectiveness to gastric procedures have not been evaluated. The aims were (1) to evaluate feasibility and safety of SPACE in the stomach, and (2) to assess its potential advantages over conventional endoscopy in preventing "blind insufflation"-related complications. A multicenter randomized preclinical animal study. Laboratories at three universities. Experiment 1: Gastric ESD was attempted in the swine (n = 17), under either SPACE or manual insufflation. Experiment 2: Gastroscopy was performed for 10 min in the perforated stomach (n = 10) under either SPACE or manual insufflation. Experiment 1: ESD time, energy device activation time, number of forceps exchanges, specimen size, en block resection rate, vital signs and any intraoperative adverse events. Experiment 2: Intra-gastric and intra-abdominal pressures, vital signs, and any adverse events. Experiment 1: Gastric ESD was completed in all animals. ESD time tended to be shorter in SPACE than in the control, though the difference was not significant (p = 0.18). Experiment 2: Although both intra-gastric and intra-abdominal pressures remained within preset values in SPACE, they showed excessive elevation in control. An animal study with small sample size. SPACE is feasible and safe for complicated and lengthy procedures such as gastric ESD, and is potentially effective in preventing serious consequences related to excessive blind insufflation.

  18. Influence of infusion method on gemcitabine pharmacokinetics: a controlled randomized multicenter trial.

    PubMed

    Simon, Nicolas; Romano, Olivier; Michel, Pierre; Pinçon, Claire; Vasseur, Michèle; Lemahieu, Nicole; Barthélémy, Christine; Hebbar, Mohamed; Décaudin, Bertrand; Odou, Pascal

    2015-10-01

    Ensuring the correct administration of antineoplastic drugs is a constantly challenging task. Nowadays, several specific infusion devices have been marketed to decrease occupational exposure to these drugs through a post-administration rinsing step. As their impact on drug pharmacokinetics has never been evaluated, the objective of this study was to assess how the infusion process may alter the pharmacokinetics of antineoplastic drugs. We developed a prospective randomized multicenter pharmacokinetic study (ONCOPERF01) to compare the influence of three infusion techniques (gravity-fed infusion-GFI, infusion pump-IP, and gravity-fed infusion with post-administration rinsing-PAR) to assess the impact of both flow rate and post-administration rinsing on gemcitabine pharmacokinetics during three consecutive administrations. Gemcitabine pharmacokinetics was determined with a two-compartment model after plasma dosing with an HPLC-UV method. Statistical comparisons of the three groups were made using repeated-measure analysis of variance (PROC MIXED). Patients received gemcitabine by gravity-fed infusion (GFI, n = 9; IP, n = 9; PAR, n = 7). Significant differences were noted between infusion duration (GFI = 30.0 ± 2.6 min, IP = 29.1 ± 1.2 min, PAR = 33.7 ± 3.5 min; p = 0.003) and AUCt (GFI = 23.5 ± 8.2 µM h, IP = 25.4 ± 9.1 µM h, PAR = 28.5 ± 6.3 µM h; p = 0.0009), which was significantly higher in the infusion group with post-administration rinsing than in the other groups. The ONCOPERF01 study indicates that post-administration rinsing leads to a significant increase in patient exposure to gemcitabine, whereas controlling flow rate has no significance. Further surveys are required to assess the impact of such infusion techniques on other antineoplastic drugs.

  19. Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

    PubMed Central

    Fitzlaff, Rüdiger; Röming, Hermann; Ameis, Detlev; Heinecke, Achim; Kunsch, Steffen; Ellenrieder, Volker; Ströbel, Philipp; Schepke, Michael; Meister, Tobias

    2014-01-01

    Objectives The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). Methods This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). Results The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates. Conclusions EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. Trial Registration ClinicalTrials.gov NCT02034929. PMID:25470133

  20. Electrolyte changes after bowel preparation for colonoscopy: A randomized controlled multicenter trial

    PubMed Central

    Lee, Kyong Joo; Park, Hong Jun; Kim, Hyun-Soo; Baik, Kwang Ho; Kim, Yeon Soo; Park, Sung Chul; Seo, Hyun Il

    2015-01-01

    AIM: To investigate the electrolyte changes between 2-L polyethylene glycol with ascorbic acid 20 g (PEG-Asc) and 4-L PEG solutions. METHODS: From August 2012 to February 2013, a total of 226 patients were enrolled at four tertiary hospitals. All patients were randomly allocated to a PEG-Asc group or a 4-L PEG. Before colonoscopy, patients completed a questionnaire to assess bowel preparation-related symptoms, satisfaction, and willingness. Endoscopists assessed the bowel preparation using the Boston Bowel Preparation Scale (BBPS). In addition, blood tests, including serum electrolytes, serum osmolarity, and urine osmolarity were evaluated both before and after the procedure. RESULTS: A total of 226 patients were analyzed. BBPS scores were similar and the adequate bowel preparation rate (BBPS ≥ 6) was not different between the two groups (PEG-Asc vs 4-L PEG, 73.2% vs 76.3%, P = 0.760). Bowel preparation-related symptoms also were not different between the two groups. The taste of PEG-Asc was better (41.1% vs 16.7%, P < 0.001), and the willingness to undergo repeated bowel preparation was higher in the PEG-Asc group (73.2% vs 59.3%, P = 0.027) than in 4-L PEG. There were no significant changes in serum electrolytes in either group. CONCLUSION: In this multicenter trial, bowel preparation with PEG-Asc was better than 4-L PEG in terms of patient satisfaction, with similar degrees of bowel preparation and electrolyte changes. PMID:25780304

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

    PubMed

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

    2015-05-01

    We previously reported the initial results of the first multicenter, randomized, double-blind, placebo-controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year. We sought to provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key end points were (1) percentage of responders at 2 years (ie, could consume 5 g of peanut powder or a 10-fold increase from baseline), (2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic end points, and (5) assessment of safety parameters. Response to treatment was evaluated in 40 subjects aged 12 to 40 years by performing a 10-g peanut powder oral food challenge after 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks, followed by another 10-g oral food challenge and an open feeding of peanut butter to assess sustained unresponsiveness. Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study's end, 4 (10.8%) of 37 SLIT-treated participants were fully desensitized to 10 g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared with nonresponders. Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-02-02

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

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

    PubMed Central

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

    2009-01-01

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

  4. Clinical curative effect of electric acupuncture on acute cerebral infarction: a randomized controlled multicenter trial.

    PubMed

    Wang, Chengwei; Wu, Zhongchao; Li, Ning; Zhao, Yu; Tian, Fengwei; Zhou, Xi; Wang, Zhuxing

    2014-12-01

    To examine whether electric acupuncture can improve the daily life of patients with ischemic cerebral apoplexy at acute stage. A stratified-block randomized controlled multicenter trial was designed for this study. Totally 340 patients with acute ischemic cerebral apoplexy were randomly divided into an electric acupuncture group and a control group. In the electric acupuncture group, 170 patients were treated with electric acupuncture and routine therapy, and 170 patients in the control group with routine therapy alone. Major indexes for judging curative effect were Barthel index at 3- and 6- months follow-up visits and number of re-hospitalized patients. Minor indexes for judging curative effect were change in the score for nervous dysfunction at 4 and 12 weeks follow-up visits and number of patients persisting in rehabilitation treatment with acupuncture during follow-up visit. Baseline data at the time of case selection between the two groups were similar. The odds ratio (OR) was 0.92, and the 95% confidence interval (CI) was 0.49-1.73 in disabled rate and 0.73 and 0.51-1.05 in the number of re-hospitalized patients in the electric acupuncture group at 6-month follow up visit compared with the control group. There was no difference in the score for nervous dysfunction at the end of 12-week follow-up visit between the two groups. The score for nervous dysfunction at the end of 4-week treatment in the electric acupuncture group was significantly higher than that in the control group (P < 0.05). The number of patients discharged from hospital who persisted in rehabilitation treatment with acupuncture in the acupuncture group was significantly higher than that in the control group. Using electric acupuncture to treat patients with acute ischemic cerebral apoplexy can effectively improve the nervous dysfunction scores after 4-week treatment and their ability to deal with daily life after 6-month follow-up visit. Systematic treatment with acupuncture may also reduce

  5. Extracorporeal shock wave therapy in the treatment of lateral epicondylitis : a randomized multicenter trial.

    PubMed

    Haake, M; König, I R; Decker, T; Riedel, C; Buch, M; Müller, H-H

    2002-11-01

    On the basis of observational trials, numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow. However, there has been no evidence of its efficacy from well-designed randomized clinical trials. The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia. A randomized multicenter trial with a parallel-group design was conducted. Following administration of local anesthesia, either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density (ED+) of 0.07 to 0.09 mJ/mm (2) or placebo therapy was applied on an outpatient basis. Treatment allocation was blinded for patients and for observers. The primary end point was based on the rate of success, as determined with the Roles and Maudsley score and whether additional treatment was required, twelve weeks after the intervention. Crossover was possible after assessment of the primary end point. Secondary end points were the Roles and Maudsley score, subjective pain rating, and grip strength after six and twelve weeks and after twelve months. The planned number of 272 patients was included in the study. The primary end point could be assessed for 90.8% of the patients. The success rate was 25.8% in the group treated with extracorporeal shock wave therapy and 25.4% in the placebo group, a difference of 0.4% with a 95% confidence interval of -10.5% to 11.3%. Similarly, there was no relevant difference between groups with regard to the secondary end points. Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention. Few side effects were reported. Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis. The previously reported success of

  6. [YANG's pricking-cupping therapy for knee osteoarthritis: a multi-center randomized controlled trial].

    PubMed

    Wang, Bo; Liu, Xiru; Hu, Zhihai; Sun, Aijun; Ma, Yanwen; Chen Yingying; Zhang, Xuzhi; Liu, Meiling; Wang, Yi; Wang, Shuoshuo; Zhang, Yunjia; Li, Yijing; Shen, Weidong

    2016-02-01

    To evaluate the clinical efficacy of YANG's pricking-cupping therapy for knee osteoar thritis (KOA). Methods This was a multi-center randomized parallel controlled trial. One hundred and seventy one patients with KOA were randomly allocated to a pricking-cupping group (89 cases) and a conventional acu puncture group (82 cases). Neixiyan (EX-LE 4), Dubi (ST 35) and ashi points were selected in the two groups. Patients in the pricking-cupping group were treated with YANG's pricking-cupping therapy; the seven-star needles were used to perform pricking at acupoints, then cupping was used until slight bleeding was observed. Patients in the conventional acupuncture group were treated with semi-standardized filiform needle therapy. The treatment was given for 4 weeks (from a minimum of 5 times to a maximum of 10 times). The follow-up visit was 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analogue scale (VAS) were adopted for the efficacy assessments. The pain score, stiffness score, physical function score and total score of WOMAC were all reduced after 4-week treatment and during follow-up visit in the two groups (all P<0. 0001). Except that the difference of stiffness score between the two groups was not significant after 4-week treatment (P>0. 05), each score and total score of WOMAC in the pricking-cupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (P<0. 0001, P<0. 01). After 2-week treatment, 4-week treatment and during follow-up visit, the VAS was all reduced compared with that before treatment (all P<0. 0001) ; with the increase of the treatment, the reducing trend of VAS was more significant (P<0. 0001). The scores of VAS in the pricking-cupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (P < 0. 01, P <0. 0001). CONCLUSION The YANG's pricking-cupping and conventional

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

    PubMed

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

    2009-03-13

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

  8. Multicenter randomized controlled trial comparing early versus late aquatic therapy after total hip or knee arthroplasty.

    PubMed

    Liebs, Thoralf R; Herzberg, Wolfgang; Rüther, Wolfgang; Haasters, Jörg; Russlies, Martin; Hassenpflug, Joachim

    2012-02-01

    To evaluate if the timing of aquatic therapy influences clinical outcomes after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Multicenter randomized controlled trial with 3-, 6-, 12-, and 24-month follow-up. Two university hospitals, 1 municipal hospital, and 1 rural hospital. Patients (N=465) undergoing primary THA (n=280) or TKA (n=185): 156 men, 309 women. Patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) after 6 versus 14 days after THA or TKA. Primary outcome was self-reported physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-, 6-, 12-, and 24-months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. Secondary outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey, Lequesne-Hip/Knee-Score, WOMAC-pain and stiffness scores, and patient satisfaction. Baseline characteristics of the 2 groups were similar. Analyzing the total study population did not result in statistically significant differences at all follow-ups. However, when performing subanalysis for THA and TKA, opposite effects of early aquatic therapy were seen between TKA and THA. After TKA all WOMAC subscales were superior in the early aquatic therapy group, with effect sizes of WOMAC physical function ranging from .22 to .39. After THA, however, all outcomes were superior in the late aquatic therapy group, with WOMAC effect sizes ranging from .01 to .19. However, the differences between treatment groups of these subanalyses were not statistically significant. Early start of aquatic therapy had contrary effects after TKA when compared with THA and it influenced clinical outcomes after TKA. Although the treatment differences did not achieve statistically significance, the effect size for early aquatic therapy after TKA had the same magnitude as the

  9. Effect of supplemental vibrational force on orthodontically induced inflammatory root resorption: A multicenter randomized clinical trial.

    PubMed

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

    2016-12-01

    A multicenter parallel 3-arm randomized clinical trial was carried out in 1 university and 2 district hospitals in the United Kingdom to investigate the effect of supplemental vibrational force on orthodontically induced inflammatory root resorption (OIIRR) during the alignment phase of fixed appliance therapy. Eighty-one subjects less than 20 years old with mandibular incisor irregularity undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20 minutes a day) use of an intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex) (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed appliances only (n = 27). OIIRR was measured blindly from long-cone periapical radiographs of the maxillary right central incisor taken at the start of treatment and the end of alignment when a 0.019 × 0.025-in stainless steel archwire was placed (mean follow-up, 201.6 days; 95% confidence interval [CI], 188.6-214.6 days). Data were analyzed blindly on a per-protocol basis because losses to follow-up were minimal, with descriptive statistics, 1-way analysis of variance, and univariable and multivariable regression modeling. Nine patients were excluded from the analysis; they were evenly distributed across the groups. Mean overall OIIRR measured among the 72 patients was 1.08 mm (95% CI, 0.89-1.27 mm). Multivariable regression indicated no significant difference in OIIRR for the AcceleDent (difference, 0.22 mm; 95% CI, -0.14-0.72; P = 0.184) and AcceleDent sham groups (difference, 0.29 mm; 95% CI, -0.15-0.99; P = 0.147) compared with the fixed-appliance-only group, after accounting for patient sex, age, malocclusion, extraction pattern, alignment time, maximum pain experienced, history of dentoalveolar trauma, and initial root length of the maxillary right central incisor. No other side-effects were recorded apart from pain and OIIRR. The use of supplemental vibrational force during the

  10. Different dosages of mifepristone versus enantone to treat uterine fibroids: A multicenter randomized controlled trial.

    PubMed

    Liu, Chongdong; Lu, Qi; Qu, Hong; Geng, Li; Bian, Meilu; Huang, Minli; Wang, Huilan; Zhang, Youzhong; Wen, Zeqing; Zheng, Shurong; Zhang, Zhenyu

    2017-02-01

    To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids. This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3.75 mg) were used. Change in volume of the largest uterine fibroid was the primary efficacy variable, and secondary efficacy variables included changes in anemia and relevant symptom. Safety evaluation included the analyses of adverse events, laboratory values, and relevant endometrial changes. After three months of treatment, the mean volume of the largest leiomyoma was significantly reduced by mifepristone 10 mg or 25 mg or enantone 3.75 mg (40.27%, 42.59% and 44.49% respectively) (P < 0.0001). Percentage change from baseline in largest leiomyoma volume was not statistically significant among the three groups (P = 0.1057). Most of the patients in all groups experienced amenorrhea after the treatment. There were also significant elevations in red blood cell count, hemoglobin and hematocrit (P < 0.0001), and significant reductions in prevalence of dysmenorrhea, pelvic pressure, non-menstrual abdominal pain (P < 0.0001) in each group, while no significant difference among the three groups.All study medications are well-tolerated, and no serious adverse event was reported. Treatment-related adverse event rate was significantly lower in mifepristone 10 mg group, compared to Enantone 3.75 mg group (13.59% vs. 32.58%, P = 0.0002). In both mifepristone groups, estradiol levels were maintained in the premenopausal range, whereas patients in the enantone group had a

  11. Reconstruction of Peri-implant Osseous Defects: A Multicenter Randomized Trial.

    PubMed

    Jepsen, K; Jepsen, S; Laine, M L; Anssari Moin, D; Pilloni, A; Zeza, B; Sanz, M; Ortiz-Vigon, A; Roos-Jansåker, A M; Renvert, S

    2016-01-01

    There is a paucity of data for the effectiveness of reconstructive procedures in the treatment of peri-implantitis. The objective of this study was to compare reconstruction of peri-implant osseous defects with open flap debridement (OFD) plus porous titanium granules (PTGs) compared with OFD alone. Sixty-three patients (36 female, 27 male; mean age 58.4 y [SD 12.3]), contributing one circumferential peri-implant intraosseous defect, were included in a multinational, multicenter randomized trial using a parallel-group design. After OFD and surface decontamination using titanium brushes and hydrogen peroxide, 33 defects received PTGs. The implants were not submerged. All patients received adjunctive perioperative systemic antibiotics. The primary outcome variable (defect fill) was assessed on digitalized radiographs. Clinical measurements of probing depth (PPD), bleeding on probing (BoP), suppuration, and plaque were taken by blinded examiners. After 12 mo, the test group (OFD plus PTG) showed a mean radiographic defect fill (mesial/distal) of 3.6/3.6 mm compared with 1.1/1.0 in the control group (OFD). Differences were statistically significant in favor of the test group (P < 0.0001). The OFD plus PTG group showed a mean reduction in PPD of 2.8 mm compared with 2.6 mm in the OFD group. BoP was reduced from 89.4% to 33.3% and from 85.8% to 40.4% for the test and control groups, respectively. There was no significant difference in complete resolution of peri-implantitis (PPD ≤4 mm and no BoP at six implant sites and no further bone loss), because this finding was accomplished at 30% of implants in the test group and 23% of implants in the control group. Reconstructive surgery using PTGs resulted in significantly enhanced radiographic defect fill compared with OFD. However, limitations in the lack of ability to discern biomaterial from osseous tissue could not be verified to determine new bone formation. Similar improvements according to clinical measures were

  12. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage.

    PubMed

    Hacker, R J; Cauthen, J C; Gilbert, T J; Griffith, S L

    2000-10-15

    A prospective, concurrently controlled, randomized, multicenter trial of an anterior Bagby and Kuslich cervical fusion cage (BAK/C; Sulzer Spine-Tech, Minneapolis, MN) for treatment of degenerative disc disease of the cervical spine. To report clinical results with maximum 24-month follow-up of fusions performed with the BAK/C fusion cage. Threaded lumbar cages have been used during the past decade as a safe and effective surgical solution for chronic disabling low back pain. Threaded cages have now been developed for use in anterior cervical interbody fusions to obviate the need for allografts or autogenous bone grafting procedures while providing initial stability during the fusion process. Patients with symptomatic cervical discogenic radiculopathy were treated with either anterior cervical discectomy with uninstrumented bone-only fusion (ACDF) or BAK/C fusion cage(s). Independent radiographic assessment of fusion was made and patient-based outcome was assessed by visual analog pain scale and a Short Form (SF)-36 Health Status Questionnaire. Data analysis included 344 patients at 1 year and 180 at 2 years. When the two cage groups (hydroxya, patite-coated or noncoated) were compared with the ACDF group, similar outcomes were noted for duration of surgery, hospital stay, improvements in neck pain and radicular pain in the affected limb, improvements in the SF-36 Physical Component subscale and Mental Component subscale, and the patients' perception of overall surgical outcome. Symptom improvements were maintained at 2 years. A greater percentage of patients with ACDF needed an iliac crest bone harvest than did BAK/C patients (67% vs.- 3%). Successful fusion for one-level procedures at 12 months was 97.9% for the BAK/C groups and 89.7% for the ACDF group (P < 0.05). The complication rate for the ACDF group was 20.4% compared with an overall complication rate of 11.8% with BAK/C. There was no difference in complications that necessitated a second operative

  13. Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial.

    PubMed

    Uranga, Ane; España, Pedro P; Bilbao, Amaia; Quintana, Jose María; Arriaga, Ignacio; Intxausti, Maider; Lobo, Jose Luis; Tomás, Laura; Camino, Jesus; Nuñez, Juan; Capelastegui, Alberto

    2016-09-01

    The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) has not been well established. To validate Infectious Diseases Society of America/American Thoracic Society guidelines for duration of antibiotic treatment in hospitalized patients with CAP. This study was a multicenter, noninferiority randomized clinical trial performed at 4 teaching hospitals in Spain from January 1, 2012, through August 31, 2013. A total of 312 hospitalized patients diagnosed as having CAP were studied. Data analysis was performed from January 1, 2014, through February 28, 2015. Patients were randomized at day 5 to an intervention or control group. Those in the intervention group were treated with antibiotics for a minimum of 5 days, and the antibiotic treatment was stopped at this point if their body temperature was 37.8°C or less for 48 hours and they had no more than 1 CAP-associated sign of clinical instability. Duration of antibiotic treatment in the control group was determined by physicians. Clinical success rate at days 10 and 30 since admission and CAP-related symptoms at days 5 and 10 measured with the 18-item CAP symptom questionnaire score range, 0-90; higher scores indicate more severe symptoms. Of the 312 patients included, 150 and 162 were randomized to the control and intervention groups, respectively. The mean (SD) age of the patients was 66.2 (17.9) years and 64.7 (18.7) years in the control and intervention groups, respectively. There were 95 men (63.3%) and 55 women (36.7%) in the control group and 101 men (62.3%) and 61 women (37.7%) in the intervention group. In the intent-to-treat analysis, clinical success was 48.6% (71 of 150) in the control group and 56.3% (90 of 162) in the intervention group at day 10 (P = .18) and 88.6% (132 of 150) in the control group and 91.9% (147 of 162) in the intervention group at day 30 (P = .33). The mean (SD) CAP symptom questionnaire scores were 24.7 (11.4) vs 27.2 (12.5) at day 5 (P = .10) and

  14. Long-Term Treatment Outcome in Adult Male Prisoners With Attention-Deficit/Hyperactivity Disorder: Three-Year Naturalistic Follow-Up of a 52-Week Methylphenidate Trial.

    PubMed

    Ginsberg, Ylva; Långström, Niklas; Larsson, Henrik; Lindefors, Nils

    2015-10-01

    Despite high rates of attention-deficit/hyperactivity disorder (ADHD) among adult lawbreakers, particularly the long-term effects of ADHD pharmacotherapy remain unclear, not the least because of ethical challenges with preventing control subjects in randomized controlled trials from receiving medication over prolonged time. We followed up adult male prisoners with ADHD who completed a 5-week randomized, double-blind, placebo-controlled trial followed by a 47-week open-label extension of osmotic-release oral system methylphenidate in a Swedish high-security prison from 2007 to 2010 (ClinicalTrials.gov: NCT00482313). Twenty-five trial completers were prospectively followed up clinically 1 year (24/25, 96% participated fully or in part) and 3 years (20/25, 80% participation) after trial regarding ADHD symptoms (observer and self-reports), psychosocial functioning, substance misuse, and criminal reoffending. Methylphenidate-related improvements in ADHD symptoms and psychosocial functioning obtained during the 52-week trial were maintained at 1- and 3-year follow-ups. Specifically, after 3 years, 75% (15/20) of the respondents had been released from prison, and 67% of these (10/15) had employment, usually full time. In contrast, nonmedicated respondents at the 3-year follow-up (5/20) reported more ADHD symptoms, functional impairment, and substance misuse compared with currently medicated respondents (15/20). Further, 40% of the respondents self-reported reoffending, indicating a substantially lower relapse rate than expected (70%-80%).In summary, although these observations need validation from new and larger samples, positive effects were maintained after 4 years of methylphenidate treatment. Most study completers were employed and had no relapse in substance misuse or criminality. These results suggest that motivational support and continued medication are important for improved outcome in adult criminal offenders with ADHD.

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

    PubMed Central

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

    2014-01-01

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

  16. A Multicenter Evaluation of a Closed-Loop Anesthesia Delivery System: A Randomized Controlled Trial.

    PubMed

    Puri, Goverdhan D; Mathew, Preethy J; Biswas, Indranil; Dutta, Amitabh; Sood, Jayashree; Gombar, Satinder; Palta, Sanjeev; Tsering, Morup; Gautam, P L; Jayant, Aveek; Arora, Inderjeet; Bajaj, Vishal; Punia, T S; Singh, Gurjit

    2016-01-01

    Closed-loop systems for anesthesia delivery have been shown to outperform traditional manual control in different clinical settings. The present trial was aimed at evaluating the feasibility and efficacy of Bispectral Index (BIS)-guided closed-loop anesthesia delivery system (CLADS) in comparison with manual control across multiple centers in India. Adult patients scheduled for major surgical procedures of an expected duration of 1 to 3 hours were randomized across 6 sites into 2 groups: a CLADS group and a manual group. In the manual control group, propofol infusion was titrated manually by the attending anesthesiologist to a BIS of 50 during induction and maintenance. Analgesia was maintained with fentanyl infusion and nitrous oxide in both groups. In the CLADS group, both induction and maintenance of anesthesia were performed automatically using CLADS. The primary outcome measure was the performance of the system as assessed by the percentage of total anesthesia time BIS remained ±10 of target BIS. The secondary outcome measures were a percentage of anesthesia-time heart rate and mean arterial pressure within 25% of the baseline, median absolute performance error, wobble, and global score. Wobble indicates intraindividual variability in the control of BIS, and global score reflects the overall performance; lower values indicate superior performance for both parameters. The performance parameters of the system also were compared among the participating sites. Two hundred forty-two patients were randomized. BIS was maintained within ±10 of target for significantly longer time in the CLADS group (81.4% ± 8.9 % of anesthesia duration) than in the manual group (55.34% ± 25%, P < 0.0001). The indices that assess performance were significantly better in the CLADS group than the manual group as follows: median absolute performance error was 10 (10, 12) (median [interquartile range]) in the CLADS group versus 18 (14, 24) in the manual group, P < 0.0001; wobble was 9

  17. [Mucosa advancement flap anoplasty in treatment of chronic anal fissures: a prospective, multicenter, randomized controlled trial].

    PubMed

    Wang, Zhen-yi; Liu, Hua; Sun, Jian-hua; Mao, Xu-ming; Xu, Wei-xiang; Wu, Ying-ge; Zhang, Hai-yan; Zhu, Li-juan; Jin, Wei; Wu, Jiong; Li, Ying; Wu, Chuang; Jiang, Zai-long; Shi, Li; Li, Yan; Dong, Wei

    2011-04-01

    Anal fissure is one of the most common anal-rectum diseases, and approximately 10 percent patients with chronic anal fissure ultimately receive surgery. Relieving postoperative pain and protecting functions of the sphincter are central issues for coloproctologists. To evaluate the efficacy and safety of anoplasty in the treatment of chronic anal fissures. In this prospective, multicenter, randomized controlled trial, 120 adult patients with chronic anal fissure were referred from Department of Coloproctology of Yueyang Hospital of Integrated Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Shanghai Municipal Hospital of Traditional Chinese Medicine. The patients were enrolled from January 2009 to April 2010 and randomly divided into study (mucosa advancement flap anoplasty, abbreviated as anoplasty) group and control (fissurectomy) group. The two groups were assessed separately, and the main outcome measures were observed for 2 weeks, with a short-term follow-up for 6 weeks. Degree of pain, haemorrhage and anal canal pressure were observed and recorded preoperatively, and on the third day, the fourteenth day and the sixth week postoperatively. The wound healing time was also recorded. Surgical complications of the two groups were recorded and compared on the third day and the sixth week postoperatively. The curative effects associated with the surgery were analyzed on the fourteenth day and the sixth week after surgery and the therapeutic results were evaluated. Three patients were dropped out due to the early discharge from hospital and losing connection (1 in study group and 2 in control group). Overall the surgery showed that the anoplasty group had better results than the fissurectomy group in the curative effect on the sixth week after operation (P<0.05). Time of wound healing in the anoplasty group was (17.22 ± 4

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

    PubMed Central

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

    2010-01-01

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

  19. Quality assurance of HIV prevention counseling in a multi-center randomized controlled trial. Project RESPECT Study Group.

    PubMed Central

    Kamb, M L; Dillon, B A; Fishbein, M; Willis, K L

    1996-01-01

    Current HIV prevention counseling strategies rely largely on interventions aimed at changing behaviors. Among these is HIV prevention counseling and testing, which has been a prominent component in the federally supported strategies for HIV/AIDS prevention in the United States. To assess the efficacy of HIV counseling in reducing risk behaviors and preventing HIV infection and other sexually transmitted diseases, a multicenter, randomized controlled trial is being conducted among sexually transmitted disease clinic patients (Project RESPECT). The trial compares three separate HIV prevention strategies on increasing condom use and decreasing new cases of sexually transmitted diseases. The strategies are (a) Enhanced HIV Prevention Counseling, a 4-session individual counseling intervention based on behavioral and social science theory; (b) HIV Prevention Counseling, a 2-session individual pre- and post test counseling strategy that attempts to increase perception of risk and reduce risk behaviors using small, achievable steps; and (c) HIV Education, a brief 2-session pre- and post-test strategy that is purely informational. One difficulty in conducting randomized trials of behavioral interventions is assuring that the interventions are being conducted both as conceptualized and in a consistent manner by different counselors and, for multicenter studies, at different study sites. This article describes the quality assurance measures that have been used for Project RESPECT. These have included development of standard tools, standard training, frequent observation and feedback to study personnel, and process evaluation. PMID:8862164

  20. 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

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

    PubMed

    Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

    2011-05-06

    status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire.Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Netherlands Trial Register (NTR): NTR2064. © 2011 Hannemann et al; licensee BioMed Central Ltd.

  2. Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

    PubMed Central

    Eshuis, Emma J; Bemelman, Willem A; van Bodegraven, Ad A; Sprangers, Mirjam AG; Bossuyt, Patrick MM; de Wit, AW Marc van Milligen; Crolla, Rogier MPH; Cahen, Djuna L; Oostenbrug, Liekele E; Sosef, Meindert N; Voorburg, Annet MCJ; Davids, Paul HP; van der Woude, C Janneke; Lange, Johan; Mallant, Rosalie C; Boom, Maarten J; Lieverse, Rob J; van der Zaag, Edwin S; Houben, Martin HMG; Vecht, Juda; Pierik, Robert EGJM; van Ditzhuijsen, Theo JM; Prins, Hubert A; Marsman, Willem A; Stockmann, Henricus B; Brink, Menno A; Consten, Esther CJ; van der Werf, Sjoerd DJ; Marinelli, Andreas WKS; Jansen, Jeroen M; Gerhards, Michael F; Bolwerk, Clemens JM; Stassen, Laurents PS; Spanier, BW Marcel; Bilgen, Ernst Jan Spillenaar; van Berkel, Anne-Marie; Cense, Huib A; van Heukelem, Henk A; van de Laar, Arnold; Slot, Warner Bruins; Eijsbouts, Quirijn A; van Ooteghem, Nancy AM; van Wagensveld, Bart; van den Brande, Jan MH; van Geloven, Anna AW; Bruin, Karien F; Maring, John K; Oldenburg, Bas; van Hillegersberg, Richard; de Jong, Dirk J; Bleichrodt, Robert; van der Peet, Donald L; Dekkers, Pascal EP; Goei, T Hauwy; Stokkers, Pieter CF

    2008-01-01

    Background With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. Methods/design The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. Discussion The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the

  3. Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

    PubMed Central

    Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

    2017-01-01

    Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

  4. Multicenter randomized trial of robot-assisted rehabilitation for chronic stroke: methods and entry characteristics for VA ROBOTICS.

    PubMed

    Lo, Albert C; Guarino, Peter; Krebs, Hermano I; Volpe, Bruce T; Bever, Christopher T; Duncan, Pamela W; Ringer, Robert J; Wagner, Todd H; Richards, Lorie G; Bravata, Dawn M; Haselkorn, Jodie K; Wittenberg, George F; Federman, Daniel G; Corn, Barbara H; Maffucci, Alysia D; Peduzzi, Peter

    2009-10-01

    Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. . To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. . The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment >/=6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. . A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. . VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010.

