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Sample records for blind randomised study

  1. Aspartame Sensitivity? A Double Blind Randomised Crossover Study

    PubMed Central

    Sathyapalan, Thozhukat; Thatcher, Natalie J.; Hammersley, Richard; Rigby, Alan S.; Pechlivanis, Alexandros; Gooderham, Nigel J.; Holmes, Elaine; le Roux, Carel W.; Atkin, Stephen L.; Courts, Fraser

    2015-01-01

    Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Results Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Conclusion Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies

  2. Efficacy of transforaminal versus interspinous corticosteroid injectionin discal radiculalgia - a prospective, randomised, double-blind study.

    PubMed

    Thomas, E; Cyteval, C; Abiad, L; Picot, M C; Taourel, P; Blotman, F

    2003-10-01

    A prospective, randomised, double-blind study was carried out to compare the respective efficacies of transforaminal and interspinous epidural corticosteroid injections in discal radiculalgia. Thirty-one patients (18 females, 13 males) with discal radicular pain of less than 3 months' duration were consecutively randomised to receive either radio-guided transforaminal or blindly performed interspinous epidural corticosteroid injections. Post-treatment outcome was evaluated clinically at 6 and 30 days, and then at 6 months, but only by mailed questionnaire. At day 6, the between-group difference was significantly in favour of the transforaminal group with respect to Schober's index, finger-to-floor distance, daily activities, and work and leisure activities on the Dallas pain scale. At day 30, pain relief was significantly better in the transforaminal group. At month 6, answers to the mailed questionnaire still showed significantly better results for transforaminal injection concerning pain, daily activities, work and leisure activities and anxiety and depression, with a decline in the Roland-Morris score. In recent discal radiculalgia, the efficacy of radio-guided transforaminal epidural corticosteroid injections was higher than that obtained with blindly-performed interspinous injections. PMID:14579160

  3. Randomised double-blind comparative study of dexmedetomidine and tramadol for post-spinal anaesthesia shivering

    PubMed Central

    Mittal, Geeta; Gupta, Kanchan; Katyal, Sunil; Kaushal, Sandeep

    2014-01-01

    Background and Aims: Dexmedetomidine (α2 adrenergic agonist) has been used for prevention of post anaesthesia shivering. Its use for the treatment of post-spinal anaesthesia shivering has not been evaluated. The aim of this study was to evaluate and compare the efficacy, haemodynamic and adverse effects of dexmedetomidine with those of tramadol, when used for control of post-spinal anaesthesia shivering. Methods: A prospective, randomised, and double-blind study was conducted in 50 American Society of Anaesthesiologists Grade I and II patients of either gender, aged between 18 and 65 years, scheduled for various surgical procedures under spinal anaesthesia. The patients were randomised in two groups of 25 patients each to receive either dexmedetomidine 0.5 μg/kg or tramadol 0.5 mg/kg as a slow intravenous bolus. Grade of shivering, onset of shivering, time for cessation of shivering, recurrence, response rate, and adverse effects were observed at scheduled intervals. Unpaired t-test was used for analysing the data. Results: Time taken for cessation of shivering was significantly less with dexmedetomidine when compared to tramadol. Nausea and vomiting was observed only in tramadol group (28% and; 20% respectively). There was not much difference in the sedation profile of both the drugs. Conclusion: We conclude that although both drugs are effective, the time taken for cessation of shivering is less with dexmedetomidine when compared to tramadol. Moreover, dexmedetomidine has negligible adverse effects, whereas tramadol is associated with significant nausea and vomiting. PMID:25024466

  4. Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study

    PubMed Central

    Thalmann, M; Sodeck, G H; Kavouras, S; Matalas, A; Skenderi, K; Yannikouris, N; Domanovits, H

    2006-01-01

    Background Ultra‐endurance running is emerging as a popular sport in Western industrialised countries. Gastrointestinal bleeding has been reported to be an adverse effect in these runners. Objective To see if the oral administration of a proton pump inhibitor would reduce the incidence of gastrointestinal bleeding in an ultramarathon. Methods In a randomised, double blinded, placebo controlled study, a prophylactic regimen of three days of an oral proton pump inhibitor (pantoprazole 20 mg) was tested in healthy athletes participating in the Spartathlon ultramarathon. The incidence of gastrointestinal bleeding was assessed by a stool guaiac test. Results Results were obtained for 70 healthy volunteers. The data for 20 of 35 runners in the intervention group and 17 of 35 runners in the placebo group were entered into the final analysis. At the end of the ultramarathon, two subjects in the intervention group and 12 in the placebo group had positive stool guaiac tests (risk difference 0.86; 95% confidence interval 0.45 to 0.96; p  =  0.001). Conclusion A short prophylactic regimen of oral proton pump inhibition can successfully decrease the incidence of gastrointestinal bleeding in participants in an ultramarathon. PMID:16556794

  5. Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study

    PubMed Central

    Wade, C; Wang, L; Zhao, W J; Cardini, F; Kronenberg, F; Gui, S Q; Ying, Z; Zhao, N Q; Chao, M T; Yu, J

    2016-01-01

    Objective To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. Setting A Menstrual Disorder Centre at a public hospital in Shanghai, China. Participants Chinese women aged 14–25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. Interventions A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. Primary and secondary outcome measures The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. Results Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (−0.71, CI −1.37 to −0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. Conclusions Acupuncture point injection of

  6. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.

    PubMed Central

    Amir, J.; Harel, L.; Smetana, Z.; Varsano, I.

    1997-01-01

    OBJECTIVES: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children. DESIGN: Randomised double blind placebo controlled study. SETTING: Day care unit of a tertiary paediatric hospital. SUBJECTS: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study. MAIN OUTCOME MEASURES: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding. INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo. RESULTS: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)). CONCLUSIONS: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment. PMID:9224082

  7. Conductive Education as a Method of Stroke Rehabilitation: A Single Blinded Randomised Controlled Feasibility Study

    PubMed Central

    Jutley-Neilson, Jagjeet; Russell, Nicholas C. C.; Sackley, Catherine M.

    2016-01-01

    Background. Conductive Education for stroke survivors has shown promise but randomised evidence is unavailable. This study assessed the feasibility of a definitive randomised controlled trial to evaluate efficacy. Methods. Adult stroke survivors were recruited through local community notices. Those completing the baseline assessment were randomised using an online program and group allocation was independent. Intervention group participants received 10 weekly 1.5-hour sessions of Conductive Education at the National Institute of Conductive Education in Birmingham, UK. The control group participants attended two group meetings. The study evaluated the feasibility of recruitment procedures, delivery of the intervention, retention of participants, and appropriateness of outcome measures and data collection methods. Independent assessments included the Barthel Index, the Stroke Impact Scale, the Timed Up and Go test, and the Hospital Anxiety and Depression Scale. Results. Eighty-two patients were enrolled; 77 completed the baseline assessment (46 men, mean age 62.1 yrs.) and were randomised. 70 commenced the intervention (n = 37) or an equivalent waiting period (n = 33). 32/37 completed the 10-week training and 32/33 the waiting period. There were no missing items from completed questionnaires and no adverse events. Discussion. Recruitment, intervention, and assessment methods worked well. Transport issues for intervention and assessment appointments require review. Conclusion. A definitive trial is feasible. This trial is registered with ISRCTN84064492. PMID:27418997

  8. Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

    PubMed Central

    Evans, E Glyn V; Sigurgeirsson, Bárdur

    1999-01-01

    Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatment

  9. Increasing work-place healthiness with the probiotic Lactobacillus reuteri: A randomised, double-blind placebo-controlled study

    PubMed Central

    Tubelius, Py; Stan, Vlaicu; Zachrisson, Anders

    2005-01-01

    Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730) on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-workers) that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo. Results In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p < 0.01). The frequency of sick-days was 0.9% in the placebo group and 0.4% in the L. reuteri group (p < 0.01). Among the 53 shift-workers, 33% in the placebo group reported sick during the study period as compared with none in the L. reuteri group(p < 0.005). PMID:16274475

  10. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial—study protocol

    PubMed Central

    Diem, Ricarda; Molnar, Fanni; Beisse, Flemming; Gross, Nikolai; Drüschler, Katharina; Heinrich, Sven P; Joachimsen, Lutz; Rauer, Sebastian; Pielen, Amelie; Sühs, Kurt-Wolfram; Linker, Ralf Andreas; Huchzermeyer, Cord; Albrecht, Philipp; Hassenstein, Andrea; Aktas, Orhan; Guthoff, Tanja; Tonagel, Felix; Kernstock, Christoph; Hartmann, Kathrin; Kümpfel, Tania; Hein, Katharina; van Oterendorp, Christian; Grotejohann, Birgit; Ihorst, Gabriele; Maurer, Julia; Müller, Matthias; Volkmann, Martin; Wildemann, Brigitte; Platten, Michael; Wick, Wolfgang; Heesen, Christoph; Schiefer, Ulrich; Wolf, Sebastian; Lagrèze, Wolf A

    2016-01-01

    Introduction Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. Methods and analysis Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. Ethics and dissemination TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki

  11. Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

    PubMed

    Williamson, I J; Reid, A; Monie, R D; Fennerty, A G; Rimmer, E M

    1997-03-01

    Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products. PMID:9135831

  12. Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

    PubMed Central

    Williamson, I. J.; Reid, A.; Monie, R. D.; Fennerty, A. G.; Rimmer, E. M.

    1997-01-01

    Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products. PMID:9135831

  13. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

    PubMed Central

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-01-01

    Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS. PMID:25595151

  14. Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study

    PubMed Central

    Kawahara, Tetsuya; Suzuki, Gen; Inazu, Tetsuya; Mizuno, Shoichi; Kasagi, Fumiyoshi; Okada, Yosuke; Tanaka, Yoshiya

    2016-01-01

    Introduction Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes. Methods and analysis DPVD is an ongoing, prospective, multicentre, randomised, double-blind and placebo-controlled outcome study in individuals with impaired glucose tolerance. Participants, men and women aged ≥30 years, will be randomised to receive eldecalcitol or placebo. They will also be given a brief (5–10 min long) talk about appropriate calorie intake from diet and exercise at each 12-week visit. The primary end point is the cumulative incidence of type 2 diabetes. Secondary endpoint is the number of participants who achieve normoglycaemia at 48, 96 and 144 weeks. Follow-up is estimated to span 144 weeks. Ethics and dissemination All protocols and an informed consent form comply with the Ethics Guideline for Clinical Research (Japan Ministry of Health, Labour and Welfare). The study protocol has been approved by the Institutional Review Board at Kokura Medical Association and University of Occupational and Environmental Health. The study will be implemented in line with the CONSORT statement. Trial registration number UMIN000010758; Pre-results. PMID:27388357

  15. Dutasteride in men receiving testosterone therapy: a randomised, double-blind study.

    PubMed

    Kacker, R; Harisaran, V; Given, L; Miner, M; Rittmaster, R; Morgentaler, A

    2015-03-01

    We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (-0.46 ± 0.81 ng ml(-1) ; P = 0.04) and in PV (-6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (-0.46 versus 0.21 ng ml(-1) ; P = 0.11), PV (-6.65% versus 3.4%; P = 0.08) and MSHQ scores (-10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy. PMID:24499051

  16. Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.

    PubMed Central

    Axon, A. T.; O'Moráin, C. A.; Bardhan, K. D.; Crowe, J. P.; Beattie, A. D.; Thompson, R. P.; Smith, P. M.; Hollanders, F. D.; Baron, J. H.; Lynch, D. A.; Dixon, M. F.; Tompkins, D. S.; Birrell, H.; Gillon, K. R.

    1997-01-01

    OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use. PMID:9055715

  17. Randomised, double blind, crossover challenge study of allergenicity of peanut oils in subjects allergic to peanuts.

    PubMed Central

    Hourihane, J. O.; Bedwani, S. J.; Dean, T. P.; Warner, J. O.

    1997-01-01

    OBJECTIVE: To determine the in vivo allergenicity of two grades of peanut oil for a large group of subjects with proved allergy to peanuts. DESIGN: Double blind, crossover food challenge with crude peanut oil and refined peanut oil. SETTING: Dedicated clinical investigation unit in a university hospital. SUBJECTS: 60 subjects allergic to peanuts; allergy was confirmed by challenge tests. OUTCOME MEASURES: Allergic reaction to the tested peanut oils. RESULTS: None of the 60 subjects reacted to the refined oil; six (10%) reacted to the crude oil. Supervised peanut challenge caused considerably less severe reactions than subjects had reported previously. CONCLUSIONS: Crude peanut oil caused allergic reactions in 10% of allergic subjects studied and should continue to be avoided. Refined peanut oil did not pose a risk to any of the subjects. It would be reasonable to recommend a change in labelling to distinguish refined from crude peanut oil. PMID:9133891

  18. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults.

    PubMed

    Rainey-Smith, Stephanie R; Brown, Belinda M; Sohrabi, Hamid R; Shah, Tejal; Goozee, Kathryn G; Gupta, Veer B; Martins, Ralph N

    2016-06-01

    Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n 96) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; time×treatment; F=3·85, P<0·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration. PMID:27102361

  19. Comparative palatability of two veterinary dewormers (Milpro® and Milbemax®): a blinded randomised crossover cat study

    PubMed Central

    Bernachon, N.; McGahie, D.; Corvaisier, D.; Benizeau, E.; Crastes, N.; Chaix, G.

    2014-01-01

    Background The combination of milbemycin oxime–praziquantel is widely used against the most common tapeworms and roundworms affecting cats. New veterinary presentations of this combination have recently been approved. Objective The objective of this study was to compare the palatability of two products using this combination, Milpro® and Milbemax®. Methods In all, 20 adult cats and 20 kittens were offered each product according to a randomisation table using a blinded crossover design. Prehension from the bowl, prehension from the hand and total consumption were assessed. Results Both presentations were very well tolerated in adult cats and kittens. Total prehension in adult cats and kittens was 100 and 45 per cent, respectively, for Milpro®, and 95 and 30 per cent, respectively, for Milbemax®. The percentages of adult cats and kittens which swallowed the pill after taking it into their mouth (total spontaneous consumption) were respectively 40 and 45 per cent for Milpro®, and 35 and 20 per cent for Milbemax®. Conclusion In this study, both presentations were highly attractive to cats and their respective coatings successfully covered the unpleasant odour of praziquantel, which usually repels cats. These results indicate that the palatability of Milpro® is at least as good as Milbemax® and both tablets are well accepted by adult cats and kittens. PMID:26392882

  20. Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study.