  5. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study

    PubMed Central

    Jacobsen, Paula L.; Harper, Linda; Chrones, Lambros; Chan, Serena

    2015-01-01

    Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery–Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ−4.2), the Clinical Global Impression Scale-Severity of Illness (Δ−1.2), and the Sheehan Disability Scale (Δ−4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20

  6. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.

    PubMed

    Jacobsen, Paula L; Harper, Linda; Chrones, Lambros; Chan, Serena; Mahableshwarkar, Atul R

    2015-09-01

    Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine

  7. Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

    PubMed Central

    2014-01-01

    Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

  8. Characteristics and Experiences of Children and Young People with Severe Intellectual Disabilities and Challenging Behaviour Attending 52-Week Residential Special Schools

    ERIC Educational Resources Information Center

    Pilling, N.; McGill, P.; Cooper, V.

    2007-01-01

    Background: This study sought to gather information about the characteristics and experiences of children and young people with severe intellectual disabilities and severe challenging behaviour attending 52-week residential special schools. Method: Staff of nine schools completed postal questionnaires on the characteristics and experiences of 156…

  9. Emergency preoperative stenting versus surgery for acute left-sided malignant colonic obstruction: a multicenter randomized controlled trial.

    PubMed

    Pirlet, Isabelle A; Slim, Karem; Kwiatkowski, Fabrice; Michot, Francis; Millat, Bertrand L

    2011-06-01

    Surgical management of left colonic cancer presenting as an acute obstruction remains controversial and still is associated with high mortality and morbidity rates. Recently, self-expandable metallic stents (SEMS) have been used as a bridge to surgery in an attempt to decompress the colon and then allow elective one-stage surgical resection without stoma placement. This study aimed to compare the outcomes of emergency surgery alone with emergency placement of colonic SEMS as a bridge to surgery in terms of efficiency and reduction of the stoma placement rate. A multicenter prospective, randomized, controlled trial was conducted according to the consolidated standards of reporting trials (CONSORT) Statement criteria. Patients eligible for the study were randomized to either emergency surgery or emergency SEMS as a bridge to surgery. The primary outcome was the need for a stoma (temporary or permanent) for any reason. The secondary end points were mortality, morbidity, and length of hospital stay. Nine centers participated in the trial. Among the 70 patients eligible for the study, 60 were randomized and included for the final analysis, 30 patients in each group. Seven patients were randomized but did not fulfill the entry requirements, whereas three further eligible patients were not randomized for various reasons. Concerning the primary outcome, 17 patients in the surgery group sustained a stoma placement versus 13 patients in the SEMS group (p=0.30). No statistically significant difference was noted concerning the secondary outcomes. A total of 16 attempts at SEMS placement (53.3%) were technical failures. Two colonic perforations directly related to the stent placement procedure occurred among the 30 randomized patients and 1 perforation occurred among the nonrandomized patients, leading to premature closure of inclusions in the study before the expected number of 80 patients was reached. This randomized trial failed to demonstrate that emergency preoperative

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

    PubMed Central

    Stark, AR; Tyson, JE; Hibberd, PL

    2010-01-01

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

  11. Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

    PubMed Central

    Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

    2014-01-01

    Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

  12. Ozenoxacin 1% cream in the treatment of impetigo: a multicenter, randomized, placebo- and retapamulin-controlled clinical trial.

    PubMed

    Gropper, Savion; Albareda, Nuria; Chelius, Klaus; Kruger, Dawie; Mitha, Ismail; Vahed, Yacoob; Gani, Mashra; García-Alonso, Fernando

    2014-01-01

    We compared the efficacy and safety of ozenoxacin (a new nonfluorinated quinolone) 1% cream with placebo in the treatment of impetigo. In a randomized, double-blind, multicenter study, patients received ozenoxacin cream or placebo cream twice daily for 5 days (a third group received retapamulin 1% ointment as a control). Clinical, microbiological and laboratory evaluations were performed during follow-up (over 2 weeks). Ozenoxacin was superior to placebo (success rate 34.8 vs 19.2%; p = 0.003). Microbiological success was 70.8% for ozenoxacin and 38.2% for placebo after 3-4 days and 79.2% versus 56.6% after 6-7 days. Ozenoxacin produced more rapid microbiological clearance than retapamulin. All treatments were well tolerated. Ozenoxacin 1% cream was effective and safe in the treatment of impetigo.

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

    PubMed

    López-del-Hoyo, Yolanda; Olivan, Barbara; Luciano, Juan V; Mayoral, Fermín; Roca, Miquel; Gili, Margalida; Andres, Eva; Serrano-Blanco, Antoni; Collazo, Francisco; Araya, Ricardo; Baños, Rosa; Botella, Cristina; Magallón, Rosa; García-Campayo, Javier

    2013-01-11

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

  14. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial.

    PubMed

    Payen, Didier M; Guilhot, Joelle; Launey, Yoann; Lukaszewicz, Anne Claire; Kaaki, Mahmoud; Veber, Benoit; Pottecher, Julien; Joannes-Boyau, Olivier; Martin-Lefevre, Laurent; Jabaudon, Matthieu; Mimoz, Olivier; Coudroy, Rémi; Ferrandière, Martine; Kipnis, Eric; Vela, Carlos; Chevallier, Stéphanie; Mallat, Jihad; Robert, René

    2015-06-01

    To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95% CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX-HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685); reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5 (-11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.

  15. Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach.

    PubMed

    Pisano, Antonio; Landoni, Giovanni; Lomivorotov, Vladimir; Comis, Marco; Gazivoda, Gordana; Conte, Massimiliano; Hajjar, Ludhmila; Finco, Gabriele; Jovic, Miomir; Mucchetti, Marta; Kunstýř, Jan; Paternoster, Gianluca; Likhvantsev, Valery; Ruggeri, Laura; Ma, Jun; Alvaro, Gabriele; Bukamal, Nazar; Borghi, Giovanni; Pasyuga, Vadim; Cabrini, Luca; Greco, Massimiliano; Guarracino, Fabio; Lembo, Rosalba; Lobreglio, Rosetta; Monaco, Fabrizio; Montisci, Andrea; Pala, Giovanni; Pasin, Laura; Pieri, Marina; Santini, Francesco; Silvetti, Simona; Zambon, Massimo; Baiardo Redaelli, Martina; Castella, Alberto; De Vuono, Giovanni; Lucchetta, Luca; Zangrillo, Alberto; Bellomo, Rinaldo

    2016-10-01

    Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. A systematic review of literature followed by web-based voting on findings of a consensus conference. A total of 555 clinicians from 61 countries. The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial

    PubMed Central

    Roncalli, Jérôme; Mouquet, Frédéric; Piot, Christophe; Trochu, Jean-Noel; Le Corvoisier, Philippe; Neuder, Yannick; Le Tourneau, Thierry; Agostini, Denis; Gaxotte, Virginia; Sportouch, Catherine; Galinier, Michel; Crochet, Dominique P.; Teiger, Emmanuel; Richard, Marie-Jeanne; Polge, Anne-Sophie; Beregi, Jean-Paul; Manrique, Alain; Carrie, Didier; Susen, Sophie; Klein, Bernard; Parini, Angelo; Lamirault, Guillaume; Croisille, Pierre; Rouard, Hélène; Bourin, Philippe; Nguyen, Jean-Michel; Delasalle, Béatrice; Vanzetto, Gérald; Van Belle, Eric; Lemarchand, Patricia F.

    2011-01-01

    Aims Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicenter study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. Methods and Results One-hundred one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n=49) or a BMC group (n=52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. BMC infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared to 7/43 (16%) in the control group (p = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (p = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (p=0.03). Moreover, a significant adverse role for active smoking (p=0.04) and a positive trend for microvascular obstruction (p=0.07) were observed. Conclusions Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate –but not in univariate – analysis. A large multicenter international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. PMID:21127322

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

    PubMed Central

    2013-01-01

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

  18. Evaluation of 5 versus 10 granulocyteaphaeresis sessions in steroid-dependent ulcerative colitis: A pilot, prospective, multicenter, randomized study

    PubMed Central

    Ricart, Elena; Esteve, Maria; Andreu, Montserrat; Casellas, Francesc; Monfort, David; Sans, Miquel; Oudovenko, Natalia; Lafuente, Raúl; Panés, Julián

    2007-01-01

    AIM: To evaluate the efficacy of 5 compared to 10 granulocyteaphaeresis sessions in patients with active steroid-dependent ulcerative colitis. METHODS: In this pilot, prospective, multicenter randomized trial, 20 patients with moderately active steroid-dependent ulcerative colitis were randomized to 5 or 10 granulocyteaphaeresis sessions. The primary objective was clinical remission at wk 17. Secondary measures included endoscopic remission and steroid consumption. RESULTS: Nine patients were randomized to 5 granulocyteaphaeresis sessions (group 1) and 11 patients to 10 granulocyteaphaeresis sessions (group 2). At wk 17, 37.5% of patients in group 1 and 45.45% of patients in group 2 were in clinical remission. Clinical remission was accompanied by endoscopic remission in all cases. Eighty-six percent of patients achieving remission were steroid-free at wk 17. Daily steroid requirements were significantly lower in group 2. Eighty-nine per cent of patients remained in remission during a one year follow-up. One serious adverse event, not related to the study therapy, was reported. CONCLUSION: Granulocyteaphaeresis is safe and effective for the treatment of steroid-dependent ulcerative colitis. In this population, increasing the number of aphaeresis sessions is not associated with higher remission rates, but affords a significant steroid-sparing effect. PMID:17465500

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed

    Sierink, Joanne C; Saltzherr, Teun Peter; Beenen, Ludo F M; Luitse, Jan S K; Hollmann, Markus W; Reitsma, Johannes B; Edwards, Michael J R; Hohmann, Joachim; Beuker, Benn J A; Patka, Peter; Suliburk, James W; Dijkgraaf, Marcel G W; Goslings, J Carel

    2012-03-30

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

  2. Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

    PubMed

    Nishizawa, Toshihiro; Maekawa, Takama; Watanabe, Noriko; Harada, Naohiko; Hosoda, Yasuo; Yoshinaga, Masahiro; Yoshio, Toshiyuki; Ohta, Hajime; Inoue, Syuuji; Toyokawa, Tatsuya; Yamashita, Haruhiro; Saito, Hiroki; Kuwai, Toshio; Katayama, Shunsuke; Masuda, Eiji; Miyabayashi, Hideharu; Kimura, Toshio; Nishizawa, Yuko; Takahashi, Masahiko; Suzuki, Hidekazu

    2015-07-01

    Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

  3. A prospective randomized multicenter trial shows improvement of sternum related complications in cardiac surgery with the Posthorax support vest.

    PubMed

    Gorlitzer, Michael; Wagner, Florian; Pfeiffer, Steffen; Folkmann, Sandra; Meinhart, Johann; Fischlein, Theodor; Reichenspurner, Hermann; Grabenwöger, Martin

    2010-05-01

    Sternal instability, dehiscence and mediastinitis are major causes of morbidity and mortality in cardiac surgery. The aim of this analysis is to determine the effect of a Posthorax support vest (Epple Inc, Vienna, Austria) after median sternotomy. One thousand five hundred and sixty cases were included in a prospective randomized multicenter trial. Patients were randomized as follows: 905 received a flexible dressing postoperatively (group A) and 655 patients were given a Posthorax support vest (group B). Patients in groups A and B were well matched. Their mean age was 68 years (range: 34-87 years). The patient characteristics and operative data were equally distributed in both groups. The mean total hospital stay was significantly shorter in group B than in group A (A: 17.33+/-17.5; B: 14.76+/-7.7; P=0.04). Sternal wound complications necessitating reoperation during the 90 days follow-up period were observed in 4.5%. Reoperation rates were as follows: 3.9% in group A and 0.6% in group B (P<0.05). The use of the Posthorax sternum support vest is a valuable adjunct to prevent sternum-related complications after cardiac surgery. In the 90 days follow-up period, additional surgical procedures were significantly reduced by the use of the support vest.

  4. Psychoeducational groups for adults with ADHD and their significant others (PEGASUS): A pragmatic multicenter and randomized controlled trial.

    PubMed

    Hirvikoski, T; Lindström, T; Carlsson, J; Waaler, E; Jokinen, J; Bölte, S

    2017-07-01

    To examine the feasibility, efficacy, and effectiveness of PEGASUS, a group-based structured psychoeducation for adults with ADHD and their significant others. A pragmatic parallel group add-on design multicenter randomized controlled trial was conducted, comparing an 8-session treatment with PEGASUS (allocated n=97; 48 with ADHD and 49 with significant others) to treatment as usual (TAU, allocated n=82; 39 with ADHD and 43 significant others). Participants (individuals with ADHD and significant others) were recruited from five psychiatric outpatient departments and block randomized to PEGASUS or TAU. Knowledge about ADHD was measured using the ADHD 20 scale pre- and post-intervention and served as primary outcome. Knowledge about ADHD (d=0.97 [95% CI: 0.61-1.31]) increased following PEGASUS participation compared to TAU. Improvements were also observed in secondary outcomes e.g. global life satisfaction (d=0.25 [95% CI: from -0.09 to 0.59]). Overall treatment satisfaction was good. Over 90% of the participants completed the program. Post-intervention data was obtained from n=89 in PEGASUS group and n=70 in TAU group and analyses were conducted per protocol. No important adverse effects or side effects were observed. Group-based structured psychoeducation PEGASUS for adults with ADHD and their significant others is a feasible, efficacious, and effective treatment option to increase ADHD knowledge and general life satisfaction in psychiatric outpatient care. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  5. A multicenter randomized comparison between high-definition white light endoscopy and narrow band imaging for detection of gastric lesions.

    PubMed

    Ang, Tiing Leong; Pittayanon, Rapat; Lau, James Yun Wong; Rerknimitr, Rungsun; Ho, Shiaw Hooi; Singh, Rajvinder; Kwek, Andrew Boon Eu; Ang, Daphne Shih Wen; Chiu, Philip Wai Yan; Luk, Sally; Goh, Khean Lee; Ong, Jeannie Peng Lan; Tan, Jessica Yi-Lyn; Teo, Eng Kiong; Fock, Kwong Ming

    2015-12-01

    Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE). This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers. Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189). NBI increased the detection rate of IM compared with HD-WLE.

  6. A randomized, double-blind, multicenter clinical trial on the efficacy of ivermectin against intestinal nematode infections in China.

    PubMed

    Wen, Li-Yong; Yan, Xiao-Lan; Sun, Feng-Hua; Fang, Yue-Yi; Yang, Ming-Jin; Lou, Lei-Jun

    2008-06-01

    To assess the efficacy of ivermectin against intestinal nematode infections, a randomized, double-blind, multicenter clinical trial was carried out in a total of 816 human individuals infected with different nematodes from three counties in China. The subjects were randomly assigned into experimental and control groups and orally given a single dose of 0.1, 0.2, 0.2 and 0.2mg/kg ivermectin against Ascaris lumbricoides, hookworm, Trichuris trichiura and Enterobius vermicularis, respectively. Parallel control groups to each of the ivermectin groups were given a single oral dose of 6.7 mg/kg albendazole. The cure rates with ivermectin and albendazole were 100% (102/102) and 99.0% (101/102) for Ascaris, and 66.7% (68/102) and 67.7% (69/102) for Trichuris, respectively, with no significant difference (P>0.05) between the two treatments. The parasitological cure rates of albendazole were 69.6% (71/102) for hookworm and 94.1% (96/102) for Enterobius, which were significantly higher than ivermectin (33.3% and 52.9%, respectively, P<0.0001). The expulsion of worm in the feces reached its peak 1-2 days after ivermectin treatment. The study showed that ivermectin, with few side effects, could be used as an additional treatment tool for intestinal nematodes, especially for the treatment of Ascaris and Trichuris infections in China.

  7. Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: A randomized, controlled multicenter clinical trial.

    PubMed

    Karimzadeh, Afshin; Raeissadat, Seyed Ahmad; Erfani Fam, Saleh; Sedighipour, Leyla; Babaei-Ghazani, Arash

    2017-03-01

    Plantar fasciitis is the most common cause of heel pain. Local injection modalities are among treatment options in patients with resistant pain. The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis. In this randomized controlled multicenter study, 36 patients with chronic plantar fasciitis were recruited. Patients were allocated randomly into three treatment groups: local autologous blood, local corticosteroid injection, and control groups receiving no injection. Patients were assessed with visual analog scale (VAS), pressure pain threshold (PPT), and plantar fasciitis pain/disability scale (PFPS) before treatment, as well as 4 and 12 weeks post therapy. Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group. At 4 weeks following treatment, patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups (higher PPT level, lower PFPS, and VAS). After 12 weeks of treatment, both corticosteroid and autologous blood groups had lower average levels of pain than control group. The corticosteroid group showed an early sharp and then more gradual improvement in pain scores, but autologous blood group had a steady gradual drop in pain. Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis. These treatments decrease pain and significantly improve function compared to no treatment.

  8. Quality of vision after femtosecond laser-assisted descemet stripping endothelial keratoplasty and penetrating keratoplasty: a randomized, multicenter clinical trial.

    PubMed

    Cheng, Yanny Y Y; van den Berg, Tom J T P; Schouten, Jan S; Pels, Elisabeth; Wijdh, Robert-Jan; van Cleynenbreugel, Hugo; Eggink, Catharina A; Rijneveld, Wilhelmina J; Nuijts, Rudy M M A

    2011-10-01

    To compare the quality of vision (straylight and contrast sensitivity) after femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS DSEK) and penetrating keratoplasty (PK). Prospective, randomized clinical trial. setting: Multicenter (5 ophthalmic centers in The Netherlands). study population: Eighty eyes of 80 patients with corneal endothelial dysfunction were included and were randomized to FS DSEK or PK. observation procedures: FS DSEK and PK. main outcome measures: Straylight, contrast sensitivity, astigmatism, uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and visual symptom score. Straylight at 12 months was 1.37 ± 0.2 logarithm of straylight for FS DSEK and 1.46 ± 0.2 logarithm of straylight for PK (P = .151). During 12 months of follow-up, there was a significant improvement of straylight and contrast sensitivity after FS DSEK (P < .001) and PK (P < .001). The change of straylight and contrast sensitivity correlated significantly with the change of BSCVA after FS DSEK (r = -0.645; r = 0.580) and PK (r = -0.370; r = 0.659). The visual symptom score was comparable between the 2 groups during the 12 months of follow-up. Improvement of straylight and contrast sensitivity was significantly correlated with an improvement of BSCVA. Straylight and contrast sensitivity were improved significantly after FS DSEK and were comparable with those after PK, although BSCVA was slightly better in the PK group. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. 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

  10. A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease.

    PubMed

    Maggiore, Salvatore Maurizio; Richard, Jean-Christophe M; Abroug, Fekri; Diehl, Jean Luc; Antonelli, Massimo; Sauder, Philippe; Mancebo, Jordi; Ferrer, Miquel; Lellouche, Francois; Lecourt, Laurent; Beduneau, Gaetan; Brochard, Laurent

    2010-01-01

    To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease. Multicenter, prospective, randomized, controlled trial. Seven intensive care units. A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, Paco2> 45 mm Hg and two among the following factors: pH <7.35, Paco2 <50 mm Hg, respiratory rate >25/min. Noninvasive ventilation randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. Duration and complications of NIV and mechanical ventilation, endotracheal intubation, discharge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p = .35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of noninvasive ventilation, length of stay, 28-day mortality, complications and adverse events were similar, although serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p = .08). Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease.

  11. Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers: A multicenter, randomized trial.

    PubMed

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

    2015-01-01

    Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signalling accelerates wound reepithelialization. In a prospective, randomized, multicenter clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C-terminus of Cx43, alpha connexin carboxy-terminal (ACT1), in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care (SOC) protocols. Adults with DFUs of at least four weeks duration were randomized to receive SOC with or without topical application of ACT1. Primary outcome was mean percent ulcer reepithelialization and safety variables included incidence of treatment related adverse events (AEs) and detection of ACT1 immunogenicity. ACT1 treatment was associated with a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks (72.1% vs. 57.1%; p = 0.03). Analysis of incidence and median time-to-complete-ulcer closure revealed that ACT1 treatment was associated with a greater percentage of participants that reached 100% ulcer reepitheliazation and a reduced median time-to-complete-ulcer closure. No AEs reported were treatment related, and ACT1 was not immunogenic. Treatment protocols that incorporate ACT1 may present a therapeutic strategy that safely augments the reepithelialization of chronic DFUs. © 2015 Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of The Wound Healing Society.

  12. Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.

    PubMed

    Saliba, F; De Simone, P; Nevens, F; De Carlis, L; Metselaar, H J; Beckebaum, S; Jonas, S; Sudan, D; Fischer, L; Duvoux, C; Chavin, K D; Koneru, B; Huang, M A; Chapman, W C; Foltys, D; Dong, G; Lopez, P M; Fung, J; Junge, G

    2013-07-01

    In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Off-pump Versus On-pump Coronary Artery Bypass Surgery: Graft Patency Assessment With Coronary Computed Tomographic Angiography: A Prospective Multicenter Randomized Controlled Pilot Study.

    PubMed

    Noiseux, Nicolas; Stevens, Louis-Mathieu; Chartrand-Lefebvre, Carl; Soulez, Gilles; Prieto, Ignacio; Basile, Fadi; Mansour, Samer; Dyub, Adel M; Kieser, Teresa M; Lamy, André

    2017-06-05

    A large multicenter randomized trial (RCT) is needed to assess off-pump coronary artery bypass graft (CABG) patency when performed by skilled surgeons. This prospective multicenter randomized pilot study compares graft patency after on-pump and off-pump techniques and addresses the feasibility of such an RCT. Consecutive patients were prospectively recruited for ≥64-slice computed tomography angiography graft patency assessment 1 year after randomization to off-pump or on-pump CABG. Blinded assessment of graft patency was performed, and the results were categorized as normal, ≥50% stenosis, or occlusion. A multilevel model with random effects on the patient was used to account for correlation of results in patients with multiple grafts. A total of 157 patients (3 centers, 84 off-pump and 73 on-pump patients, 512 grafts, assessability rate 98.4%) were included. Patency index (% nonoccluded grafts) was 89% for the off-pump technique and 95% for the on-pump technique (P=0.09). Patency was similar for arterial and vein grafts (both 92%; P=0.88), as well as between target territories (89% to 94%; P=0.53). In this pilot study, 1-year graft patency results after off-pump and on-pump surgery were similar. This feasibility trial demonstrates that a large multicenter RCT to compare CABG patency after on-pump with that after off-pump techniques is feasible and can be reliably undertaken using computed tomography angiography.

  14. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial.

    PubMed

    Li, Sheyu; Chen, Xiang; Li, Qianrui; Du, Juan; Liu, Zhimin; Peng, Yongde; Xu, Mian; Li, Qifu; Lei, Minxiang; Wang, Changjiang; Zheng, Shaoxiong; Zhang, Xiaojuan; Yu, Hongling; Shi, Jinyu; Tao, Shibing; Feng, Ping; Tian, Haoming

    2016-09-01

    To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC). This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up. A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events. ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  15. Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: a multicenter, prospective, randomized, double blind clinical trial.

    PubMed

    Moreso, Francesc; Crespo, Marta; Ruiz, Juan C; Torres, Armando; Gutierrez-Dalmau, Alex; Osuna, Antonio; Perelló, Manel; Pascual, Julio; Torres, Irina B; Redondo-Pachón, Dolores; Rodrigo, Emilio; Lopez-Hoyos, Marcos; Seron, Daniel

    2017-09-26

    There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m(2) and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m(2) ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions and DSA at one year. The planned sample size was 25 patients per group. During 2012-2015, twenty-five patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2±14.4 vs. -6.6±12.0 mL/min/1.73 m(2,) p-value=0.475), increase of proteinuria (+0.9±2.1 vs. +0.9±2.1 g/day, p-value=0.378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. 1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

    PubMed

    Landgrebe, Michael; Hajak, Göran; Wolf, Stefan; Padberg, Frank; Klupp, Philipp; Fallgatter, Andreas J; Polak, Thomas; Höppner, Jacqueline; Haker, Rene; Cordes, Joachim; Klenzner, Thomas; Schönfeldt-Lecuona, Carlos; Kammer, Thomas; Graf, Erika; Koller, Michael; Kleinjung, Tobias; Lehner, Astrid; Schecklmann, Martin; Pöppl, Timm B; Kreuzer, Peter; Frank, Elmar; Langguth, Berthold

    2017-08-05

    Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. Controlled Trials: http://www.isrctn.com/ISRCTN89848288. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics.

    PubMed

    Yoritaka, Asako; Abe, Takashi; Ohtsuka, Chigumi; Maeda, Tetsuya; Hirayama, Masaaki; Watanabe, Hirohisa; Saiki, Hidemoto; Oyama, Genko; Fukae, Jiro; Shimo, Yasushi; Hatano, Taku; Kawajiri, Sumihiro; Okuma, Yasuyuki; Machida, Yutaka; Miwa, Hideto; Suzuki, Chikako; Kazama, Asuka; Tomiyama, Masahiko; Kihara, Takeshi; Hirasawa, Motoyuki; Shimura, Hideki; Hattori, Nobutaka

    2016-05-12

    Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) score of Parkinson's disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial. Changes in the total UPDRS scores from baseline to the 8(th), 24(th), 48(th), and 72(nd) weeks, and after the 8(th) week, will be evaluated. The primary endpoint of the efficacy of this treatment in PD is the change in the total UPDRS score from baseline to the 72(nd) week. The changes in UPDRS part II, UPDRS part III, each UPDRS score, PD Questionnaire-39 (PDQ-39), and the modified Hoehn and Yahr stage at these same time-points, as well as the duration until the protocol is finished because additional levodopa is required or until the disease progresses, will also be analyzed. Adverse events and screening laboratory studies will also be examined. Participants in the hydrogen water group will drink 1000 mL/day of H2 water, and those in the placebo water group will drink normal water. One-hundred-and-seventy-eight participants with PD (89 women, 89 men; mean age: 64.2 [SD 9.2] years, total UPDRS: 23.7 [11.8], with levodopa medication: 154 participants, without levodopa medication: 24 participants; daily levodopa dose: 344.1 [202.8] mg, total levodopa equivalent dose: 592.0 [317.6] mg) were enrolled in 14 hospitals and were randomized. This study will confirm whether H2 water can improve PD symptoms. UMIN000010014 (February, 13, 2013).

  18. Does the Use of a Decision Aid Improve Decision Making in Prosthetic Heart Valve Selection? A Multicenter Randomized Trial.

    PubMed

    Korteland, Nelleke M; Ahmed, Yunus; Koolbergen, David R; Brouwer, Marjan; de Heer, Frederiek; Kluin, Jolanda; Bruggemans, Eline F; Klautz, Robert J M; Stiggelbout, Anne M; Bucx, Jeroen J J; Roos-Hesselink, Jolien W; Polak, Peter; Markou, Thanasie; van den Broek, Inge; Ligthart, Rene; Bogers, Ad J J C; Takkenberg, Johanna J M

    2017-02-01

    A Dutch online patient decision aid to support prosthetic heart valve selection was recently developed. A multicenter randomized controlled trial was conducted to assess whether use of the patient decision aid results in optimization of shared decision making in prosthetic heart valve selection. In a 5-center randomized controlled trial, patients were allocated to receive either standard preoperative care (control group) or additional access to the patient decision aid (intervention group). Legally capable adult patients accepted for elective isolated or combined aortic and mitral valve replacement were included. Primary outcome was preoperative decisional conflict (Decisional Conflict Scale); secondary outcomes included patient knowledge, involvement in valve selection, anxiety and depression, (valve-specific) quality of life, and regret. Out of 306 eligible patients, 155 were randomized (78 control and 77 intervention). Preoperative decisional conflict did not differ between the groups (34% versus 33%; P=0.834). Intervention patients felt better informed (median Decisional Conflict Scale informed subscore: 8 versus 17; P=0.046) and had a better knowledge of prosthetic valves (85% versus 68%; P=0.004). Intervention patients experienced less anxiety and depression (median Hospital Anxiety and Depression Scale score: 6 versus 9; P=0.015) and better mental well-being (mean Short Form Health Survey score: 54 versus 50; P=0.032). Three months postoperatively, valve-specific quality of life and regret did not differ between the groups. A patient decision aid to support shared decision making in prosthetic heart valve selection does not lower decisional conflict. It does result in more knowledgeable, better informed, and less anxious and depressed patients, with a better mental well-being. http://www.trialregister.nl. Unique identifier: NTR4350. © 2017 American Heart Association, Inc.

  19. 17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial.

    PubMed

    Combs, C Andrew; Garite, Thomas J; Maurel, Kimberly; Abril, Diana; Das, Anita; Clewell, William; Heyborne, Kent; How, Helen; Huang, Wilson; Lewis, David; Lu, George; Miller, Hugh; Nageotte, Michael; Porreco, Richard; Sheikh, Asad; Tran, Lan

    2015-09-01

    Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes. This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 34(0/7) weeks of gestation or documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women. From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  2. The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers: A Multicenter, Randomized Trial

    PubMed Central

    Ghatnekar, Gautam S; Grek, Christina L; Armstrong, David G; Desai, Sanjay C; Gourdie, Robert G

    2015-01-01

    The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways. PMID:25072595

  3. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands

    SciTech Connect

    Treurniet-Donker, A.D.; van Putten, W.L.; Wereldsma, J.C.; Bruggink, E.D.; Hoogenraad, W.J.; Roukema, J.A.; Snijders-Keilholz, A.; Meijer, W.S.; Meerwaldt, J.H.; Wijnmaalen, A.J. )

    1991-04-15

    The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

  4. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands.

    PubMed

    Treurniet-Donker, A D; van Putten, W L; Wereldsma, J C; Bruggink, E D; Hoogenraad, W J; Roukema, J A; Snijders-Keilholz, A; Meijer, W S; Meerwaldt, J H; Wijnmaalen, A J

    1991-04-15

    The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

  5. Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial.

    PubMed

    Kuppermann, Baruch D; Goldstein, Michaella; Maturi, Raj K; Pollack, Ayala; Singer, Michael; Tufail, Adnan; Weinberger, Dov; Li, Xiao-Yan; Liu, Ching-Chi; Lou, Jean; Whitcup, Scott M

    2015-01-01

    To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients. © 2015 S. Karger AG, Basel.

  6. Structured information during the ICU stay to reduce anxiety: study protocol of a multicenter randomized controlled trial

    PubMed Central

    Fleischer, Steffen; Berg, Almuth; Neubert, Thomas R; Koller, Michael; Behrens, Johann; Becker, Ralf; Horbach, Annegret; Radke, Joachim; Rothmund, Mathias; Kuss, Oliver

    2009-01-01

    Background ICU stay is often associated with negative experiences for the individual patient. Many patients are disabled and their communication is restricted during the ICU stay. Specific information on procedures, sensations and coping behavior are thought to reduce anxiety on the ICU. Until now information programs to reduce anxiety were mainly delivered preoperatively, completely neglecting informational needs of non-elective ICU patients. Methods The trial is designed as a prospective multicenter randomized controlled trial in the cities of Marburg, Halle and Stuttgart. Elective and non-elective ICU patients will be included. The trial includes an intervention and a control group on the ICU. The control group receives a trivial conversation without any ICU-specific information. The intervention group receives an information program with specific procedural, sensory and coping information about their ICU stay. Both conversations take place in the ICU and are planned to take about 10 minutes. Discussion In contrast to former trials on information programs on the ICU-stay our intervention will take place in the ICU itself. This approach will ensure to compensate for memory effects due to anesthesia or preoperative stress. Further the results will be applicable to non-elective ICU-patients. Trial Registration ClinicalTrials NCT00764933 PMID:19751500

  7. The Pregnancy in Polycystic Ovary Syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial.

    PubMed

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

    2014-01-01

    To summarize baseline characteristics from a large multicenter infertility clinical trial. Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene). Academic Health Centers throughout the United States. Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study. None. Historic, biometric, biochemical, and questionnaire parameters. Females averaged 30 years and were obese (body mass index [BMI] 35) with ∼20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (∼2), and antimüllerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimüllerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters. The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. NCT00719186. Copyright © 2014 American Society for Reproductive Medicine. All rights reserved.

  8. The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial.

    PubMed

    Ghatnekar, Gautam S; Grek, Christina L; Armstrong, David G; Desai, Sanjay C; Gourdie, Robert G

    2015-01-01

    The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.

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

    PubMed Central

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

    2010-01-01

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

  10. A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

    PubMed

    Bennett-Guerrero, Elliott; Berry, Scott M; Bergese, Sergio D; Fleshner, Phillip R; Minkowitz, Harold S; Segura-Vasi, Alvaro M; Itani, Kamal M F; Henderson, Karen W; Rackowski, Felicia P; Aberle, Laura H; Stryjewski, Martin E; Corey, G Ralph; Allenby, Kent S

    2017-06-01

    SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Effectiveness of a 16-Week Multimodal Exercise Program on Individuals With Dementia: Study Protocol for a Multicenter Randomized Controlled Trial

    PubMed Central

    Scharpf, Andrea; Barisch-Fritz, Bettina; Niermann, Christina; Woll, Alexander

    2017-01-01

    Background The increasing prevalence of dementia in the next decades is accompanied by various societal and economic problems. Previous studies have suggested that physical activity positively affects motor and cognitive skills in individuals with dementia (IWD). However, there is insufficient evidence probably related to several methodological limitations. Moreover, to date adequate physical activity interventions specifically developed for IWD are lacking. Objective This study aims to investigate the effectiveness of a multimodal exercise program (MEP) on motor and cognitive skills in IWD in a high-quality multicenter trial. Methods A multicenter randomized controlled trial with baseline and postassessments will be performed. It is planned to enroll 405 participants with dementia of mild to moderate stage, aged 65 years and older. The intervention group will participate in a 16-week ritualized MEP especially developed for IWD. The effectiveness of the MEP on the primary outcomes balance, mobility, and gait will be examined using a comprehensive test battery. Secondary outcomes are strength and function of lower limbs, activities of daily living, and cognition (overall cognition, language, processing speed, learning and memory, and visual spatial cognition). Results Enrollment for the study started in May 2015. It is planned to complete postassessments by the beginning of 2017. Results are expected to be available in the first half of 2017. Conclusions This study will contribute to enhancing evidence for the effects of physical activity on motor and cognitive skills in IWD. Compared to previous studies, this study is characterized by a dementia-specific intervention based on scientific knowledge, a combination of motor and cognitive tasks in the intervention, and high standards regarding methodology. Findings are highly relevant to influence the multiple motor and cognitive impairments of IWD who are often participating in limited physical activity. Trial

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

    PubMed Central

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

    2015-01-01

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

  13. Multicenter randomized controlled trial of conventional versus laparoscopic surgery for colorectal cancer within an enhanced recovery programme: EnROL.

    PubMed

    Kennedy, Robin H; Francis, E Anne; Wharton, Rose; Blazeby, Jane M; Quirke, Philip; West, Nicholas P; Dutton, Susan J

    2014-06-10

    Laparoscopic resection and a multimodal approach known as an enhanced recovery program (ERP) have been major changes in colorectal perioperative care that have improved clinical outcomes for colorectal cancer resection. EnROL (Enhanced Recovery Open Versus Laparoscopic) is a multicenter randomized controlled trial examining whether the benefits of laparoscopy still exist when open surgery is optimized within an ERP. Adults with colorectal cancer suitable for elective resection were randomly assigned at a ratio of 1:1 to laparoscopic or open surgery within an ERP, stratified by center, cancer site (colon v rectum), and age group (<66 v 66-75 v >75 years) using minimization. The primary outcome was physical fatigue at 1 month postsurgery. Secondary outcomes included hospital stay, complications, other patient-reported outcomes (PROs), and physical function. Patients and outcome assessors were blinded until 7 days postsurgery or discharge if earlier. Central independent and blinded pathologic assessment of surgical quality was undertaken. A total of 204 patients (laparoscopy, n=103; open surgery, n=101) were recruited from 12 UK centers from July 2008 to April 2012. One-month physical fatigue scores were similar in both groups (mean: laparoscopy, 12.28; 95% CI, 11.37 to 13.19 v open surgery, 12.05; 95% CI, 11.14 to 12.96; adjusted mean difference, -0.23; 95% CI, -1.52 to 1.07). Median total hospital stay was significantly shorter after laparoscopic surgery (median: laparoscopy, 5; interquartile range [IQR], 4 to 9 v open surgery, 7; IQR, 5 to 11 days; P=.033). There were no differences in other secondary outcomes or in specimen quality after central pathologic review. In patients treated by experienced surgeons within an ERP, physical fatigue and other PROs were similar in both groups, but laparoscopic surgery significantly reduced length of hospital stay. © 2014 by American Society of Clinical Oncology.

  14. Clinical and ultrasound-based composite disease activity indices in rheumatoid arthritis: results from a multicenter, randomized study.

    PubMed

    Mandl, P; Balint, P V; Brault, Y; Backhaus, M; D'Agostino, M A; Grassi, W; van der Heijde, D; de Miguel, E; Wakefield, R J; Logeart, I; Dougados, M

    2013-06-01

    To evaluate the metrologic properties of composite disease activity indices in rheumatoid arthritis (RA), utilizing information derived from clinical, gray-scale (GS), and power Doppler (PD) ultrasound examinations, and to assess the classification of patients according to disease activity using such indices. This ancillary study utilized data from a multicenter, prospective, randomized, parallel-group study conducted in subjects with moderate RA randomized to receive etanercept and methotrexate (ETN + MTX) or usual care (various disease-modifying antirheumatic drugs [DMARDs]). In multimodal indices, the 28 swollen joint count was either supplemented or replaced by clinically nonswollen joints in which the presence of synovitis was detected either by GS and/or PD and was calculated according to the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Reliability, external validity, and discriminative capacity were calculated at baseline/screening by intraclass correlation coefficient, Pearson's correlation, and standardized response mean, respectively. Data from 62 patients (mean ± SD age 53.8 ± 13.2 years, mean ± SD disease duration 8.8 ± 7.7 years, mean ± SD disease activity 4.6 ± 0.5 [DAS28] and 20.9 ± 5.9 [SDAI]) were analyzed, with 32 receiving ETN + MTX and 30 receiving DMARDs. The metrologic properties were at least as good for GS- and/or PD-based indices as for their clinical counterparts. Using GS- and PD-supplemented indices, an additional 67.8% and 32.3% of patients (DAS28-derived and SDAI-derived indices, respectively) could be classified as having high disease activity at the screening visit. Multimodal indices incorporating ultrasound and clinical data had similar metrologic properties to their clinical counterparts; certain indices allowed for a significantly larger number of patients to be classified to either high or moderate disease activity at the screening visit. Copyright © 2013 by the American

  15. Safety and efficacy of vertebroplasty in the treatment of osteoporotic vertebral compression fractures: a prospective multicenter international randomized controlled study

    PubMed Central

    Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Doria, Carlo

    2016-01-01

    Summary Background Vertebral compression fractures (VCFs) treated non-operatively can diminish function and quality of life, and lead to chronic health effects. The short-term safety and effectiveness of vertebroplasty for symptomatic VCFs are well-documented, but long-term follow-up is needed. Purpose The aim of this paper was to analyse a multicenter international experience of 200 compression fractures treated with percutaneous vertebroplasty (VP) and compare the results of this procedure with the result of 200 patients treated conservatively. To estimate cost-effectiveness of VP compared to conservative care in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. Materials and methods 400 patients have been enrolled in a prospective randomized controlled study with painful VCFs with bone edema on MR imaging, local back pain for 6 weeks or less, osteoporosis and aged 55 years or older; after obtaining informed consent patients are included and randomized for VP or conservative care. Before treatment and at follow-up with regular intervals during 1-year period were administered to patients standard questionnaires addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score for pain, Oswestry Disability Index (ODI) score to evaluate functional activity. Results 200 patients treated with PV compared with 200 patients treated conservatively had significantly better VAS and used less analgesics 1 day after treatment. Twenty-four hours after VP, there was a reduction in pain scores and an improvement in physical functions, whereas remain unchanged in the patients treated conservatively. Conclusions Pain relief and improvement of mobility and function after PV is immediate and significantly better in the short term compared with non-surgical care treatment. PMID:28228788

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

    PubMed

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

    2016-01-01

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

  17. Lifestyle INtervention for Diabetes prevention After pregnancy (LINDA-Brasil): study protocol for a multicenter randomized controlled trial.

    PubMed

    Schmidt, Maria Inês; Duncan, Bruce B; Castilhos, Cristina; Wendland, Eliana Márcia; Hallal, Pedro C; Schaan, Beatriz D'Agord; Drehmer, Michele; Costa e Forti, Adriana; Façanha, Cristina; Nunes, Maria Angélica

    2016-03-30

    Gestational diabetes mellitus (GDM), a hyperglycemic state detected during pregnancy, is an established risk factor for diabetes. However, treatment during pregnancy in and of itself is not able to eliminate this risk, and a considerable fraction of women with GDM will develop frank diabetes in the decade following pregnancy. Our aim is to conduct a multicenter randomized controlled trial to investigate the effectiveness of a lifestyle intervention program implemented after a pregnancy complicated by GDM in delaying or preventing the development of type 2 diabetes. Women aged 18 or older identified as having recent GDM are recruited and followed by telephone to assess eligibility for the trial. To be eligible, women must have used insulin during pregnancy or present intermediate hyperglycemia postpartum. Women are encouraged to enter the trial as early as 10 weeks, and are permitted to do so up to 2 years after a pregnancy with GDM. An estimated 740 women will be randomized to either conventional care or to coach-based interventions focused on breastfeeding, weight loss, healthy eating, and increased physical activity, and predominantly delivered by telephone. Women are followed annually to detect new onset diabetes, the primary outcome, and additional secondary outcomes which include reversion to normoglycemia, weight loss, physical activity and fitness, and insulin resistance. Though previous studies have demonstrated that type 2 diabetes can be delayed or prevented, no study has yet demonstrated the feasibility and effectiveness of similar interventions implemented in the postpartum period for women with recent GDM. If shown to be successful, this approach could become an important means of preventing diabetes in primary care settings. ClinicalTrials.gov Identifier: NCT02327286; Registered 23 December 2014.

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

    PubMed Central

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

    2016-01-01

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

  19. Minocycline and celecoxib as adjunctive treatments for bipolar depression: a study protocol for a multicenter factorial design randomized controlled trial

    PubMed Central

    Husain, Muhammad I; Chaudhry, Imran B; Hamirani, Munir M; Minhas, Fareed A; Kazmi, Ajmal; Hodsoll, John; Haddad, Peter M; Deakin, John FW; Husain, Nusrat; Young, Allan H

    2017-01-01

    Background Evidence suggests that the use of anti-inflammatory agents may improve depressive symptoms in patients with bipolar affective disorder. However, there are few well-designed clinical trials demonstrating the efficacy of these newer treatment strategies. Patients and methods This is a multicenter, 3-month, randomized, placebo-controlled, double-blind, factorial design trial of minocycline and/or celecoxib added to TAU for the treatment of depressive symptoms in patients experiencing a DSM-5 bipolar I or II disorder and a current major depressive episode. A total of 240 participants will undergo screening and randomization followed by four assessment visits. The primary outcome measure will be mean change from baseline to week 12 on the Hamilton Depression Scale scores. Clinical assessments using the Clinical Global Impression scale, Patient Health Questionnaire-9, and the Generalized Anxiety Disorder 7-item scale will be carried out at every visit as secondary outcomes. Side-effect checklists will be used to monitor the adverse events at each visit. Complete blood count and plasma C-reactive protein will be measured at baseline and at the end of the treatment. Minocycline will be started at 100 mg once daily and increased to 200 mg at 2 weeks. Celecoxib will be started at 200 mg once daily and increased to 400 mg at 2 weeks. Discussion Anti-inflammatory agents have been shown to be potentially efficacious in the treatment of depressive symptoms. The aim of this study is to determine whether the addition of minocycline and/or celecoxib to TAU improves depressive symptoms in patients with bipolar affective disorder. PMID:28031712

  20. Frovatriptan versus zolmitriptan for the acute treatment of migraine: a double-blind, randomized, multicenter, Italian study.

    PubMed

    Tullo, Vincenzo; Allais, Gianni; Ferrari, Michel D; Curone, Marcella; Mea, Eliana; Omboni, Stefano; Benedetto, Chiara; Zava, Dario; Bussone, Gennaro

    2010-06-01

    The objective of this study is to assess patients' satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or Z 2.5 mg. The study had a multicenter, randomized, double-blind, cross-over design, with each of the two treatment periods lasting no more than 3 months. At the end of the study, patients were asked to assign preference to one of the treatments (primary endpoint). The number of pain-free (PF) and pain-relief (PR) episodes at 2 h, and number of recurrent and sustained pain-free (SPF) episodes within 48 h were the secondary study endpoints. Seventy-seven percent of patients expressed a preference. Average score of preference was 2.9 +/- 1.3 (F) versus 3.0 +/- 1.3 (Z; p = NS). Rate of PF episodes at 2 h was 26% with F and 31% with Z (p = NS). PR episodes at 2 h were 57% for F and 58% for Z (p = NS). Rate of recurrence was 21 (F) and 24% (Z; p = NS). Time to recurrence within 48 h was better for F especially between 4 and 16 h (p < 0.05). SPF episodes were 18 (F) versus 22% (Z; p = NS). Drug-related adverse events were significantly (p < 0.05) less under F (3 vs. 10). In conclusion, our study suggests that F has a similar efficacy of Z, with some advantage as regards tolerability and recurrence.

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

    PubMed

    Savi, Lidia; Omboni, Stefano; Lisotto, Carlo; Zanchin, Giorgio; Ferrari, Michel D; Zava, Dario; Pinessi, Lorenzo

    2011-04-01

    The objective of this study was to assess patient satisfaction with acute treatment of migraine with frovatriptan or rizatriptan by preference questionnaire. 148 subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack per month in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or rizatriptan 10 mg treating 1-3 attacks. The study had a multicenter, randomized, double-blind, cross-over design, with treatment periods lasting <3 months. At the end of the study, patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain-free and pain relief episodes at 2 h, and recurrent and sustained pain-free episodes within 48 h. 104 of the 125 patients (83%, intention-to-treat population) expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (2.9±1.3) and rizatriptan (3.2±1.1). The rates of pain-free (33% frovatriptan vs. 39% rizatriptan) and pain relief (55 vs. 62%) episodes at 2 h were not significantly different between the two treatments. The rate of recurrent episodes was significantly (p<0.001) lower under frovatriptan (21 vs. 43% rizatriptan). No significant differences were observed in sustained pain-free episodes (26% frovatriptan vs. 22% rizatriptan). The number of patients with adverse events was not significantly different between rizatriptan (34) and frovatriptan (25, p=NS). The results suggest that frovatriptan has a similar efficacy to rizatriptan, but a more prolonged duration of action. © Springer-Verlag 2010

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

    PubMed

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

    2011-06-01

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

  3. Rationale and design of a multicenter randomized clinical trial with memantine and dextromethorphan in ketamine-responder patients.

    PubMed

    Pickering, Gisèle; Pereira, Bruno; Morel, Véronique; Tiberghien, Florence; Martin, Elodie; Marcaillou, Fabienne; Picard, Pascale; Delage, Noémie; de Montgazon, Géraldine; Sorel, Marc; Roux, Delphine; Dubray, Claude

    2014-07-01

    The N-methyl-D-aspartate receptor plays an important role in central sensitization of neuropathic pain and N-methyl-D-aspartate receptor antagonists, such as ketamine, memantine and dextromethorphan may be used for persistent pain. However, ketamine cannot be repeated too often because of its adverse events. A drug relay would be helpful in the outpatient to postpone or even cancel the next ketamine infusion. This clinical trial evaluates if memantine and/or dextromethorphan given as a relay to ketamine responders may maintain or induce a decrease of pain intensity and have a beneficial impact on cognition and quality of life. This trial is a multi-center, randomized, controlled and single-blind clinical study (NCT01602185). It includes 60 ketamine responder patients suffering from neuropathic pain. They are randomly allocated to memantine, dextromethorphan or placebo. After ketamine infusion, 60 patients received either memantine (maximal dose 20 mg/day), or dextromethorphan (maximal dose 90 mg/day), or placebo for 12 weeks. The primary endpoint is pain measured on a (0-10) Numeric Rating Scale 1 month after inclusion. Secondary outcomes include assessment of neuropathic pain, sleep, quality of life, anxiety/depression and cognitive function at 2 and 3 months. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. This study will explore if oral memantine and/or dextromethorphan may be a beneficial relay in ketamine responders and may diminish ketamine infusion frequency. Preservation of cognitive function and quality of life is also a central issue that will be analyzed in these vulnerable patients. Copyright © 2014. Published by Elsevier Inc.

  4. Adjustment of Open-Loop Settings to Improve Closed-Loop Results in Type 1 Diabetes: A Multicenter Randomized Trial

    PubMed Central

    Dassau, Eyal; Brown, Sue A.; Basu, Ananda; Pinsker, Jordan E.; Kudva, Yogish C.; Gondhalekar, Ravi; Patek, Steve; Lv, Dayu; Schiavon, Michele; Lee, Joon Bok; Dalla Man, Chiara; Hinshaw, Ling; Castorino, Kristin; Mallad, Ashwini; Dadlani, Vikash; McCrady-Spitzer, Shelly K.; McElwee-Malloy, Molly; Wakeman, Christian A.; Bevier, Wendy C.; Bradley, Paige K.; Kovatchev, Boris; Cobelli, Claudio; Zisser, Howard C.

    2015-01-01

    Context: Closed-loop control (CLC) relies on an individual's open-loop insulin pump settings to initialize the system. Optimizing open-loop settings before using CLC usually requires significant time and effort. Objective: The objective was to investigate the effects of a one-time algorithmic adjustment of basal rate and insulin to carbohydrate ratio open-loop settings on the performance of CLC. Design: This study reports a multicenter, outpatient, randomized, crossover clinical trial. Patients: Thirty-seven adults with type 1 diabetes were enrolled at three clinical sites. Interventions: Each subject's insulin pump settings were subject to a one-time algorithmic adjustment based on 1 week of open-loop (i.e., home care) data collection. Subjects then underwent two 27-hour periods of CLC in random order with either unchanged (control) or algorithmic adjusted basal rate and carbohydrate ratio settings (adjusted) used to initialize the zone-model predictive control artificial pancreas controller. Subject's followed their usual meal-plan and had an unannounced exercise session. Main Outcomes and Measures: Time in the glucose range was 80–140 mg/dL, compared between both arms. Results: Thirty-two subjects completed the protocol. Median time in CLC was 25.3 hours. The median time in the 80–140 mg/dl range was similar in both groups (39.7% control, 44.2% adjusted). Subjects in both arms of CLC showed minimal time spent less than 70 mg/dl (median 1.34% and 1.37%, respectively). There were no significant differences more than 140 mg/dL. Conclusions: A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm. PMID:26204135

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Preoperative very low-calorie diet and operative outcome after laparoscopic gastric bypass: a randomized multicenter study.

    PubMed

    Van Nieuwenhove, Yves; Dambrauskas, Zilvinas; Campillo-Soto, Alvaro; van Dielen, Francois; Wiezer, René; Janssen, Ignace; Kramer, Michael; Thorell, Anders

    2011-11-01

    A 14-day very low-calorie diet (VLCD) regimen before a laparoscopic gastric bypass procedure will improve perioperative and postoperative outcomes. Multicenter, randomized, single-blind study. Five high-volume bariatric centers in Sweden, the Netherlands, Lithuania, Spain, and Belgium. Two hundred ninety-eight morbidly obese patients undergoing laparoscopic gastric bypass from March 1, 2009, through December 5, 2010. Patients were randomly allocated to a 2-week preoperative VLCD regimen or no preoperative dietary restriction (control group). Operating time, surgeon's perceived difficulty of the operation, liver lacerations, intraoperative bleeding and complications, 30-day weight loss, and morbidity. Mean (SD) preoperative weight change was -4.9 (3.6) kg in the VLCD group vs -0.4 (3.2) kg in the control group (P < .001). Although the surgeon's perceived difficulty of the procedure was lower in the VLCD group (median [interquartile range], 26 [15-42] vs 35 [18-50] mm on a visual analog scale; P = .04), no differences were found regarding mean (SD) operating time (81 [21] vs 80 [23] min; P = .53), estimated blood loss (P = .62), or intraoperative complications (P = .88). At the 30-day follow-up, the number of complications was greater in the control compared with the VLCD group (18 vs 8; P = .04). Although weight reduction with a 14-day VLCD regimen before laparoscopic gastric bypass performed in high-volume centers seems to reduce the perceived difficulty of the procedure, only minor effects on operating time, intraoperative complications, and short-term weight loss could be expected. However, the finding of reduced postoperative complication rates suggests that such a regimen should be recommended before bariatric surgery.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial.

    PubMed

    Kamm, Christian P; El-Koussy, Marwan; Humpert, Sebastian; Findling, Oliver; Burren, Yuliya; Schwegler, Guido; Donati, Filippo; Müller, Martin; Müller, Felix; Slotboom, Johannes; Kappos, Ludwig; Naegelin, Yvonne; Mattle, Heinrich P

    2014-01-01

    Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS). In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study. 27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated. Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months. ClinicalTrials.gov NCT01111656.

  13. Promoting medication adherence among patients with bipolar disorder: a multicenter randomized controlled trial of a multifaceted intervention.

    PubMed

    Pakpour, A H; Modabbernia, A; Lin, C-Y; Saffari, M; Ahmadzad Asl, M; Webb, T L

    2017-10-01

    The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD). A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions. Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention. Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD. The trial was registered with theClinicalTrials.gov database (NCT02241863) https://clinicaltrials.gov/ct2/show/NCT02241863.

  14. Effectiveness and safety of Chinese massage therapy (Tui Na) on post-stroke spasticity: a prospective multicenter randomized controlled trial.

    PubMed

    Yang, Yu-Jie; Zhang, Jun; Hou, Ying; Jiang, Bao-Yin; Pan, Hua-Fei; Wang, Jian; Zhong, Da-Yong; Guo, Hai-Ying; Zhu, Yi; Cheng, Jie

    2017-07-01

    To evaluate the effectiveness and safety of Chinese massage therapy (Tui Na) for patients with post-stroke spasticity. A prospective, multicenter, blinded, randomized, placebo-controlled intervention trial. A total of 90 patients with post-stroke spasticity were randomly assigned to the experimental (Tui Na therapy) group ( n = 45) or control (placebo Tui Na therapy) group ( n = 45). Participants in the experimental group received Tui Na therapy, while those in the control group received placebo-Tai Na (gentle rubbing) for 20-25 minutes per limb, once per day, five days per week for a total of four weeks. All participants in both groups received conventional rehabilitation. The Modified Ashworth Scale, the Fugl-Meyer Assessment and the Modified Barthel Index were used to assess the severity of spasticity, motor function of limbs and activities of daily living, respectively. Assessments were performed at baseline, at four weeks and at three months. Tui Na group had a significantly greater reduction in Modified Ashworth Scale in only four muscle groups than the control did (elbow flexors, P = 0.026; wrist flexors, P = 0.005; knee flexors, P = 0.023; knee extensors, P = 0.017). Improvements were sustained at three months follow-up. There was no significant difference between the two groups in Fugl-Meyer Assessment ( P = 0.503) and Modified Barthel Index ( P = 0.544). No adverse reaction was recorded in any of the cases mentioned at all study sites. Tui Na might be a safe and effective treatment to reduce post-stroke spasticity of several muscle groups.

  15. A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

    PubMed

    Healy, D A; Boyle, E; McCartan, D; Bourke, M; Medani, M; Ferguson, J; Yagoub, H; Bashar, K; O'Donnell, M; Newell, J; Canning, C; McMonagle, M; Dowdall, J; Cross, S; O'Daly, S; Manning, B; Fulton, G; Kavanagh, E G; Burke, P; Grace, P A; Moloney, M Clarke; Walsh, S R

    2015-11-01

    A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed. © The Author(s) 2015.

  16. Refeeding Low Weight Hospitalized Adolescents With Anorexia Nervosa: A Multicenter Randomized Controlled Trial.

    PubMed

    O'Connor, Graeme; Nicholls, Dasha; Hudson, Lee; Singhal, Atul

    2016-10-01

    Refeeding patients with anorexia nervosa (AN) is associated with high morbidity and mortality. A lack of evidence from interventional studies has hindered refeeding practice and led to worldwide disparities in management recommendations. In the first randomized controlled trial in this area, we tested the hypothesis that refeeding adolescents with AN with a higher energy intake than what many guidelines recommend improved anthropometric outcomes without adversely affecting cardiac and biochemical markers associated with refeeding. Participants aged 10-16 years with a body mass index (BMI) <78% of the median (mBMI) for age and sex were recruited from 6 UK hospitals and randomly allocated to start refeeding at 1200 kcal/d (n = 18, intervention) or 500 kcal/d (n = 18, control). Compared with controls, adolescents randomized to high energy intake had greater weight gain (mean difference between groups after 10 days of refeeding, -1.2% mBMI; 95% confidence interval, -2.4% to 0.0%; P = .05), but randomized groups did not differ statistically in QTc interval and other outcomes. The nadir in postrefeeding phosphate concentration was significantly related to percentage mBMI at the start of refeeding (baseline; P = .04) and baseline white blood cell count (P = .005) but not to baseline energy intake (P = .08). Refeeding adolescents with AN with a higher energy intake was associated with greater weight gain but without an increase in complications associated with refeeding when compared with a more cautious refeeding protocol-thus challenging current refeeding recommendations. © 2016 American Society for Parenteral and Enteral Nutrition.

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

    PubMed Central

    2014-01-01

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

  18. Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

    PubMed

    Visser, Laura; de Boer, Marjon A; de Groot, Christianne J M; Nijman, Tobias A J; Hemels, Marieke A C; Bloemenkamp, Kitty W M; Bosmans, Judith E; Kok, Marjolein; van Laar, Judith O; Sueters, Marieke; Scheepers, Hubertina; van Drongelen, Joris; Franssen, Maureen T M; Sikkema, J Marko; Duvekot, Hans J J; Bekker, Mireille N; van der Post, Joris A M; Naaktgeboren, Christiana; Mol, Ben W J; Oudijk, Martijn A

    2017-07-14

    Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous

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

    PubMed Central

    2013-01-01

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

  20. Lateral asymmetric decubitus position for the rotation of occipito-posterior positions: multicenter randomized controlled trial EVADELA.

    PubMed

    Le Ray, Camille; Lepleux, Flavie; De La Calle, Aurélie; Guerin, Jessy; Sellam, Nathalie; Dreyfus, Michel; Chantry, Anne A

    2016-10-01

    Fetal occiput posterior positions are associated with poorer maternal outcomes than occiput anterior positions. Although methods that include instrumental and manual rotation can be used at the end of labor to promote the rotation of the fetal head, various maternal postures may also be performed from the beginning of labor in occiput posterior position. Such postures might facilitate flexion of the fetal head and favor its rotation into an occiput anterior position. The purpose of this study was to determine whether a lateral asymmetric decubitus posture facilitates the rotation of fetal occiput posterior into occiput anterior positions. Evaluation of Decubitus Lateral Asymmetric posture was a multicenter randomized controlled trial that included 322 women from May 2013 through December 2014. Study participants were women who labored with ruptured membranes and a term fetus that was confirmed by ultrasound imaging to be in cephalic posterior position. Women who were assigned to the intervention group were asked to lie in a lateral asymmetric decubitus posture on the side opposite that of the fetal spine during the first hour and encouraged to maintain this position for as long as possible during the first stage of labor. In the control group, women adopted a dorsal recumbent posture during the first hour after random assignment. The primary outcome was occiput anterior position at 1 hour after random assignment. Secondary outcomes were occiput anterior position at complete dilation, mode of delivery, speed of dilation during the active first stage, maternal pain, and women's satisfaction. One hundred sixty women were assigned to the intervention group, and 162 women were assigned to the control group. One hour after random assignment, the rates of occiput anterior position did not differ between the intervention and control groups (21.9% vs 21.6%, respectively; P=.887). Occiput anterior rates did not differ between groups at complete dilation (43.7% vs 43

  1. Multicenter, randomized controlled trial of pain-related behaviors following routine neutering in dogs.

    PubMed

    Wagner, Ann E; Worland, Grace A; Glawe, J Christopher; Hellyer, Peter W

    2008-07-01

    To evaluate the degree of postoperative pain in dogs undergoing elective castration or ovariohysterectomy (OHE); determine whether an association exists between surgeon experience, incision length, or surgery duration and degree of postoperative pain; and determine whether analgesic treatment decreases expression of postoperative pain behaviors. Randomized controlled clinical trial. 426 client-owned dogs undergoing OHE or castration. Dogs underwent OHE or castration performed by an experienced veterinarian or a fourth-year veterinary student. Dogs were randomly assigned to 1 of 4 treatment groups: no perioperative analgesic treatment (n = 44), preoperative administration of morphine (144), preoperative administration of nalbuphine (119), and postoperative administration of ketoprofen (119). Dogs were evaluated while in the hospital before anesthesia and for 4 hours after surgery and once a day at home for 3 days after surgery. Dogs in all 4 groups had significant increases in overall pain scores after surgery, compared with baseline scores. There were significant differences among groups, with control dogs having significantly higher increases in overall pain scores than dogs in the other groups. Factors that did not influence the frequency or severity of pain-related behaviors included breed, individual hospital, anesthetic induction protocol, surgeon experience, and duration of surgery. Results suggested that dogs expressed behaviors suggestive of pain following OHE and castration, that analgesic treatment mitigated the expression of pain-related behaviors, and that surgeon experience and surgery duration did not have any effect on expression of pain-related behaviors.

  2. Costs of Home Versus Inpatient Treatment for Fever and Neutropenia: Analysis of a Multicenter Randomized Trial

    PubMed Central

    Hendricks, Ann M.; Loggers, Elizabeth Trice; Talcott, James A.

    2011-01-01

    Purpose For patients with cancer who have febrile neutropenia, relative costs of home versus hospital treatment, including unreimbursed costs borne by patients and families, are poorly characterized. We estimated costs from a randomized trial of patients with low-risk febrile neutropenia for whom outpatient care was feasible, comparing inpatient treatment with discharge to home care after inpatient observation. Methods We collected direct medical and self-reported indirect costs for 57 inpatient and 35 outpatient treatment episodes of patients enrolled in a randomized trial from 1996 through 2000. Charges from hospital bills were converted to costs using Medicare cost-to-charge ratios. Patients kept daily logs of out-of-pocket payments and time spent by informal caregivers providing care. Dollar amounts were standardized to June 2008. Results Mean total charges for the hospital arm were 49% higher than for the home treatment arm ($16,341 v $10,977; P < .01). Mean estimated total costs for the hospital arm were 30% higher ($10,143 v $7,830; P < .01). Inspection of sparse available data suggests that payments made were similar by treatment arm. Inpatients and their caregivers spent more out of pocket than their outpatient counterparts (mean, $201 v $74; P < .01). Informal caregivers for both treatment arms reported similar time caring and lost from work. Conclusion Home intravenous antibiotic treatment was less costly than continued inpatient care for carefully selected patients with cancer having febrile neutropenia without significantly increased indirect costs or caregiver burden. PMID:21931037

  3. Repair or replace for severe ischemic mitral regurgitation: prospective randomized multicenter data.

    PubMed

    LaPar, Damien J; Acker, Michael A; Gelijns, Annetine C; Kron, Irving L

    2015-09-01

    Ischemic mitral regurgitation (IMR) is a subset of functional mitral regurgitation (MR) that has the potential to impact an increasing number of patients in the future. This is in the context of a worldwide population, which continues to live longer with improved survival after myocardial infarction. Substantial data have accumulated over the past few decades demonstrating the negative effects of IMR. Further, significant research has been done to define the optimal surgical approach and several studies have compared mitral repair versus replacement for patients with severe mitral regurgitation (SMR). Studies supporting performance of mitral repair cite superior operative morbidity and mortality rates, while proponents of mitral replacement cite improved long-term durability and correction of MR. Lack of clinically robust Level I randomized controlled trial data have curtailed attempts to better define appropriate surgical treatment allocation over the past few decades. Recently, however, the Cardiothoracic Surgical Trials Network (CTSN) conducted the first randomized controlled trial, funded by the National Heart, Lung, and Blood Institute, the National Institute for Neurological Diseases and Stroke and the Canadian Institute for Health Research, to compare the performance of mitral repair versus replacement for SMR. Herein, the present review describes the design, results and implications of the CTSN SMR trial and its efforts to identify the most efficacious surgical approach to SMR. This review also describes CTSN investigation to predict the recurrence of MR after mitral repair.