    PubMed Central

    Wilding, P.; Clark, M.; Thompson Coon, J.; Lewis, S.; Rushton, L.; Bennett, J.; Oborne, J.; Cooper, S.; Tattersfield, A. E.

    1997-01-01

    OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control. PMID:9167559

  1. Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity.

    PubMed

    Gueniche, A; Philippe, D; Bastien, P; Reuteler, G; Blum, S; Castiel-Higounenc, I; Breton, L; Benyacoub, J

    2014-06-01

    In recent decades, the prevalence of subjects with reactive skin has considerably increased in industrialised countries. 50% of women and 30% of men report cutaneous discomfort classified under reactive/sensitive skin. Several topical approaches have been proposed, in particular through improvement of galenic forms or protection of epidermal surface. We propose to act differently, deeply from inside the body via an innovative nutritional approach. To this purpose, Lactobacillus paracasei NCC 2461 (ST11) was selected because of its specific beneficial skin properties discovered in in vitro studies, i.e. diminution of neurogenic inflammation and promotion of the recovery of skin barrier function. We designed a randomised double-blind placebo-controlled clinical study with a two-month supplementation in two female treatment groups (n=32 per group). A capsaicin test was performed to monitor the time course of skin sensitivity. Moreover, transepidermal water loss was assessed to analyse the rate of skin barrier function recovery; dryness of the leg and roughness of the cheeks was investigated by a dermatologist as well as by self-assessment. The results of the present clinical trial show that oral supplementation with the probiotic decreases skin sensitivity and increases the rate of barrier function recovery. Thus, the data provide evidence that daily intake of ST11 could improve reactive skin condition. PMID:24322879

  2. Double-blind controlled randomised study of lactulose and lignin hydrolysed combination in complex therapy of atopic dermatitis

    PubMed Central

    Perlamutrov, Yuri N.; Olhovskaya, Kira B.; Zakirova, Svetlana A.

    2016-01-01

    Background Atopic dermatitis (AD) is an immune mediated disease with complex pathogenesis characterised by persistency, frequent exacerbations, and inefficacy of existing therapies. Damaged or weakened intestinal microbiocenosis is considered as an important aetiological factor of AD. The aim of this study was to evaluate the efficacy and safety of medical preparation Lactofiltrum (lactulose and sorbent (lignin hydrolysed)) in comparison with placebo in complex with standard therapy of AD. Methods Double-blind, placebo controlled, randomised comparative study of effectiveness and safety of 400 mg lactulose and 120 mg lignin hydrolysed combination as a part of standard combined AD treatment, conducted in parallel groups of patients aged 18–60. Results Comparison of clinical efficacy of Lactofiltrum in combination with the standard treatment has been demonstrated by measuring the following parameters: administration of Lactofiltrum results in 1) distinct clinical improvement in 56.75% of patients, 2) decrease of the mean values of scoring atopic dermatitis (SCORAD) index in 71.94% of patients, 3) elimination of itching in 50% of patients, and 4) life quality improvement for 76.41%. In the placebo group, 1) distinct clinical improvement was observed in 20% of patients, 2) decrease in SCORAD index values observed by 56.98%, 3) itching relief in 15.56%, and 4) life quality improvement by 36.38%. Conclusions Clinical improvement and persistent termination of clinical symptoms provide evidence of effectiveness in use of Lactofiltrum combined with the standard treatment of AD. PMID:27341938

  3. Memantine for axial signs in Parkinson's disease: a randomised, double-blind, placebo-controlled pilot study

    PubMed Central

    Moreau, Caroline; Delval, Arnaud; Tiffreau, Vincent; Defebvre, Luc; Dujardin, Kathy; Duhamel, Alain; Petyt, Gregory; Hossein-Foucher, Claude; Blum, David; Sablonnière, Bernard; Schraen, Susanna; Allorge, Delphine; Destée, Alain; Bordet, Régis; Devos, David

    2013-01-01

    Background Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD). Methods We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day memantine versus placebo (ClinicalTrials.gov:NCT01108029). The main inclusion criterion was the presence of a severe gait disorder and an abnormal, forward-leaning stance. The following parameters were analysed under standardised conditions before and after acute administration of L-dopa: gait (stride length as primary criterion), the United-Parkinson's-Disease-Rating-Scale (UPDRS) motor score and its axial subscore, the hypertonia and strength of the axial extensors and flexors (isokinetic dynamometer), the Dyskinesia Rating Scale score (DRS) and its axial subscore. Results Twenty-five patients were included. The memantine and placebo group did not differ significantly in terms of stride length. However, in the memantine group, we observed significantly better results (vs placebo) for the overall UPDRS score (F(1,21)=4.9; p=0.039(−1)) and its axial subscore (F(1,21)=7.2; p=0.014(−1.1)), axial hypertonia, the axial and overall DRS and axial strength. Conclusions Memantine treatment was associated with lower axial motor symptom and dyskinesia scores but did not improve gait. These benefits must be confirmed in a broader population of patients. PMID:23077087

  4. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study.

    PubMed

    Dubertret, Louis; Zalupca, Lavinia; Cristodoulo, Tania; Benea, Vasile; Medina, Iris; Fantin, Sara; Lahfa, Morad; Pérez, Iñaki; Izquierdo, Iñaki; Arnaiz, Eva

    2007-01-01

    This randomised, double-blind, placebo-controlled, parallel-group, international, dose-ranging study investigated the effect of treatment with rupatadine 5, 10 and 20 mg once daily for 4 weeks on symptoms and interference with daily activities and sleep in 12-65 years-old patients with moderate-to-severe chronic idiopathic urticaria (CIU). Rupatadine 10 and 20 mg significantly reduced pruritus severity by 62.05% and 71.87% respectively, from baseline, over a period of 4 weeks compared to reduction with placebo by 46.59% (p < 0.05). Linear trends were noted for reductions in mean number of wheals and interference with daily activities and sleep with rupatadine 10 and 20 mg over the 4-week treatment period. The two most frequently reported AEs were somnolence (2.90% for placebo, 4.29% for 5 mg-, 5.41% for 10 mg- and 21.43% for 20 mg-rupatadine-treated group) and headache (4.35% for placebo, 2.86% for 5 mg-, 4.05% for 10 mg- and 4.29% for 20 mg-rupatadine-treated group). These findings suggest that rupatadine 10 and 20 mg is a fast-acting, efficacious and safe treatment for the management of patients with moderate-to-severe CIU. Rupatadine decreased pruritus severity, in a dose- and time-dependent manner. PMID:17478385

  5. Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Katayama, Kanako; Misawa, Sonoko; Sato, Yasunori; Sobue, Gen; Yabe, Ichiro; Watanabe, Osamu; Nishizawa, Masatoyo; Kusunoki, Susumu; Kikuchi, Seiji; Nakashima, Ichiro; Ikeda, Shu-ichi; Kohara, Nobuo; Kanda, Takashi; Kira, Jun-ichi; Hanaoka, Hideki; Kuwabara, Satoshi

    2015-01-01

    Introduction Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease. Methods and analysis The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study. Adults with POEMS syndrome who have no indication for transplantation are assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100–300 mg daily) plus dexamethasone (12 mg/m2 on days 1–4 of a 28-day cycle) or placebo plus dexamethasone. Both treatments were administered for 24 weeks (six cycles; randomised comparative study period). Patients who complete the randomised study period or show subacute deterioration during the randomised period participate in the subsequent 48-week open-label safety study (long-term safety period). The primary end point of the study is the reduction rate of serum VEGF levels at 24 weeks. Ethics and dissemination The protocol was approved by the Institutional Review Board of each hospital. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716). The J-POST Trial is currently ongoing and is due to finish in August 2015. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations and will also be disseminated to participants. Trial registration number

  6. Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study

    PubMed Central

    Ossoukhova, Anastasia; Owen, Lauren; Ibarra, Alvin; Pipingas, Andrew; He, Kan; Roller, Marc; Stough, Con

    2010-01-01

    Rationale Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. Objectives The availability of a highly standardised extract of P. quinquefolius (Cereboost™) led us to evaluate its neurocognitive properties in humans for the first time. Methods This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost™ (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. Results There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and ‘calmness’ were significantly improved by 100 mg. There were no changes in blood glucose levels. Conclusions This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile. PMID:20676609

  7. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects.

    PubMed

    Ramnani, P; Costabile, A; Bustillo, A G R; Gibson, G R

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log10 9·6 (sd 0·4)) and lactobacilli (log10 7·7 (sd 0·8)) compared with placebo (log10 9·2 (sd 0·4); P = 0·00) (log10 7·4 (sd 0·7); P = 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2 concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. The in vitro models showed similar increases in bifidobacterial and lactobacilli populations to that observed with the in vivo trial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbers in vitro and in vivo but did not influence other products of fermentation. PMID:26090092

  8. Sildenafil citrate as a medical expulsive therapy for distal ureteric stones: A randomised double-blind placebo-controlled study

    PubMed Central

    Shokeir, Ahmed A.; Tharwat, Mohamed A.; Abolazm, Ahmed Elhussein; Harraz, Ahmed

    2016-01-01

    Objective To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). Patients and methods This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18–65 years, normal renal function, and a single radiopaque unilateral DUS of 5–10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. Results In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P < 0.001). A multivariable Cox proportional hazards model showed that receiving sildenafil citrate was the only independent factor that had a significant impact on stone passage with a hazard ratio of 2.7 (95% confidence interval 1.5–4.8; P < 0.001). Conclusion Sildenafil citrate enhances spontaneous passage of 5–10 mm DUS. PMID:26966585

  9. Tolerability of Nasal Delivery of Humidified and Warmed Air at Different Temperatures: A Randomised Double-Blind Pilot Study

    PubMed Central

    Bibby, Susan; Reddy, Sumeet; Cripps, Terrianne; McKinstry, Steve; Weatherall, Mark; Beasley, Richard; Pilcher, Janine

    2016-01-01

    Objectives. Delivery of warmed, humidified air via nasal high flow therapy could potentially reduce replication of temperature-sensitive viruses in the upper respiratory tract. This study investigates whether nasal high flow therapy is well tolerated by healthy adults at 37°C and 41°C. Methods. In this randomised, double-blind, controlled crossover pilot trial, nasal high flow therapy was used to deliver humidified air at 35 L/min, at either 37°C or 41°C, for three one-hour sessions of use over one day. The alternative was delivered at least 14 days later. Ten healthy, nonsmoking adults were asked, via questionnaire after each day's use, whether they would use nasal high flow therapy while being unwell with a cold or flu if it was demonstrated to improve symptoms. Results. All participants completed both interventions. Eighty percent responded “yes” to future use of nasal high flow therapy, for both 37°C and 41°C. There was no significant change from baseline in saccharin times following either intervention or in the following morning. Conclusions. Delivering humidified air via nasal high flow therapy at both 37°C and 41°C is well tolerated by healthy adults. This supports investigation into the potential use of nasal high flow therapy as treatment in viral upper respiratory tract infections. Trial Registration. This trial is registered with ACTRN12614000183684 (tolerability study of nasal delivery of humidified & warmed air). PMID:27127650

  10. A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the treatment of constipation in children

    PubMed Central

    2014-01-01

    Background Chronic constipation is frequent in children. The objective of this study is to compare the efficacy and safety of PEG 4000 and lactulose for the treatment of chronic constipation in young children. Methods This randomised, double-blind study enrolled 88 young children aged 12 to 36 months, who were randomly assigned to receive lactulose (3.3 g per day) or PEG 4000 (8 g per day) for four weeks. The primary efficacy variable was stool frequency during the fourth week of treatment. Secondary outcomes were the number and frequency of subjective symptoms associated with defecation at each visit. Results Stool frequency was comparable in the two groups at baseline (lactulose: 0.7 ± 0.5; PEG 4000: 0.5 ± 0.55). Mean stool frequency increased from 0.70 ± 0.50 stools/day at baseline to 0.80 ± 0.41 at Week 4 in the lactulose group and from 0.50 ± 0.55 to 1.10 ± 0.55 stools/day in the PEG 4000 group. A significant difference was observed in the adjusted mean change from baseline, which was 0.15 stools/day in the lactulose group and 0.51 stools/day in the PEG 4000 group, with a least-squares mean difference of 0.36 stools/day [95% CI: 0.16 to 0.56]. With respect to secondary outcome variables, stool consistency and ease of stool passage improved more in the PEG 4000 group (p = 0.001). The incidence of adverse events was similar in both groups, the majority of which were mild. Conclusions PEG 4000 has superior efficacy to lactulose for the treatment of chronic constipation in young children and is well tolerated. Trial registration US National Institute of Health Clinical Trials database; study NCT00255372 first registered 17th November 2005. PMID:24943105

  11. Acute Dietary Nitrate Supplementation and Exercise Performance in COPD: A Double-Blind, Placebo-Controlled, Randomised Controlled Pilot Study

    PubMed Central

    Curtis, Katrina J.; O’Brien, Katie A.; Tanner, Rebecca J.; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I.; Edwards, Lindsay M.; Hopkinson, Nicholas S.