  4. A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients.

    PubMed

    Spies, Claudia; Macguill, Martin; Heymann, Anja; Ganea, Christina; Krahne, Daniel; Assman, Angelika; Kosiek, Heinrich-Rudolf; Scholtz, Kathrin; Wernecke, Klaus-Dieter; Martin, Jörg

    2011-03-01

    To compare the quality of analgesia provided by a remifentanil-based analgesia regime with that provided by a fentanyl-based regime in critically ill patients. This was a registered, prospective, two-center, randomized, triple-blind study involving adult medical and surgical patients requiring mechanical ventilation (MV) for more than 24 h. Patients were randomized to either remifentanil infusion or a fentanyl infusion for a maximum of 30 days. Sedation was provided using propofol (and/or midazolam if required). Primary outcome was the proportion of patients in each group maintaining a target analgesia score at all time points. Secondary outcomes included duration of MV, discharge times, and morbidity. At planned interim analysis (n = 60), 50% of remifentanil patients (n = 28) and 63% of fentanyl patients (n = 32) had maintained target analgesia scores at all time points (p = 0.44). There were no significant differences between the groups with respect to mean duration of ventilation (135 vs. 165 h, p = 0.80), duration of hospital stay, morbidity, or weaning. Interim analysis strongly suggested futility and the trial was stopped. The use of remifentanil-based analgesia in critically ill patients was not superior regarding the achievement and maintenance of sufficient analgesia compared with fentanyl-based analgesia.

  5. Costs of repair of abdominal aortic aneurysm with different devices in a multicenter randomized trial.

    PubMed

    Matsumura, Jon S; Stroupe, Kevin T; Lederle, Frank A; Kyriakides, Tassos C; Ge, Ling; Freischlag, Julie A

    2015-01-01

    Prior analysis in the Open vs Endovascular Repair Veterans Affairs (VA) Cooperative Study (CSP #498) demonstrated that survival, quality of life, and total health care costs are not significantly different between the open and endovascular methods of repair of abdominal aortic aneurysm. The device is a major cost of this method of repair, and the objective of this study was to evaluate the costs of the device, abdominal aortic aneurysm repair, and total health care costs when different endograft systems are selected for the endovascular repair (EVR). Within each selected system, EVR costs are compared with open repair costs. The study randomized 881 patients to open (n = 437) or EVR (n = 444). Device selection was recorded before randomization; therefore, open repair controls were matched to each device cohort. Data were excluded for two low-volume devices, implanted in only 13 individuals, leaving 423 control and 431 endovascular patients: 166 Zenith (Cook Medical, Bloomington, Ind), 177 Excluder (W. L. Gore & Associates, Flagstaff, Ariz), and 88 AneuRx (Medtronic, Minneapolis, Minn). Mean device, hospitalization, and total health care costs from randomization to 2 years were compared. Health care utilization data were obtained from patients and national VA and Medicare data sources. VA costs were determined using methods previously developed by the VA Health Economics Resource Center. Non-VA costs were obtained from Medicare claims data and billing data from the patient's health care providers. Implant costs were 38% of initial hospitalization costs. Mean device (range, $13,600-$14,400), initial hospitalization (range, $34,800-$38,900), and total health care costs at 2 years in the endovascular (range, $72,400-$78,200) and open repair groups (range, $75,600-$82,100) were not significantly different among device systems. Differences between endovascular and corresponding open repair cohorts showed lower mean costs for EVR (range, $3200-$8300), but these were not

  6. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy.

    PubMed

    Ledford, Dennis; Busse, William; Trzaskoma, Benjamin; Omachi, Theodore A; Rosén, Karin; Chipps, Bradley E; Luskin, Allan T; Solari, Paul G

    2017-07-01

    Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab. We sought to evaluate the benefit and persistence of response in subjects continuing or withdrawing from long-term omalizumab treatment. Evaluating the Xolair Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab. Subjects were randomized by using a hierarchical dynamic randomization scheme to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. The primary outcome was any protocol-defined severe asthma exacerbation. The secondary outcome was time to first protocol-defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire and Asthma Control Test scores. Significantly more subjects in the omalizumab group (67%) had no protocol-defined exacerbation than in the placebo group (47.7%); an absolute difference of 19.3% (95% CI, 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol-defined exacerbation analysis revealed a significantly different between-group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to week 52: Asthma Control Test score, -1.16 [4.14] vs placebo, -2.88 [5.38], P = .0188; Asthma Control Questionnaire score, 0.22 [0.66] vs placebo, 0.63 [1.13], P = .0039). Discontinuation of omalizumab was associated with an increase in free IgE levels and an increase in basophil expression of the high-affinity IgE receptor. No safety concerns were noted. Continuation of omalizumab after long-term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk. Copyright © 2016 The

  7. Postacute care for older people in community hospitals: a multicenter randomized, controlled trial.

    PubMed

    Young, John; Green, John; Forster, Anne; Small, Neil; Lowson, Karin; Bogle, Sue; George, James; Heseltine, David; Jayasuriya, Tilak; Rowe, Jed

    2007-12-01

    To compare the effects of community hospital care on independence for older people needing rehabilitation with that of general hospital care. Randomized, controlled trial. Seven community hospitals and five general hospitals in the midlands and north of England. Four hundred ninety patients needing rehabilitation after hospital admission with an acute illness. Multidisciplinary team care for older people in community hospitals. The primary outcome was the Nottingham extended activities of daily living scale (NEADL); secondary outcomes were the Barthel Index, Nottingham Health Profile, Hospital Anxiety and Depression Scale, mortality, discharge destination, 6-month residence status, and satisfaction with services. Loss of independence at 6 months was significantly less likely in the community hospital group (mean adjusted NEADL change score group difference 3.27; 95% confidence interval 0.26-6.28; P=.03). The results for the secondary outcome measures were similar for the two groups. Postacute community hospital rehabilitation care for older people is associated with greater independence.

  8. Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease.

    PubMed

    Hauser, Robert A; Schapira, Anthony H V; Rascol, Olivier; Barone, Paolo; Mizuno, Yoshikuni; Salin, Laurence; Haaksma, Monika; Juhel, Nolwenn; Poewe, Werner

    2010-11-15

    The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID. © 2010 Movement Disorder Society.

  9. Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study.

    PubMed

    Hagen, Neil A; du Souich, Patrick; Lapointe, Bernard; Ong-Lam, May; Dubuc, Benoit; Walde, David; Love, Robin; Ngoc, Anh Ho

    2008-04-01

    Cancer pain is a serious public health issue and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker. This randomized, placebo-controlled, parallel design study of subcutaneous tetrodotoxin, in patients with moderate or severe unrelieved cancer pain persisting despite best available treatment, involved 22 centers across Canada. The design called for tetrodotoxin administered subcutaneously over Days 1-4 with a period of observation to Day 15 or longer. All patients could enroll into an open-label extension efficacy and safety trial. The primary endpoint was the proportion of analgesic responders in each treatment arm. Eighty-two patients were randomized, and results on 77 were available for analysis. There was a nonstatistically significant trend toward more responders in the active treatment arm based on the primary endpoint (pain intensity difference). However, analysis of secondary endpoints, and an exploratory post hoc analysis, suggested there may be a robust analgesic effect if a composite endpoint is used, including either fall in pain level, or fall in opioid dose, plus improvement in quality of life. Most patients described transient perioral tingling or other mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but one patient experienced a serious, adverse event, truncal and gait ataxia. This trial suggests tetrodotoxin may potentially relieve moderate to severe, treatment-resistant cancer pain in a large proportion of patients, and often for prolonged periods following treatment, but further study is warranted using a composite primary endpoint.

  10. Continued smoking abstinence in diabetic patients in primary care: a cluster randomized controlled multicenter study.

    PubMed

    Pérez-Tortosa, Santiago; Roig, Lydia; Manresa, Josep M; Martin-Cantera, Carlos; Puigdomènech, Elisa; Roura, Pilar; Armengol, Angelina; Advani, Mamta

    2015-01-01

    To assess the effectiveness of an intensive smoking cessation intervention based on the transtheoretical model of change (TTM) in diabetic smokers attending primary care. A cluster randomized controlled clinical trial was designed in which the unit of randomization (intervention vs. usual care) was the primary care team. An intensive, individualized intervention using motivational interview and therapies and medications adapted to the patient's stage of change was delivered. The duration of the study was 1 year. A total of 722 people with diabetes who were smokers (345 in the intervention group and 377 in the control group) completed the study. After 1 year, continued abstinence was recorded in 90 (26.1%) patients in the intervention group and in 67 (17.8%) controls (p=0.007). In patients with smoking abstinence, there was a higher percentage in the precontemplation and contemplation stages at baseline in the intervention group than in controls (21.2% vs. 13.7%, p=0.024). When the precontemplation stage was taken as reference (OR=1.0), preparation/action stage at baseline showed a protective effect, decreasing 3.41 times odds of continuing smoking (OR=0.293 95% CI 0.179-0.479, p<0.001). Contemplation stage at baseline also showed a protective effect, decreasing the odds of continuing smoking (OR=0.518, 95% CI 0.318-0.845, p=0.008). An intensive intervention adapted to the individual stage of change delivered in primary care was feasible and effective, with a smoking cessation rate of 26.1% after 1 year. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a multicenter, nonblinded, randomized controlled trial.

    PubMed

    Kim, Jung-Eun; Seo, Byung-Kwan; Choi, Jin-Bong; Kim, Hyeong-Jun; Kim, Tae-Hun; Lee, Min-Hee; Kang, Kyung-Won; Kim, Joo-Hee; Shin, Kyung-Min; Lee, Seunghoon; Jung, So-Young; Kim, Ae-Ran; Shin, Mi-Suk; Jung, Hee-Jung; Park, Hyo-Ju; Kim, Sung-Phil; Baek, Yong-Hyeon; Hong, Kwon-Eui; Choi, Sun-Mi

    2015-07-26

    The causes of chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) are not clearly known, and there are no definitive treatments for them. Therefore, patients with CFS and ICF are interested in Oriental medicine or complementary and alternative medicine. For this reason, the effectiveness of complementary and alternative treatments should be verified. We investigated the effectiveness of two forms of acupuncture added to usual care for CFS and ICF compared to usual care alone. A three-arm parallel, non-blinded, randomized controlled trial was performed in four hospitals. We divided 150 participants into treatment and control groups at the same ratio. The treatment groups (Group A, body acupuncture; Group B, Sa-am acupuncture) received 10 sessions for 4 weeks. The control group (Group C) continued usual care alone. The primary outcome was the Fatigue Severity Scale (FSS) at 5 weeks after randomization. Secondary outcomes were the FSS at 13 weeks and a short form of the Stress Response Inventory (SRI), the Beck Depression Inventory (BDI), the Numeric Rating Scale (NRS), and the EuroQol-5 Dimension (EQ-5D) at 5 and 13 weeks. Group A showed significantly lower FSS scores than Group C at 5 weeks (P = 0.023). SRI scores were significantly lower in the treatment groups than in the control group at 5 (Group A, P = 0.032; B, P <0.001) and 13 weeks (Group A, P = 0.037; B, P <0.001). Group B showed significantly lower BDI scores than Group C at 13 weeks (P = 0.007). NRS scores from the treatment groups were significantly reduced compared to control at 5 (Group A and B, P <0.001) and 13 weeks (Group A, P = 0.011; B, P = 0.002). Body acupuncture for 4 weeks in addition to usual care may help improve fatigue in CFS and ICF patients. Clinical Research Information Service (CRIS) KCT0000508; Registered on 12 August 2012.

  12. Multicenter randomized trial comparing compression with elastic stocking versus bandage after surgery for varicose veins.

    PubMed

    Mariani, Fabrizio; Marone, Enrico Maria; Gasbarro, Vincenzo; Bucalossi, Matteo; Spelta, Sara; Amsler, Felix; Agnati, Michele; Chiesa, Roberto

    2011-01-01

    Postoperative limb compression is widely used after venous surgery to prevent thromboembolism and to reduce hemorrhage, edema, hematoma, and pain. Only limited studies have been published regarding the most adequate postoperative compression therapy after varicose vein surgery. This study evaluated the effectiveness of a new stocking kit used for postoperative limb compression. The study compared the clinical practicability, ease to use, effectiveness, and safety of a postoperative stocking system (23 to 32 mmHg at the ankle) with compression bandages (control group). This prospective, randomized, open-label clinical trial, was performed in three Italian centers specializing in venous surgery. Sixty consecutive patients (classification CEAP C₂,(S)) underwent unilateral varicose vein surgery at one of the three centers. After surgery, patients were randomized for postoperative compression therapy with a new stocking system (Sigvaris Postoperative Kit; Ganzoni Sigvaris Corp, Winterthur, Switzerland) or standard stretch bandages (30 patients per group). Primary end points were incidence of venous thromboembolism, hemorrhage, limb hematoma, or edema. No episodes of venous thromboembolism were observed. The mean area of thigh hematoma on postoperative days 7 and 14 was 75.70 cm² and 2.93 cm², respectively, for the stocking group, and 92.97 cm² and 5.42 cm² for the bandage group (not significant). On postoperative day 7, edema was found in 50% of the patients wearing bandages and in 20% of the patients wearing the stocking kit, which was a significant reduction. No statistical difference was recorded for postoperative pain; however, better patient acceptance and quality of life after the operation were recorded in the stocking group. Patients can be effectively treated with the Sigvaris Postoperative Kit. Patients treated with stockings have less edema compared with standard bandaging, and the application of the stocking kit improves patient quality of life and

  13. Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial.

    PubMed

    Giovannini, Marcello; Verduci, Elvira; Gregori, Dario; Ballali, Simonetta; Soldi, Sara; Ghisleni, Diana; Riva, Enrica

    2014-01-01

    The objective of the study was to investigate the effects of a galacto-oligosaccharides (GOS)-supplemented formula on the intestinal microbiota in healthy term infants, with a specific consideration for gastrointestinal symptoms as colic, stool frequency and consistency, regurgitation. This was a randomized, double-blind, controlled, parallel-group clinical trial performed simultaneously by 6 centers in Italy. Three groups were considered: breastfed, formula-fed, and GOS-supplemented formula-fed infants. Formula-fed infants were randomized to receive either the control or the study formula and consume the assigned formula exclusively until the introduction of complementary feeding. The nutritional composition of the 2 formulas were identical, apart from the supplemented GOS (0.4 g/100 mL) in the study formula. Four different types of bacteria were evaluated in order to assess the efficacy of GOS-supplemented formula on infants: Bifidobacterium, Lactobacillus, and Clostridium, Escherichia coli. A total of 199 breastfed infants and 163 formula-fed infants were recruited. When considering stool frequency and consistency, GOS-supplemented formula presented normal and soft stools in the majority of episodes (89%). In the supplemented group the incidence of colic was lower with respect to the control group. A significantly lower count of Clostridium and a higher count of Bifidobacterium were found when comparing study formula and control formula in infants with colic. In children with colic the ratio between Clostridium count and Bifidobacterium and Lactobacillus count was in favor of the latter two when considering the GOS-supplemented formula group with respect to the control one. The prebiotic-supplemented formula mimicked the effect of human milk in promoting Bifidobacterium and Lactobacillus growth and in inhibiting Clostridium growth, resulting in a significantly lower presence of colic.

  14. The Kinetics of Integrilin Limited by Obesity (KILO): A Multicenter Randomized Pharmacokinetic and Pharmacodynamic Clinical Trial

    PubMed Central

    Vavalle, John P.; Stevens, Susanna R.; Hassinger, Nancy; Cohen, Mauricio G.; Arnold, Anita; Kandzari, David E.; Aguirre, Frank V.; Gretler, Daniel D.; Alexander, John H.

    2013-01-01

    Background KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight-adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Methods Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight-based (ABW) dosing with no upper limit, or ideal body weight-based (IBW) dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg/min infusion. Plasma eptifibatide concentrations were drawn at 12–18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Results Sixty-seven patients were randomized to standard (n=22), ABW (n=23), or IBW (n=22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1740 ng/mL (1350, 2350), 1780 ng/mL (1510, 2350), and 1055 ng/mL (738, 1405), respectively (P<0.001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively, (P=0.001). Conclusions ABW eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients. PMID:22137072

  15. The kinetics of integrilin limited by obesity: a multicenter randomized pharmacokinetic and pharmacodynamic clinical trial.

    PubMed

    Vavalle, John P; Stevens, Susanna R; Hassinger, Nancy; Cohen, Mauricio G; Arnold, Anita; Kandzari, David E; Aguirre, Frank V; Gretler, Daniel D; Alexander, John H

    2011-12-01

    KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P < .001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P = .001). Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients. Copyright © 2011 Mosby, Inc. All rights reserved.

  16. Family Access to a Dentist Study (FADS): A Multi-Center Randomized Controlled Trial

    PubMed Central

    Nelson, Suchitra; Riedy, Christine; Albert, Jeffrey M; Lee, Wonik; Slusar, Mary Beth; Curtan, Shelley; Ferretti, Gerald; Cunha-Cruz, Joana; Milgrom, Peter

    2015-01-01

    Introduction Many low-income parent/caregivers do not understand the importance of cavity-free primary (baby) teeth and the chronic nature of dental caries (tooth decay). As a consequence, dental preventive and treatment utilization is low even when children are screened in schools and referred for care. This study aims to test a referral letter and Dental Information Guide (DIG) designed using the Common-Sense Model of Self-Regulation (CSM) framework to improve caregivers’ illness perception of dental caries and increase utilization of care by children with restorative dental needs. Methods A multi-site randomized controlled trial with caregivers of Kindergarten to 4th grade children in urban Ohio and rural Washington State will compare five arms: (1) CSM referral letter alone; (2) CSM referral letter + DIG; (3) reduced CSM referral letter alone; (4) reduced CSM referral letter + DIG; (5) standard (control) referral. At baseline, children will be screened at school to determine restorative dental needs. If in need of treatment, caregivers will be randomized to study arms and an intervention packet will be sent home. The primary outcome will be dental care based on a change in oral health status by clinical examination 7 months post-screening (ICDAS sealant codes 1 and 2; restoration codes 3–8; extraction). Enrollment commenced summer 2015 with results in summer 2016. Conclusion This study uses the CSM framework to develop and test behavioral interventions to increase dental utilization among low-income caregivers. If effective this simple intervention has broad applicability in clinical and community-based settings. PMID:26500170

  17. A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis.

    PubMed

    Dulhunty, Joel M; Roberts, Jason A; Davis, Joshua S; Webb, Steven A R; Bellomo, Rinaldo; Gomersall, Charles; Shirwadkar, Charudatt; Eastwood, Glenn M; Myburgh, John; Paterson, David L; Starr, Therese; Paul, Sanjoy K; Lipman, Jeffrey

    2015-12-01

    Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing. To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis. We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure-free days at Day 14, and duration of bacteremia. We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20 days (interquartile range, 3-24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24). In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion. Australian New Zealand Clinical Trials Registry number (ACT RN12612000138886).

  18. The United Kingdom Glaucoma Treatment Study: a multicenter, randomized, double-masked, placebo-controlled trial: baseline characteristics.

    PubMed

    Lascaratos, Gerassimos; Garway-Heath, David F; Burton, Robyn; Bunce, Catey; Xing, Wen; Crabb, David P; Russell, Richard A; Shah, Ameet

    2013-12-01

    The United Kingdom Glaucoma Treatment Study (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog, compared with placebo, reduces the frequency of visual field (VF) deterioration events in patients with open-angle glaucoma (OAG) by 50% over a 2-year period. Additional goals are to evaluate study power with novel clinical trial outcomes: (1) VF deterioration velocity and (2) VF and quantitative imaging measurements modeled as joint outcomes. The UKGTS is a randomized, double-masked, placebo-controlled, multicenter treatment trial for OAG. A total of 516 patients with newly diagnosed (previously untreated) OAG were prospectively recruited at 10 UK centers between 2007 and 2010. Eligible patients were randomly assigned to treatment with latanoprost 0.005% or placebo. The observation period was 2 years, with subjects monitored by VF testing, quantitative imaging, optic disc photography, and tonometry at 11 visits. The primary outcome measure is time to VF deterioration within 24 months. Secondary outcomes include the deterioration velocity of VF and quantitative imaging measures. The main source of referrals was optometrists (88%). A total of 777 subjects were assessed for eligibility, and 261 were excluded because they did not meet the inclusion criteria or declined to participate. The mean age of the 516 participants was 66 years, and 52.9% were male; 90.1% of the participants were white, and approximately one third (32.2%) reported a family history of glaucoma. A total of 777 eyes were eligible at initial assessment. Both eyes were eligible for 265 participants. Mean (standard deviation) intraocular pressure (IOP) at baseline for the eyes with better versus worse mean deviation (MD) was 18.9 (4.1) and 19.9 (4.7) mmHg, respectively (P = 0.0053). Some 56.1% of all eligible eyes had IOP <20 mmHg at baseline. The median (interquartile range) VF MD for all eligible eyes was -2.9 dB (-1.6 to -4.8 dB). This is the first randomized, placebo

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

    PubMed Central

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

    2015-01-01

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

  20. Randomized, multicenter, comparative study of NEURO versus CIMT in poststroke patients with upper limb hemiparesis: the NEURO-VERIFY Study.

    PubMed

    Abo, Masahiro; Kakuda, Wataru; Momosaki, Ryo; Harashima, Hiroaki; Kojima, Miki; Watanabe, Shigeto; Sato, Toshihiro; Yokoi, Aki; Umemori, Takuma; Sasanuma, Jinichi

    2014-07-01

    Many poststroke patients suffer functional motor limitation of the affected upper limb, which is associated with diminished health-related quality of life. The aim of this study is to conduct a randomized, multicenter, comparative study of low-frequency repetitive transcranial magnetic stimulation combined with intensive occupational therapy, NEURO (NovEl intervention Using Repetitive TMS and intensive Occupational therapy) versus constraint-induced movement therapy in poststroke patients with upper limb hemiparesis. In this randomized controlled study of NEURO and constraint-induced movement therapy, 66 poststroke patients with upper limb hemiparesis were randomly assigned at 2:1 ratio to low-frequency repetitive transcranial magnetic stimulation plus occupational therapy (NEURO group) or constraint-induced movement therapy (constraint-induced movement therapy group) for 15 days. Fugl-Meyer Assessment and Wolf Motor Function Test and Functional Ability Score of Wolf Motor Function Test were used for assessment. No differences in patients' characteristics were found between the two groups at baseline. The Fugl-Meyer Assessment score was significantly higher in both groups after the 15-day treatment compared with the baseline. Changes in Fugl-Meyer Assessment scores and Functional Ability Score of Wolf Motor Function Test were significantly higher in the NEURO group than in the constraint-induced movement therapy group, whereas the decrease in the Wolf Motor Function Test log performance time was comparable between the two groups (changes in Fugl-Meyer Assessment score, NEURO: 5·39 ± 4·28, constraint-induced movement therapy: 3·09 ± 4·50 points; mean ± standard error of the mean; P < 0·05) (changes in Functional Ability Score of Wolf Motor Function Test, NEURO: 3·98 ± 2·99, constraint-induced movement therapy: 2·09 ± 2·96 points; P < 0·05). The results of the 15-day rehabilitative protocol showed the superiority of NEURO

  1. Design of a multicentered randomized controlled trial on the clinical and cost effectiveness of schema therapy for personality disorders

    PubMed Central

    2012-01-01

    Background Despite international guidelines describing psychotherapy as first choice for people with personality disorders (PDs), well-designed research on the effectiveness and cost-effectiveness of psychotherapy for PD is scarce. Schema therapy (ST) is a specific form of psychological treatment that proved to be effective for borderline PD. Randomized controlled studies on the effectiveness of ST for other PDs are lacking. Another not yet tested new specialized treatment is Clarification Oriented Psychotherapy (COP). The aim of this project is to perform an effectiveness study as well as an economic evaluation study (cost effectiveness as well as cost-utility) comparing ST versus COP versus treatment as usual (TAU). In this study, we focus on avoidant, dependent, obsessive-compulsive, paranoid, histrionic and narcissistic PD. Methods/Design In a multicentered randomized controlled trial, ST, and COP as an extra experimental condition, are compared to TAU. Minimal 300 patients are recruited in 12 mental health institutes throughout the Netherlands, and receive an extensive screening prior to enrolment in the study. When eligible, they are randomly assigned to one of the intervention groups. An economic evaluation and a qualitative research study on patient and therapist perspectives on ST are embedded in this trial. Outcome assessments (both for clinical effectiveness and economic evaluation) take place at 6,12,18,24 and 36 months after start of treatment. Primary outcome is recovery from PD; secondary measures include general psychopathological complaints, social functioning and quality of life. Data for the cost-effectiveness and cost-utility analyses are collected by using a retrospective cost interview. Information on patient and therapist perspectives is gathered using in-depth interviews and focus groups, and focuses on possible helpful and impeding aspects of ST. Discussion This trial is the first to compare ST and COP head-to-head with TAU for people with

  2. Efficacy and safety of valsartan, an angiotensin II receptor antagonist, in hypertension after renal transplantation: a randomized multicenter study.

    PubMed

    Andrés, A; Morales, E; Morales, J M; Bosch, I; Campo, C; Ruilope, L M

    2006-10-01

    The prevalence of posttransplant hypertension is high, and it appears to be a major risk factor for graft and patient survival. The aim of this study was to assess the efficacy and safety of valsartan, an angiotensin-receptor blocker (ARB), in the treatment of posttransplant hypertension. A multinational, multicenter, prospective, randomized, double-blind, placebo-controlled study was performed on the treatment of hypertension (systolic blood pressure [BP] >/= 140 and/or diastolic BP >/= 90 mm Hg) in adult cyclosporin-treated renal transplant recipients randomized to receive either valsartan (80 mg once daily) or a matching placebo for 8 weeks. After the first 4 weeks, furosemide 20 mg twice daily was added on a open basis if systolic BP remained >/= 130 mm Hg and/or diastolic BP remained >/= 85 mm Hg. One hundred fifteen (valsartan = 57, placebo = 58) uncontrolled hypertensive patients despite monotherapy for hypertension, other than angiotensin-converting enzyme inhibitor or ARB, were randomized. In the valsartan group, significant decreases were seen in systolic BP (from 153 +/- 11 to 140.9 +/- 18.35 mm Hg at 4 weeks, and 136.5 +/- 15 mm Hg at 8 weeks) and diastolic BP (from 93 +/- 9 to 85.2 +/- 11.28 mm Hg at 4 weeks, and 83.8 +/- 9.2 mm Hg at 8 weeks). There was no significant change in the placebo group. In the valsartan group, a statistically but not clinically significant reduction was observed in the mean hemoglobin concentration (12.9 +/- 1.6 g/dL versus 13.8 +/- 1.6 g/dL at 4 weeks, P < .01; and 12.3 +/- 1.6 versus 13.8 +/- 1.7 at 8 weeks; P < .001) as well as a significant increase in serum potassium (4.4 +/- 0.5 mmol/L versus 4.1 +/- 0.4 mmol/L at 4 weeks, P < .01) vs placebo. Valsartan is effective in the treatment of posttransplant hypertension and is well tolerated.

  3. [A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

    PubMed

    Lu, Quan

    2010-03-01

    To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P < 0.05) and except nasal congestion, the efficacy in all the other symptoms of trial group was better than that in the control group as well on the 7th day (P < 0.01). The improvement rate for combined symptoms of Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

  4. Quality of life in schizophrenia: a multicenter, randomized, naturalistic, controlled trial comparing olanzapine to first-generation antipsychotics.

    PubMed

    Silva de Lima, Maurício; de Jesus Mari, Jair; Breier, Alan; Maria Costa, Anna; Pondé de Sena, Eduardo; Hotopf, Matthew

    2005-07-01

    To assess the effectiveness of olanzapine for treating schizophrenia and to assess if olanzapine promotes a better quality of life than first-generation antipsychotics (FGAs). Multicenter, naturalistic, randomized controlled study, comparing olanzapine with FGAs, at hospitalization and during a 9-month follow-up. Outcome assessors were blind to the allocated drug. The dose of antipsychotic was determined by doctors according to their clinical practice routines. Data collection was performed from April 1999 to August 2001. 197 patients with DSM-IV-diagnosed schizophrenia were allocated to olanzapine (N = 104) and FGA (N = 93). Patients taking olanzapine showed greater improvements in Positive and Negative Syndrome Scale (PANSS) negative symptoms (mean difference = 2.3, 95% CI = 0.6 to 4.1) and general psychopathology (mean difference = 4.0, 95% CI = 0.8 to 7.2) sub-scales and fewer incidences of tardive dyskinesia (RR = 2.4, 95% CI = 1.4 to 4.2, p < .0001). Olanzapine was also associated with greater improvement in a number of health-related quality-of-life outcomes on the Medical Outcomes Study 36-item Short-Form Health Survey, including physical functioning (mean difference = 6.6, 95% CI = 1.2 to 11.9), physical role limitations (mean difference = 13.7, 95% CI = 3.0 to 24.3), and emotional role limitations (mean difference = 12.1, 95% CI = 0.7 to 23.5). Patients taking olanzapine gained significantly more weight during the trial than patients taking FGAs, with a correspondent endpoint increase in the body mass index (BMI) of 28.7 versus 25.3 (p < .001). Compared with FGAs, olanzapine has advantages in terms of improvements of negative symptoms and quality of life. It is also associated with fewer incidences of tardive dyskinesia and greater increases in weight and BMI. These findings are highlighted by the naturalistic approach adopted in this trial.

  5. Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial.

    PubMed

    Courneya, Kerry S; Segal, Roanne J; Mackey, John R; Gelmon, Karen; Friedenreich, Christine M; Yasui, Yutaka; Reid, Robert D; Jespersen, Diana; Cook, Diane; Proulx, Carolyn; Trinh, Linda; Dolan, Lianne B; Wooding, Evyanne; Forbes, Cynthia C; McKenzie, Donald C

    2014-04-01

    To examine the effects of different doses and types of exercise on sleep quality in breast cancer patients receiving chemotherapy. A multicenter trial in Canada randomized 301 breast cancer patients between 2008 and 2011 to thrice weekly, supervised exercise during chemotherapy consisting of either a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101), or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104). The secondary sleep outcomes in the trial were assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline, twice during chemotherapy, and postchemotherapy. We analyzed the global PSQI and the component scores. Repeated measures analyses of variance indicated that the HIGH group was statistically superior to the STAN group for global sleep quality (mean group difference = -0.90; 95 % CI -0.05 to -1.76; p = 0.039) as well as subjective sleep quality (p = 0.028) and sleep latency (p = 0.049). The COMB group was borderline statistically superior to the STAN group for global sleep quality (mean group difference = -0.76; 95 % CI +0.11 to -1.62; p = 0.085) as well as sleep duration (p = 0.051); and statistically superior for sleep efficiency (p = 0.040), and percentage of poor sleepers (p = 0.045). Compared to a standard volume of aerobic exercise, higher volumes of both aerobic and combined exercise improved some aspects of sleep quality during breast cancer chemotherapy. Exercise may be an attractive option to manage sleep dysfunction in cancer patients during chemotherapy.

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

    PubMed Central

    2012-01-01

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

  7. Efficacy of urea therapy in children with ichthyosis. A multicenter randomized, placebo-controlled, double-blind, semilateral study.