    2015-01-01

    Background Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD. Methods We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage. Results 21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve. Conclusions Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype. Trial Registration ISRCTN Registry ISRCTN66099139 PMID:26698120

  12. Rupatadine 10 mg and cetirizine 10 mg in seasonal allergic rhinitis: a randomised, double-blind parallel study.

    PubMed

    Martínez-Cócera, C; De Molina, M; Martí-Guadaño, E; Pola, J; Conde, J; Borja, J; Pérez, I; Arnaiz, E; Izquierdo, I

    2005-01-01

    This randomised, double-blind, parallel-group, multicentre clinical trial evaluated the efficacy and safety of rupatadine, a new antihistamine with antiplatelet-activating factor (PAF) activity, and cetirizine in the treatment of patients with seasonal allergic rhinitis (SAR). A total 249 patients were randomised to receive rupatadine 10 mg once daily (127 patients) or cetirizine 10 mg (122 patients) for two weeks. The main efficacy variable was the mean total daily symptom score (mTDSS) and was based on the daily subjective assessment of the severity of each rhinitis symptom--nasal (runny nose, sneezing, nasal itching and nasal obstruction) and non-nasal (conjunctival itching, tearing, and pharyngeal itching)--recorded by patients in their diaries. The mTDSS was 0.7 for both treatment groups (intention to treat analysis). In the investigator's global evaluation of efficacy at the seventh day, 93.3% and 83.7% patients in the rupatadine and cetirizine groups, respectively, showed some or great improvement (p = 0.022). In the per protocol analysis (n = 181), runny nose at the seventh day of treatment was absent or mild in 81.1% of patients in the rupatadine group and in 68.6% of patients in the cetirizine group (p = 0.029). In any case statistical significance was not maintained at the second week. Overall, all treatments were well tolerated. Adverse events (AEs) were similar in both treatment groups, i.e. headache, somnolence and fatigue/asthenia as the most often reported. Somnolence was reported in 9.6% and 8.5% of patients treated with rupatadine or cetirizine, respectively. The most reported AEs (67%) were mild in intensity. Our results suggest that rupatadine 10 mg may be a valuable and safe alternative for the symptomatic treatment of SAR. PMID:15864879

  13. Chiropractic spinal manipulative therapy for migraine: a study protocol of a single-blinded placebo-controlled randomised clinical trial

    PubMed Central

    Chaibi, Aleksander; Šaltytė Benth, Jūratė; Tuchin, Peter J; Russell, Michael Bjørn

    2015-01-01

    Introduction Migraine affects 15% of the population, and has substantial health and socioeconomic costs. Pharmacological management is first-line treatment. However, acute and/or prophylactic medicine might not be tolerated due to side effects or contraindications. Thus, we aim to assess the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraineurs in a single-blinded placebo-controlled randomised clinical trial (RCT). Method and analysis According to the power calculations, 90 participants are needed in the RCT. Participants will be randomised into one of three groups: CSMT, placebo (sham manipulation) and control (usual non-manual management). The RCT consists of three stages: 1 month run-in, 3 months intervention and follow-up analyses at the end of the intervention and 3, 6 and 12 months. The primary end point is migraine frequency, while migraine duration, migraine intensity, headache index (frequency x duration x intensity) and medicine consumption are secondary end points. Primary analysis will assess a change in migraine frequency from baseline to the end of the intervention and follow-up, where the groups CSMT and placebo and CSMT and control will be compared. Owing to two group comparisons, p values below 0.025 will be considered statistically significant. For all secondary end points and analyses, a p value below 0.05 will be used. The results will be presented with the corresponding p values and 95% CIs. Ethics and dissemination The RCT will follow the clinical trial guidelines from the International Headache Society. The Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services have approved the project. Procedure will be conducted according to the declaration of Helsinki. The results will be published at scientific meetings and in peer-reviewed journals. Trial registration number NCT01741714. PMID:26586317

  14. Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate

    PubMed Central

    2013-01-01

    Background Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania. Methods/design A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression–Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-‘Vigilance Algorithm Leipzig’ (VIGALL). Discussion A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives. Trial registration ClinicalTrials.gov: NCT 01541605 PMID:23446109

  15. Regional diffusion of botulinum toxin in facial muscles: a randomised double-blind study and a consideration for clinical studies with split-face design.

    PubMed

    Punga, Anna Rostedt; Eriksson, Annika; Alimohammadi, Mohammad

    2015-11-01

    Despite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic treatments, the potential spreading of BoNTA to surrounding tissues remains unknown. A patient with hemifacial paralysis upon blepharospasm treatment with low dose of BoNTA, prompted us to investigate the spreading effect. A randomised, double-blind study was conducted in which 5 healthy women (33-52 years) were treated with different doses of onabotulinum toxin unilaterally in the corrugator muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks following BoNTA injection. CMAP of the treated glabellar muscles was reduced to approximately 40% in all dose groups. Additionally, contralateral CMAP reduction was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA in facial muscle application, which raises question on the reliability of split-face models in BoNTA studies. PMID:25766591

  16. Efficacy and safety of flupirtine maleate and tramadol hydrochloride in postoperative pain management--a prospective randomised double blinded study.

    PubMed

    Naser, Syed Mohammed; Sarkar, Niladri; Biswas, Arunava; Kamal, Firdaus; Prakash, Raghu; Rahaman, Q M; Das, Anup Kumar

    2012-03-01

    The study was conducted to evaluate the efficacy and safety of flupirtine maleate 100 mg thrice daily compared to tramadol hydrochloride 50 mg thrice daily as postoperative pain management for 5 days. A total of 113 postoperative patients were recruited for the study. Those who met the inclusion criteria (n = 104) were randomised into two treatment groups. One of the groups received flupirtine maleate and the other tramadol hydrochloride both orally. The pain intensity was assessed by visual analogue scale. Patients were informed to report any adverse effect encountered during the study period. The overall effect of the drug (global assessment of the study medication) on pain and side-effects was assessed by the patients at the end of the trial on a categorical scale. There was significant reduction in pain score (p < 0.001) in the flupirtine group with almost equal efficacy to that of tramadol group but the incidence of adverse effects were much less (7.4%) and didn't need discontinuation of the study. All drugs were assessed as good. Therefore it can be concluded that oral flupirtine can deliver the same analgesic efficacy as oral tramadol for postoperative pain relief, which might be beneficial for avoiding the adverse effects ofopioids and non-steroidal anti-inflammatory drug therapy. PMID:23029946

  17. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study

    PubMed Central

    Terkeltaub, R; Sundy, J S; Schumacher, H R; Murphy, F; Bookbinder, S; Biedermann, S; Wu, R; Mellis, S; Radin, A

    2009-01-01

    Background: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1β (IL1β) pathway may offer a new treatment strategy for gout. Objective: To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study. Methods: This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up. Results: Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients’ self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly. Conclusions: This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication. PMID:19635719

  18. A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study.

    PubMed

    Hsu, C-H; Lin, P-C; Kuo, F-C; Wang, J-W

    2015-07-01

    Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA. PMID:26130344

  19. Efficacy of Rivaroxaban for thromboprophylaxis after Knee Arthroscopy (ERIKA). A phase II, multicentre, double-blind, placebo-controlled randomised study.

    PubMed

    Camporese, Giuseppe; Bernardi, Enrico; Noventa, Franco; Bosco, Mario; Monteleone, Giuseppe; Santoro, Luca; Bortoluzzi, Cristiano; Freguja, Stefano; Nardin, Michela; Marullo, Matteo; Zanon, Giacomo; Mazzola, Claudio; Damiani, Guido; Maniscalco, Pietro; Imberti, Davide; Lodigiani, Corrado; Becattini, Cecilia; Tonello, Chiara; Agnelli, Giancarlo

    2016-08-01

    Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted. PMID:27075710

  20. Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

    PubMed Central

    2013-01-01

    Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

  1. Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia

    PubMed Central

    Lambert, Saba M.; Nigusse, Shimelis D.; Alembo, Digafe T.; Walker, Stephen L.; Nicholls, Peter G.; Idriss, Munir H.; Yamuah, Lawrence K.; Lockwood, Diana N. J.

    2016-01-01

    Background Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. Methods and Results Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. Conclusions This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients’ assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid–sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a

  2. Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period

    PubMed Central

    Mofid, Layla S; Casapía, Martín; Montresor, Antonio; Rahme, Elham; Fraser, William D; Marquis, Grace S; Vercruysse, Jozef; Allen, Lindsay H; Gyorkos, Theresa W

    2015-01-01

    Introduction Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes. Methods and analysis A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis. Ethics and dissemination Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences. Trial registration number Clinicaltrials.gov: NCT01748929. PMID:26084556

  3. Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo

    PubMed Central

    Burgess, Ian F; Brunton, Elizabeth R; French, Rebecca; Burgess, Nazma A

    2014-01-01

    Objectives To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations. Setting Randomised, double-blind, cross-over, community study in Cambridgeshire, UK. Participants 63 male and female schoolchildren aged 4–16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated. Interventions Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray. Primary and secondary outcome measures The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use. Results Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days. Conclusions Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly. Trial registration number ISRCTN09524995. PMID:24879825

  4. The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study.

    PubMed

    Sousa, Ana R; Riley, John H; Church, Alison; Zhu, Chang-Qing; Punekar, Yogesh S; Fahy, William A

    2016-01-01

    Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0-6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0-6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (-1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372). PMID:27334739

  5. The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study

    PubMed Central

    Sousa, Ana R; Riley, John H; Church, Alison; Zhu, Chang-Qing; Punekar, Yogesh S; Fahy, William A

    2016-01-01

    Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0–6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0–6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (−1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372). PMID:27334739

  6. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study

    PubMed Central

    Thomas, Michael; Sheran, Jane; Smith, Natalie; Fonseca, Sofia; Lee, Amanda J

    2007-01-01

    Background Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma. Methods We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means. Results No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8). Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15. Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant

  7. Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial

    PubMed Central

    Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N

    2013-01-01

    Introduction Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Methods and analysis Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m2) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. Ethics and dissemination The protocol was approved by the National Research Ethics Service (East Midlands—Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52

  8. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

    PubMed Central

    Cluver, Catherine A; Walker, Susan P; Mol, Ben W; Theron, Gerard B; Hall, David R; Hiscock, Richard; Hannan, N; Tong, S

    2015-01-01

    Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB

  9. A Randomised, Double-Blind, Placebo-Controlled Trial of Actovegin in Patients with Post-Stroke Cognitive Impairment: ARTEMIDA Study Design

    PubMed Central

    Guekht, Alla; Skoog, Ingmar; Korczyn, Amos D.; Zakharov, Vladimir; Eeg, Martin; Vigonius, Ulf

    2013-01-01

    Background No drug treatment to date has shown convincing clinical evidence of restoring cognitive function or preventing further decline after stroke. The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI) and will explore whether Actovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment. Design ARTEMIDA is a 12-month, multicentre trial in patients (planned a total of 500, now recruited) with cognitive impairment following ischaemic stroke. The study consists of a baseline screening (≤7 days after stroke), after which eligible patients are randomised to Actovegin (2,000 mg/day for up to 20 intravenous infusions followed by 1,200 mg/day orally) or placebo for a 6-month double-blind treatment period. Patients will be followed up for a further 6 months, during which time they will be treated in accordance with standard clinical practice. The primary study endpoint is change from baseline in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version. Secondary outcomes include: Montreal Cognitive Assessment; dementia diagnosis (ICD-10); National Institutes of Health Stroke Scale; Barthel Index; EQ-5D; Beck Depression Inventory, version II, and safety. Conclusion There is a clear need for effective treatments for PSCI. ARTEMIDA should provide important insights into the use of a novel drug therapy for PSCI. PMID:24516413

  10. Supplementation of xylitol-containing chewing gum with probiotics: a double blind, randomised pilot study focusing on saliva flow and saliva properties.

    PubMed

    Gueimonde, Laura; Vesterlund, Satu; García-Pola, María J; Gueimonde, Miguel; Söderling, Eva; Salminen, Seppo

    2016-03-01

    The aim of this study was to investigate the impact of daily chewing, for 12 weeks, of 2 different probiotic gums compared with placebo on saliva flow rate, saliva IgA levels and saliva pH. The intervention study included 54 adult volunteers with hyposalivation in a double-blind, randomised and placebo-controlled design with three parallel groups. Volunteers were randomly assigned to 3 different groups: subjects in group A (n = 19) were given placebo chewing gum, group B (n = 17) received Bifidobacterium animalis ssp. lactis Bb12 (ATCC 27536) and group C (n = 18) received Lactobacillus rhamnosus LGG (ATCC 53103), Bifidobacterium longum 46 (DSM 14583) and Bifidobacterium longum 2C (DSM 14579) gums, during 3 months. Two volunteers from group B left the study for personal reasons leaving 19, 15 and 18 volunteers, respectively, for analyses. Clinical examinations, personal interviews, sialometries and saliva sampling were conducted at baseline and after 1, 2, 3 and 4 months. No statistically significant differences were found between probiotic and placebo groups for any of the parameters analysed. No side effects of probiotic or placebo chewing gums were observed. Chewing gum, with and without probiotics, had a positive impact on salivary flow rate and saliva pH and IgA levels. PMID:26913493

  11. Topical antimycotic treatment of atopic dermatitis in the head/neck area. A double-blind randomised study.

    PubMed

    Broberg, A; Faergemann, J

    1995-01-01

    In order for us to evaluate the effect of topical antimycotic treatment in patients with atopic dermatitis affecting the head and neck area, 60 patients (36 females and 24 males; median age 28 years; range 14-53 years) were included in a double-blind study during 6 weeks. Of the 53 evaluable patients, 55% had positive skin prick tests to Pityrosporum ovale. In addition to oral antibiotic treatment, patients in group A (n = 26) were given miconazole-hydrocortisone cream and ketoconazole shampoo, whereas patients in group B (n = 27) were given hydrocortisone cream and placebo shampoo. At the start of the study P. ovale cultures were positive in 83% of all patients (no significant difference between the groups). After 4 weeks of treatment, there was a decrease in P. ovale colonisation in group A (p < 0.001) but not in group B. Patients in both groups improved (p < 0.001). The decrease in eczema score did not differ between group A and group B after 4 weeks' treatment. A further decrease of the eczema score was seen in both groups at the end of the study, but no difference was found between the groups. PMID:7747534

  12. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study

    PubMed Central

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

  13. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study.

    PubMed

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

  14. Comparative evaluation of intrathecal morphine and intrathecal dexmedetomidine in patients undergoing gynaecological surgeries under spinal anaesthesia: A prospective randomised double blind study

    PubMed Central

    Kurhekar, Pranjali; Kumar, S Madan; Sampath, D

    2016-01-01

    Background and Aims: Inrathecal opioids like morphine added to local anaesthetic agents have been found to be effective in achieving prolonged post-operative analgesia. Intrathecal dexmedetomidine may be devoid of undesirable side effects related to morphine and hence, this study was designed to evaluate analgesic efficacy, haemodynamic stability and adverse effects of both these adjuvants in patients undergoing gynaecological surgeries. Methods: This was a prospective, randomised, double blind study involving 25 patients in each group. Group M received 15 mg of 0.5% hyperbaric bupivacaine with 250 μg of morphine while Group D received 15 mg of 0.5% hyperbaric bupivacaine with 2.5 μg of dexmedetomidine. Characteristics of spinal block, time for first rescue analgesic and total dose of rescue analgesics were noted. Vital parameters and adverse effects were noted perioperatively. Data analysis was done with independent two sample t-test and Mann–Whitney U test. Results: Time for first rescue analgesic (P = 0.056) and total analgesic demand were similar in both groups. Duration of sensory (P = 0.001) and motor (P = 000) block was significantly higher in dexmedetomidine group. Itching was noticed in 36% and nausea in 52% of patients in the morphine group, either of which was not seen in dexmedetomidine group. Conclusion: Intrathecal dexmedetomidine produces prolonged motor and sensory blockade without undesirable side effects but intraoperative hypotension was more frequent in dexmedetomidine group. PMID:27330198

  15. Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude.

    PubMed

    Martin, Daniel S; Gilbert-Kawai, Edward T; Meale, Paula M; Fernandez, Bernadette O; Cobb, Alexandra; Khosravi, Maryam; Mitchell, Kay; Grocott, Michael P W; Levett, Denny Z H; Mythen, Michael G; Feelisch, Martin

    2013-11-01

    The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients. PMID:24028941

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

    PubMed Central

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

    2010-01-01

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

  17. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group.

    PubMed Central

    Bräutigam, M.; Nolting, S.; Schopf, R. E.; Weidinger, G.

    1995-01-01

    OBJECTIVE--To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium. DESIGN--Multicentre, double blind, parallel group study. SETTING--17 university hospitals, one army hospital, and five dermatology practices. PATIENTS--195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy. INTERVENTIONS--Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks. MAIN OUTCOME MEASURES--Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment. RESULTS--At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION--Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection. PMID:7580551

  18. Impact of anti-Giardia and anthelminthic treatment on infant growth and intestinal permeability in rural Bangladesh: a randomised double-blind controlled study.

    PubMed

    Goto, Rie; Mascie-Taylor, C G Nicholas; Lunn, Peter G

    2009-05-01

    In order to test the impact of Giardia and geohelminthic infection on infant growth faltering in Bangladesh, a randomised double-blind placebo controlled intervention of 36 weeks' duration was conducted in a rural community located 40 km northwest of Dhaka. Infants aged between 3 and 15 months were randomly assigned to either anti-Giardia and anthelminthic treatment, anti-Giardia treatment only, or a control. Weight and supine length were recorded every 4 weeks. Every 12 weeks intestinal permeability (lactulose/mannitol ratio), haemoglobin, plasma albumin, alpha-1-acid glycoprotein, IgG and Giardia-specific IgM (GSIgM) and eggs of the three common geohelminths and G. intestinalis cysts were determined. Data on 222 fully compliant infants were analysed. No significant differences in intestinal permeability, biochemical or anthropometric variables were found between the intervention groups, although there were associations between improvement in small intestinal mucosal function and better weight-for-age and weight-for-height (length) Z-scores. GSIgM titres indicated high endemicity with rapid re-infection of Giardia among infants; over 95% of infants were positive throughout the study, whereas the stool examination showed very few infants with either geohelminth eggs or Giardia cysts. PMID:18789466

  19. A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil

    PubMed Central

    POMPEO, A C L; ROSENBLATT, C; BERTERO, E; DA ROS, C T; CAIROLI, C E D; DAMIÃO, R; WROCLAWSKI, E R; KOFF, W J; MESQUITA, F; PINHEIRO, G E

    2006-01-01

    Brazilian patients with benign prostatic hyperplasia were randomised in a 12-week, double-blind, double-dummy study to receive doxazosin gastrointestinal therapeutic system (GITS) 4 mg q.i.d. (n = 82) or tamsulosin 0.4 q.i.d. (n = 83). Primary endpoints were the absolute and percentage change from baseline in symptoms measured by International Prostate Symptom Score (IPSS). Secondary endpoints included IPSS, quality-of-life (QOL) question from the IPSS, and questions 6 and 7 of the Sexual Function Abbreviated Questionnaire (SFAQ) at weeks 4 and 12. Doxazosin GITS and tamsulosin improved IPSS with no significant differences between groups at week 12. During weeks 4–8, tamsulosin-treated patients demonstrated a slower improvement (p < 0.001) in IPSS than doxazosin GITS-treated patients. The proportion of satisfied patients was observed earlier with doxazosin GITS (p = 0.006) vs. tamsulosin. At week 12, the proportion of patients with little or no difficulty at ejaculation (Q6 of SFAQ) was higher in the doxazosin GITS group (p = 0.019). Both treatments were well tolerated. PMID:16942589

  20. Efficacy and safety of ceftriaxone for amyotrophic lateral sclerosis: results of a multi-stage, randomised, double-blind, placebo-controlled, phase 3 study

    PubMed Central

    Cudkowicz, Merit E; Titus, Sarah; Kearney, Marianne; Yu, Hong; Sherman, Alexander; Schoenfeld, David; Hayden, Douglas; Shui, Amy; Brooks, Benjamin; Conwit, Robin; Felsenstein, Donna; Greenblatt, David J.; Keroack, Myles; Kissel, John T; Miller, Robert; Rosenfeld, Jeffrey; Rothstein, Jeffrey; Simpson, Ericka; Tolkoff-Rubin, Nina; Zinman, Lorne; Shefner, Jeremy M.

    2014-01-01

    Background Glutamate excitotoxicity may contribute to the pathophysiology of amyotrophic lateral sclerosis (ALS). Studies in ALS animal models show decreased excitatory amino acid transporter 2 (EAAT2) overexpression delays onset and prolongs survival, and that ceftriaxone increases EAAT2 activity in rodent brains. Phase 1, 2, and 3 clinical studies of ceftriaxone for ALS were combined into a three-stage, nonstop study. Methods 514 participants were randomised to ceftriaxone (n=341) or placebo (n=173); 66 participants were enrolled in stages 1 (pharmacokinetics) and 2 (safety) to determine cerebrospinal fluid and blood pharmacokinetics and safety of two dosages: 2 grams and 4 grams/day of ceftriaxone. All participants continued into stage 3 (efficacy) in blinded fashion with participants who began treatment on the discontinued dose analysed in the same group as those on the dose that that was continued. In stage 3, 44 participants previously assigned to 2 or 4 g ceftriaxone in stage 2 received 4 g ceftriaxone; 21 participants assigned to placebo in stage 2 continued on placebo. 448 new participants were randomized in stage 3 to 4 g ceftriaxone or placebo (2:1). Participants, family members and all site staff were blinded to treatment assignment. Computerized randomisation sequence using permuted blocks of 3 was stratified by riluzole use and blocked by site. Participants received 2g ceftriaxone or placebo BID via a central venous catheter (CVC) administered in the home setting by a trained caregiver. To minimize biliary side effects, participants assigned to ceftriaxone also received 300 mg ursodiol BID in a blinded manner; those assigned to placebo received matched placebo capsules BID. The co-primary efficacy outcomes were survival and functional decline, using the slope of scores on the ALS Functional Rating Scale-Revised (ALSFRS-R). The first participant entered the trial on September 4, 2006 (stage 1); the first stage-3 participant entered on June 4, 2009. The

  1. Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies

    PubMed Central

    2014-01-01

    Background AZD9164 has demonstrated potential as an inhaled, long-acting, muscarinic antagonist (LAMA) bronchodilator. However, in patients with COPD, but not in healthy subjects, a transient initial drop in FEV1 was observed following inhalation of nebulised doses of AZD9164 in citrate buffer. Two additional studies were conducted to further assess the safety and tolerability of multiple ascending doses of AZD9164 in 27 white and 18 Japanese healthy subjects and in 4 patients with COPD. In these studies, AZD9164 was inhaled via Turbuhaler™. Methods These were Phase I, randomised, double-blind, placebo-controlled, multiple ascending dose (MAD) studies conducted in Sweden and UK. Healthy subjects (mean age 25.9 yrs) and patients with COPD (mean age 66 yrs, mean post-bronchodilator FEV1 60.1% predicted normal value) were randomised 2:1 to active treatment (400, 1000 or 2800 μg delivered doses of AZD9164) or placebo. Results No safety or tolerability concerns were identified in the healthy subjects at doses up to and including 2800 μg and both studies confirmed the bronchodilator effect of AZD9164. However, the first 3 patients in the COPD cohort who received AZD9164 (1000 μg) experienced a transient fall in FEV1 5 to 15 minutes after inhalation of AZD9164 while the patient receiving placebo did not. The study safety review process then resulted in cessation of further activities on AZD9164. Retrospective analysis showed that two healthy subjects had also had transient falls in FEV1 shortly after inhalation of AZD9164 400 and 2800 μg respectively, although neither reported any related respiratory symptoms or other AEs. Conclusions These results show that transient paradoxical bronchoconstriction can occur in some healthy subjects, in addition to patients with COPD, following inhalation of AZD9164 and that the citrate buffer used in the nebulised formulation cannot have been the only cause of the drop in FEV1 in previous studies. As preclinical data do not

  2. Video-based instructions for surgical hand disinfection as a replacement for conventional tuition? A randomised, blind comparative study

    PubMed Central

    Weber, Uwe; Constantinescu, Mihai A.; Woermann, Ulrich; Schmitz, Felix; Schnabel, Kai

    2016-01-01

    Introduction: Various different learning methods are available for planning tuition regarding the introduction to surgical hand disinfection. These learning methods should help to organise and deal with this topic. The use of a video film is an alternative to conventional tuition due to the real presentation possibilities of practical demonstration. Objective: This study examines by way of comparison which form of communication is more effective for learning and applying surgical hand disinfection for medical students in their first year of studies: video-based instruction or conventional tuition. Methodology: A total of 50 first-year medical students were randomly allocated either to the “Conventional Instruction” (CI) study group or to the “Video-based Instruction” (VI) study group. The conventional instruction was carried out by an experienced nurse preceptor/nurse educator for the operating theatre who taught the preparatory measures and the actual procedure in a two-minute lesson. The second group watched a two-minute video sequence with identical content. Afterwards, both groups demonstrated practically the knowledge they had acquired at an individual practical test station. The quality (a) of the preparation and (b) of the procedure as well as (c) the quality of the results was assessed by 6 blind experts using a check list. The acceptability of the respective teaching method was also asked about using a questionnaire. Results: The group performance did not differ either in the preparation (t=-78, p<0.44) or in the quality (t=-99, p<0.34). With respect to performance, it was possible to demonstrate a strong treatment effect. In the practical (t=-3.33, p<0.002, d=0.943) and in the total score (t=-2.65, p<0.011, d=0.751), the group with video-based instruction achieved a significantly better result. In response to the question as to which of the two learning methods they would prefer, the significant majority (60.4%) of students stated video

  3. Study of Mental Activity and Regular Training (SMART) in at risk individuals: A randomised double blind, sham controlled, longitudinal trial

    PubMed Central

    2011-01-01

    Background The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects. Methods SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk × 6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS). Discussion SMART will provide a novel evaluation of the immediate and long term

  4. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

    PubMed Central

    Schlesinger, Naomi; Mysler, Eduardo; Lin, Hsiao-Yi; De Meulemeester, Marc; Rovensky, Jozef; Arulmani, Udayasankar; Balfour, Alison; Krammer, Gerhard; Sallstig, Peter; So, Alexander

    2011-01-01

    Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. PMID:21540198

  5. Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer.

    PubMed

    Unger, C; Häring, B; Kruse, A; Thumann, A; Schneider, B; Clemm, C; Weber, B; Clevert, H D; Hockertz, S; Kalousek, M B

    2001-01-01

    The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU. PMID:11367875

  6. A single-blind randomised controlled trial of the effects of a web-based decision aid on self-testing for cholesterol and diabetes. study protocol

    PubMed Central

    2012-01-01

    Background Self-tests, tests on body materials to detect medical conditions, are widely available to the general public. Self-testing does have advantages as well as disadvantages, and the debate on whether self-testing should be encouraged or rather discouraged is still ongoing. One of the concerns is whether consumers have sufficient knowledge to perform the test and interpret the results. An online decision aid (DA) with information on self-testing in general, and test specific information on cholesterol and diabetes self-testing was developed. The DA aims to provide objective information on these self-tests as well as a decision support tool to weigh the pros and cons of self-testing. The aim of this study is to evaluate the effect of the online decision aid on knowledge on self-testing, informed choice, ambivalence and psychosocial determinants. Methods/Design A single blind randomised controlled trial in which the online decision aid 'zelftestwijzer' is compared to short, non-interactive information on self-testing in general. The entire trial will be conducted online. Participants will be selected from an existing Internet panel. Consumers who are considering doing a cholesterol or diabetes self-test in the future will be included. Outcome measures will be assessed directly after participants have viewed either the DA or the control condition. Weblog files will be used to record participants' use of the decision aid. Discussion Self-testing does have important pros and cons, and it is important that consumers base their decision whether they want to do a self-test or not on knowledge and personal values. This study is the first to evaluate the effect of an online decision aid for self-testing. Trial registration Dutch Trial Register: NTR3149 PMID:22216905

  7. A pilot double-blind randomised placebo-controlled dose–response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol

    PubMed Central

    Fernando, Shavi; Osianlis, Tiki; Vollenhoven, Beverley; Wallace, Euan; Rombauts, Luk

    2014-01-01

    Introduction High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3–4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose–response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. Methods and analyses We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2′-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethics and dissemination Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. Trial registration number ACTRN

  8. The effect of metoprolol succinate on the cardiac function of patients with thalassaemia cardiomyopathy: a double-blind randomised study

    PubMed Central

    Kojury, Javad; Zolghadrasli, Abdolali; Karimi, Mehran; Babaee Beighi, Mohammad Ali; Namazi, Soha

    2014-01-01

    Background Heart failure is the most common cause of mortality in β-thalassaemia major. However, the management of this disease, apart from chelation therapy, is largely empirical. Therefore, we decided to evaluate the effect of metoprolol succinate on patients with thalassaemia cardiomyopathy (TCM). Materials and methods In this clinical trial, 45 patients with TCM were randomised to receive either metoprolol (n=26) or placebo (n=19). Echocardiography and a 6 min walk test were performed at baseline and repeated after 6 months and the values compared. Results In the metoprolol group, left ventricular ejection fraction (LVEF) rose from 38.65% to 42.84% (p<0.001), while it decreased in the placebo group from 37.89% to 35.84% (p=0.01); the difference between the two groups was significant (p<0.001). Left ventricular (LV) mass in the metoprolol group decreased from 154.31 to 144.26 g (p=0.02), while in the placebo group it increased from 174.32 to 200.15 g (p=0.68); the difference between the two groups was significant (p<0.001). End systolic volume (ESV) decreased in the metoprolol group from 42.19 to 36.73 cm3 (p<0.001) but increased from 47.37 to 57.42 cm3 in the placebo group (p=0.144); the difference between the groups was significant (p<0.001). No differences in exercise capacity or pulmonary capillary wedge pressure were seen between the two groups (p=0.268 and p=0.535, respectively). Conclusions Metoprolol succinate as a β-blocker may have the potential to significantly improve systolic function in patients with TCM and reverse LV remodelling to the same extent as in other types of cardiomyopathy. Trial registration number NCT01863173. PMID:27326168

  9. Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

    PubMed Central

    Zuckerman, J. N.; Sabin, C.; Craig, F. M.; Williams, A.; Zuckerman, A. J.