    PubMed

    Küster, W; Bohnsack, K; Rippke, F; Upmeyer, H J; Groll, S; Traupe, H

    1998-01-01

    Ichthyoses are genetic disorders of keratinization which are uncomfortable due to their conspicuous scaling, itching and cosmetic problems. Especially in childhood, ichthyoses can lead to social discrimination and psychological problems. Efficient therapies are necessary which are safe and well tolerated. The aim of the study was to investigate the keratolytic and moisturizing properties as well as the tolerance of a new urea lotion when applied to hyperkeratotic and ichthyotic skin in childhood. The study was conducted as a multicenter, randomized, placebo-controlled, double-blind, semilateral investigation. Sixty children between 1 and 16 years treated one side of the most affected extremity with Laceran 10% urea lotion for 8 weeks. On the other side the urea-free Laceran lotion base was given. On each side of the body a control area was left untreated. The investigators evaluated the global severity of ichthyotic symptoms with the help of a visual analogue scale. The analysis of the global estimation of severity of ichthyosis showed improvements being stronger in the body areas treated with Laceran 10% urea lotion (from 4.8 to 2.0 points) than in the areas treated with the urea-free Laceran lotion base (from 4.8 to 2.5 points). The response rates were 65% after 4 weeks and 78% after 8 weeks for Laceran 10% urea lotion, 50% after 4 weeks and 72% after 8 weeks for the urea-free Laceran lotion base. It can be ascertained that Laceran 10% urea lotion has a strong positive effect on generalized ichthyotic keratinization disorders.

  8. Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial

    PubMed Central

    Lee, Belinda T.; Gabardi, Steven; Grafals, Monica; Hofmann, R. Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A.; Adey, Deborah B.; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine

    2014-01-01

    Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression. PMID:24482066

  9. Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial.

    PubMed

    Ubbink, D T; Spincemaille, G H; Prins, M H; Reneman, R S; Jacobs, M J

    1999-08-01

    Patients with non-reconstructable critical limb ischemia generally undergo medical treatment only to prevent or postpone amputation. There is some evidence that spinal cord stimulation (SCS) stimulates ischemic wound healing. Thus, this could benefit limb survival through improved skin perfusion. We investigated the effect of SCS versus conservative treatment on skin microcirculation in relation to treatment outcome in patients with non-reconstructable critical limb ischemia. Standard medical treatment plus SCS was compared with only standard medical treatment in a multicenter randomized controlled trial comprised of 120 patients with surgically non-reconstructable chronic rest pain or ulceration. We investigated skin microcirculation by means of capillary microscopy, laser Doppler perfusion, and transcutaneous oxygen measurements in the foot. The microcirculatory status just before treatment was classified in three categories (poor, intermediate, and good) and was related to limb survival after a minimum follow-up period of 18 months. Clinical parameters, peripheral blood pressures, and limb survival rates showed no significant differences between the SCS and standard groups during the follow-up period. In both treatment groups, amputation frequency after 18 months was high in patients with an initially poor microcirculatory skin perfusion (SCS 80% vs standard treatment 71%; NS) and low in those with a good skin perfusion (29% vs 11 %, respectively; NS). In patients with an intermediate skin microcirculation amputation, frequency was twice as low in patients additionally treated with SCS as in the standard treatment group (48% vs 24%; P =.08). In these patients, microcirculatory reactive hyperemia during the follow-up period reduced in the standard group but not in the SCS group (P <.01). Selection on the basis of the initial microcirculatory skin perfusion identifies patients in whom SCS can improve local skin perfusion and limb survival.

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. A Randomized, Controlled, Multicenter Study of Juvéderm Voluma for Enhancement of Malar Volume in Chinese Subjects.

    PubMed

    Li, Dong; Wang, Xiaojun; Wu, Yan; Sun, Jiaming; Li, Qin; Guo, Shuzhong; Jia, Yi; Murphy, Diane K

    2017-06-01

    Hyaluronic acid gels are used to restore volume to the midface, but there are few data published on this use in Asian subjects. This study evaluated the safety and effectiveness in Chinese subjects of Juvéderm Voluma, a 20-mg/ml hyaluronic acid gel formulated for midface volumizing. This prospective, multicenter study randomized 119 subjects aged 18 years or older to a treatment group and 27 subjects to a no-treatment control group. The primary effectiveness endpoint was the objectively measured magnitude of change from baseline in volume of the midface area (right and left combined) calculated by digital analysis at month 6 using three-dimensional images for all subjects in both groups. Effectiveness was protocol-defined as a mean change for the treatment group that was significantly greater than that for the control group at month 6 using a one-side two-group t test performed at the 5 percent level. With a median volume of 2 ml of Voluma injected, the primary effectiveness endpoint was met, with the mean change from baseline to 6 months in malar volume for the treatment group (1.83 ml) being significantly greater than that for the control group (0.11 ml; p < 0.001). The secondary effectiveness endpoints of responder rate (malar volumization rated improved or much improved) using the Global Aesthetic Improvement Scale as assessed at month 6 by the investigator and by the subject were 98.2 and 93.8 percent, respectively. The most common treatment-related adverse events were mild injection-site swelling and bruising. Juvéderm Voluma is effective and well tolerated for midface augmentation in Chinese subjects. Therapeutic, II.

  13. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) A Multicenter Placebo-Controlled Randomized Trial: Age Analysis

    PubMed Central

    Portman, Michael A.; Slee, April; Olson, Aaron K.; Cohen, Gordon; Karl, Tom; Tong, Elizabeth; Hastings, Laura; Patel, Hitendra; Reinhartz, Olaf; Mott, Antonio R.; Mainwaring, Richard; Linam, Justin; Danzi, Sara

    2011-01-01

    Background Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. Methods and Results The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7–22) for placebo and 20 hours (CI, 16–45) for Triostat and (hazard ratio, 0.60; P=0.0220). Conclusions T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417. PMID:20837917

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

    PubMed

    Zielinski, Stephanie M; Viveiros, Helena; Heetveld, Martin J; Swiontkowski, Marc F; Bhandari, Mohit; Patka, Peter; Van Lieshout, Esther M M

    2012-01-08

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

  15. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

    PubMed

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-08-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p<0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

  16. Spectra Optia granulocyte apheresis collections result in higher collection efficiency of viable, functional neutrophils in a randomized, crossover, multicenter trial.

    PubMed

    Cancelas, Jose A; Padmanabhan, Anand; Le, Tuan; Ambruso, Daniel R; Rugg, Neeta; Worsham, D Nicole; Pinkard, Susan L; Graminske, Sharon; Buck, Jennifer; Goldberg, Julie; Bill, Jerry

    2015-04-01

    Granulocyte transfusion from healthy donors is used in the treatment of patients with granulocyte function defects, or transient neutropenia and severe bacterial or fungal infections resistant to maximal antimicrobial treatment. This study evaluated the performance and safety of the newly developed granulocyte collection protocol of the Spectra Optia in a prospective, multicenter, open-label, randomized, paired crossover trial compared with the COBE Spectra apheresis system in a population of 32 evaluable healthy subjects. All subjects received granulocyte-colony-stimulating factor and dexamethasone before collection. Granulocyte procedures from Spectra Optia apheresis procedures had an approximately 23% higher polymorphonuclear (PMN) collection efficiency (CE) than the COBE Spectra collections (mean, 53.7% vs. 43.2%; p < 0.01), while the platelet CE (10.9% vs. 10.8%, respectively) and hematocrit (7.4% vs. 7.4%) were comparable between collections on both devices. Spectra Optia collections generated a higher total PMN yield per liter of blood processed than those produced by the COBE Spectra (with means of 8.6 × 10(10) vs. 6.8 × 10(10) , respectively). Granulocyte viability was more than 99% with both devices, and chemotaxic and bacterial killing activities of circulating versus collected granulocytes were similarly preserved. Fewer operator adjustments were required with Spectra Optia and there was no significant difference in the number or intensity of adverse events between instruments. CE of the granulocyte collection procedure with the Spectra Optia was approximately 10 percentage points higher than with the COBE Spectra, required less operator involvement, and is safe for clinical implementation. © 2014 AABB.

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

    PubMed Central

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

    2015-01-01

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

  18. Multicenter international randomized comparison of objective and subjective outcomes between electronic and traditional chest drainage systems.

    PubMed

    Pompili, Cecilia; Detterbeck, Frank; Papagiannopoulos, Kostas; Sihoe, Alan; Vachlas, Kostas; Maxfield, Mark W; Lim, Henry C; Brunelli, Alessandro

    2014-08-01

    The aim of this study was to assess the impact of digital versus traditional drainage devices on chest tube removal and patient satisfaction. A randomized trial of digital versus traditional devices after lobectomy/segmentectomy was conducted at 4 international centers (United Kingdom, Europe, Asia, United States). Patients were managed with overnight suction followed by gravity drainage. Chest tubes were removed when an air leak was not evident anymore and the drained fluid was less than 400 mL/d. The groups (digital, 191 patients; traditional, 190 patients) were well matched for baseline and surgical characteristics. There were 325 lobectomies/bilobectomies and 56 segmentectomies, 308 of which were performed by video-assisted thoracic surgery (VATS). Patients randomized to digital systems had a significantly shorter air leak duration (1.0 versus 2.2 days; p=0.001), duration of chest tube placement (3.6 versus 4.7 days; p=0.0001), and postoperative length of stay (4.6 versus 5.6 days; p<0.0001). Subjective end points revealed a perceived improved ability to arise from bed (p=0.008), system convenience for patients and personnel (p=0.02), and the potential for being comfortable when discharged home with the device (p=0.06). A mean difference of 2.6 days from air leak cessation to tube removal was observed, which was similar in the 2 groups (p=0.7). Multivariable regression analysis showed that duration of chest tube placement after air leak cessation was directly associated with the amount of fluid drained during the first 48 hours (p=0.01) and the duration of air leak (p=0.008), independent of hospital location. Patients managed with digital drainage systems experienced a shorter duration of chest tube placement, shorter hospital stays, and higher satisfaction scores compared with those managed with traditional devices. ( NCT01747889.). Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Alfapump® system vs. large volume paracentesis for refractory ascites: A multicenter randomized controlled study.

    PubMed

    Bureau, Christophe; Adebayo, Danielle; Chalret de Rieu, Mael; Elkrief, Laure; Valla, Dominique; Peck-Radosavljevic, Markus; McCune, Anne; Vargas, Victor; Simon-Talero, Macarena; Cordoba, Juan; Angeli, Paolo; Rosi, Silvia; MacDonald, Stewart; Malago, Massimo; Stepanova, Maria; Younossi, Zobair M; Trepte, Claudia; Watson, Randall; Borisenko, Oleg; Sun, Sun; Inhaber, Neil; Jalan, Rajiv

    2017-06-21

    Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with a poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump® [AP]) compared with LVP standard of care [SoC]. A randomized controlled trial, in seven centers, with six month patient observation was conducted. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition, hemodynamics, and renal injury biomarkers were assessed in a sub-study at three months. Sixty patients were randomized and 58 were analyzed (27 AP, 31 SoC, mean age 61.9years, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after six months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0days (HR 0.13; 95%CI 13.0-22.0; p<0.001), and AP patients also showed significantly improved Chronic Liver Disease Questionnaire (CLDQ) scores compared with SoC patients (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC. The AP system is effective for reducing the need for paracentesis and improving HRQoL in cirrhotic patients with RA. Although the frequency of Quality of Life (and by inference hospitalizations) was significantly higher in the AP group, they were generally limited and did not impact survival. www

  20. Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins.

    PubMed

    de Boer, J; De Meester, J; Smits, J M; Groenewoud, A F; Bok, A; van der Velde, O; Doxiadis, I I; Persijn, G G

    1999-01-01

    The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW: 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33% of either HTK-(n = 105) or UW-(n = 99) preserved kidneys (P = NS), and in 29% of the HTK-(n = 85) and in 43% of the EC-(n = 119) preserved kidneys (P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73%, compared to 68% for UW-preserved kidneys in the UW-HTK study (P = NS); while the 3-year graft survival of HTK preserved kidneys was 70% compared to 67% for EC-preserved kidneys in the EC-HTK study (P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided.

  1. Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy.

    PubMed

    Borovicka, J; Fischer, J; Neuweiler, J; Netzer, P; Gschossmann, J; Ehmann, T; Bauerfeind, P; Dorta, G; Zürcher, U; Binek, J; Meyenberger, C

    2006-09-01

    The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four

  2. Treatment of recurrent respiratory papillomatosis with human leukocyte interferon. Results of a multicenter randomized clinical trial.

    PubMed

    Healy, G B; Gelber, R D; Trowbridge, A L; Grundfast, K M; Ruben, R J; Price, K N

    1988-08-18

    Recurrent respiratory papillomatosis is a relentless disease of viral origin in which squamous papillomas frequently obstruct the respiratory tract of children and young adults. No therapy has been proved to be curative for this process. Recent reports have suggested that interferon may cure or dramatically control airway papillomatosis. We evaluated the efficacy of human leukocyte interferon in the treatment of respiratory papillomatosis. One hundred twenty-three patients were randomly assigned to receive treatment with either surgery plus interferon or surgery alone. Interferon (2 X 10(6) IU per square meter of body-surface area) was given daily for one week, then three times per week for one year; treatment was followed by a year of observation, without the drug. Both study groups underwent serial endoscopy to remove papillomas and to document the efficacy of treatment during the two years of study. During the first six months, the growth rate of papillomas in the interferon group was significantly lower than in the control group (P = 0.0007). This difference diminished during the second six months and was no longer statistically significant (P = 0.68). Our data do not show that interferon is either curative or of substantial value as an adjunctive agent in the long-term management of recurrent respiratory papillomatosis. The initial benefit of interferon is not sustained.

  3. Comparative cost-effectiveness of three intrauterine devices: a multi-center randomized trial.

    PubMed

    Wen, Jin; Li, Ying; Li, Youping; Wang, Li; Zhou, Jian; Ba, Lei; Shen, Suqi; Wu, Yulin

    2010-05-01

    To determine the relative cost-effectiveness of three intrauterine devices (IUDs), MLCu375, TCu380A, and YuangongCu365. Cost-effectiveness of three IUDs, namely MLCu375, TCu380A, and YuangongCu365, was analyzed from the provider's perspective by means of a randomized trial with one-year follow-up carried out in six centers in China. YuangongCu 365 had the lowest termination and pregnancy rates (4.17% and 0.54%, respectively), followed by TCu380A (8.59% and 1.11%, respectively) and MLCu375 (14.17% and 2.04%, respectively). YuangongCu365 was more effective yet more costly than the MLCu375. There was a favorably dominating trend of cost-effectiveness for TCu380A comparing with MLCu375 when taking continuation rate as the effectiveness indicator, but there was no difference in cost-effectiveness between the two IUDs when using the pregnancy avoidance rate as the effectiveness measure. TCu380A is slightly more cost-effective than the MLCu375. YuangongCu365 is the most effective of the three devices and be used provided it is economically affordable. The comparative long-term safety and cost-effectiveness of these devices need to be further investigated. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

  4. Moist exposed burn ointment for treating pressure ulcers: A multicenter randomized controlled trial.

    PubMed

    Li, Wei; Ma, Yubo; Yang, Qi; Pan, Yu; Meng, Qinggang

    2017-07-01

    Pressure ulcers often seriously affect the quality of life of patients. Moist Exposed Burn Ointment (MEBO) has been developed to treat patients with pressure ulcers. The present study aimed to evaluate the efficacy and safety of MEBO in the treatment of pressure ulcers in Chinese patients. Seventy-two patients with pressure ulcers were randomly assigned to 2 groups who received a placebo or MEBO for 2 months. The primary outcomes included the wound surface area (WSA) and pressure ulcer scale for healing (PUSH) tool. The secondary outcomes included a visual analog scale (VAS), questionnaire of ulcer status, and adverse effects. Sixty-seven patients completed the study. After 2 months of treatment, the difference of mean change from the baseline was greater for MEBO (vs placebo) for WSA mean (SD) -6.0 (-8.8, -3.3), PUSH Tool -2.6 (-4.7, -1.5), and VAS score -2.9 (-4.4, -1.7). On the basis of the questionnaire, the pressure ulcers were "completely healed" (50.0% vs 16.7%) (P < .05) in patients after 2 months of treatment with MEBO versus placebo. No major adverse effects were found in the 2 groups. We showed that MEBO is effective and well tolerated for improving wound healing in Chinese patients with pressure ulcers.

  5. The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

    PubMed

    Frank, Jonathan M; Kayupov, Erdan; Moric, Mario; Segreti, John; Hansen, Erik; Hartman, Curtis; Okroj, Kamil; Belden, Katherine; Roslund, Brian; Silibovsky, Randi; Parvizi, Javad; Della Valle, Craig J

    2017-01-01

    for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. Level I, therapeutic study.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  8. Pediatric emergency medicine asynchronous e-learning: a multicenter randomized controlled Solomon four-group study.

    PubMed

    Chang, Todd P; Pham, Phung K; Sobolewski, Brad; Doughty, Cara B; Jamal, Nazreen; Kwan, Karen Y; Little, Kim; Brenkert, Timothy E; Mathison, David J

    2014-08-01

    Asynchronous e-learning allows for targeted teaching, particularly advantageous when bedside and didactic education is insufficient. An asynchronous e-learning curriculum has not been studied across multiple centers in the context of a clinical rotation. We hypothesize that an asynchronous e-learning curriculum during the pediatric emergency medicine (EM) rotation improves medical knowledge among residents and students across multiple participating centers. Trainees on pediatric EM rotations at four large pediatric centers from 2012 to 2013 were randomized in a Solomon four-group design. The experimental arms received an asynchronous e-learning curriculum consisting of nine Web-based, interactive, peer-reviewed Flash/HTML5 modules. Postrotation testing and in-training examination (ITE) scores quantified improvements in knowledge. A 2 × 2 analysis of covariance (ANCOVA) tested interaction and main effects, and Pearson's correlation tested associations between module usage, scores, and ITE scores. A total of 256 of 458 participants completed all study elements; 104 had access to asynchronous e-learning modules, and 152 were controls who used the current education standards. No pretest sensitization was found (p = 0.75). Use of asynchronous e-learning modules was associated with an improvement in posttest scores (p < 0.001), from a mean score of 18.45 (95% confidence interval [CI] = 17.92 to 18.98) to 21.30 (95% CI = 20.69 to 21.91), a large effect (partial η(2) = 0.19). Posttest scores correlated with ITE scores (r(2) = 0.14, p < 0.001) among pediatric residents. Asynchronous e-learning is an effective educational tool to improve knowledge in a clinical rotation. Web-based asynchronous e-learning is a promising modality to standardize education among multiple institutions with common curricula, particularly in clinical rotations where scheduling difficulties, seasonality, and variable experiences limit in-hospital learning. © 2014 by the Society for Academic

  9. Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).

    PubMed

    Vermöhlen, Vanessa; Schiller, Petra; Schickendantz, Sabine; Drache, Marion; Hussack, Sabine; Gerber-Grote, Andreas; Pöhlau, Dieter

    2017-08-01

    Evidence-based complementary treatment options for multiple sclerosis (MS) are limited. To investigate the effect of hippotherapy plus standard care versus standard care alone in MS patients. A total of 70 adults with MS were recruited in five German centers and randomly allocated to the intervention group (12 weeks of hippotherapy) or the control group. Primary outcome was the change in the Berg Balance Scale (BBS) after 12 weeks, and further outcome measures included fatigue, pain, quality of life, and spasticity. Covariance analysis of the primary endpoint resulted in a mean difference in BBS change of 2.33 (95% confidence interval (CI): 0.03-4.63, p = 0.047) between intervention ( n = 32) and control ( n = 38) groups. Benefit on BBS was largest for the subgroup with an Expanded Disability Status Scale (EDSS) ⩾ 5 (5.1, p = 0.001). Fatigue (-6.8, p = 0.02) and spasticity (-0.9, p = 0.03) improved in the intervention group. The mean difference in change between groups was 12.0 ( p < 0.001) in physical health score and 14.4 ( p < 0.001) in mental health score of Multiple Sclerosis Quality of Life-54 (MSQoL-54). Hippotherapy plus standard care, while below the threshold of a minimal clinically important difference, significantly improved balance and also fatigue, spasticity, and quality of life in MS patients.

  10. Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial.

    PubMed

    Dörr, Helmuth G; Bettendorf, Markus; Binder, Gerhard; Karges, Beate; Kneppo, Carolin; Schmidt, Heinrich; Voss, Egbert; Wabitsch, Martin; Dötsch, Jörg

    2015-01-01

    Levothyroxine (L-T4) treatment of euthyroid children with Hashimoto thyroiditis (HT) is a controversial issue. We conducted a prospective, randomized, controlled clinical trial. Out of 79 identified euthyroid patients, 59 started the study; 25 patients (21 female, 4 male; age: 11.8 ± 2.3 years) received L-T4 at a mean dose of 1.6 µg/kg (SD, 0.8) daily, and 34 (27 female, 7 male; age: 12.6 ± 1.2 years) were not treated. Patients developing subclinical hypothyroidism during follow-up (n = 13) were treated with L-T4 and removed from the observation group. As the main outcome measures, thyroid gland volume (determined by ultrasound) as well as serum levels of TSH, free T4, and antibodies against thyroid peroxidase and thyroglobulin were assessed every 6 months for 36 months. At the start, the mean thyroid volume (standard deviation score, SDS) was 2.5 in the treatment group and 1.6 in the observation group. There was a constant decline in mean thyroid volume (SDS) from 2.13 (month 12) to 1.12 (month 30) in the treated group, with a delta thyroid volume of -1.01 SDS. In the observation group, the mean delta thyroid volume increased to +0.27 SDS. The change of the delta thyroid volume was statistically significantly different between both groups during the 12- and 30-month time points (p < 0.05). L-T4 had no effect on thyroid function and serum thyroid antibodies. L-T4 treatment can decrease the thyroid volume in euthyroid children with HT, but the effect is limited to a definite time period. © 2015 S. Karger AG, Basel.

  11. Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial.

    PubMed

    Isaacsohn, J L; Moser, M; Stein, E A; Dudley, K; Davey, J A; Liskov, E; Black, H R

    1998-06-08

    Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However, much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled. To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia. This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low-density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical-looking tablet, also given 3 times per day with meals. The main outcome measures included levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment. Twenty-eight patients (43% male; mean +/- SD age, 58 +/- 14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57 +/- 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients. Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia.

  12. A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children.

    PubMed

    Brousseau, David C; Scott, J Paul; Badaki-Makun, Oluwakemi; Darbari, Deepika S; Chumpitazi, Corrie E; Airewele, Gladstone E; Ellison, Angela M; Smith-Whitley, Kim; Mahajan, Prashant; Sarnaik, Sharada A; Casper, T Charles; Cook, Lawrence J; Dean, J Michael; Leonard, Julie; Hulbert, Monica L; Powell, Elizabeth C; Liem, Robert I; Hickey, Robert; Krishnamurti, Lakshmanan; Hillery, Cheryl A; Nimmer, Mark; Panepinto, Julie A

    2015-10-01

    Magnesium, a vasodilator, anti-inflammatory, and pain reliever, could alter the pathophysiology of sickle cell pain crises. We hypothesized that intravenous magnesium would shorten length of stay, decrease opioid use, and improve health-related quality of life (HRQL) for pediatric patients hospitalized with sickle cell pain crises. The Magnesium for Children in Crisis (MAGiC) study was a randomized, double-blind, placebo-controlled trial of intravenous magnesium vs normal saline placebo conducted at 8 sites within the Pediatric Emergency Care Applied Research Network (PECARN). Children 4 to 21 years old with hemoglobin SS or Sβ(0) thalassemia requiring hospitalization for pain were eligible. Children received 40 mg/kg of magnesium or placebo every 8 hours for up to 6 doses plus standard therapy. The primary outcome was length of stay in hours from the time of first study drug infusion, compared using a Van Elteren test. Secondary outcomes included opioid use and HRQL. Of 208 children enrolled, 204 received the study drug (101 magnesium, 103 placebo). Between-group demographics and prerandomization treatment were similar. The median interquartile range (IQR) length of stay was 56.0 (27.0-109.0) hours for magnesium vs 47.0 (24.0-99.0) hours for placebo (P = .24). Magnesium patients received 1.46 mg/kg morphine equivalents vs 1.28 mg/kg for placebo (P = .12). Changes in HRQL before discharge and 1 week after discharge were similar (P > .05 for all comparisons). The addition of intravenous magnesium did not shorten length of stay, reduce opioid use, or improve quality of life in children hospitalized for sickle cell pain crisis. This trial was registered at www.clinicaltrials.gov as #NCT01197417.

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

    PubMed Central

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

    2012-01-01

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

  14. A 12-month multicenter, randomized study comparing the levonorgestrel intrauterine system with the etonogestrel subdermal implant.

    PubMed

    Apter, Dan; Briggs, Paula; Tuppurainen, Marjo; Grunert, Julia; Lukkari-Lax, Eeva; Rybowski, Sarah; Gemzell-Danielsson, Kristina

    2016-07-01

    To compare the levonorgestrel intrauterine system (LNG-IUS 8), which has an average levonorgestrel release rate of ∼8 μg/24 hours during the first year (total levonorgestrel content 13.5 mg; Jaydess/Skyla), with the etonogestrel (ENG) subdermal implant (total content, 68 mg) with regard to the 12-month discontinuation rate (primary outcome). Randomized, open-label, phase III study. Thirty-eight centers in six European countries. Study population of 766 healthy nulliparous and parous women aged 18-35 years. The LNG-IUS 8 or the ENG implant. Discontinuation rate, by treatment group, at Month 12. The 12-month discontinuation rates were 19.6% and 26.8% in the LNG-IUS 8 and ENG implant groups, respectively. The -7.2% difference was statistically significant (95% confidence interval -13.2%, -1.2%). Fewer women in the LNG-IUS 8 group than in the ENG implant group discontinued because of increased bleeding (3.2% vs. 11.3%) or adverse events (14.3% vs. 21.8%). At 12 months, more women in the LNG-IUS 8 group than in the ENG implant group were "very/somewhat satisfied" with their bleeding pattern (60.9% vs. 33.6%) and reported a preference to use their study treatment after study completion (70.1% vs. 58.5%). The LNG-IUS 8 was associated with a significantly lower 12-month discontinuation rate compared with the ENG implant; mainly because ENG implant users frequently discontinued due to increased bleeding. More LNG-IUS 8 users than ENG implant users reported being "very/somewhat satisfied" with their bleeding pattern, and reported a preference to continue using their study treatment after the study. NCT01397097. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2013-01-01

    There are presently no available therapeutic options for patients with peanut allergy. We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo (P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free. Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD. Published by Mosby, Inc.

  16. Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial

    PubMed Central

    Puccio, Giuseppe; Alliet, Philippe; Cajozzo, Cinzia; Janssens, Elke; Corsello, Giovanni; Sprenger, Norbert; Wernimont, Susan; Egli, Delphine; Gosoniu, Laura; Steenhout, Philippe

    2017-01-01

    ABSTRACT Objectives: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. Methods: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk–based infant formula (control, n = 87) or the same formula with 1.0 g/L 2′fucosyllactose (2′FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. Results: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: −0.30 [−1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [−3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004–0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). Conclusions: Infant formula with 2′FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies. PMID:28107288

  17. Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

    PubMed

    Puccio, Giuseppe; Alliet, Philippe; Cajozzo, Cinzia; Janssens, Elke; Corsello, Giovanni; Sprenger, Norbert; Wernimont, Susan; Egli, Delphine; Gosoniu, Laura; Steenhout, Philippe

    2017-04-01

    The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

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

    PubMed Central

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

    2015-01-01

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

  19. Preoperative pain neuroscience education for lumbar radiculopathy: a multicenter randomized controlled trial with 1-year follow-up.

    PubMed

    Louw, Adriaan; Diener, Ina; Landers, Merrill R; Puentedura, Emilio J

    2014-08-15

    Multicenter, randomized, controlled trial on preoperative pain neuroscience education (NE) for lumbar radiculopathy. To determine if the addition of NE to usual preoperative education would result in superior outcomes with regard to pain, function, surgical experience, and health care utilization postsurgery. One in 4 patients after lumbar surgery (LS) for radiculopathy experience persistent pain and disability, which is nonresponsive to perioperative treatments. NE focusing on the neurophysiology of pain has been shown to decrease pain and disability in populations with chronic low back pain. Eligible patients scheduled for LS for radiculopathy were randomized to receive either preoperative usual care (UC) or a combination of UC plus 1 session of NE delivered by a physical therapist (verbal one-on-one format) and a NE booklet. Sixty-seven patients completed the following outcomes prior to LS (baseline), and 1, 3, 6, and 12 months after LS: low back pain (numeric rating scale), leg pain (numeric rating scale), function (Oswestry Disability Index), various beliefs and experiences related to LS (10-item survey with Likert scale responses), and postoperative utilization of health care (utilization of health care questionnaire). At 1-year follow-up, there were no statistical differences between the experimental and control groups with regard to primary outcome measure of low back pain (P = 0.183), leg pain (P = 0.075), and function (P = 0.365). In a majority of the categories regarding surgical experience, the NE group scored significantly better: better prepared for LS (P = 0.001); preoperative session preparing them for LS (P < 0.001) and LS meeting their expectations (P = 0.021). Health care utilization post-LS also favored the NE group (P = 0.007) resulting in 45% less health care expenditure compared with the control group in the 1-year follow-up period. NE resulted in significant behavior change. Despite a similar pain and functional trajectory during the 1-year

  20. Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.

    PubMed

    So, Jimmy Bok-Yan; Rao, Jaideepraj; Wong, Andrew Siang-Yih; Chan, Yiong-Huak; Pang, Ning Qi; Tay, Amy Yuh Ling; Yung, Man Yee; Su, Zheng; Phua, Janelle Niam Sin; Shabbir, Asim; Ng, Enders Kwok Wai

    2017-04-05

    The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.

  1. 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.

  2. 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.

  3. Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus penetrating keratoplasty: a randomized multicenter clinical trial.

    PubMed

    Cheng, Yanny Y Y; Visser, Nienke; Schouten, Jan S; Wijdh, Robert-Jan; Pels, Elisabeth; van Cleynenbreugel, Hugo; Eggink, Catharina A; Zaal, Michel J W; Rijneveld, Wilhelmina J; Nuijts, Rudy M M A

    2011-02-01

    To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). Randomized, multicenter clinical trial. Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. The DALK procedure was performed according to Anwar's big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemet's membrane (12 months: 27.7% ± 11.1% vs. 12.9% ± 17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39 ± 0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31 ± 0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37 ± 2.3 diopters (D) and -3.76 ± 2.1 D (P = 0.53), and 3.57 ± 2.3 D and 4.16 ± 2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemet's membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemet's membrane were included in the (intention-to-treat) analysis (12 months: 19.1 ± 21.6 vs. 27.7 ± 11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. One year after DALK performed without perforation of Descemet

  4. Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Miki, Keisuke; Maekura, Ryoji; Nagaya, Noritoshi; Nakazato, Masamitsu; Kimura, Hiroshi; Murakami, Shinsuke; Ohnishi, Shunsuke; Hiraga, Toru; Miki, Mari; Kitada, Seigo; Yoshimura, Kenji; Tateishi, Yoshitaka; Arimura, Yasuji; Matsumoto, Nobuhiro; Yoshikawa, Masanori; Yamahara, Kenichi; Kangawa, Kenji

    2012-01-01

    Background Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. Methodology/Principal Findings In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. Conclusions/Significance In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between

  5. Effectiveness of work-related medical rehabilitation in cancer patients: study protocol of a cluster-randomized multicenter trial.

    PubMed

    Wienert, Julian; Schwarz, Betje; Bethge, Matthias

    2016-07-27

    Work is a central resource for cancer survivors as it not only provides income but also impacts health and quality of life. Additionally, work helps survivors to cope with the perceived critical life event. The German Pension Insurance provides medical rehabilitation for working-age patients with chronic diseases to improve and restore their work ability, and support returning to or staying at work, and thus tries to sustainably avoid health-related early retirement. Past research showed that conventional medical rehabilitation programs do not support returning to work sufficiently and that work-related medical rehabilitation programs report higher return-to-work rates across several health conditions, when compared to medical rehabilitation. Therefore, the current study protocol outlines an effectiveness study of such a program for cancer survivors. To evaluate the effectiveness of work-related medical rehabilitation in cancer patients we conduct a cluster-randomized multicenter trial. In total, 504 rehabilitation patients between 18 and 60 years with a Karnofsky Performance Status of ≥70 %, a preliminary positive social-medical prognosis of employability for at least 3 h/day within the next 6 months and an elevated risk of not returning to work will be recruited in four inpatient rehabilitation centers. Patients are randomized to the work-related medical rehabilitation program or the conventional medical rehabilitation program based on their week of arrival at each rehabilitation center. The work-related medical rehabilitation program comprises additional work-related diagnostics, multi-professional team meetings, an introductory session as well as work-related functional capacity training, work-related psychological groups, and social counseling. All additional components are aimed at the adjustment of the patients' capacity in relation to their individual job demands. Role functioning defines the main study outcome and will be assessed with the EORTC

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  8. Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study.