    1997-01-01

    OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard. RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. CONCLUSION: A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres. PMID:9040320

  10. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study

    PubMed Central

    Berth-Jones, John; Damstra, Robert J; Golsch, Stefan; Livden, John K; Van Hooteghem, Oliver; Allegra, Fulvio; Parker, Christine A

    2003-01-01

    Objective To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis. Design Randomised, double blind, parallel group study of 20 weeks' duration. Setting Dermatology outpatient clinics (6 countries, 39 centres). Participants Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare. Methods Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected. Main outcome measure Time to relapse of atopic dermatitis during maintenance phase. Results 376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events. Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly

  11. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

    PubMed Central

    Philipp, T.; Anlauf, M.; Distler, A.; Holzgreve, H.; Michaelis, J.; Wellek, S.

    1997-01-01

    OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers. PMID:9251545

  12. Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

    PubMed Central

    Ställberg, Björn; Selroos, Olof; Vogelmeier, Claus; Andersson, Eva; Ekström, Tommy; Larsson, Kjell

    2009-01-01

    Background Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation. Methods This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home. A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined. Results Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified. Conclusion High dose budesonide/formoterol was as

  13. Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.

    PubMed Central

    Banerjee, S; Hellier, J; Romeo, R; Dewey, M; Knapp, M; Ballard, C; Baldwin, R; Bentham, P; Fox, C; Holmes, C; Katona, C; Lawton, C; Lindesay, J; Livingston, G; McCrae, N; Moniz-Cook, E; Murray, J; Nurock, S; Orrell, M; O'Brien, J; Poppe, M; Thomas, A; Walwyn, R; Wilson, K; Burns, A

    2013-01-01

    OBJECTIVE: Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. DESIGN: Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. SETTING: Nine English old-age psychiatry services. PARTICIPANTS: A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. EXCLUSIONS: clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. INTERVENTIONS: (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily. MAIN OUTCOME MEASURES: OUTCOME: CSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed. RESULTS: Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine). OUTCOME: Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112). HARMS: Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine

  14. The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial- study protocol

    PubMed Central

    2013-01-01

    Background Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition. This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. Methods/Designs This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. Discussion This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ

  15. A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients

    PubMed Central

    Stricker, Kirstin; Yu, Sue; Krammer, Gerhard

    2008-01-01

    Background Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions. Methods This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (n = 154) or rofecoxib 25 mg od (n = 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs. Results Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (p < 0.05). A

  16. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.

    PubMed

    Gaussem, Pascale; Alhenc-Gelas, Martine; Thomas, Jean-Louis; Bachelot-Loza, Christilla; Remones, Veronique; Ali, Fouad Dali; Aiach, Martine; Scarabin, Pierre-Yves

    2011-03-01

    Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this. PMID:21225090

  17. Single-blinded, randomised preliminary study evaluating the effects of 2 Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty

    PubMed Central

    Tzeng, Chung-Yuh; Chang, Shih-Liang; Wu, Chih-Cheng; Chang, Chu-Ling; Chen, Wen-Gii; Tong, Kwok-Man; Huang, Kui-Chou; Hsieh, Ching-Liang

    2015-01-01

    Objective To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA), Methods In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 (Zusanli) and GB34 (Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann–Whitney test was used to show the difference between two groups and the Kruskal–Wallis test to show the difference between the three groups. Results The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p<0.001) and 90.7±94.8 min in the NPG (p<0.001); there was no difference between the EAG and NPG groups (p>0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups. Conclusions In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen. PMID:25910930

  18. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn’s disease: Results from a randomised double-blind placebo-controlled study

    PubMed Central

    Raftery, Tara; Martineau, Adrian R; Greiller, Claire L; Ghosh, Subrata; McNamara, Deirdre; Bennett, Kathleen; Meddings, Jon

    2015-01-01

    Background Vitamin D (vitD) supplementation may prolong remission in Crohn’s disease (CD); however, the clinical efficacy and mechanisms are unclear. Aim To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation. Methods In a double-blind randomised placebo-controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL-37 in ng/mL), human-beta-defensin-2 (hBD2 in pg/mL), disease activity (Crohn’s Disease Activity Index (CDAI)), C-reactive protein (CRP in mg/L), fecal calprotectin (µg/g), Quality of Life (QoL) and serum 25-hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos. Results At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro-duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L. Conclusion Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388). PMID:26137304

  19. Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)

    PubMed Central

    Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup; Poulsen, Jakob Lykke; Dahan, Albert; Wilder-Smith, Oliver; Madzak, Adnan; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr

    2015-01-01

    Introduction Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of the N-methyl-d-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. Methods and analysis 40 patients with CP will be enrolled. Patients are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8 weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP. Ethics and dissemination The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be

  20. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group.

    PubMed Central

    Bodsworth, N J; Crooks, R J; Borelli, S; Vejlsgaard, G; Paavonen, J; Worm, A M; Uexkull, N; Esmann, J; Strand, A; Ingamells, A J; Gibb, A

    1997-01-01

    OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection in immunocompetent individuals. METHODS: 739 patients with a history of recurrent genital HSV infection received either oral valaciclovir (500 mg twice daily) or aciclovir (200 mg five times daily) for 5-days for treatment of their next recurrent episode in a controlled, randomised, double blind trial. Patients self initiated therapy at the first signs and/or symptoms of the HSV recurrence, then were assessed in clinic on five occasions over 7 days, and twice weekly thereafter until lesions had healed. Safety was evaluated through adverse experience reports and haematology and biochemistry monitoring. RESULTS: No significant differences were detected between valaciclovir and aciclovir for the primary endpoint, the duration of all signs and symptoms which included lesion healing and pain/discomfort. The hazard ratio [95% confidence interval] for valaciclovir v aciclovir was 0.93 [0.79, 1.08]. Lesion healing time was similar in each treatment group (hazard ratio valaciclovir v aciclovir 0.96 [0.80, 1.14]). The odds ratio of valaciclovir v aciclovir in preventing the development of vesicular/ulcerative lesions was 1.08 [0.82, 1.42]. Percentages of patients in whom all HSV cultures were negative were similar in the valaciclovir and aciclovir groups at 59% and 54% respectively; for patients having equal to or more than one positive culture result after treatment initiation, cessation of virus shedding was similarly rapid for the two treatments (hazard ratio 0.98 [0.75, 1.27]). The safety profiles of valaciclovir and aciclovir were comparable with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that valaciclovir 500 mg twice daily is equivalent in efficacy to aciclovir 200 mg five times daily as episodic treatment of recurrent

  1. Training of attentional control in mild cognitive impairment with executive deficits: results from a double-blind randomised controlled study.

    PubMed

    Gagnon, Lyssa G; Belleville, Sylvie

    2012-01-01

    This study evaluated the efficacy of a cognitive intervention for attentional control in older adults with mild cognitive impairment (MCI) with an executive deficit. It also sought to verify if the benefits of training generalised to primary and secondary outcome measures. Participants (n = 24) were randomly assigned to a training programme or active control condition. The experimental group completed a computer-based training programme involving Variable Priority (VP) coordination of both components of a dual task, to which was added a self-regulatory strategy designed to augment meta-cognition. The active control group performed Fixed Priority (FP) training: rote practice of the same dual task involving a visual detection task combined with an alpha-arithmetic task. Six one-hour training sessions were held three times a week for two weeks. Participants were tested pre- and post-training to detect improvement and transfer effects. Both groups improved on the visual detection and alpha-arithmetic tasks completed in focused attention, but only participants receiving VP training significantly improved their dual-task cost in accuracy for the visual detection task. As for transfer effects, both FP and VP training produced improvements on select outcome measures: focused attention, speed of processing, and switching abilities. No reliable advantage for generalisability of VP over FP training was found. Overall, these findings indicate that cognitive intervention may improve attentional control in persons with MCI and an executive deficit. PMID:22712452

  2. The therapeutic efficacy of somatic acupuncture is not increased by auriculotherapy: a randomised, blind control study in cervical myofascial pain.

    PubMed

    Ceccherelli, Francesco; Tortora, Paola; Nassimbeni, Cecilia; Casale, Roberto; Gagliardi, Giuseppe; Giron, Giampiero

    2006-03-01

    Auriculotherapy (ear acupuncture) is a therapeutic technique in which points on the auricle are stimulated with needles. Usually it is combined with somatic acupuncture because of possible synergy, although the efficacy of this pairing has neither been confirmed nor disproved. The aim of this study was to verify: (1) if somatic acupuncture can reduce myofascial cervical pain; (2) if concomitant auriculotherapy improves the efficacy of somatic acupuncture. A group of 62 patients affected by cervical myofascial pain was randomly divided into two groups of 31. Group A (6 males and 25 females) underwent eight sessions of somatic acupuncture. Group B (7 males and 24 females) underwent eight sessions of somatic acupuncture in the same way as group A, paired with auriculotherapy. Pain was scored using the McGill Pain Questionnaire before and at the end of treatment, and 1 and 3 months later. The results showed that both somatic acupuncture and somatic plus ear acupuncture have a positive effect in reducing pain. The pain intensity score was 40.70 +/- 17.78 in group A before therapy and 13.32 +/- 9.62 after therapy; in group B it was 38.90 +/- 15.31 and 13.43 +/- 10.96. Somatic plus auriculotherapy was therefore not statistically significantly superior to somatic therapy alone in the treatment of cervical myofascial pain. PMID:16473753

  3. Temporary sympathectomy in chronic refractory angina: a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Denby, Christine; Eleuteri, Antonio; Tsang, Hoo kee; Leach, Austin; Hammond, Clare; Bridson, John D; Fisher, Michael; Elt, Matthew; Laflin, Robert; Fisher, Anthony C

    2015-01-01

    Background: Temporary sympathectomy by injection of bupivacaine at the site of the left stellate ganglion is used in the management of refractory angina at several UK centres. Although patients frequently report significant reduction in symptoms, efficacy has not been established by double-blind, randomised placebo-controlled trial (RCT). Objective: To investigate the efficacy of the procedure for the first time by a double-blind RCT. Methods: Consecutive patients referred to the authors’ National Health Service (NHS) angina centre who were candidates for temporary sympathectomy were invited to participate in a trial. A total of 65 patients were randomised to receive either bupivacaine or saline injections. Identical syringes were prepared remotely, blinding patients and staff from randomisation. Cardiac autonomic function was measured 3 hours pre- and post-injection using new heart rate variability (HRV) analyses. Angina episodes were recorded contemporaneously by patients in study diaries in the 7-day periods pre- and post-injection. Results: In 51 patients suitable for analysis, no significant differences between the active and placebo groups were found in patient-recorded frequency or intensity of angina episodes pre- and post-injection. However, across both groups combined, a significant difference was found in the frequency of angina episodes pre- and post-injection. Conclusion: The reduction in frequency of angina episodes produced by this procedure may not be due to drug pharmacology. It may be a placebo response or due to the mechanical effects of the injection of fluid. There is a need for further work using a larger patient cohort considering both mechanical and psychological factors. PMID:26516570

  4. A randomised, multi-centre, prospective, double blind pilot-study to evaluate safety and efficacy of the non-absorbable Optilene® Mesh Elastic versus the partly absorbable Ultrapro® Mesh for incisional hernia repair

    PubMed Central

    2010-01-01

    Background Randomised controlled trials with a long term follow-up (3 to 10 years) have demonstrated that mesh repair is superior to suture closure of incisional hernia with lower recurrence rates (5 to 20% versus 20 to 63%). Yet, the ideal size and material of the mesh are not defined. So far, there are few prospective studies that evaluate the influence of the mesh texture on patient's satisfaction, recurrence and complication rate. The aim of this study is to evaluate, if a non-absorbable mesh (Optilene® Mesh Elastic) will result in better health outcomes compared to a partly absorbable mesh (Ultrapro® Mesh). Methods/Design In this prospective, randomised, double blind study, eighty patients with incisional hernia after a midline laparotomy will be included. Primary objective of this study is to investigate differences in the physical functioning score from the SF-36 questionnaire 21 days after mesh insertion. Secondary objectives include the evaluation of the patients' daily activity, pain, wound complication and other surgical complications (hematomas, seromas), and safety within six months after intervention. Discussion This study investigates mainly from the patient perspective differences between meshes for treatment of incisional hernias. Whether partly absorbable meshes improve quality of life better than non-absorbable meshes is unclear and therefore, this trial will generate further evidence for a better treatment of patients. Trial registration NCT00646334 PMID:20624273

  5. Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP)

    PubMed Central

    Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas

    2016-01-01

    Introduction In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. Methods and analysis In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. Results Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. Ethics and dissemination The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. Trial registration number NCT02254980. PMID:27388352

  6. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study

    PubMed Central

    Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

    2016-01-01

    Introduction Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. Methods and analysis The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10 269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. Ethics and dissemination TIME has ethical approval in the UK, and results will be published in a

  7. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study

    PubMed Central

    Fizazi, Karim; Carducci, Michael; Smith, Matthew; Damião, Ronaldo; Brown, Janet; Karsh, Lawrence; Milecki, Piotr; Shore, Neal; Rader, Michael; Wang, Huei; Jiang, Qi; Tadros, Sylvia; Dansey, Roger; Goessl, Carsten

    2011-01-01

    Summary Background Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. Methods In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. Findings 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab compared with 17·1

  8. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence.

    PubMed

    Gual, Antoni; He, Yuan; Torup, Lars; van den Brink, Wim; Mann, Karl

    2013-11-01

    This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence. Seven hundred and eighteen patients (placebo=360; nalmefene=358), ≥ 18 years of age, with a diagnosis of alcohol dependence, ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening, were randomised (1:1) to 24 weeks of as-needed placebo or nalmefene 18 mg/day. The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days (group difference: -1.7 days/month [95% CI -3.1; -0.4]; p=0.012) and a better but not significant effect in reducing total alcohol consumption (group difference: -5.0 g/day last month [95% CI -10.6; 0.7]; p=0.088). A subgroup analysis showed that patients who did not reduce their drinking prior to randomisation benefitted more from nalmefene. Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group. Adverse events were more common with nalmefene; the incidence of adverse events leading to dropout was similar in both groups. This study provides evidence for the efficacy of nalmefene, which constitutes a new pharmacological treatment paradigm in terms of treatment goal (reduced drinking) and dosing regimen (as-needed), in alcohol dependent patients unable to reduce alcohol consumption on their own. PMID:23562264

  9. Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

    PubMed Central

    2011-01-01

    Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

  10. Study protocol for a double blind, randomised, placebo-controlled trial of continuous subpectoral local anaesthetic infusion for pain and shoulder function following mastectomy: SUB-pectoral Local anaesthetic Infusion following MastEctomy (SUBLIME) study

    PubMed Central

    Langford, R; Brown, I; Vickery, J; Mitchell, K; Pritchard, C; Creanor, S

    2014-01-01

    Introduction Over 16 000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy. Methods and analysis This is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24 h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24 h; VAS pain scores and shoulder function by goniometry at 24 h, 14 days (approximately) and 6 months; Verbal Rating Scale pain scores in first 24 h; Brief Pain Inventory and Oxford Shoulder Score at 6 months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness. Ethics and dissemination The study is approved by the South West England Research Ethics Committee (12/SW/0149). Results will be published in a peer-reviewed journal and presented

  11. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

    PubMed Central

    Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

    2013-01-01

    Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

  12. Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

    PubMed Central

    Strasser, F; Lutz, T A; Maeder, M T; Thuerlimann, B; Bueche, D; Tschöp, M; Kaufmann, K; Holst, B; Brändle, M; von Moos, R; Demmer, R; Cerny, T

    2008-01-01

    Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 μg kg−1 (lower-dose) ghrelin; 11 received 8 μg kg−1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4–5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml−1 with lower-dose and 42 ng ml−1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml−1) than at baseline (990 pg ml−1). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group. PMID:18182992

  13. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

    PubMed Central

    Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

    2013-01-01

    Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

  14. Efficacy of orally disintegrating film of ondansetron versus intravenous ondansetron in prophylaxis of postoperative nausea and vomiting in patients undergoing elective gynaecological laparoscopic procedures: A prospective randomised, double-blind placebo-controlled study

    PubMed Central

    Hegde, Harihar V; Yaliwal, Vijay G; Annigeri, Rashmi V; Sunilkumar, KS; Rameshkumar, R; Rao, P Raghavendra

    2014-01-01

    Background and Aims: Ondansetron is one of the most widely used drugs for postoperative nausea and vomiting (PONV) prophylaxis. Orally disintegrating film (ODF) formulations are relatively recent innovations. We evaluated the efficacy of ODF of ondansetron for the prophylaxis of PONV. Methods: One hundred and eighty American Society of Anaesthesiologists-I or II women, in the age group 18-65 years, scheduled for elective gynaecological laparoscopic procedures were studied in a prospective randomised, double-blind, placebo-controlled trial. The patients were randomised into four groups: Placebo, intravenous (IV) ondansetron 4 mg, ODF of ondansetron 4 mg (ODF4) and 8 mg (ODF8) groups. PONV was assessed in two epochs of 0-6 and 7-24 h. Primary outcome measure was the incidence of PONV and secondary outcome measures were severity of nausea, need for rescue anti-emetic, analgesic consumption, time to oral intake, overall patient satisfaction and side effects such as headache and dizziness. PONV was compared using analysis of variance or Mann–Whitney U-test as applicable. Results: Data of 173 patients were analysed. The incidence of postoperative nausea was significantly lower (P = 0.04) only during the 0-6 h in the ODF8 group when compared with the placebo group. During the 0-6 h interval postoperatively, the ODF8 group had a significantly lower incidence of vomiting when compared with the placebo (P = 0.002) and the IV group (P = 0.044). During the 0-24 h interval postoperatively, ODF4 (P = 0.01) and ODF8 (P = 0.002) groups had a significantly lower incidence of vomiting compared to the placebo group. Conclusions: Orally disintegrating film of ondansetron is an efficacious, novel, convenient and may be a cost-effective option for the prophylaxis of PONV. PMID:25197110

  15. Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

    PubMed

    Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

    2016-03-01

    There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation

  16. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study

    PubMed Central

    Peterfy, Charles; Emery, Paul; Tak, Paul P; Østergaard, Mikkel; DiCarlo, Julie; Otsa, Kati; Navarro Sarabia, Federico; Pavelka, Karel; Bagnard, Marie-Agnes; Gylvin, Lykke Hinsch; Bernasconi, Corrado; Gabriele, Annarita

    2016-01-01

    Objective To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Methods Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Results Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (−0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. Conclusions This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. Trial registration number NCT00578305 PMID:25355728

  17. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia

    PubMed Central

    MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G

    2014-01-01

    Introduction Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). Methods and analysis FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. Ethics and dissemination FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be

  18. Comparison of ondansetron and granisetron for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia: a prospective, randomised, and double blind study

    PubMed Central

    2016-01-01

    Objectives To compare the efficacy of intravenous ondansetron (4 mg, 2 mL) and granisetron (2 mg, 2 mL) for preventing postoperative nausea and vomiting (PONV) in patients during oral and maxillofacial surgical procedures under general anesthesia. Materials and Methods A prospective, randomized, and double blind clinical study was carried out with 60 patients undergoing oral and maxillofacial surgical procedures under general anesthesia. Patients were divided into two groups of 30 individuals each. Approximately two minutes before induction of general anesthesia, each patient received either 4 mg (2 mL) ondansetron or 2 mg (2 mL) granisetron intravenously in a double blind manner. Balanced anesthetic technique was used for all patients. Patients were assessed for episodes of nausea, retching, vomiting, and the need for rescue antiemetic at intervals of 0-2, 3, 6, 12, and 24 hours after surgery. Incidence of complete response and adverse effects were assessed at 24 hours postoperatively. Data was tabulated and subjected to statistical analysis using the chi-square test, unpaired t-test, or the Mann-Whitney U-test as appropriate. A P-value less than 0.05 was considered statistically significant. Results There was no statistically significant difference between the two groups for incidence of PONV or the need for rescue antiemetic. Both study drugs were well tolerated with minimum adverse effects; the most common adverse effect was headache. The overall incidence of complete response in the granisetron group (86.7%) was significantly higher than the ondansetron group (60.0%). Conclusion Granisetron at an intravenous dose of 2 mg was found to be safe, well tolerated, and more effective by increasing the incidence of complete response compared to 4 mg intravenous ondansetron when used for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia. Benefits of granisetron include high receptor specificity and high potency, which make it a

  19. RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies

    PubMed Central

    Dahlberg, K; Odencrants, S; Hagberg, L

    2016-01-01

    Introduction Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. Methods and analysis This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery. The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A–C) at 1 and 2 weeks and (D) at 1 and 4 months. Trial registration number NCT02492191; Pre

  20. Delayed-release prednisone improves fatigue and health-related quality of life: findings from the CAPRA-2 double-blind randomised study in rheumatoid arthritis

    PubMed Central

    Alten, Rieke; Grahn, Amy; Holt, Robert J; Rice, Patricia; Buttgereit, Frank

    2015-01-01

    Objectives Like morning stiffness, fatigue is a common, debilitating symptom of rheumatoid arthritis (RA). Delayed-release (DR) prednisone is designed for evening administration (approximately 22:00) and releases 4 h later to coincide with the rise of nocturnal inflammatory cytokines associated with development of morning stiffness. The impact of DR prednisone on fatigue and other related patient-reported outcomes was analysed with data obtained from the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA) 2 study. Methods Patients with symptomatic RA (n=350) despite treatment with a disease-modifying antirheumatic drug (DMARD) were randomised 2:1 to receive additional therapy with DR prednisone 5 mg or placebo once daily for 12 weeks. Fatigue was assessed using validated instruments: the fatigue scale of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the vitality domain of the Short Form-36 (SF-36). General quality of life was assessed using the general score and individual domains of Functional Assessment of Cancer Therapy-General (FACT-G) and SF-36. Results The change from baseline to week 12 in FACIT-F score was statistically significantly different with DR prednisone/DMARD (3.8) versus placebo/DMARD (1.6; difference 2.2, p=0.0032). Improvement in FACIT-F score correlated positively with clinical response. Compared with placebo/DMARD, DR prednisone/DMARD showed a significantly greater improvement in SF-36 vitality score (5.6, p=0.001), physical component of SF-36 (2.3, p=0.0003) and general score with FACT-G (2.6, p=0.0233). Conclusions DR prednisone in addition to a DMARD significantly improves fatigue and other aspects of health-related quality of life in patients with symptomatic RA compared with DMARD treatment alone. Trial registration number ClinicalTrials.gov NCT00650078. PMID:26535146

  1. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression

    PubMed Central

    Atsumi, Tatsuya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Okada, Toshiyuki; Miyasaka, Nobuyuki; Koike, Takao

    2016-01-01

    Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. Methods MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. Results 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. Conclusions In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. Trial registration number (NCT01451203). PMID:26139005

  2. Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study.

    PubMed

    Watanabe, Yoshihisa; Higuchi, Hitoshi; Ishii-Maruhama, Minako; Honda, Yuka; Yabuki-Kawase, Akiko; Yamane-Hirano, Ayaka; Tomoyasu, Yumiko; Maeda, Shigeru; Miyawaki, Takuya

    2016-05-01

    Some patients have transient hypertension before dental treatment as a result of anxiety and stress. Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension. We have evaluated in a randomised, controlled trial whether a low dose of midazolam can lower blood pressure in dental patients to an acceptable level without excessive sedation. Suitable patients were randomised to be given midazolam (trial group) or physiological saline (control group) intravenously. Blood pressure, heart rate, degree of anxiety, and amount of sedation were measured before and after injection. After injection, blood pressure in the trial group significantly decreased to clinically acceptable levels compared with controls. The degree of anxiety in the trial group was also significantly less than that in the control group, but there were no significant differences in sedation. These results suggest that injection of a low dose of midazolam stabilises the blood pressure of dental patients with transient hypertension. PMID:27006286

  3. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    PubMed

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. PMID:26932256

  4. A randomised, double-blind, placebo controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread in healthy volunteers

    PubMed Central

    2012-01-01

    Background Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS) at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. Methods A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA) levels in saliva were also measured. Results Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. Conclusions AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated. PMID:22657950

  5. Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: A randomised, double-blind, crossover study

    PubMed Central

    Akbulut, Nihat; Atakan, Cemal; Çölok, Gülümser

    2014-01-01

    Objectives: To compare the three non-steroidal anti-inflammatory agents (NSAIDs) diclofenac potassium, etodolac and naproxen sodium in relation to pain, swelling and trismus following impacted third molar surgery. Study Design: The study was a randomized and a double-blinded study which included 42 healthy young individuals with impacted third molars and bone retention. Patients were randomly assigned to 3 groups (n: 14) to which diclofenac potassium, naproxen sodium and etodolac were administered orally an hour before the operation. Impacted third molars were surgically extracted with local anaesthesia. Visual analog scales (VAS) were used to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th days postoperatively. Swelling was evaluated using ultrasound (US) and mouth opening (trismus) was measured with a composing stick pre and post operatively on the 2nd and 7th days respectively. Results: Regarding pain alleviation, diclofenac potassium was better than naproxen sodium and naproxen sodium was better than etodolac but these differences were not statistically significant. US measurements showed that the swelling on postoperative 2nd day was significantly lowest with diclofenac potassium as compared to others (p= 0.027) while naproxen sodium and etodolac acted similarly (p=0.747). No difference was noted regarding trismus in any of the groups. Conclusions: NSAIDs (diclofenac, naproxen and etodolac) are somehow similarly effective for controlling pain and trismus following extraction of mandibular third molars but diclofenac potassium surpasses others in reduction of swelling. Key words:Diclofenac potassium, naproxen sodium, etodolac, impacted third molar surgery, pain, swelling, trismus. PMID:24316711

  6. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users

    PubMed Central

    Hindocha, Chandni; Freeman, Tom P.; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K.; Morgan, Celia J.A.; Curran, H. Valerie

    2015-01-01

    Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. PMID:25534187

  7. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.