    PubMed

    Holdaas, Hallvard; Rostaing, Lionel; Serón, Daniel; Cole, Edward; Chapman, Jeremy; Fellstrøm, Bengt; Strom, Erik H; Jardine, Alan; Midtvedt, Karsten; Machein, Uwe; Ulbricht, Bettina; Karpov, Alexander; O'Connell, Philip J

    2011-08-27

    Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain. ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m) were randomized to everolimus with CNI elimination (n=127) or CNI minimization (n=144), or continued CNI unchanged (controls, n=123) to assess the effect on measured GFR at month 24 after randomization. Renal function was stable in all groups to month 24. Mean measured GFR at month 24, the primary endpoint, was 48.0±22.0 mL/min/1.73 m, 46.6±21.1 mL/min/1.73 m, and 46.0±20.4 mL/min/1.73 m in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m, 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m, 95% CI -3.88 to 5.07, P=0.79) versus controls at month 24 were nonsignificant that is, the primary endpoint was not met. No efficacy endpoint differed significantly between groups. Post hoc analyses showed that patients with baseline creatinine clearance (CrCl) more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination versus controls (difference 11.4 mL/min/1.73 m, 95% CI 2.1 to 20.8 mL/min/1.73 m, P=0.017). Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs. CNI elimination; P=0.020 vs. CNI minimization). Conversion to everolimus with CNI elimination or minimization a mean of 5.6 years after kidney transplantation had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with CrCl more than 50 mL/min may benefit from a change in therapy more than 6 months after renal transplantation.

  9. Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial.

    PubMed

    Iijima, Kazumoto; Sako, Mayumi; Oba, Mari Saito; Ito, Shuichi; Hataya, Hiroshi; Tanaka, Ryojiro; Ohwada, Yoko; Kamei, Koichi; Ishikura, Kenji; Yata, Nahoko; Nozu, Kandai; Honda, Masataka; Nakamura, Hidefumi; Nagata, Michio; Ohashi, Yasuo; Nakanishi, Koichi; Yoshikawa, Norishige

    2014-02-01

    An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine. Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment. Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.

  10. Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children: A Multicenter Randomized Phase II Trial

    PubMed Central

    Sako, Mayumi; Oba, Mari Saito; Ito, Shuichi; Hataya, Hiroshi; Tanaka, Ryojiro; Ohwada, Yoko; Kamei, Koichi; Ishikura, Kenji; Yata, Nahoko; Nozu, Kandai; Honda, Masataka; Nakamura, Hidefumi; Nagata, Michio; Ohashi, Yasuo; Nakanishi, Koichi; Yoshikawa, Norishige

    2014-01-01

    Summary Background and objectives An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine. Design, setting, participants, & measurements Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600–700 ng/ml for the first 6 months and 450–550 ng/ml for the next 18 months; for group B, it was set to 450–550 ng/ml for the first 6 months and 300–400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment. Results Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. Conclusion The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved

  11. [Efficacy and safety of drospirenone-ethinylestradiol on contraception in healthy Chinese women: a multicenter randomized controlled trial].

    PubMed

    Fan, Guang-sheng; Bian, Mei-lu; Cheng, Li-nan; Cao, Xiao-ming; Huang, Zi-rong; Han, Zi-yan; Jing, Xiao-ping; Li, Jian; Wu, Shu-ying; Xiong, Cheng-liang; Xiong, Zheng-ai; Yue, Tian-fu

    2009-01-01

    To evaluate the contraception efficacy, mode of bleeding, side effects and other positive effects of drospirenone-ethinylestradiol (Yasmin) in healthy Chinese women. This was a multicenter, randomized, control study of 768 healthy Chinese women who consulted about contraception. The subjects were randomized into Yasmin group (30 microg ethinylestradiol plus 3 mg drospirenone, 573 cases) or desogestrel group (30 microg ethinylestradiol plus 150 microg desogestrel, 195 cases) with the ratio of 3:1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment Weight, height, body mass index were evaluated at each visit. The menstrual distress questionnaire (MDQ) was given to the women at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). The values of basal features were similar between two groups (P > 0.05). The Pearl index (method failure) of Yasmin was 0. 208/hundred women year which was lower than that of desogestrel (0. 601/hundred women year). The mode of bleeding was similar between two groups after trial without showing any significant difference. According to MDQ subscale, the improvement of water retention and increasing appetite during inter-menstrual period and water retention and general well-being during menstrual period in the Yasmin group (-0.297, -0.057, 0.033, 0.150 respectively) was more obvious than that in the desogestrel group (-0.108, 0.023, 0.231, -0.023 respectively) with a significant difference (P < 0.05). Some other values which improved in both two groups, especially the improvement of breast tenderness and pain and skin abnormality in Yasmin group (18.0%, 89/494; 12.6%, 62/494) was more distinct than that in desogestrel group (11.3%, 19/168; 5.4%, 9/168). The mean weight increased in desogestrel group (0.57 kg) while it decreased in Yasmin group (-0.28 kg) with a significant difference (P < 0.01). Both Yasmin and desogestrel have good efficacy on contraception and

  12. Multisite prediction of 4-week and 52-week treatment outcomes in patients with first-episode psychosis: a machine learning approach.

    PubMed

    Koutsouleris, Nikolaos; Kahn, René S; Chekroud, Adam M; Leucht, Stefan; Falkai, Peter; Wobrock, Thomas; Derks, Eske M; Fleischhacker, Wolfgang W; Hasan, Alkomiet

    2016-10-01

    At present, no tools exist to estimate objectively the risk of poor treatment outcomes in patients with first-episode psychosis. Such tools could improve treatment by informing clinical decision-making before the commencement of treatment. We tested whether such a tool could be successfully built and validated using routinely available, patient-reportable information. By applying machine learning to data from 334 patients in the European First Episode Schizophrenia Trial (EUFEST; International Clinical Trials Registry Platform number, ISRCTN68736636), we developed a tool to predict poor versus good treatment outcome (Global Assessment of Functioning [GAF] score ≥65 vs GAF <65, respectively) after 4 weeks and 52 weeks of treatment. To enable the unbiased estimation of the predictive system's generalisability to new patients, we used repeated nested cross-validation to prevent information leaking between patients used for training and validating the models. In pursuit of everyday clinical applicability, we retrained the 4-week outcome predictor with only the top ten predictors of the pooled prediction system and then tested this tool in 108 independent patients with 4-week outcome labels. Discontinuation and readmission to hospital events in patients with predicted poor versus good outcomes were assessed with Kaplan-Meier log-rank analyses, whereas generalised linear mixed-effects models were used to investigate the GAF-based predictions against several clinically meaningful outcome indicators, including treatment adherence, symptom remission, and quality of life. The generalisability of our outcome predictions were estimated with cross-validation (test-fold balanced accuracy [BAC] of 75·0% for 4-week outcomes and 73·8% for and 52-week outcomes), and leave-site-out validation across 44 European sites (BAC of 72·1% for 4-week outcomes and 71·1% for 52-week outcomes). We identified a smaller group of ten predictors still providing a BAC of 71·7% in 108 patients

  13. Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study.

    PubMed

    Gálvez, Rafael; Navez, Marie-Louise; Moyle, Graeme; Maihöfner, Christian; Stoker, Malcolm; Ernault, Etienne; Nurmikko, Turo J; Attal, Nadine

    2017-10-01

    To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain. A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using "bedside tests" and Brief Pain Inventory (question 5). Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12. Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

  14. Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic agents for rheumatoid arthritis is a novel predictor for 52-week remission.

    PubMed

    Nakajima, Arata; Aoki, Yasuchika; Sonobe, Masato; Takahashi, Hiroshi; Saito, Masahiko; Nakagawa, Koichi

    2017-02-01

    We have shown that serum levels of reactive oxygen metabolites (ROM) were associated with C-reactive protein (CRP) and disease activity score based on the examination of 28 joints (DAS28) in patients with rheumatoid arthritis (RA); however, their clinical significance as biomarkers has not been elucidated. Forty-eight biologic agent (BA)-naïve RA patients were included in this study. Associations between serum levels of ROM, CRP, matrix metalloproteinase-3 (MMP-3), DAS28-erythrocyte sedimentation rate (ESR), and Health Assessment Questionnaire (HAQ) at 12 weeks of treatment and DAS28 (ESR) remission at 52 weeks (52-week remission) were investigated. The ROM serum level at baseline in the remission group (n = 34) was 527 ± 132 Carratelli units (U.Carr) (normal range <300), decreased to 335 ± 79.1 at 4 weeks, and remained low thereafter. In the non-remission group (n = 14), the ROM serum level at baseline was 592 ± 113 U.Carr, decreased to 450 ± 152 at 4 weeks, but gradually increased thereafter. Among significantly different factors at 12 weeks between the remission and non-remission groups, ROM and DAS28 (ESR) were identified as predictors of 52-week remission (p = 0.045, odds ratio 0.985, 95% confidence interval 0.97-1.000 for ROM). The cutoff value of ROM was determined to be 381.5 U.Carr (sensitivity 0.833, specificity 0.871). These results show that serum ROM levels can predict remission with high accuracy and could be a useful biomarker for achieving remission in the current treat-to-target strategy for RA.

  15. Efficacy and Safety of a Chinese Herbal Formula (Invigorating Kidney and Strengthening Spleen) in Chronic Hepatitis B Virus Carrier: Results from a Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

    PubMed Central

    He, Jinsong; Zhou, Daqiao; Tong, Guangdong; Xing, Yufeng; Chen, Yingjie; Zhang, Xiaohui; Zhan, Bolin; Gao, Hui; Zhou, Xiaozhou; Xiong, Yiqun; Liu, Xinliang; Peng, Lisheng; Qiu, Mei; Zheng, Yingjun

    2013-01-01

    A Chinese Herbal Formula (CHF) has acquired a certain therapeutic effect on chronic HBV infection. To assess the efficacy and safety of CHF on HBV replication in chronic HBV carriers, we performed a randomized, double-blind, and placebo-controlled trial involving patients from 16 centers. A total of 300 confirmed chronic HBV carriers were randomized at baseline in a ratio of 2 : 1 to receive either CHF or placebo for 52 weeks. The results showed that a greater proportion of CHF than placebo treated patients achieved virological response at week 52; the mean decline of serum HBsAg levels in the CHF group dropped more obviously than that in the control group at all stages of the treatment; however, the rates of HBeAg loss and seroconversion had no difference between the two groups. Meanwhile, were presented significant increases in IFN-γ; IL-2 levels and reductions in IL-4 and IL-10 levels in the treatment group compared to the control group at week 52. There were no drug-related serious adverse events. In conclusion, the treatment with 52-week CHF is safe and effective in inhibiting HBV replication in chronic HBV carriers. The ability of the compound to modulate host immune function probably contributed to this effect. PMID:23935692

  16. Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole.

    PubMed

    Ishigooka, Jun; Nakamura, Jun; Fujii, Yasuo; Iwata, Nakao; Kishimoto, Toshifumi; Iyo, Masaomi; Uchimura, Naohisa; Nishimura, Ryoji; Shimizu, Naoaki

    2015-02-01

    This study was designed to evaluate efficacy and safety of aripiprazole once-monthly (AOM) by verifying non-inferiority of AOM to oral aripiprazole in Asian patients with schizophrenia. The study consisted of a screening phase and three phases: an oral conversion phase (≤12weeks), an oral stabilization phase (≤12weeks) and a 52-week double-blind phase. Patients meeting stabilization criteria for 4weeks during the oral stabilization phase were randomly assigned (1:1) to AOM (400mg) or oral aripiprazole (6-24mg/day). The primary endpoint was Kaplan-Meier estimated rate of non-exacerbation of psychotic symptoms/non-relapse at Week 26. A total of 724 patients were screened, and 502 patients entered the oral stabilization phase. Of 455 patients randomized in the double-blind phase, 228 received AOM and 227 received oral aripiprazole. The non-exacerbation of psychotic symptoms/non-relapse rates at Week 26 were 95.0% (AOM) and 94.7% (oral aripiprazole) and the difference was 0.3% (95% CI: -3.9,4.5), thus non-inferiority of AOM compared to oral aripiprazole with respect to non-exacerbation of psychotic symptoms/non-relapse rate was shown with a margin of -3.9% which is well above the pre-defined non-inferiority limit (-15%). The proportions of patients meeting exacerbation of psychotic symptoms/relapse criteria and stabilization of psychotic symptoms/maintenance criteria were 6.6% and 92.5% in both groups. Discontinuation rates due to all reasons were 25.9% (AOM) and 33.5% (oral aripiprazole). AOM was well tolerated as well as oral aripiprazole. Non-inferiority of AOM to oral aripiprazole was established. AOM is efficacious in maintenance treatment of stabilized schizophrenia, with comparable efficacy and tolerability to oral aripiprazole. JapicCTI-101175. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed Central

    2014-01-01

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

  18. Portable Video Media Versus Standard Verbal Communication in Surgical Information Delivery to Nurses: A Prospective Multicenter, Randomized Controlled Crossover Trial.

    PubMed

    Kam, Jonathan; Ainsworth, Hannah; Handmer, Marcus; Louie-Johnsun, Mark; Winter, Matthew

    2016-10-01

    Continuing education of health professionals is important for delivery of quality health care. Surgical nurses are often required to understand surgical procedures. Nurses need to be aware of the expected outcomes and recognize potential complications of such procedures during their daily work. Traditional educational methods, such as conferences and tutorials or informal education at the bedside, have many drawbacks for delivery of this information in a universal, standardized, and timely manner. The rapid uptake of portable media devices makes portable video media (PVM) a potential alternative to current educational methods. To compare PVM to standard verbal communication (SVC) for surgical information delivery and educational training for nurses and evaluate its impact on knowledge acquisition and participant satisfaction. Prospective, multicenter, randomized controlled crossover trial. Two hospitals: Gosford District Hospital and Wyong Hospital. Seventy-two nursing staff (36 at each site). Information delivery via PVM--7-minute video compared to information delivered via SVC. Knowledge acquisition was measured by a 32-point questionnaire, and satisfaction with the method of education delivery was measured using the validated Client Satisfaction Questionnaire (CSQ-8). Knowledge acquisition was higher via PVM compared to SVC 25.9 (95% confidence interval [CI] 25.2-26.6) versus 24.3 (95% CI 23.5-25.1), p = .004. Participant satisfaction was higher with PVM 29.5 (95% CI 28.3-30.7) versus 26.5 (95% CI 25.1-27.9), p = .003. Following information delivery via SVC, participants had a 6% increase in knowledge scores, 24.3 (95% CI 23.5-25.1) versus 25.7 (95% CI 24.9-26.5) p = .001, and a 13% increase in satisfaction scores, 26.5 (95% CI 25.1-27.9) versus 29.9 (95% CI 28.8-31.0) p < .001, when they crossed-over to information delivery via PVM. PVM provides a novel method for providing education to nurses that improves knowledge retention and satisfaction with the

  19. A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery.

    PubMed

    Davis, P J; Lerman, J; Suresh, S; McGowan, F X; Coté, C J; Landsman, I; Henson, L G

    1997-05-01

    Remifentanil hydrochloride is a new, ultrashort-acting opioid metabolized by nonspecific plasma and tissue esterases. We conducted this multicenter study to examine the hemodynamic response and recovery profile of premedicated children undergoing strabismus repair who were randomly assigned to receive one of four treatment drugs (remifentanil, alfentanil, isoflurane, or propofol) along with nitrous oxide and oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 microgram/kg over 30-60 s, followed by a constant infusion of 1.0 microgram.kg-1.min-1, alfentanil 100 micrograms/kg bolus followed by a constant infusion of 2.5 micrograms.kg-1.min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 micrograms.kg-1.min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those

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

    PubMed

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

    2016-01-01

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

  1. Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial.

    PubMed

    Levy, Robert M; Harvey, Richard L; Kissela, Brett M; Winstein, Carolee J; Lutsep, Helmi L; Parrish, Todd B; Cramer, Steven C; Venkatesan, Lalit

    2016-02-01

    This prospective, single-blinded, multicenter study assessed the safety and efficacy of electrical epidural motor cortex stimulation (EECS) in improving upper limb motor function of ischemic stroke patients with moderate to moderately severe hemiparesis. Patients ≥ 4 months poststroke were randomized 2:1 to an investigational (n = 104) or control (n = 60) group, respectively. Investigational patients were implanted (n = 94) with an epidural 6-contact lead perpendicular to the primary motor cortex and a pulse generator. Both groups underwent 6 weeks of rehabilitation, but EECS was delivered to investigational patients during rehabilitation. The primary efficacy endpoint (PE) was defined as attaining a minimum improvement of 4.5 points in the upper extremity Fugl-Meyer (UEFM) scale as well as 0.21 points in the Arm Motor Ability Test (AMAT) 4 weeks postrehabilitation. Follow-up assessments were performed 1, 4, 12, and 24 weeks postrehabilitation. Safety was evaluated by monitoring adverse events (AEs) that occurred between enrollment and the end of rehabilitation. Primary intent-to-treat analysis showed no group differences at 4 weeks, with PE being met by 32% and 29% of investigational and control patients, respectively (P = .36). Repeated-measures secondary analyses revealed no significant treatment group differences in mean UEFM or AMAT scores. However, post hoc comparisons showed that a greater proportion of investigational (39%) than control (15%) patients maintained or achieved PE (P = .003) at 24 weeks postrehabilitation. Investigational group mean AMAT scores also improved significantly (P < .05) when compared to the control group at 24 weeks postrehabilitation. Post hoc analyses also showed that 69% (n = 9/13) of the investigational patients who elicited movement thresholds during stimulation testing met PE at 4 weeks, and mean UEFM and AMAT scores was also significantly higher (P < .05) in this subgroup at the 4-, 12-, and 24-week assessments when

  2. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.

    PubMed

    Schleussner, Ekkehard; Kamin, Gabriele; Seliger, Gregor; Rogenhofer, Nina; Ebner, Susanne; Toth, Bettina; Schenk, Michael; Henes, Melanie; Bohlmann, Michael K; Fischer, Thorsten; Brosteanu, Oana; Bauersachs, Rupert; Petroff, David

    2015-05-05

    A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable. To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL. Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387). 14 university hospitals and perinatal care centers in Germany and Austria. 449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography. Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation. Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications. At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH). Placebo injections were not used, and neither trial staff nor patients were blinded. Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not

  3. A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

    PubMed

    Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

    2017-01-01

    In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  5. Variation in Institutional Review Board (IRB) Responses to a Standard Protocol for a Multicenter Randomized Controlled Surgical Trial

    PubMed Central

    Helfand, Brian T.; Mongiu, Anne K.; Roehrborn, Claus G.; Donnell, Robert F.; Bruskewitz, Reginald; Kaplan, Steven A.; Kusek, John W.; Coombs, Laura; McVary, Kevin T.

    2016-01-01

    Purpose The primary responsibility of Institutional Review Boards (IRBs) is to protect human research subjects and therefore ensure that studies are conducted in accordance with a standard set of ethical principles. A number of studies have compared the responses from IRBs in multicenter clinical trials involving medical therapies. To date, none have been conducted in trials investigating surgical interventions. The intent of this study was to investigate the consistency of the recommendations issued from one institutional IRB to another in the Minimally Invasive Surgical Therapies (MIST) for benign prostatic hyperplasia (BPH), a multicenter trial with a uniform consent and study protocol. Materials and Methods We obtained the IRB responses from six of the seven participating institutions after the initial submission of the MIST study protocol and classified the responses. We then re-distributed the approved protocols to an IRB at another participating institution and analyzed their review of these protocols. Results We found that both the number and types of responses required for IRB approval of an identical study protocol varied significantly among the participating institutions. We also found that IRB responses were inconsistent in the second review, although all protocols were ultimately approved. Conclusion We conclude that the current system of local IRB review in the context of a multicenter surgical trial is inefficient in the review process and may not provide expertise in overseeing surgical trials. Based on these results, a central surgical IRB may be needed to improve of the ethical review process in multicenter trials. PMID:19375101

  6. A Randomized Controlled Multicenter US Food and Drug Administration Trial of the Safety and Efficacy of the Minerva Endometrial Ablation System: One-Year Follow-Up Results.

    PubMed

    Laberge, Philippe; Garza-Leal, Jose; Fortin, Claude; Grainger, David; Johns, Delbert Alan; Adkins, Royce T; Presthus, James; Basinski, Cindy; Swarup, Monte; Gimpelson, Richard; Leyland, Nicholas; Thiel, John; Harris, Micah; Burnett, Pamela E; Ray, Gene F

    2017-01-01

    To assess the safety and effectiveness of the Minerva Endometrial Ablation System for the treatment of heavy menstrual bleeding in premenopausal women. Multicenter, randomized, controlled, international study (Canadian Task Force classification I). Thirteen academic and private medical centers. Premenopausal women (n = 153) suffering from heavy menstrual bleeding (PALM-COEIN: E, O). Patients were treated using the Minerva Endometrial Ablation System or rollerball ablation. At 1-year post-treatment, study success (alkaline hematin ≤80 mL) was observed in 93.1% of Minerva subjects and 80.4% of rollerball subjects with amenorrhea reported by 71.6% and 49% of subjects, respectively. The mean procedure times were 3.1 minutes for Minerva and 17.2 minutes for rollerball. There were no intraoperative adverse events and/or complications reported. The results of this multicenter randomized controlled trial demonstrate that at the 12-month follow-up, the Minerva procedure produces statistically significantly higher rates of success, amenorrhea, and patient satisfaction as well as a shorter procedure time when compared with the historic criterion standard of rollerball ablation. Safety results were excellent and similar for both procedures. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  7. Efficacy of NiTi Hand CAC 30 for jejunojejunostomy in gastric cancer surgery: results from a multicenter prospective randomized trial.

    PubMed

    Hur, Hoon; Kim, Hyung Ho; Hyung, Woo Jin; Cho, Gyu Seok; Kim, Wook; Ryo, Seung Wan; Han, Sang-Uk

    2011-06-01

    Although a novel technique for the performance of intestinal sutureless anastomosis using a compression device has recently been investigated, it has not yet received widespread acceptance. We performed a multicenter prospective randomized trial in order to determine the clinical efficacy of the NiTi Hand CAC 30, a type of compression anastomosis clip (CAC), for jejunojejunostomy in gastric cancer surgery. Forty-seven patients from 6 institutions, who were diagnosed with gastric adenocarcinoma, were enrolled; these patients were randomized to a CAC group and a hand-sewn (control) group. Three patients dropped out for various reasons, and results for 44 patients were finally analyzed. The CAC group consisted of 20 patients, and there were 24 patients in the control group. Anastomosis time, the primary endpoint of this trial, was shorter in the CAC group than in the control group (P < 0.001). However, total operation times (P = 0.055) did not differ. All reconstructions were completed by Roux-en-Y anastomosis, and the complication rates of the two groups did not differ (P = 0.908); however, jejunojejunostomy leakage occurred in two patients in the CAC group. Our prospective multicenter clinical trial showed that the use of the NiTi Hand CAC™ 30 for jejunojejunostomy in gastric cancer surgery was feasible and could reduce anastomosis time. However, considering that there were two cases of leakage, extended use of the NiTi Hand CAC™ 30 should be carefully applied.

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

    PubMed

    Nusselt, Thomas; Hofmann, Alexander; Wachtlin, Daniel; Gorbulev, Stanislav; Rommens, Pol Maria

    2014-03-08

    Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. ClinicalTrials.gov: NCT01828905.

  9. The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133(+) stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy.

    PubMed

    Noiseux, Nicolas; Mansour, Samer; Weisel, Richard; Stevens, Louis-Mathieu; Der Sarkissian, Shant; Tsang, Katherine; Crean, Andrew M; Larose, Eric; Li, Shu-Hong; Wintersperger, Bernd; Vu, Minh Quan; Prieto, Ignacio; Li, Ren-Ke; Roy, Denis Claude; Yau, Terrence M

    2016-12-01

    The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133(+) stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133(+), CD34(+), CD45(+) triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133(+) cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  10. Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, multicenter, Italian, comparative study versus zolmitriptan.

    PubMed

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

    2011-05-01

    Menstrually related migraine (MRM) is a particularly difficult-to-treat pain condition, associated with substantial disability. Aim of this study was to compare the efficacy and safety of frovatriptan and zolmitriptan in the treatment of MRM attacks, analyzing data from a multicenter, randomized, double blind, cross-over study. We analyzed the subset of 76 regularly menstruating women who participated in one head-to-head multicenter, randomized, double blind, cross-over clinical trial and who took the study drugs to treat MRM attacks. In a randomized sequence, each patient received frovatriptan 2.5 mg or zolmitriptan 2.5 mg: after treating three episodes of migraine in no more than 3 months with the first treatment, the patient had to switch to the other treatment. MRM was defined according to the criteria listed in the Appendix of the last Classification of Headache disorders of the International Headache Society. A total of 73 attacks, classified as MRM, were treated with frovatriptan and 65 with zolmitriptan. Rate of pain relief at 2 h was 52% for frovatriptan and 53% for zolmitriptan (p = NS), while rate of pain free at 2 h was 22 and 26% (p = NS), respectively. At 24 h, 74 and 83% of frovatriptan-treated and 69 and 82% of zolmitriptan-treated patients were pain free and had pain relief, respectively (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (15 vs. 22% zolmitriptan). Frovatriptan proved to be effective in the immediate treatment of MRM attacks, similarly to zolmitriptan, but showed lower recurrence rates, and thus a better sustained relief.

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

    PubMed

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

    2002-02-01

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

  12. Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

    PubMed

    Brzheskiy, Vladimir V; Efimova, Elena L; Vorontsova, Tatiana N; Alekseev, Vladimir N; Gusarevich, Olga G; Shaidurova, Ksenia N; Ryabtseva, Alla A; Andryukhina, Olga M; Kamenskikh, Tatiana G; Sumarokova, Elena S; Miljudin, Eugeny S; Egorov, Eugeny A; Lebedev, Oleg I; Surov, Alexander V; Korol, Andrii R; Nasinnyk, Illia O; Bezditko, Pavel A; Muzhychuk, Olena P; Vygodin, Vladimir A; Yani, Elena V; Savchenko, Alla Y; Karger, Elena M; Fedorkin, Oleg N; Mironov, Alexander N; Ostapenko, Victoria; Popeko, Natalia A; Skulachev, Vladimir P; Skulachev, Maxim V

    2015-12-01

    This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. Mitotech LLC.

  13. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study.

    PubMed

    Vinik, Aaron I; Perrot, Serge; Vinik, Etta J; Pazdera, Ladislav; Jacobs, Hélène; Stoker, Malcolm; Long, Stephen K; Snijder, Robert J; van der Stoep, Marjolijne; Ortega, Enrique; Katz, Nathaniel

    2016-12-06

    This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN). Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function. Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%). In

  14. Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study.

    PubMed

    Yamasaki, K; Nakagawa, H; Kubo, Y; Ootaki, K

    2017-03-01

    A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE. This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters. A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment-related. Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

  15. Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials.

    PubMed

    Emoto, Masanori; Oura, Tomonori; Matsui, Akiko; Kazama, Hirotaka; Iwamoto, Noriyuki

    2017-02-27

    The effects of incretin therapies on pancreatic safety are currently being evaluated. In 3 phase 3 clinical studies of once weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D), symptoms suggestive of acute pancreatitis as well as pancreatic enzymes were assessed and the risk of acute pancreatitis was evaluated. Patients who met any of the predefined criteria (clinical signs/symptoms of acute pancreatitis, confirmed amylase or lipase level ≥3 times the upper limit of normal [ULN], abdominal imaging of the pancreas) were adjudicated for acute pancreatitis by a blinded external committee. A total of 43 events in 40 patients (dulaglutide, 35/917 patients; liraglutide, 2/137 patients; insulin glargine, 2/180 patients; and placebo, 2/70 patients) were adjudicated (1 patient had events adjudicated during both placebo and dulaglutide treatment); 2 patients treated with dulaglutide had acute pancreatitis confirmed (2/917 [0.2%]; 2.651 patients/1,000 patient-years). One of these patients was diagnosed by the investigator with acute pancreatitis related to dulaglutide, but there was no typical abdominal pain. The event in the other patient occurred following an endoscopic ultrasound-guided fine needle aspiration. Transient increases in lipase ≥3×ULN were observed in 2% of patients in both the dulaglutide and liraglutide groups; the incidence in dulaglutide-treated patients was not significantly different from the incidences in liraglutide, placebo-, or insulin glargine-treated patients. Results of systematic assessments of pancreatic safety in 3 phase 3 studies for up to 52 weeks do not suggest an increased risk of acute pancreatitis in Japanese patients treated with dulaglutide.

  16. Rationale and study design of ViPS – variable pressure support for weaning from mechanical ventilation: study protocol for an international multicenter randomized controlled open trial

    PubMed Central

    2013-01-01

    Background In pressure support ventilation (PSV), a non-variable level of pressure support is delivered by the ventilator when triggered by the patient. In contrast, variable PSV delivers a level of pressure support that varies in a random fashion, introducing more physiological variability to the respiratory pattern. Experimental studies show that variable PSV improves gas exchange, reduces lung inflammation and the mean pressure support, compared to non-variable PSV. Thus, it can theoretically shorten weaning from the mechanical ventilator. Methods/design The ViPS (variable pressure support) trial is an international investigator-initiated multicenter randomized controlled open trial comparing variable vs. non-variable PSV. Adult patients on controlled mechanical ventilation for more than 24 hours who are ready to be weaned are eligible for the study. The randomization sequence is blocked per center and performed using a web-based platform. Patients are randomly assigned to one of the two groups: variable PSV or non-variable PSV. In non-variable PSV, breath-by-breath pressure support is kept constant and targeted to achieve a tidal volume of 6 to 8 ml/kg. In variable PSV, the mean pressure support level over a specific time period is targeted at the same mean tidal volume as non-variable PSV, but individual levels vary randomly breath-by-breath. The primary endpoint of the trial is the time to successful weaning, defined as the time from randomization to successful extubation. Discussion ViPS is the first randomized controlled trial investigating whether variable, compared to non-variable PSV, shortens the duration of weaning from mechanical ventilation in a mixed population of critically ill patients. This trial aims to determine the role of variable PSV in the intensive care unit. Trial registration clinicaltrials.gov NCT01769053 PMID:24176188

  17. Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection.

    PubMed

    Huang, David T; Angus, Derek C; Chang, Chung-Chou H; Doi, Yohei; Fine, Michael J; Kellum, John A; Peck-Palmer, Octavia M; Pike, Francis; Weissfeld, Lisa A; Yabes, Jonathan; Yealy, Donald M

    2017-08-29

    Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns. The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection. We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation. ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

  18. A multicenter randomized controlled trial for bright light therapy in adults with intellectual disabilities and depression: Study protocol and obstacle management.

    PubMed

    Hamers, Pauline C M; Evenhuis, Heleen M; Hermans, Heidi

    2017-01-01

    Due to the limited cognitive and communicative abilities of adults with intellectual disabilities (ID), current treatment options for depression are often limited to lifestyle changes and pharmacological treatment. Bright light therapy (BLT) is an effective intervention for both seasonal and non-seasonal depression in the general population. BLT is an inexpensive, easy to carry out intervention with minimal side effects. However, knowledge on its anti-depressant effect in adults with ID is lacking. Obstacles in realizing a controlled intervention study in this particular study population may have contributed to this lack. To study the effect of BLT on depression in this population, it is necessary to successfully execute a multicenter randomized controlled trial (RCT). Therefore, the study protocol and the management of anticipated obstacles regarding this trial are presented.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial.