    PubMed

    Hindocha, Chandni; Freeman, Tom P; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K; Morgan, Celia J A; Curran, H Valerie

    2015-03-01

    Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. PMID:25534187

  8. Co-ingestion of carbohydrate and whey protein isolates enhance PGC-1α mRNA expression: a randomised, single blind, cross over study

    PubMed Central

    2013-01-01

    Background Whey protein isolates (WPI) supplementation is known to improve resistance training adaptations. However, limited information is available on the effects of WPI plus carbohydrate (CHO) supplementation on endurance training adaptations. Method Six endurance trained male cyclists and triathletes (age 29 ± 4 years, weight 74 ± 2 kg, VO2 max 63 ± 3 ml oxygen. kg-1. Min-1, height 183 ± 5 cm; mean ± SEM) were randomly assigned to one of two dietary interventions in a single blind cross over design; CHO or CHO + WPI. Each dietary intervention was followed for 16 days which included the last 2 days having increased CHO content, representing a CHO loading phase. The dietary interventions were iso-caloric and carbohydrate content matched. On completion of the dietary intervention, participants performed an exercise bout, consisting of cycling for 60 min at 70% VO2 max, followed by time trial to exhaustion at 90% VO2 max and recovered in the laboratory for 6 hours. Blood samples and muscle biopsies were taken at various time points at rest and through the exercise trial and recovery. Results Compared to CHO, CHO + WPI increased plasma insulin during recovery at 180 mins (P < 0.05) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) mRNA expression at the end of 6 hours of recovery (P < 0.05). Muscle glycogen did not differ between the two trials. Conclusion This study showed co-ingestion of CHO + WPI may have beneficial effects on recovery and adaptations to endurance exercise via, increased insulin response and up regulation of PGC-1α mRNA expression. PMID:23402493

  9. Randomised, double blind, placebo‐controlled trial of selenium supplementation in adult asthma

    PubMed Central

    Shaheen, Seif O; Newson, Roger B; Rayman, Margaret P; Wong, Angela P‐L; Tumilty, Michael K; Phillips, Joanna M; Potts, James F; Kelly, Frank J; White, Patrick T; Burney, Peter G J

    2007-01-01

    Background Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. Methods A randomised, double blind, placebo‐controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high‐selenium yeast preparation (100 µg daily, n = 99) or placebo (yeast only, n = 98) for 24 weeks. The primary outcome was asthma‐related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by “intention to treat”. Results There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (−0.05 (95% CI −0.19 to 0.09); p = 0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. Conclusions Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids. PMID:17234657

  10. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study

    PubMed Central

    Idorn, Thomas; Knop, Filip K; Jørgensen, Morten; Jensen, Tonny; Resuli, Marsela; Hansen, Pernille M; Christensen, Karl B; Holst, Jens J; Hornum, Mads; Feldt-Rasmussen, Bo

    2013-01-01

    Introduction Diabetes is the leading cause of end-stage renal disease (ESRD). Owing to renal clearance, several antidiabetic agents cannot be used in patients with ESRD. The present protocol describes an investigator-initiated trial aiming to test safety and efficacy of treatment with the glucagon-like peptide-1 receptor agonist liraglutide in patients with type 2 diabetes and dialysis-dependent ESRD. Methods and analysis Twenty patients with type 2 diabetes and ESRD will be compared with 20 matched patients with type 2 diabetes and normal kidney function in a randomised, parallel, placebo-controlled (1 : 1), double-blinded setting. All participants will receive 12 weeks of daily treatment with liraglutide/placebo in an individually titrated dose of 0.6, 1.2 or 1.8 mg. Over nine visits, plasma liraglutide, glycaemic control, β-cell response, cardiovascular parameters, various biomarkers and adverse events will be assessed. The primary endpoint will be evaluated from dose-corrected plasma trough liraglutide concentration at the final trial visit to determine potential accumulation in the ESRD group. Ethics and dissemination The study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the study. The results of the study will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals. Trial registration ClinicalTrials.gov Identifier: NCT01394341 PMID:23624993

  11. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine†

    PubMed Central

    Montgomery, Stuart A; Nielsen, Rebecca Z; Poulsen, Lis H; Häggström, Lars

    2014-01-01

    Objective This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine (10–20 mg/day) versus agomelatine (25–50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin–noradrenaline reuptake inhibitor (SNRI) monotherapy. Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms (Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life (EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale). Results Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p < 0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence. Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated. PMID:25087600

  12. Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

    PubMed

    Hautaniemi, Elina J; Tikkakoski, Antti J; Tahvanainen, Anna; Nordhausen, Klaus; Kähönen, Mika; Mattsson, Tiina; Luhtala, Satu; Turpeinen, Anu M; Niemelä, Onni; Vapaatalo, Heikki; Korpela, Riitta; Pörsti, Ilkka H

    2015-08-14

    We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory. PMID:26168857

  13. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

    PubMed Central

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Iwasaki, Manabu; Ishikura, Hiroaki; Saeki, Satoshi; Kaneko, Yuichiro

    2016-01-01

    Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results. PMID:26672064

  14. MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16

    PubMed Central

    Østergaard, M; Jacobsson, L T H; Schaufelberger, C; Hansen, M Sejer; Bijlsma, J W J; Dudek, A; Rell-Bakalarska, M; Staelens, F; Haake, R; Sundman-Engberg, B; Bliddal, H

    2015-01-01

    Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0–4; CZP 200 mg every 2 weeks at weeks 6–16) or placebo→CZP (placebo at weeks 0–2; CZP loading dose at weeks 2–6; CZP 200 mg every 2 weeks at weeks 8–16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges–Lehmann estimate of median change, −1.5, p=0.049) and osteitis scores (−2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1–2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials. Trial registration number ClinicalTrials.gov, NCT01235598. PMID:25512675

  15. β2-1 Fructan supplementation alters host immune responses in a manner consistent with increased exposure to microbial components: results from a double-blinded, randomised, cross-over study in healthy adults.

    PubMed

    Clarke, Sandra T; Green-Johnson, Julia M; Brooks, Stephen P J; Ramdath, D Dan; Bercik, Premysl; Avila, Christian; Inglis, G Douglas; Green, Judy; Yanke, L Jay; Selinger, L Brent; Kalmokoff, Martin

    2016-05-01

    β2-1 Fructans are purported to improve health by stimulating growth of colonic bifidobacteria, increasing host resistance to pathogens and stimulating the immune system. However, in healthy adults, the benefits of supplementation remain undefined. Adults (thirteen men, seventeen women) participated in a double-blinded, placebo-controlled, randomised, cross-over study consisting of two 28-d treatments separated by a 14-d washout period. Subjects' regular diets were supplemented with β2-1 fructan or placebo (maltodextrin) at 3×5 g/d. Fasting blood and 1-d faecal collections were obtained at the beginning and at the end of each phase. Blood was analysed for clinical, biochemical and immunological variables. Determinations of well-being and general health, gastrointestinal (GI) symptoms, regularity, faecal SCFA content, residual faecal β2-1 fructans and faecal bifidobacteria content were undertaken. β2-1 Fructan supplementation had no effect on blood lipid or cholesterol concentrations or on circulating lymphocyte and macrophage numbers, but significantly increased serum lipopolysaccharide, faecal SCFA, faecal bifidobacteria and indigestion. With respect to immune function, β2-1 fructan supplementation increased serum IL-4, circulating percentages of CD282+/TLR2+ myeloid dendritic cells and ex vivo responsiveness to a toll-like receptor 2 agonist. β2-1 Fructans also decreased serum IL-10, but did not affect C-reactive protein or serum/faecal Ig concentrations. No differences in host well-being were associated with either treatment, although the self-reported incidence of GI symptoms and headaches increased during the β2-1 fructan phase. Although β2-1 fructan supplementation increased faecal bifidobacteria, this change was not directly related to any of the determined host parameters. PMID:26987626

  16. Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial

    PubMed Central

    Tønnesen, Philip; Lauri, Hans; Perfekt, Roland; Mann, Karl; Batra, Anil

    2012-01-01

    A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% versus 16.1%; relative success rate (RR) 1.62, 95% CI 1.09–2.41), week 24 (15.7% versus 6.8%; RR 2.30, 95% CI 1.23–4.30), and week 52 (13.8% versus 5.6%; RR 2.48, 95% CI 1.24–4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray versus 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo. PMID:22323576

  17. Prospective multicentre randomised, double-blind, equivalence study comparing clonidine and midazolam as intravenous sedative agents in critically ill children: the SLEEPS (Safety profiLe, Efficacy and Equivalence in Paediatric intensive care Sedation) study.

    PubMed Central

    Wolf, Andrew; McKay, Andrew; Spowart, Catherine; Granville, Heather; Boland, Angela; Petrou, Stavros; Sutherland, Adam; Gamble, Carrol

    2014-01-01

    BACKGROUND Children in paediatric intensive care units (PICUs) require analgesia and sedation but both undersedation and oversedation can be harmful. OBJECTIVE Evaluation of intravenous (i.v.) clonidine as an alternative to i.v. midazolam. DESIGN Multicentre, double-blind, randomised equivalence trial. SETTING Ten UK PICUs. PARTICIPANTS Children (30 days to 15 years inclusive) weighing ≤ 50 kg, expected to require ventilation on PICU for > 12 hours. INTERVENTIONS Clonidine (3 µg/kg loading then 0-3 µg/kg/hour) versus midazolam (200 µg/kg loading then 0-200 µg/kg/hour). Maintenance infusion rates adjusted according to behavioural assessment (COMFORT score). Both groups also received morphine. MAIN OUTCOME MEASURES Primary end point Adequate sedation defined by COMFORT score of 17-26 for ≥ 80% of the time with a ± 0.15 margin of equivalence. Secondary end points Percentage of time spent adequately sedated, increase in sedation/analgesia, recovery after sedation, side effects and safety data. RESULTS The study planned to recruit 1000 children. In total, 129 children were randomised, of whom 120 (93%) contributed data for the primary outcome. The proportion of children who were adequately sedated for ≥ 80% of the time was 21 of 61 (34.4%) - clonidine, and 18 of 59 (30.5%) - midazolam. The difference in proportions for clonidine-midazolam was 0.04 [95% confidence interval (CI) -0.13 to 0.21], and, with the 95% CI including values outside the range of equivalence (-0.15 to 0.15), equivalence was not demonstrated; however, the study was underpowered. Non-inferiority of clonidine to midazolam was established, with the only values outside the equivalence range favouring clonidine. Times to reach maximum sedation and analgesia were comparable hazard ratios: 0.99 (95% CI 0.53 to 1.82) and 1.18 (95% CI 0.49 to 2.86), respectively. Percentage time spent adequately sedated was similar [medians clonidine 73.8% vs. midazolam 72.8%: difference in

  18. Effect of supplementation of fermented milk drink containing probiotic Lactobacillus casei Shirota on the concentrations of aflatoxin biomarkers among employees of Universiti Putra Malaysia: a randomised, double-blind, cross-over, placebo-controlled study.

    PubMed

    Mohd Redzwan, Sabran; Abd Mutalib, Mohd Sokhini; Wang, Jia-Sheng; Ahmad, Zuraini; Kang, Min-Su; Abdul Rahman, Nurul 'Aqilah; Nikbakht Nasrabadi, Elham; Jamaluddin, Rosita

    2016-01-14

    Human exposure to aflatoxin is through the diet, and probiotics are able to bind aflatoxin and prevent its absorption in the small intestine. This study aimed to determine the effectiveness of a fermented milk drink containing Lactobacillus casei Shirota (LcS) (probiotic drink) to prevent aflatoxin absorption and reduce serum aflatoxin B1-lysine adduct (AFB1-lys) and urinary aflatoxin M1 concentrations. The present study was a randomised, double-blind, cross-over, placebo-controlled study with two 4-week intervention phases. In all, seventy-one subjects recruited from the screening stage were divided into two groups--the Yellow group and the Blue group. In the 1st phase, one group received probiotic drinks twice a day and the other group received placebo drinks. Blood and urine samples were collected at baseline, 2nd and 4th week of the intervention. After a 2-week wash-out period, the treatments were switched between the groups, and blood and urine samples were collected at the 6th, 8th and 10th week (2nd phase) of the intervention. No significant differences in aflatoxin biomarker concentrations were observed during the intervention. A within-group analysis was further carried out. Aflatoxin biomarker concentrations were not significantly different in the Yellow group. Nevertheless, ANOVA for repeated measurements indicated that AFB1-lys concentrations were significantly different (P=0·035) with the probiotic intervention in the Blue group. The 2nd week AFB1-lys concentrations (5·14 (SD 2·15) pg/mg albumin (ALB)) were significantly reduced (P=0·048) compared with the baseline (6·24 (SD 3·42) pg/mg ALB). Besides, the 4th week AFB1-lys concentrations were significantly lower (P<0·05) with probiotic supplementation than with the placebo. Based on these findings, a longer intervention study is warranted to investigate the effects of continuous LcS consumption to prevent dietary aflatoxin exposure. PMID:26490018

  19. Low serum enterolactone concentration is associated with low colonic Lactobacillus-Enterococcus counts in men but is not affected by a synbiotic mixture in a randomised, placebo-controlled, double-blind, cross-over intervention study.