    PubMed

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

    2015-06-01

    Investigators are urgently searching for options to treat negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. Meta-analyses based on small proof-of-principle trials suggest efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of negative symptoms and call for adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex for the treatment of predominant negative symptoms in schizophrenia. A multicenter randomized, sham-controlled, rater-blinded and patient-blinded trial was conducted from 2007-2011. Investigators randomly assigned 175 patients with schizophrenia with predominant negative symptoms and a high-degree of illness severity into two treatment groups. After a 2-week pretreatment phase, 76 patients were treated with 10-Hz rTMS applied 5 days per week for 3 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81 patients were subjected to sham rTMS applied similarly. There was no statistically significant difference in improvement in negative symptoms between the two groups at day 21 (p = .53, effect size = .09) or subsequently through day 105. Also, symptoms of depression and cognitive function showed no differences in change between groups. There was a small, but statistically significant, improvement in positive symptoms in the active rTMS group (p = .047, effect size = .30), limited to day 21. Application of active 10-Hz rTMS to the left dorsolateral prefrontal cortex was well tolerated but was not superior compared with sham rTMS in improving negative symptoms; this is in contrast to findings from three meta-analyses. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-05-01

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

  3. Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings.

    PubMed

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

    2015-09-01

    Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. The Kids-DOTT trial is a multicenter RCT investigating non-inferiority of a 6-week (shortened) versus 3-month (conventional) duration of anticoagulation in patients aged < 21 years with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded-endpoint, parallel-cohort RCT design. No eligibility violations or randomization errors occurred. Of the enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in prespecified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Interobserver agreement between local and blinded central determination of venous occlusion by imaging at 6 weeks after diagnosis was strong (k-statistic = 0.75; 95% confidence interval [CI] 0.48-1.0). The primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (95% CI 0.03-7.4%). The P/F phase of the Kids-DOTT trial has demonstrated the validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention and endpoint rates to inform the fully powered RCT. © 2015 International Society on Thrombosis and Haemostasis.

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

    PubMed Central

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

    2015-01-01

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

  5. Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial.

    PubMed

    Onland, Wes; Offringa, Martin; Cools, Filip; De Jaegere, Anne P; Rademaker, Karin; Blom, Henry; Cavatorta, Eric; Debeer, Anne; Dijk, Peter H; van Heijst, Arno F; Kramer, Boris W; Kroon, Andre A; Mohns, Thilo; van Straaten, Henrica L; te Pas, Arjan B; Theyskens, Claire; van Weissenbruch, Mirjam M; van Kaam, Anton H

    2011-11-09

    Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.

  6. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    PubMed

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

  7. Multi-Center Randomized Controlled Trial on the Effect of Triclosan-Coated Sutures on Surgical Site Infection after Colorectal Surgery.

    PubMed

    Mattavelli, Ilaria; Rebora, Paola; Doglietto, Gianbattista; Dionigi, Paolo; Dominioni, Lorenzo; Luperto, Margherita; La Porta, Angela; Garancini, Mattia; Nespoli, Luca; Alfieri, Sergio; Menghi, Roberta; Dominioni, Tommaso; Cobianchi, Lorenzo; Rotolo, Nicola; Soldini, Gabriele; Valsecchi, Maria Grazia; Chiarelli, Marco; Nespoli, Angelo; Gianotti, Luca

    2015-06-01

    Surgical site infection (SSI) remains the most frequent complication after colorectal resection. The role of sutures coated with antimicrobial agents such as triclosan in reducing SSI is controversial. This was a multi-center randomized controlled trial with patients and outcome assessors blinded to treatment. The study was performed in four university referral hospitals. Patient candidates for elective colorectal resection were assigned randomly to abdominal incision closure with polyglactin 910 triclosan-coated sutures (triclosan group) or with polyglactin 910 without triclosan (control group). The primary outcome was the rate of SSI within 30 d after hospital discharge. The secondary outcomes were the overall rate of incision complications and length of hospital stay (LOS). Two hundred eighty-one patients (triclosan group: 140; control group: 141) were analyzed after randomization. The rate of SSI was 12.9% (18/140) in the triclosan group versus 10.6% (15/141) in the control group (odds ratio: 1.24; 95% confidence interval: 0.60-2.57; p=0.564). Secondary outcome analysis showed an overall incision complication rate of 38.3% in the control group versus 45.7% in the triclosan group (odds ratio: 1.36; 95% confidence interval: 0.84-2.18; p=0.208). Median LOS was 11 d in both groups (p=0.55). Surgical sutures coated with triclosan do not appear to be effective in reducing the rate of SSI.

  8. Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

    PubMed Central

    2011-01-01

    Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

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

    PubMed Central

    2014-01-01

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

  10. A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.

    PubMed

    Semler, Matthew W; Janz, David R; Russell, Derek W; Casey, Jonathan D; Lentz, Robert J; Zouk, Aline N; deBoisblanc, Bennett P; Santanilla, Jairo I; Khan, Yasin A; Joffe, Aaron M; Stigler, William S; Rice, Todd W

    2017-10-01

    Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  11. [Sucrose gel for treatment of bacterial vaginosis: a randomized, double-blind, multi-center, parallel-group, phase III clinical trial].

    PubMed

    Xiao, Bing-bing; Zhang, Dai; Chen, Rui; Shi, Hui-rong; Xin, Xiao-ran; Wang, Hui-lan; Pang, Yi-cun; Zhu, Sai-nan; Yao, Chen; Liao, Qin-ping

    2015-12-18

    To evaluate the cure effectiveness and safety of sucrose gel in the treatment of bacterial vaginosis through a multi-center, randomized, double-blind, parallel controlled clinical study. A clinical research method of multi-center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 533 patients with bacterial vaginosis were randomly divided into two groups, which included 214 cases in the control group (5.0 g metronidazole gel) and 319 cases in the trial group (5.0 g sucrose gel ). The patients were treated with different medication according to the group where they were. All the cases in these two groups were treated with drugs vaginally twice in a day, morning and evening separately, for 5 days. The curative effect and safety evaluation were assessed from 7 to 10 days and 21 to 30 days after treatment respectively. The efficacy of the comprehensive clinical treatment showed that the cure rate of metronidazole gel group and sucrose gel group were 70.53% and 80.83% respectively 7 to 10 days after treatment. The recovery rate of Nugent score for vaginal smear were 71.50% and 81.15% respectively. The differences in the efficacy between these two groups were significant statistically (P<0.05). However, the cure rates of metronidazole gel group and sucrose gel group were 63.29% and 61.98% respectively 21 to 30 days after treatment. No statistically significant difference (P>0.05) could be found in the cure rates of the two groups. The clinical comprehensive efficacy and recovery of vaginal bacteria of sucrose gel group in the treatment of bacterial vaginosis were obviously superior to those of metronidazole gel 7 to 10 days after treatment. The susucrose gel could improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina according to the Nugent score. The curative efficacy of sucrose gel was

  12. Treatment of uterine prolapse stage 2 or higher: a randomized multicenter trial comparing sacrospinous fixation with vaginal hysterectomy (SAVE U trial).

    PubMed

    Detollenaere, Renée J; den Boon, Jan; Stekelenburg, Jelle; Alhafidh, Akeel H H; Hakvoort, Robert A; Vierhout, Mark E; van Eijndhoven, Hugo W F

    2011-02-15

    Pelvic organ prolapse is a common health problem, affecting up to 40% of parous women over 50 years old, with significant negative influence on quality of life. Vaginal hysterectomy is currently the leading treatment method for patients with symptomatic uterine prolapse. Several studies have shown that sacrospinous fixation in case of uterine prolapse is a safe and effective alternative to vaginal hysterectomy. However, no large randomized trials with long-term follow-up have been performed to compare efficacy and quality of life between both techniques.The SAVE U trial is designed to compare sacrospinous fixation with vaginal hysterectomy in the treatment of uterine prolapse stage 2 or higher in terms of prolapse recurrence, quality of life, complications, hospital stay, post-operative recovery and sexual functioning. The SAVE U trial is a randomized controlled multi-center non-inferiority trial. The study compares sacrospinous fixation with vaginal hysterectomy in women with uterine prolapse stage 2 or higher. The primary outcome measure is recurrence of uterine prolapse defined as: uterine descent stage 2 or more assessed by pelvic organ prolapse quantification examination and prolapse complaints and/or redo surgery at 12 months follow-up. Secondary outcomes are subjective improvement in quality of life measured by generic (Short Form 36 and Euroqol 5D) and disease-specific (Urogenital Distress Inventory, Defecatory Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments, complications following surgery, hospital stay, post-operative recovery and sexual functioning (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and considering an upper-limit of 7% to be non-inferior (beta 0.2 and one sided alpha 0.025), 104 patients are needed per group. The SAVE U trial is a randomized multicenter trial that will

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

    PubMed

    de Zwaan, Martina; Herpertz, Stephan; Zipfel, Stephan; Tuschen-Caffier, Brunna; Friederich, Hans-Christoph; Schmidt, Frauke; Gefeller, Olaf; Mayr, Andreas; Lam, Tony; Schade-Brittinger, Carmen; Hilbert, Anja

    2012-11-21

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

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

    PubMed Central

    2012-01-01

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

  15. Effect and Predictive Elements for 52 Weeks' Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B.

    PubMed

    Zhu, Xiao-Feng; Lu, Li-Xia; Wang, Ying; Xu, Kong-Wen; Li, Da-Jiang; Zhu, Xia; Liu, Li; Liu, Cong; Wang, Jin-Rong; Tang, Hong; Wang, Li-Chun

    2011-12-01

    Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses. To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment. A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24. The reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower

  16. Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study.

    PubMed

    Maschmeyer, G; Heinz, W J; Hertenstein, B; Horst, H-A; Requadt, C; Wagner, T; Cornely, O A; Löffler, J; Ruhnke, M

    2013-05-01

    Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n = 81) or deferred (n = 66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p = 0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset.

  17. Effect of a Growing-up Milk Containing Synbiotics on Immune Function and Growth in Children: A Cluster Randomized, Multicenter, Double-blind, Placebo Controlled Study

    PubMed Central

    Xuan, Ninh Nguyen; Wang, Dantong; Grathwohl, Dominik; Lan, Phuong Nguyen Thi; Kim, Hoa Vu Thi; Goyer, Amélie; Benyacoub, Jalil

    2013-01-01

    Common infectious diseases, such as diarrhea, are still the major cause of death in children under 5-years-old, particularly in developing countries. It is known that there is a close relationship between nutrition and immune function. To evaluate the effect of a growing-up milk containing synbiotics on immune function and child growth, we conducted a cluster randomized, multicenter, double-blind, placebo controlled clinical trial in children between 18 and 36 months of age in Vietnam. Eligible children from eight and seven kindergartens were randomly assigned to receive test and isocaloric/ isoproteic control milk, respectively, for 5 months. We found that the blood immunoglobulin A (IgA) level and growth parameters were increased in the test group. Compared to the control group, there was also a trend of decreased vitamin A deficiency and fewer adverse events in the test group. These data suggest that a growing-up milk containing synbiotics may be useful in supporting immune function and promoting growth in children. PMID:24353451

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

    PubMed Central

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

    2016-01-01

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

  19. Postoperative Analgesia after Laparoscopic Ovarian Cyst Resection: Double-blind Multicenter Randomized Control Trial Comparing Intraperitoneal Nebulization and Peritoneal Instillation of Ropivacaine.

    PubMed

    Scalia Catenacci, Stefano; Lovisari, Federica; Peng, Shuo; Allegri, Massimo; Somaini, Marta; Ghislanzoni, Luca; Greco, Massimiliano; Rossini, Valeria; D'Andrea, Luca; Buda, Alessandro; Signorelli, Mauro; Pellegrino, Antonio; Sportiello, Debora; Bugada, Dario; Ingelmo, Pablo M

    2015-01-01

    To compare the effects of local anesthetic intraperitoneal nebulization with intraperitoneal instillation during laparoscopic ovarian cystectomy on postoperative morphine consumption and pain. Multicenter, randomized, case-control trial. Canadian Task Force Classification I. University hospitals in Italy. One hundred forty patients scheduled for laparoscopic ovarian cystectomy. Patients were randomized to receive either nebulization of ropivacaine 150 mg before surgery or instillation of ropivacaine 150 mg before surgery. Nebulization was performed using the Aeroneb Pro device (Aerogen, Galway, Ireland). One hundred forty patients were enrolled, and 123 completed the study. There was no difference between the 2 groups in average morphine consumption (7.3 ± 7.5 mg in the nebulization group vs 9.2 ± 7.2 mg in the instillation group; p = .17). Eighty-two percent of patients in the nebulization group required morphine compared with 96% in the instillation group (p < .05). Patients receiving nebulization had a lower dynamic Numeric Ranking Scale compared with those in the instillation group in the postanesthesia care unit postanesthesia care unit and 4 hours after surgery (p < .05). Ten patients (15%) in the nebulization group experienced shivering in the postanesthesia care unit compared with 2 patients (4%) in the instillation group (p = .035). Nebulization of ropivacaine prevents the use of morphine in a significant proportion of patients, reduced postoperative pain during the first hours after surgery, and was associated with a higher incidence of postoperative shivering when compared with instillation. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2013-11-20

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

  1. A randomized, double-masked, multicenter comparison of the safety of continuous intrathecal labor analgesia using a 28-gauge catheter versus continuous epidural labor analgesia.

    PubMed

    Arkoosh, Valerie A; Palmer, Craig M; Yun, Esther M; Sharma, Shiv K; Bates, James N; Wissler, Richard N; Buxbaum, Jodie L; Nogami, Wallace M; Gracely, Edward J

    2008-02-01

    Continuous intrathecal labor analgesia produces rapid analgesia or anesthesia and allows substantial flexibility in medication choice. The US Food and Drug Administration, in 1992, removed intrathecal microcatheters (27-32 gauge) from clinical use after reports of neurologic injury in nonobstetric patients. This study examined the safety and efficacy of a 28-gauge intrathecal catheter for labor analgesia in a prospective, randomized, multicenter trial. Laboring patients were randomly assigned to continuous intrathecal analgesia with a 28-gauge catheter (n = 329) or continuous epidural analgesia with a 20-gauge catheter (n = 100), using bupivacaine and sufentanil. The primary outcome was the incidence of neurologic complications, as determined by masked neurologic examinations at 24 and 48 h postpartum, plus telephone follow-up at 7-10 and 30 days after delivery. The secondary outcomes included adequacy of labor analgesia, maternal satisfaction, and neonatal status. No patient had a permanent neurologic change. The continuous intrathecal analgesia patients had better early analgesia, less motor blockade, more pruritus, and higher maternal satisfaction with pain relief at 24 h postpartum. The intrathecal catheter was significantly more difficult to remove. There were no significant differences between the two groups in neonatal status, post-dural puncture headache, hemodynamic stability, or obstetric outcomes. Providing intrathecal labor analgesia with sufentanil and bupivacaine via a 28-gauge catheter has an incidence of neurologic complication less than 1%, and produces better initial pain relief and higher maternal satisfaction, but is associated with more technical difficulties and catheter failures compared with epidural analgesia.

  2. Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

    PubMed Central

    Lee, Kang Nyeong; Lee, Oh Young; Choi, Myung-Gyu; Choi, Seok Reyol; Lee, Dong Ho; Lee, Yong Chan; Kim, Tae Nyeun; Choi, Suck Chei; Rew, Jong Sun

    2011-01-01

    In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects. PMID:21860559

  3. A prospective, multicenter, randomized, double-blind study comparing ertapenem and ceftriaxone followed by appropriate oral therapy for complicated urinary tract infections in adults.

    PubMed

    Jimenez-Cruz, Fernando; Jasovich, Abel; Cajigas, Jaime; Jiang, Qi; Imbeault, Danielle; Woods, Gail L; Gesser, Richard M

    2002-07-01

    To compare the efficacy and safety of ertapenem, a new once-daily parenteral beta-lactam, with that of ceftriaxone for the initial empiric treatment of adults with complicated urinary tract infections (cUTIs). In a multicenter, prospective, double-blind study, patients with cUTIs were stratified as to whether they had acute pyelonephritis or other cUTIs (without pyelonephritis) and randomized to receive ertapenem, 1 g once a day, or ceftriaxone, 1 g once a day. After 3 days, patients with a satisfactory clinical response could be switched to an oral antimicrobial agent. Of 258 randomized patients, 97 (55.4%) in the ertapenem group and 53 (63.9%) in the ceftriaxone group were evaluated microbiologically. Almost all patients in each treatment group were switched to oral therapy. The mean duration of therapy was similar in both treatment groups: parenteral, approximately 4 days; total, approximately 13 days. The most common pathogen was Escherichia coli. At the primary efficacy endpoint, 5 to 9 days after treatment, 85.6% of patients who received ertapenem and 84.9% who received ceftriaxone had a favorable microbiologic response, indicating that the two treatment groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of cUTI in adults, was generally well tolerated, and had a similar safety profile.

  4. Effect of a Growing-up Milk Containing Synbiotics on Immune Function and Growth in Children: A Cluster Randomized, Multicenter, Double-blind, Placebo Controlled Study.

    PubMed

    Xuan, Ninh Nguyen; Wang, Dantong; Grathwohl, Dominik; Lan, Phuong Nguyen Thi; Kim, Hoa Vu Thi; Goyer, Amélie; Benyacoub, Jalil

    2013-01-01

    Common infectious diseases, such as diarrhea, are still the major cause of death in children under 5-years-old, particularly in developing countries. It is known that there is a close relationship between nutrition and immune function. To evaluate the effect of a growing-up milk containing synbiotics on immune function and child growth, we conducted a cluster randomized, multicenter, double-blind, placebo controlled clinical trial in children between 18 and 36 months of age in Vietnam. Eligible children from eight and seven kindergartens were randomly assigned to receive test and isocaloric/ isoproteic control milk, respectively, for 5 months. We found that the blood immunoglobulin A (IgA) level and growth parameters were increased in the test group. Compared to the control group, there was also a trend of decreased vitamin A deficiency and fewer adverse events in the test group. These data suggest that a growing-up milk containing synbiotics may be useful in supporting immune function and promoting growth in children.

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

    PubMed Central

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

    2015-01-01

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

  6. Prevention of NSAID-associated gastroduodenal injury in healthy volunteers-a randomized, double-blind, multicenter study comparing DA-9601 with misoprostol.

    PubMed

    Lee, Kang Nyeong; Lee, Oh Young; Choi, Myung-Gyu; Choi, Seok Reyol; Lee, Dong Ho; Lee, Yong Chan; Kim, Tae Nyeun; Choi, Suck Chei; Rew, Jong Sun; Seol, Sang-Yong

    2011-08-01

    In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

  7. Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial

    PubMed Central

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

    2017-01-01

    Background Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. Aim The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. Materials and methods The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). Results After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05–3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. Conclusion In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. Trial registration http://controlled-trials.com ISRCTN44212338. PMID:28493922

  8. Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial.

    PubMed

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

    2017-01-01

    Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. http://controlled-trials.com ISRCTN44212338.

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

    PubMed Central

    2012-01-01

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

  10. One-Year Multicenter Double-Blind Randomized Clinical Trial on the Efficacy and Safety of Generic Cyclosporine (Iminoral) in De Novo Kidney Transplant Recipients.

    PubMed

    Khatami, Seyyed Mohammad Reza; Taheri, Shahram; Azmandian, Jalal; Sagheb, Mohammad Mahdi; Nazemian, Fatemeh; Razeghi, Effat; Shahidi, Sharzad; Sadri, Farzaneh; Shamshiri, Ahmad Reza; Sayyah, Mohammad

    2015-06-01

    Iminoral is the generic microemulsion of cyclosporine. We performed a randomized double-blind multicenter trial to evaluate its efficacy and safety compared with the innovator medication Neoral for preventing acute rejection episodes in adult patients during the first year after renal transplant. We used 221 de novo renal transplant recipients from 6 transplant centers in Iran enrolled between April 2008, and January 2010. They were randomized to receive either Iminoral or Neoral as the calcineurin inhibitor component of the immunosuppressive regimen in addition to mycophenolate mofetil and oral corticosteroids. They were followed-up for 1 year. The primary endpoint was the rate of acute allograft rejection. Secondary endpoints consisted of 1-year graft survival rates, daily dosages of cyclosporine, trough and C2 cyclosporine blood level, serum creatinine levels, patient death rates, discontinuing the study drug, tolerability, and adverse events. The risk of acute rejection episode during the first month after transplant was 9% for Iminoral and 10% for Neoral; these declined to 4% and 2% during next 11 months. One-year graft survival rate was 0.86 for both groups. Renal function stabilized during the first month. Declination of the creatinine levels was similar between the 2 groups and reached a stable value of 114.9 μmol/L five months after the transplant. The frequency of clinical complications was similar between the groups. Iminoral is safe and effective when used in de novo kidney transplant patients as an immunosuppressive medication.

  11. eEduHeart I: A Multicenter, Randomized, Controlled Trial Investigating the Effectiveness of a Cardiac Web-Based eLearning Platform - Rationale and Study Design.

    PubMed

    Frederix, Ines; Vandenberk, Thijs; Janssen, Leen; Geurden, Anne; Vandervoort, Pieter; Dendale, Paul

    2017-01-01

    Cardiac telerehabilitation includes, in its most comprehensive format, telemonitoring, telecoaching, social interaction, and eLearning. The specific role of eLearning, however, was seldom assessed. The aim of eEduHeart I is to investigate the medium-term effectiveness of the addition of a cardiac web-based eLearing platform to conventional cardiac care. In this prospective, multicenter randomized, controlled trial, 1,000 patients with coronary artery disease will be randomized 1:1 to an intervention group (receiving 1-month unrestricted access to the cardiac eLearning platform in addition to conventional cardiac care) or to conventional cardiac care alone. The primary endpoint is health-related quality of life, assessed by the HeartQoL questionnaire at the 1- and 3-month follow-ups. Secondary endpoints include pathology-specific knowledge and self-reported eLearning platform user experience. Data on the eLearning platform usage will be gathered through web logging during the study period. eEduHeart I will be one of the first studies to report on the added value of eLearning. If the intervention is proven effective, current cardiac telerehabilitation programs can be augmented by including eLearning, too. The platform can then be used as a model for other chronic diseases in which patient education plays a key role. © 2016 S. Karger AG, Basel.

  12. Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial

    PubMed Central

    von Koch, Lena

    2016-01-01

    Background. Balance and walking impairments are frequent in people with multiple sclerosis (MS). Objective. The aim was to investigate the effects of a group-based balance exercise program targeting core stability, dual tasking, and sensory strategies (CoDuSe) on balance, postural sway, walking, perceived walking limitations, and balance confidence. Design. A single-blinded randomized multicenter trial. No intervention was given to controls. Participants. People with MS able to walk 100 meters but unable to maintain tandem stance ≥30 seconds. Eighty-seven participants were randomized to intervention or control. Intervention. The 60-minute CoDuSe group program, twice weekly for seven weeks, supervised by physical therapists. Measurements. Primary outcome was dynamic balance (Berg Balance Scale (BBS)). Secondary outcomes were postural sway, walking (Timed-Up and Go test; Functional Gait Assessment (FGA)), MS Walking Scale, and Activities-specific Balance Confidence (ABC) Scale. Assessments were performed before and after (week 8) the intervention. Results. 73 participants fulfilled the study. There were significant differences between the intervention and the control groups in change in the BBS and in the secondary measures: postural sway with eyes open, FGA, MS Walking Scale, and ABC scale in favor of the intervention. Conclusions. The seven-week CoDuSe program improved dynamic balance more than no intervention. PMID:28042485

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

    PubMed

    Watanabe, Shinichi; Kishida, Hiroshi; Okubo, Akihiro

    2017-03-23

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

  14. Oats in the Diet of Children with Celiac Disease: Preliminary Results of a Double-Blind, Randomized, Placebo-Controlled Multicenter Italian Study

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-02-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. © 2013 Wiley Periodicals, Inc.

  16. Effectiveness and Safety of Electroacupuncture on Poststroke Urinary Incontinence: Study Protocol of a Pilot Multicentered, Randomized, Parallel, Sham-Controlled Trial

    PubMed Central

    2016-01-01

    This pilot multicentered, randomized, parallel, sham-controlled trial is intended to evaluate the effectiveness and safety of electroacupuncture therapy for poststroke patients with urinary incontinence. Forty stroke survivors aged >19 years will be recruited in 2 hospitals in the Republic of Korea. Patients who experienced stroke within 2 years and satisfy criteria of urinary frequencies ≥2 with either 3 to 4 points on the Patient Perception of Intensity of Urgency Scale or 13 points or more on the Korean version of the International Prostate Symptom Scale (K-IPSS) will be identified, along with other eligibility criteria. Patients will be randomly allocated to either a treatment or control group to receive 10 sessions of electroacupuncture or sham therapies, respectively. Patients and outcome assessors will be blinded. The primary outcome is the change of Total Urgency and Frequency Score between the baseline and the trial endpoint. The K-IPSS, the International Consultation on Incontinence Questionnaire for Urinary Incontinence Short Form, and the Lower Urinary Tract Symptoms Outcome Score will be evaluated for effectiveness assessment. Adverse events will be reported after every session. The Blinding Index will also be calculated. Data will be statistically analyzed with 0.05 significance levels by 2-sided testing. PMID:28042304

  17. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

    PubMed

    Fermand, J P; Ravaud, P; Chevret, S; Divine, M; Leblond, V; Belanger, C; Macro, M; Pertuiset, E; Dreyfus, F; Mariette, X; Boccacio, C; Brouet, J C

    1998-11-01

    Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

  18. Costs and resource use following defunctioning stoma in low anterior resection for cancer - A long-term analysis of a randomized multicenter trial.

    PubMed

    Floodeen, H; Hallböök, O; Hagberg, L A; Matthiessen, P

    2017-02-01

    Defunctioning stoma in low anterior resection (LAR) for rectal cancer can prevent major complications, but overall cost-effectiveness for the healthcare provider is unknown. This study compared inpatient healthcare resources and costs within 5 years of LAR between two randomized groups of patients undergoing LAR with and without defunctioning stoma. Five-year follow-up of a randomized, multicenter trial on LAR (NCT 00636948) with (stoma; n = 116) or without (no stoma; n = 118) defunctioning stoma comparing inpatient healthcare resources and costs. Unplanned stoma formation, days with stoma, length of hospital stay, reoperations, and total associated inpatient costs were analyzed. Average costs were € 21.663 per patient with defunctioning stoma and € 15.922 per patient without defunctioning stoma within 5 years of LAR, resulting in an average cost-saving of € 5.741. There was no difference between groups regarding the total number of days with any stoma (stoma = 33 398 vs. no stoma = 34 068). The total number of unplanned reoperations were 70 (no stoma) and 32 (stoma); p < 0.001. In the group randomized to no stoma at LAR, 30.5% (36/118) required an unplanned stoma later. Randomization to defunctioning stoma in LAR was more expensive than no stoma, despite the cost-savings associated with a reduced frequency of anastomotic leakage. Both groups required the same total number of days with a stoma within five years of LAR. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  19. Randomized multicenter study of multiple plastic stents vs. covered self-expandable metallic stent in the treatment of biliary stricture in chronic pancreatitis.

    PubMed

    Haapamäki, Carola; Kylänpää, Leena; Udd, Marianne; Lindström, Outi; Grönroos, Juha; Saarela, Arto; Mustonen, Harri; Halttunen, Jorma

    2015-07-01

    The use of covered self-expandable metallic stents (cSEMS) in benign biliary indications is evolving. The aim of the study was to assess the safety and feasibility of cSEMS compared with multiple plastic stents in the treatment of benign biliary stricture (BBS) caused by chronic pancreatitis. This was a prospective, multicenter, randomized study of 60 patients with BBS caused by chronic pancreatitis. All patients received an initial plastic stent before randomization. At randomization, the stent was replaced either with a single cSEMS or three plastic stents. After 3 months, the position of the cSEMS was checked or another three plastic stents were added. At 6 months after randomization, all stents were removed. Clinical follow-up including abdominal ultrasound and laboratory tests were performed at 6 months and 2 years after stent removal. Two patients dropped out of the cSEMS group before stent removal. In April 2014, the median follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one late recurrence in the plastic stent group 50 months after stent removal. Stent migration occurred three times (10 %) in the plastic stent group and twice in the cSEMS group (7 %; P = 1.000). A 6-month treatment with either six 10-Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of biliary stricture caused by chronic pancreatitis.Study registered at ClinicalTrials.gov (NCT01085747). © Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed Central

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

    2011-01-01

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

  1. Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study)

    PubMed Central

    2013-01-01

    Background Although results of case series support the use of spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain, no confirmatory randomized controlled trial has been undertaken in this patient group to date. PROMISE is a multicenter, prospective, randomized, open-label, parallel-group study designed to compare the clinical effectiveness of spinal cord stimulation plus optimal medical management with optimal medical management alone in patients with failed back surgery syndrome and predominant low back pain. Method/Design Patients will be recruited in approximately 30 centers across Canada, Europe, and the United States. Eligible patients with low back pain exceeding leg pain and an average Numeric Pain Rating Scale score ≥5 for low back pain will be randomized 1:1 to spinal cord stimulation plus optimal medical management or to optimal medical management alone. The investigators will tailor individual optimal medical management treatment plans to their patients. Excluded from study treatments are intrathecal drug delivery, peripheral nerve stimulation, back surgery related to the original back pain complaint, and experimental therapies. Patients randomized to the spinal cord stimulation group will undergo trial stimulation, and if they achieve adequate low back pain relief a neurostimulation system using the Specify® 5-6-5 multi-column lead (Medtronic Inc., Minneapolis, MN, USA) will be implanted to capture low back pain preferentially in these patients. Outcome assessment will occur at baseline (pre-randomization) and at 1, 3, 6, 9, 12, 18, and 24 months post randomization. After the 6-month visit, patients can change treatment to that received by the other randomized group. The primary outcome is the proportion of patients with ≥50% reduction in low back pain at the 6-month visit. Additional outcomes include changes in low back and leg pain, functional disability, health-related quality of life, return to work

  2. Effectiveness of the head CT choice decision aid in parents of children with minor head trauma: study protocol for a multicenter randomized trial.

    PubMed

    Hess, Erik P; Wyatt, Kirk D; Kharbanda, Anupam B; Louie, Jeffrey P; Dayan, Peter S; Tzimenatos, Leah; Wootton-Gorges, Sandra L; Homme, James L; Pencille R N, Laurie; LeBlanc, Annie; Westphal, Jessica J; Shepel, Kathy; Shah, Nilay D; Branda, Megan; Herrin, Jeph; Montori, Victor M; Kuppermann, Nathan

    2014-06-25

    Blunt head trauma is a common cause of death and disability in children worldwide. Cranial computed tomography (CT), the reference standard for the diagnosis of traumatic brain injury (TBI), exposes children to ionizing radiation which has been linked to the development of brain tumors, leukemia, and other cancers. We describe the methods used to develop and test the effectiveness of a decision aid to facilitate shared decision-making with parents regarding whether to obtain a head CT scan or to further observe their child at home. This is a protocol for a multicenter clinician-level parallel randomized trial to compare an intervention group receiving a decision aid, 'Head CT Choice', to a control group receiving usual care. The trial will be conducted at five diverse emergency departments (EDs) in Minnesota and California. Clinicians will be randomized to decision aid or usual care. Parents visiting the ED with children who are less than 18-years-old, have experienced blunt head trauma within 24 hours, and have one or two risk factors for clinically-important TBI (ciTBI) from the Pediatric Emergency Care Applied Research Network head injury clinical prediction rules will be eligible for enrollment. We will measure the effect of Head CT Choice on: (1) parent knowledge regarding their child's risk of ciTBI, the available diagnostic options, and the risks of radiation exposure associated with a cranial CT scan (primary outcome); (2) parent engagement in the decision-making process; (3) the degree of conflict parents experience related to feeling uninformed; (4) patient and clinician satisfaction with the decision made; (5) the rate of ciTBI at seven days; (6) the proportion of patients in whom a cranial CT scan is obtained; and (7) seven-day healthcare utilization. To capture these outcomes, we will administer parent and clinician surveys immediately after each clinical encounter, obtain video recordings of parent-clinician discussions, administer parent healthcare

  3. Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo-controlled multi-center trial

    PubMed Central

    Lu, Lun-Gen; Zeng, Min-De; Mao, Yi-Min; Li, Ji-Qiang; Wan, Mo-Bin; Li, Cheng-Zhong; Chen, Cheng-Wei; Fu, Qing-Chun; Wang, Ji-Yao; She, Wei-Min; Cai, Xiong; Ye, Jun; Zhou, Xia-Qiu; Wang, Hui; Wu, Shan-Ming; Tang, Mei-Fang; Zhu, Jin-Shui; Chen, Wei-Xiong; Zhang, Hui-Quan

    2003-01-01

    AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 wk, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B. PMID:14606080

  4. A randomized controlled multicenter trial on the multimodal treatment of adult attention-deficit hyperactivity disorder: enrollment and characteristics of the study sample.

    PubMed

    Philipsen, Alexandra; Graf, Erika; Jans, Thomas; Matthies, Swantje; Borel, Patricia; Colla, Michael; Gentschow, Laura; Langner, Daina; Jacob, Christian; Groß-Lesch, Silke; Sobanski, Esther; Alm, Barbara; Schumacher-Stien, Martina; Roesler, Michael; Retz, Wolfgang; Retz-Junginger, Petra; Kis, Bernhard; Abdel-Hamid, Mona; Heinrich, Viola; Huss, Michael; Kornmann, Catherine; Bürger, Arne; van Elst, Ludger Tebartz; Berger, Mathias

    2014-03-01

    Adult ADHD is a frequent psychiatric disorder affecting relevant aspects of an individual's life. The aim of our study group was to carry out the first randomized controlled multicenter study to evaluate the effects of psychotherapy compared to clinical management in combination with psychopharmacological treatment with methylphenidate (MPH) or placebo (Plac) in a factorial four-arm design. Here, we present the enrollment procedure and description of adult ADHD patients recruited for the trial. Four hundred and thirty-three adult patients with ADHD were randomized at seven study sites in Germany to four treatment conditions: manualized dialectical-behavioral-therapy-based group psychotherapy (GPT) plus MPH or Plac, or clinical management (CM) including supportive counseling plus MPH or Plac with weekly sessions in the first 12 weeks and monthly sessions thereafter. Assessment for eligibility included standardized scales and instruments. After prescreening of 1,480 patients, 518 were evaluated for trial participation and 433 were randomized. The main reasons for prescreening failure were lack of interest in participating (n = 205), difficulties in meeting the time and effort requirements for participation (n = 186), and contraindications for psychopharmacological treatment with MPH (n = 194). The full analysis set (FAS) comprised 419 adult ADHD patients (mean age 35.2 years, males/females 1:1). Fifty-seven percent of the patients suffered from the combined ADHD subtype. Prevalence of at least one current or lifetime axis-I comorbidity was 66 %. Axis-II comorbidity rates was 18 % (patients with comorbid borderline and antisocial personality disorders were excluded). Our network was able to recruit an adult ADHD sample essentially comparable to community samples. A selection bias was created by excluding patients unable or unwilling to participate, or who had somatic and psychiatric contraindications for stimulant treatment (Current Controlled Trials ISRCTN54096201

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

    PubMed Central

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

    2015-01-01

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

  6. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial.

    PubMed

    Gaul, Charly; Diener, Hans-Christoph; Danesch, Ulrich

    2015-01-01

    Non-medical, non-pharmacological and pharmacological treatments are recommended for the prevention of migraine. The purpose of this randomized double-blind placebo controlled, multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium, riboflavin and Q10 as prophylactic treatment for migraine. 130 adult migraineurs (age 18 - 65 years) with ≥ three migraine attacks per month were randomized into two treatment groups: dietary supplementation or placebo in a double-blind fashion. The treatment period was 3 months following a 4 week baseline period without prophylactic treatment. Patients were assessed before randomization and at the end of the 3-month-treatment-phase for days with migraine, migraine pain, burden of disease (HIT-6) and subjective evaluation of efficacy. Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group (p = 0.23 compared to placebo). The intensity of migraine pain was significantly reduced in the supplement group compared to placebo (p = 0.03). The sum score of the HIT-6 questionnaire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group (p = 0.01). The evaluation of efficacy by the patient was better in the supplementation group compared to placebo (p = 0.01). Treatment with a proprietary supplement containing magnesium, riboflavin and Q10 (Migravent® in Germany, Dolovent® in USA) had an impact on migraine frequency which showed a trend towards statistical significance. Migraine symptoms and burden of disease, however, were statistically significantly reduced compared to placebo in patients with migraine attacks.

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

    PubMed Central

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

    2015-01-01

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

  8. Multicenter cluster-randomized trial of a multifactorial intervention to improve antihypertensive medication adherence and blood pressure control among patients at high cardiovascular risk (the COM99 study).

    PubMed

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

    2010-09-21

    Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥ 50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39). A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

  9. Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

    PubMed

    McVary, Kevin T; Gange, Steven N; Gittelman, Marc C; Goldberg, Kenneth A; Patel, Kalpesh; Shore, Neal D; Levin, Richard M; Rousseau, Michael; Beahrs, J Randolf; Kaminetsky, Jed; Cowan, Barrett E; Cantrill, Christopher H; Mynderse, Lance A; Ulchaker, James C; Larson, Thayne R; Dixon, Christopher M; Roehrborn, Claus G

    2016-05-01

    This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezūm® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-01-01

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

  11. Reduced infections with perioperative immunonutrition in head and neck cancer: exploratory results of a multicenter, prospective, randomized, double-blind study.

    PubMed

    Falewee, M N; Schilf, A; Boufflers, E; Cartier, C; Bachmann, P; Pressoir, M; Banal, A; Michel, C; Ettaiche, M

    2014-10-01

    Head and neck cancer surgery is affected by complications in 20-60% of cases, with risk factors being malnutrition, alcoholism and immunosuppression due to cancer. The aim of the study was to investigate whether preoperative or perioperative immunonutrition could reduce postoperative infectious complications (IC) and surgical-site infections (SSI) in this population. This was a multicenter, prospective, randomized, double-blind study. Patients with oropharyngeal and pharyngolaryngeal tumour were randomly allocated to three groups: a) perioperative formula of Impact(®) without immune nutrients, named "reference diet" (group A, control); b) preoperative Impact(®) and "reference diet" postoperatively (group B); c) Impact(®) perioperatively (group C). Products were available in oral and enteral formula and were given 7 days before surgery and for 7-15 days postoperatively. The primary and secondary endpoints were the incidence of IC and SSI, respectively. Of 312 randomized patients, 205 were evaluable for ITT analysis. There was no significant difference in IC and SSI. However out of this population, only 64 patients had taken at least 75% of the theoretical intake from surgery to day 10 (per-protocol population). In this condition, a significant difference in IC (OR = 0.24, p = 0.05), SSI (OR = 0.17, p = 0.04) and also in the median length of postoperative stay (18 vs. 25 days, p = 0.05) was demonstrated between groups A and C. In the ITT population, no significant difference in IC, SSI and LOS was demonstrated. Positive exploratory results on the perioperative Impact(®) per-protocol population, encourage further study in head and neck cancer patients. Registered under ClinicalTrials.gov Identifier no. NCT00765440. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  12. Randomized single-blind multicenter trial comparing the effects of standard and augmented acupuncture protocols on sleep quality and depressive symptoms in patients with depression.

    PubMed

    Wen, Xiuyun; Wu, Qian; Liu, Jianhua; Xu, Zhenhua; Fan, Li; Chen, Xiaokai; He, Qing; Ma, Rui; Wu, Yanan; Jiang, Shuo; Xu, Shujun; Fu, Wenbin

    2017-09-12

    The study was aimed to compare the effects of standard and augmented acupuncture on depressive symptoms and sleep disturbances in patients with depression. This is a randomized, single-blind, multicenter trial. 140 subjects with clinical insomnia (score of ≥ 7 on the Pittsburgh Sleep Quality Index (PSQI)) were randomized to the standard (LI4, LIV3, EX-HN3, and GV20) or augmented (LI4, LIV3, EX-HN3, GV20, LU7, and KID6, including intradermal needles for sustained treatment) acupuncture groups. Participants received two sessions weekly for six weeks. In trial, The primary outcomes were improvements in PSQI and the Hamilton Rating Scale (HAMD). Secondary outcomes were treatment credibility and adverse events. Outcomes were assessed at baseline, week 3, end of treatment, and 4-week follow-up. From the 105 randomized patients, 89 completed the trial and were included in the final analyses. Better efficacy was observed in the augmented group compared with the standard acupuncture to improve the PSQI and HAMD at week 3, end of treatment, and 4-week follow-up (all p < .05). The HAMD scores improved with time, except between end of treatment and 4-week follow-up, while in the standard group, HAMD scored improved from baseline to week 3, and stopped improving thereafter. The PSQI scores improved with time in the two groups, except between end of treatment and 4-week follow-up. Compared with the standard protocol, the augmented acupuncture protocol had a better efficacy to treat depression and to improve sleep quality of patients with depression.

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

    PubMed

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

    2013-05-01

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

  14. Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study versus rizatriptan.

    PubMed

    Savi, Lidia; Omboni, Stefano; Lisotto, Carlo; Zanchin, Giorgio; Ferrari, Michel D; Zava, Dario; Pinessi, Lorenzo

    2011-12-01

    The objectives of this study are to assess the efficacy and safety of frovatriptan, and rizatriptan in the subgroup of women with menstrually related migraine of a multicenter, randomized, double blind, cross-over study. Each patient received frovatriptan 2.5 mg or rizatriptan 10 mg in a randomized sequence: after treating 3 episodes of migraine in not more than 3 months with the first treatment, the patient had to switch to the other treatment. Menstrually related migraine was defined according to the criteria listed in the Appendix of the last IHS Classification of Headache disorders. 99 out of the 125 patients included in the intention-to-treat analysis of the main study were of a female gender: 93 had regular menstrual cycles and were, thus, included in this analysis. A total of 49 attacks classified as menstrually related migraine were treated with frovatriptan and 59 with rizatriptan. Rate of pain relief at 2 h was 58% for frovatriptan and 64% for rizatriptan (p = NS), while rate of pain free at 2 h was 31 and 34% (p = NS), respectively. At 24 h, 67 and 81% of frovatriptan-treated, and 61 and 74% of rizatriptan-treated patients were pain free and had pain relief, respectively (p = NS). Recurrence at 24 h was significantly (p < 0.01) lower with frovatriptan (10 vs. 32% rizatriptan). Frovatriptan was as effective as rizatriptan in the immediate treatment of menstrually related migraine attacks while showing a favorable sustained effect with a lower rate of migraine recurrence. These results need to be confirmed by randomized, double-blind, prospective, large clinical trials.

  15. Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial.

    PubMed

    Liu, Jin-Tao; Tang, De-Zhi; Li, Xiao-Feng; Zhang, Zhi-Gang; Ji, Wan-Bo; Tao, Shuai; Wang, Yong-Jun; Jiang, Hong

    2013-11-13

    Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. ClinicalTrials.gov identifier: ChiCTR-TRC-13003418.

  16. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  17. Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial.

    PubMed

    Fernandez, M Mar; González-Castro, Alejandro; Magret, Monica; Bouza, M Teresa; Ibañez, Marcos; García, Carolina; Balerdi, Begoña; Mas, Arantxa; Arauzo, Vanesa; Añón, José M; Ruiz, Francisco; Ferreres, José; Tomás, Roser; Alabert, Marta; Tizón, Ana Isabel; Altaba, Susana; Llamas, Noemi; Fernandez, Rafael

    2017-09-22

    Spontaneous breathing trials (SBT) can be exhausting, but the preventive role of rest has never been studied. This study aimed to evaluate whether reconnection to mechanical ventilation (MV) for 1 h after the effort of a successful SBT could reduce the need for reintubation in critically ill patients. Randomized multicenter trial conducted in 17 Spanish medical-surgical intensive care units (Oct 2013-Jan 2015). Patients under MV for longer than 12 h who fulfilled criteria for planned extubation were randomly allocated after a successful SBT to direct extubation (control group) or reconnection to the ventilator for a 1-h rest before extubation (rest group). The primary outcome was reintubation within 48 h. Analysis was by intention to treat. We recruited 243 patients randomized to the control group and 227 to the rest group. Median time from intubation to SBT did not differ between groups [5.5 (2.7, 9.6) days in the control group vs. 5.7 (2.7, 10.6) in the rest group; p = 0.85]. Reintubation within 48 h after extubation was more common in the control than in the rest group [35 (14%) vs. 12 (5%) patients; OR 0.33; 95% CI 0.16-0.65; p < 0.001]. A multivariable regression model demonstrated that the variables independently associated with reintubation were rest [OR 0.34 (95%CI 0.17-0.68)], APACHE II [OR 1.04 (1.002-1.077)], and days of MV before SBT [OR 1.04 (1.001-1.073)], whereas age, reason for admission, and type and duration of SBT were not. One-hour rest after a successful SBT reduced the rates of reintubation within 48 h after extubation in critically ill patients. Trial registration Clinicaltrials.gov identifier NCT01915563.

  18. Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. Methods/Design This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. Discussion This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. Trial registration ClinicalTrials.gov identifier: ChiCTR-TRC-13003418 PMID:24220504

  19. Preventive pancreatic stents in the management of acute biliary pancreatitis (PREPAST trial): pre-study protocol for a multicenter, prospective, randomized, interventional, controlled trial.

    PubMed

    Dubravcsik, Zsolt; Madácsy, László; Gyökeres, Tibor; Vincze, Áron; Szepes, Zoltán; Hegyi, Péter; Hritz, István; Szepes, Attila

    2015-01-01

    The outcome of the most common biliary form of acute pancreatitis has not changed even with the better described indications for early endoscopic intervention. It may be due to the fact that this intrevention theoretically can cause further pancreatic injury or cannot always relieve the pancreatic duct obstruction. We hypothesize that maintaining the outflow of the pancreatic duct with preventive pancreatic stents at the early ERCP improves the outcome of acute biliary pancreatitis. PREPAST is a prospective, randomized, controlled, multicenter trial. Patients with acute biliary pancreatitis with coexisting cholangitis are randomized to undergo urgent endoscopic intervention with or without pancreatic stenting within 48 h from the onset of pain, and in addition patients without signs of cholangitis but cholestasis are randomly allocated to recieve conservative treatment or early endoscopic intervention with or without pancreatic stenting within 48 h from the onset of pain. Patients without acute cholangitis and signs of cholestasis recieve conservative treatment. 230 patients are planned to be enrolled during a 48 months period from different centers. The primary endpoint is the outcome of acute biliary pancreatitis as described by the latest guidelines. Secondary endpoints include mortality data, and other variables not analyzed as a primary endpoint but related to the pancreatitis or the pancreatic stenting. The PREPAST trial is designed to show whether early endoscopic intervention with the usage of preventive pancreatic stenting improves the outcome of acute biliary pancreatitis. The study has been registered at the International Standard Randomised Controlled Trial Number (ISRCTN) Register (trial ID: ISRCTN13517695). Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

    PubMed

    Hung, Ivan F N; To, Kelvin K W; Lee, Cheuk-Kwong; Lee, Kar-Lung; Yan, Wing-Wa; Chan, Kenny; Chan, Wai-Ming; Ngai, Chun-Wai; Law, Kin-Ip; Chow, Fu-Loi; Liu, Raymond; Lai, Kang-Yiu; Lau, Candy C Y; Liu, Shao-Haei; Chan, Kwok-Hung; Lin, Che-Kit; Yuen, Kwok-Yung

    2013-08-01

    Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

  3. A multicenter, randomized, controlled trial of transureteral and shock wave lithotripsy--which is the best minimally invasive modality to treat distal ureteral calculi in children?

    PubMed

    Basiri, Abbas; Zare, Samad; Tabibi, Ali; Sharifiaghdas, Farzaneh; Aminsharifi, Alireza; Mousavi-Bahar, Seyed Habibollah; Ahmadnia, Hassan

    2010-09-01

    Since there is insufficient evidence to determine the best treatment modality in children with distal ureteral calculi, we designed a multicenter, randomized, controlled trial to evaluate the efficacy and complications of transureteral and shock wave lithotripsy in these patients. A total of 100 children with distal ureteral calculi were included in the study. Of the patients 50 were randomized consecutively to undergo shock wave lithotripsy using a Compact Delta II lithotriptor (Dornier MedTech, Kennesaw, Georgia), and 50 were randomized to undergo transureteral lithotripsy with holmium laser and pneumatic lithotriptor between February 2007 and October 2009. Stone-free, complication and efficiency quotient rates were assessed in each group. Mean +/- SD patient age was 6.5 +/- 3.7 years (range 1 to 13). Mean stone surface was 35 mm(2) in the transureteral group and 37 mm(2) in the shock wave lithotripsy group. Stone-free rates at 2 weeks after transureteral lithotripsy and single session shock wave lithotripsy differed significantly, at 78% and 56%, respectively (p = 0.004). With 2 sessions of shock wave lithotripsy the stone-free rate increased to 72%. Efficiency quotient was significantly higher for transureteral vs shock wave lithotripsy (81% vs 62%, p = 0.001). Minor complications were comparable and negligible between the groups. Two patients (4%) who underwent transureteral lithotripsy sustained a ureteral perforation. In the short term it seems that transureteral and shock wave lithotripsy are acceptable modalities for the treatment of distal ureteral calculi in children. However, transureteral lithotripsy has a higher efficacy rate when performed meticulously by experienced hands using appropriate instruments. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males.

    PubMed

    Wycherley, T P; Brinkworth, G D; Clifton, P M; Noakes, M

    2012-08-13

    A high-protein (HP), low-fat weight-loss diet may be advantageous for improving cardiometabolic health outcomes and body composition. To date, only limited research has been conducted in male participants. To evaluate the medium to long-term effects of two, low-fat, hypocaloric diets differing in carbohydrate:protein ratio on body composition and cardiometabolic health outcomes in overweight and obese males. One hundred and twenty males (age 50.8±9.3 (s.d.) years, body mass index 33.0±3.9 kg m(-2)) were randomly assigned and consumed a low-fat, isocaloric, energy-restricted diet (7 MJ per day) with either HP (protein:carbohydrate:fat %energy, 35:40:25) or high carbohydrate (HC; 17:58:25). Body weight, body composition and cardiometabolic risk factors were assessed at baseline and after 12 and 52 weeks. Sixty-eight participants completed the study (HP, n=33; HC, n=35). At 1 year both the groups experienced similar reductions in body weight (HP, -12.3±8.0 kg (-12%); HC, -10.9±8.6 kg (-11%); P=0.83 time × group interaction) and fat mass (-9.9±6.0 kg (-27%) vs -7.3±5.8 kg (-22%); P=0.11). Participants who consumed the HP diet lost less fat-free mass (-2.6±3.7 kg (-4%) vs -3.8±4.7 kg (-6%); P<0.01). Both groups experienced similar increases in high-density lipoprotein cholesterol (8%) and reductions in total cholesterol (-7%), low-density lipoprotein cholesterol (-9%), triglycerides (-24%), glucose (-3%), insulin (-38%), blood pressure (-7/-12%) and C-reactive protein (-29%), (P0.14). In overweight and obese men, both a HP and HC diet reduced body weight and improved cardiometabolic risk factors. Consumption of a HP diet was more effective for improving body composition compared with an HC diet.

  5. Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males

    PubMed Central

    Wycherley, T P; Brinkworth, G D; Clifton, P M; Noakes, M

    2012-01-01

    Background: A high-protein (HP), low-fat weight-loss diet may be advantageous for improving cardiometabolic health outcomes and body composition. To date, only limited research has been conducted in male participants. Objective: To evaluate the medium to long-term effects of two, low-fat, hypocaloric diets differing in carbohydrate:protein ratio on body composition and cardiometabolic health outcomes in overweight and obese males. Design: One hundred and twenty males (age 50.8±9.3 (s.d.) years, body mass index 33.0±3.9 kg m−2) were randomly assigned and consumed a low-fat, isocaloric, energy-restricted diet (7 MJ per day) with either HP (protein:carbohydrate:fat %energy, 35:40:25) or high carbohydrate (HC; 17:58:25). Body weight, body composition and cardiometabolic risk factors were assessed at baseline and after 12 and 52 weeks. Results: Sixty-eight participants completed the study (HP, n=33; HC, n=35). At 1 year both the groups experienced similar reductions in body weight (HP, −12.3±8.0 kg (−12%); HC, −10.9±8.6 kg (−11%); P=0.83 time × group interaction) and fat mass (−9.9±6.0 kg (−27%) vs −7.3±5.8 kg (−22%); P=0.11). Participants who consumed the HP diet lost less fat-free mass (−2.6±3.7 kg (−4%) vs −3.8±4.7 kg (−6%); P<0.01). Both groups experienced similar increases in high-density lipoprotein cholesterol (8%) and reductions in total cholesterol (−7%), low-density lipoprotein cholesterol (−9%), triglycerides (−24%), glucose (−3%), insulin (−38%), blood pressure (−7/−12%) and C-reactive protein (−29%), (P⩾0.14). Conclusion: In overweight and obese men, both a HP and HC diet reduced body weight and improved cardiometabolic risk factors. Consumption of a HP diet was more effective for improving body composition compared with an HC diet. PMID:23448804

  6. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.

    PubMed

    Guekht, Alla B; Moessler, Herbert; Novak, Philipp H; Gusev, Evgenyi I

    2011-01-01

    No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimer's Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinician's Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.

  7. The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart Transplant Recipients with Renal Insufficiency: A Multicenter, Randomized Trial

    PubMed Central

    Derthoo, David; Van Caenegem, Olivier; De Pauw, Michel; Nellessen, Eric; Duerinckx, Nathalie; Droogne, Walter; Vörös, Gábor; Meyns, Bart; Belmans, Ann; Janssens, Stefan; Vanhaecke, Johan

    2017-01-01

    In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30–60 mL/min/1.73 m2) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (p < 0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function. PMID:28316834

  8. Mechanism of action in CBT (MAC): methods of a multi-center randomized controlled trial in 369 patients with panic disorder and agoraphobia.

    PubMed

    Gloster, A T; Wittchen, H U; Einsle, F; Höfler, M; Lang, T; Helbig-Lang, S; Fydrich, T; Fehm, L; Hamm, A O; Richter, J; Alpers, G W; Gerlach, A L; Ströhle, A; Kircher, T; Deckert, J; Zwanzger, P; Arolt, V

    2009-11-01

    Cognitive behavioral therapy (CBT) is efficacious for panic disorder with agoraphobia (PD/A). Nevertheless, the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown. The mechanisms of action in CBT (MAC) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center, randomized controlled design, with two active treatment conditions in which the administration of exposure was varied, and a wait-list control group. The special feature of MAC is the way in which imbedded experimental, psychophysiological, and neurobiological paradigms were included to elucidate therapeutic and psychopathological processes. This paper describes the aims and goals of the MAC study and the methods utilized to achieve them. All aspects of the research design (e.g., assessments, treatment, experimental procedures) were implemented so as to facilitate the detection of active therapeutic components, and the mediators and moderators of therapeutic change. To this end, clinical, behavioral, physiological, experimental, and genetic data were collected and will be integrated.

  9. Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial.

    PubMed

    Peng, Nan; Zhang, Yi; Ma, Cong; Yu, Ming-Wei; Yang, Guo-Wang; Fu, Qi; Xu, Wei-Ru; Wang, Xiao-Min

    2014-05-15

    Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. The results of this study will provide a new strategy to help relieve AIMSS. ISRCTN06129599 (assigned 14 August 2013).

  10. Ertapenem Once a Day Versus Piperacillin–Tazobactam Every 6 Hours for Treatment of Acute Pelvic Infections: A Prospective, Multicenter, Randomized, Double-Blind Study

    PubMed Central

    Roy, Subir; Higareda, Iliana; Angel-Muller, Edith; Ismail, Mahmoud; Hague, Caren; Adeyi, Ben; Teppler, Hedy

    2003-01-01

    Objective: To compare ertapenem therapy with piperacillin–tazobactam therapy for the management of acute pelvic infections. Methods: In a multicenter, double-blind study, 412 women with acute pelvic infection were assigned to one of two strata, namely obstetric/postpartum infection or gynecologic/postoperative infection, and were then randomized to ertapenem, 1 g once a day, or piperacillin–tazobactam, 3.375 g every 6 hours, both administered intravenously. Results: In total, 163 patients in the ertapenem group and 153 patients in the piperacillin–tazobactam group were clinically evaluable. The median duration of therapy was 4.0 days in both treatment groups. The most common single pathogen was Escherichia coli . At the primary efficacy endpoint 2–4 weeks post therapy, 93.9% of patients who received ertapenem and 91.5% of those who received piperacillin–tazobactam were cured (95% confidence interval for the difference, adjusting for strata, –4% to 8.8%), indicating that cure rates for both treatment groups were equivalent. Cure rates for both treatment groups were also similar when compared by stratum and severity of infection. The frequency and severity of drug-related adverse events were generally similar in both groups. Conclusions: In this study, ertapenem was as effective as piperacillin–tazobactam for the treatment of acute pelvic infection, was generally well tolerated, and had an overall safety profile similar to that of piperacillin–tazobactam. PMID:12839630

  11. Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation.

    PubMed

    Van Gurp, Eveline; Bustamante, Jesus; Franco, Antonio; Rostaing, Lionel; Becker, Thomas; Rondeau, Eric; Czajkowski, Zenon; Rydzewski, Andrzej; Alarcon, Antonio; Bachleda, Petr; Samlik, Jiri; Burmeister, Dirk; Pallardo, Luis; Moal, Marie-Christine; Rutkowski, Boleslaw; Wlodarczyk, Zbigniew

    2010-01-01

    In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL, N = 318) or tacrolimus with MMF (Tac/MMF, N = 316). Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P < .05) while CMV, leukopenia, and diarrhea incidences were higher with Tac/MMF (P < .05). The incidence of any antidiabetic treatment for >30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens.

  12. Efficacy and safety of autologous cultured melanocytes delivered on poly (DL-lactic acid) film: a prospective, open-label, randomized, multicenter study.

    PubMed

    Ghosh, Deepa; Kuchroo, Pushpa; Viswanathan, Chandra; Sachan, Shailendra; Shah, Bela; Bhatt, Deepa; Parasramani, Shrichand; Savant, Satish

    2012-12-01

    Small vitiliginous patches have been treated with epidermal grafts or their cell suspensions. In an attempt to overcome some of the shortcomings of cell suspension delivery, we have delivered melanocytes on a polymeric film. To evaluate the clinical effectiveness of a cultured graft consisting of autologous cultured melanocytes on a poly (DL-lactic acid) (PLA) film in subjects with stable vitiligo. A prospective open-label, randomized, multicenter clinical trial was conducted with 22 patients. Each subject was treated with cultured graft and polyurethane dressing (control arm) after epidermal ablation and followed for up to 9 months. The extent of repigmentation in the treated sites was compared with that control sites at days 90, 180, and 270. In the treatment arm, a minimum of 70% repigmentation was observed in five subjects at day 90; nine at day 180, and 10 at day 270. In the control arm, only one subject showed repigmentation until day 270. None of the test sites reported any recurrence of vitiliginous patches by the end of the study. Cultured melanocytes delivered on PLA film were efficacious and safe when applied on patients with stable vitiligo. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  13. Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).

    PubMed

    Malerba, Mario; Ponticiello, Antonio; Radaeli, Alessandro; Bensi, Giuliano; Grassi, Vittorio

    2004-01-01

    The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.

  14. Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.

    PubMed

    Tejani, Furqan H; Thompson, Randall C; Iskandrian, Ami E; McNutt, Bruce E; Franks, Billy

    2011-02-01

    Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

  15. Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind, randomized, multicenter, Italian study.

    PubMed

    Tullo, Vincenzo; Allais, Gianni; Curone, Marcella; Ferrari, Michel D; Omboni, Stefano; Benedetto, Chiara; Colombo, Bruno; Zava, Dario; Bussone, Gennaro

    2012-05-01

    Migraine with aura affects ~20-30 % of migraineurs and it is much less common than migraine without aura. The aim of this study was to compare the efficacy of frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with aura. Analysis was carried out in a subset of 18 subjects with migraine with aura (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double-blind, cross-over study. According to the study design, each patient had to treat three episodes of migraine in no more than 3 months with one drug, before switching to the other treatment. The rate of pain-free episodes at 2 h was significantly (p < 0.05) larger under frovatriptan (45.8 %) than under zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent episodes were similar between the two treatments, while sustained pain-free episode was significantly (p < 0.05) more frequent during frovatriptan treatment (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior to zolmitriptan in the immediate treatment of patients with migraine with aura, and it is capable of maintaining its acute analgesic effect over 48 h.

  16. Comparative efficacy and tolerability of pholcodine and dextromethorphan in the management of patients with acute, non-productive cough : a randomized, double-blind, multicenter study.

    PubMed

    Equinozzi, Roberto; Robuschi, Maria

    2006-01-01

    The aim of this study was to compare the efficacy and tolerability of pholcodine with that of dextromethorphan, one of the most used cough sedative products, in patients with acute, non-productive cough. 129 adults with a diagnosis of acute, frequent, non-productive cough participated in a randomized, double-blind, parallel-group, multicenter trial. Medications were in a syrup formulation and were taken orally three times daily for 3 days. The efficacy endpoints were the change from baseline in the daytime and night-time cough frequency on 5-point scales at day 3, and cough intensity. A reduction of 1.4 and 1.3 points in the mean daytime cough frequency at day 3 was seen in the pholcodine and dextromethorphan groups, respectively, in the per-protocol population. The reduction in mean night-time cough was 1.3 for both groups. Cough intensity reduction was 0.7 for pholcodine and 0.8 for dextromethorphan. These findings indicate that the efficacy of a 3-day course of pholcodine is similar to that of dextromethorphan in the treatment of adult patients with acute, non-productive cough. Both medications were well tolerated.

  17. Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

    PubMed Central

    Park, Dae Won; Peck, Kyong Ran; Chung, Moon Hyun; Lee, Jin Seo; Park, Yoon Soo; Kim, Hyo Youl; Lee, Mi Suk; Kim, Jung Yeon; Yeom, Joon Sup

    2012-01-01

    The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs. PMID:22563210

  18. [A multicenter, double-masked, randomized evaluation of olopatadine 0.2% using the conjunctival allergen challenge model in Japanese patients with allergic conjunctivitis].

    PubMed

    Ohno, Shigeaki

    2012-12-01

    Olopatadine hydrochloride ophthalmic solution, 0.2% (olopatadine 0.2%) is approved for allergic conjunctivitis when instilled twice-daily. The objective of this study was to evaluate the efficacy and safety of olopatadine 0.2% (instilled twice-daily) versus vehicle and olopatadine 0.1% (instilled 4-times daily) in Japanese patients with allergic conjunctivitis. A multicenter, parallel-group, double-masked, randomized, conjunctival allergen challenge (CAC) study. Patients > or = 18 years of age with histories of allergic conjunctivitis were treated with either olopatadine 0.2% or olopatadine 0.1% in a single eye and the vehicle in the contralateral eye at 1 visit. Overall, 267 patients were enrolled. Olopatadine 0.2% was superior to its vehicle for ocular itching (p < 0.0001 at the time of observation) and marginally superior for total redness (p = 0.0543 at the time of observation). Olopatadine 0.2% was similar to olopatadine 0.1% for ocular itching at the time of observation. No trends were identified through a review of safety parameters. Olopatadine 0.2% (instilled twice-daily) is safe, well tolerated, superior to the vehicle, and similar to olopatadine 0.1% in preventing ocular itching. Olopatadine 0.2%, which can be instilled less often than olopatadine 0.1%, is a useful new option for allergic conjunctivitis in Japanese patients that could potentially result in better treatment compliance.

  19. Comparison of ertapenem and ceftriaxone therapy for acute pyelonephritis and other complicated urinary tract infections in Korean adults: a randomized, double-blind, multicenter trial.

    PubMed

    Park, Dae Won; Peck, Kyong Ran; Chung, Moon Hyun; Lee, Jin Seo; Park, Yoon Soo; Kim, Hyo Youl; Lee, Mi Suk; Kim, Jung Yeon; Yeom, Joon Sup; Kim, Min Ja

    2012-05-01

    The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.

  20. Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial

    PubMed Central

    2014-01-01

    Background Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. Methods/design To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. Discussion The results of this study will provide a new strategy to help relieve AIMSS. Trial registration ISCTN: ISRCTN06129599 (assigned 14 August 2013). PMID:24885324

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

    PubMed Central

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

    2016-01-01

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

  2. A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures.

    PubMed

    Elger, Christian E; Stefan, Hermann; Mann, Allison; Narurkar, Milind; Sun, Yijun; Perdomo, Carlos

    2010-02-01

    To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs). A 24-week multicenter Phase II clinical study was conducted (n=647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase. The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase - the primary efficacy outcome measure - was statistically significant in favor of rufinamide (estimated slope=-0.049, P=0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a >or=50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P=0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were obse