    PubMed

    Holma, Reetta; Kekkonen, Riina A; Hatakka, Katja; Poussa, Tuija; Vapaatalo, Heikki; Adlercreutz, Herman; Korpela, Riitta

    2014-01-28

    The aims of the present study were to assess the possible differences in faecal microbiota between men with a low serum enterolactone concentration and those with a high concentration, and to investigate the impact of a synbiotic mixture on serum enterolactone concentration in men with a low concentration. We compared faecal microbiota between ten men with the lowest serum enterolactone concentration and ten men with the highest concentration at recruitment (n 84). Furthermore, we carried out a randomised, double-blind, placebo-controlled, cross-over intervention study (6-week intervention periods and 4-week washout period) to investigate the impact of a synbiotic mixture (two Lactobacillus strains, one Bifidobacterium strain, one Propionibacterium strain and galacto-oligosaccharides (32 g/l)) on serum enterolactone concentration in fifty-two men who had a concentration < 20 nmol/l. Serum sensitive C-reactive protein (CRP) concentration was measured at the end of the first intervention period. Men with a low serum enterolactone concentration when compared with those with a high concentration had less faecal bacteria, especially those belonging to the Lactobacillus-Enterococcus group (median 8·2 (interquartile range 7·8-8·4) log10 colony-forming units/g v. median 8·8 (interquartile range 8·5-8·9) log10 colony-forming units/g, P= 0·009). The synbiotic mixture that was used did not have a significant effect on serum enterolactone (synbiotic v. placebo ratio 0·96 (95 % CI 0·76, 1·22), P= 0·724) or serum sensitive CRP (synbiotic v. placebo ratio 0·99 (95 % CI 0·74, 1·33), P= 0·954) concentration. Men with a low serum enterolactone concentration harbour less colonic bacteria, especially those belonging to the Lactobacillus-Enterococcus group. A synbiotic mixture does not increase serum enterolactone concentration. PMID:23919920

  20. Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain

    PubMed Central

    Raphael, Jon H; Duarte, Rui V; Southall, Jane L; Nightingale, Peter; Kitas, George D

    2013-01-01

    Objective This study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the level of pain intensity. Design Randomised, double-blind, controlled, parallel group trial. Setting Department of Pain Management, Russells Hall Hospital, Dudley, UK. Participants 24 patients with non-cancer pain implanted with morphine reservoirs were assessed for eligibility. Interventions Participants were randomly allocated to one of two parallel groups in which one of the groups had no change in morphine dose and the other group had a small reduction (20%) in dosage every week during a 10-week follow-up. Outcome Primary outcomes were visual analogue scale (VAS) pain score change and withdrawal from the study due to lack of efficacy. Results 9 of the patients assessed for eligibility declined to participate in the study. 15 patients were randomised to control (n=5) or intervention (n=10) and included in an intention-to-treat analysis. Owing to worsening of pain, seven patients withdrew from the study prematurely. None knew prior to withdrawal which arm of the study they were in, but all turned out to be in the dose-reduction arm. The calculation of dropout rates between groups indicated a significant statistical difference (p=0.026) and recruitment was ceased. The VAS change between baseline and the last observation was smaller in the control group (median, Mdn=11) than in the intervention group (Mdn=30.5), although not statistically significant, Z=−1.839, p=0.070; r=−0.47. Within groups, VAS was significantly lower at baseline (Mdn=49.5) than at the last observation (Mdn=77.5) for the reduction group, Z=−2.805, p=0.002; r=−0.627 but not for the control group (p=0.188). Conclusions This double-blind randomised controlled trial of chronic intrathecal morphine administration suggests the effectiveness of this therapy for the management of

  1. Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.

    PubMed

    Denny, Lynette; Hendricks, Bronwyn; Gordon, Chivaugn; Thomas, Florence; Hezareh, Marjan; Dobbelaere, Kurt; Durand, Christelle; Hervé, Caroline; Descamps, Dominique

    2013-11-19

    In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339. PMID:24091311

  2. Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial

    PubMed Central

    2014-01-01

    Background Advanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes. Methods/Design Thirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40–60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks. After a 2-week washout period, study subjects will crossover to receive the alternative dietary treatment for 12 weeks. The primary outcome is the difference in markers of the advanced glycation pathway carboxymethyllysine (CML) and methylglyoxal (MG) between experimental and control treatments. Secondary outcomes include HbA1c, insulin sensitivity, lipid levels, blood pressure, serum glutathione, adiponectin, IL-6, E-selectin, myeloperoxidase, C-reactive protein, Toll-like Receptor 4 (TLR4), soluble receptor

  3. Double blind randomised controlled trial of two different breathing techniques in the management of asthma

    PubMed Central

    Slader, C A; Reddel, H K; Spencer, L M; Belousova, E G; Armour, C L; Bosnic‐Anticevich, S Z; Thien, F C K; Jenkins, C R

    2006-01-01

    Background Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non‐specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. Methods After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Results Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Conclusion Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non‐specific upper body exercises. PMID:16517572

  4. Lubiprostone decreases the small bowel transit time by capsule endoscopy: an exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.

    PubMed

    Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

    2014-01-01

    The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE. PMID:25614738

  5. Lubiprostone Decreases the Small Bowel Transit Time by Capsule Endoscopy: An Exploratory, Randomised, Double-Blind, Placebo-Controlled 3-Way Crossover Study

    PubMed Central

    Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

    2014-01-01

    The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117–407) minutes in the P-P regimen, 122.5 (27–282) minutes in the L-P regimen, and 110.5 (11–331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE. PMID:25614738

  6. Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies.

    PubMed

    Salih, Hiba; Anghelescu, Ion; Kezic, Iva; Sinha, Vikash; Hoeben, Eef; Van Nueten, Luc; De Smedt, Heidi; De Boer, Peter

    2015-04-01

    Metabotropic glutamate receptor-2 positive allosteric modulator, JNJ-40411813 (ADX71149), was characterised for clinical effects in healthy volunteers in two phase-1 studies. In study 1, healthy men received 50-, 100-, 150- or 225 mg and women received 100 mg JNJ-40411813 (n=6, each cohort) or placebo (n=2, each cohort) twice daily for seven days; smoking men (n=30) received placebo twice daily on days 1-7, 100 mg JNJ-40411813 (n=20) or placebo (n=10) on days 8-14. In study 2, healthy men received intravenous 0.005 mg/kg S(+) ketamine over 60 min at 3 (n=24; cohort 1), 12 h (n=8; cohort 3), and 24 h (n=8; cohort 2) after a single oral dose of 500 mg JNJ-40411813 or placebo. The pharmacokinetics and effects of JNJ-40411813 on cognition and subjective awareness were evaluated. Plasma JNJ-40411813 exposure was dose-dependent, t max ranged from 3-4 h and t 1/2 19.4-34.2 h across the dose levels. JNJ-40411813 significantly (p=0.02) reduced continuity of attention score (150 mg dose) and ameliorated smoking withdrawal-induced changes in power of attention and quality of episodic memory versus placebo. A modest reduction in alertness was observed at 150-225 mg doses, JNJ-40411813 (500 mg) reduced S(+) ketamine-induced negative symptoms by approximately 43% and 30% in cohorts 1 and 3, respectively. JNJ-40411813 was generally well-tolerated. PMID:25735992

  7. A comparison of antibody responses to commercial equine influenza vaccines following primary vaccination of Thoroughbred weanlings--a randomised blind study.

    PubMed

    Gildea, Sarah; Arkins, Sean; Walsh, Cathal; Cullinane, Ann

    2011-11-15

    Many racing authorities, sales companies and equestrian bodies have mandatory vaccination policies for equine influenza (EI). The consequences of lack of vaccine efficacy include clinical disease, disruption to training programmes, the cancellation of equestrian events and the introduction of virus to susceptible populations. The correlation between antibody against the virus haemagglutinin and protection against influenza has been well established. The objective of this study was to compare the antibody responses of 66 unvaccinated Thoroughbred weanlings on four different stud farms, following primary vaccination (V1, V2 and V3) with the five EI vaccines commercially available in Ireland (Duvaxyn IET Plus, Equilis Resequin, Equip FT, Equilis Prequenza Te, ProteqFlu Te). Antibody responses were monitored for 6 months post V3 by single radial haemolysis. The pattern of antibody response was similar for all vaccines and for all antigens tested. A rapid decline of antibody level was observed by 3 months post V2 for all vaccines. The antibody response of the horses vaccinated with the whole virus vaccine Duvaxyn IET Plus was significantly higher than that of the horses vaccinated with the other four products. Five weanlings had maternally derived antibodies (MDA) at the time of V1. The canary pox recombinant vaccine, subunit vaccine and whole virus inactivated vaccines administered to these weanlings did not induce a detectable antibody response against the background of MDA but effectively primed the animals as revaccination resulted in a strong antibody response. In this study 43% of the weanlings failed to seroconvert after V1. This high incidence of poor responders has not been reported in previous experimental studies relating to these products. The poor responders were observed in all vaccine groups except those vaccinated with Duvaxyn IET Plus. Post V2 the incidence of poor responders was reduced to 7% and all horses responded to V3. The study demonstrates that

  8. Potential of Spirulina Platensis as a Nutritional Supplement in Malnourished HIV-Infected Adults in Sub-Saharan Africa: A Randomised, Single-Blind Study

    PubMed Central

    Azabji-Kenfack, M.; Dikosso, S. Edie; Loni, E.G.; Onana, E.A.; Sobngwi, E.; Gbaguidi, E.; Kana, A.L. Ngougni; Nguefack-Tsague, G.; Von der Weid, D.; Njoya, O.; Ngogang, J.

    2011-01-01

    compared between the two groups at the end of the trial, FFM was significantly higher in the spirulina group (42.2 vs. 39.0 Kg, P = 0.01). The haemoglobin level rose significantly within groups (P < 0.001 for each group) with no difference between groups (P = 0.77). Serum albumin level did not increase significantly within groups (P < 0.90 vs. P < 0.82) with no difference between groups (P = 0.39). The increase in CD4 cell count within groups was significant (P < 0.01 in both groups), with a significantly higher CD4 count in the spirulina group compared to subjects on soya beans at the end of the study (P = 0.02). Within each group, HIV viral load significantly reduced at the end of the study (P < 0.001 and P = 0.04 for spirulina and soya beans groups respectively). Between the groups, the viral load was similar at baseline but significantly reduced in the spirulina group at the end of the study (P = 0.02). Conclusion: We therefore conclude in this preliminary study, firstly, that both spirulina and soja improve on nutritional status of malnourished HIV-infected patients but in terms of quality of nutritional improvement, subjects on spirulina were better off than subjects on soya beans. Secondly, nutritional rehabilitation improves on immune status with a consequent drop in viral load but further investigations on the antiviral effects of this alga and its clinical implications are strongly needed. PMID:23946659

  9. A prospective, comparative, randomised, double blind study on the efficacy of addition of clonidine to 0.25% bupivacaine in scalp block for supratentorial craniotomies

    PubMed Central

    Wajekar, Anjana Sagar; Oak, Shrikanta P; Shetty, Anita N; Jain, Ruchi A

    2016-01-01

    Background and Aims: Scalp blocks combined with general anaesthesia reduce pin and incision response, along with providing stable perioperative haemodynamics and analgesia. Clonidine has proved to be a valuable additive in infiltrative blocks. We studied the efficacy and safety of addition of clonidine 2 μg/kg to scalp block with 0.25% bupivacaine (Group B) versus plain 0.25% bupivacaine (Group A) for supratentorial craniotomies. Methods: Sixty patients were randomly divided into two groups to receive scalp block: Group A (with 0.25% bupivacaine) and Group B (with 0.25% bupivacaine and clonidine (2 μg/kg). Bilateral scalp block was given immediately after induction. All the patients received propofol based general anaesthesia. Intraoperatively, propofol infusion was maintained at 75 to 100 μg/kg/h up to dura closure and reduced to 50-75 μg/kg/h up to skin closure with atracurium infusion stopped at dura closure. Heart rate (HR) and mean arterial pressure (MAP) were monitored at pin insertion, at 5 minute intervals from incision till dura opening and again at 5 minute interval from dura closure up to skin closure. Fentanyl 0.5 μg/kg was given if a 20% increase in either HR and/or MAP was observed. Postoperative haemodynamics and verbal rating scores (VRS) were recorded. When the VRS score increased above 3, rescue analgesia was given. Any intraoperative haemodynamic complications were noted. Results: Group A showed a significant increase in haemodynamic variables during the perioperative period as compared to group B (P < 0.05). Addition of clonidine 2 μg/kg in the infiltrative block also provided significantly prolonged postoperative analgesia. Conclusions: Addition of clonidine to scalp block provided better perioperative haemodynamic stability and significantly prolonged analgesia. PMID:26962254

  10. Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial)

    PubMed Central

    Aoyagi, Reiko; Hamada, Hiromichi; Sato, Yasunori; Suzuki, Hiroyuki; Onouchi, Yoshihiro; Ebata, Ryota; Terauchi, Moe; Terai, Masaru; Hanaoka, Hideki; Hata, Akira

    2015-01-01

    Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca2+/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. Methods and analysis This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. Ethics and dissemination The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number JMA-IIA00174; Pre-results. PMID:26628527

  11. Sources of Bias in Outcome Assessment in Randomised Controlled Trials: A Case Study

    ERIC Educational Resources Information Center

    Ainsworth, Hannah; Hewitt, Catherine E.; Higgins, Steve; Wiggins, Andy; Torgerson, David J.; Torgerson, Carole J.

    2015-01-01

    Randomised controlled trials (RCTs) can be at risk of bias. Using data from a RCT, we considered the impact of post-randomisation bias. We compared the trial primary outcome, which was administered blindly, with the secondary outcome, which was not administered blindly. From 44 schools, 522 children were randomised to receive a one-to-one maths…

  12. Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

    PubMed Central

    Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

    1979-01-01

    In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

  13. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

    PubMed Central

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Holst, Jens Juul; Madsbad, Sten; Andersen, Henrik Ullits

    2015-01-01

    Introduction Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled design. Methods and analysis In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m2) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this investigator initiated, double-blinded, placebo-controlled parallel study. The primary end point is glycaemic control as measured by changes in HbA1c. Secondary end points include changes in the insulin dose, hypoglyacemic events, body weight, lean body mass, fat mass, food preferences and adverse events. Glycaemic excursions, postprandial glucagon levels and gastric emptying rate during a standardised liquid meal test will also be studied. Ethics and dissemination The study is approved by the Danish Medicines Authority, the Regional Scientific-Ethical Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Trial registration number NCT01612468. PMID:25838513

  14. How "Blind" Are Double-Blind Studies?

    ERIC Educational Resources Information Center

    Margraf, Jurgen; And Others

    1991-01-01

    Compared alprazolam, imipramine, and placebo in the treatment of panic disorder patients (n=59) to investigate concerns about the internal validity of the double-blind design. Found that the great majority of patients and physicians were able to rate accurately whether active drug or placebo had been given and physicians could distinguish between…

  15. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.

    PubMed

    Nurmikko, Turo J; Serpell, Mick G; Hoggart, Barbara; Toomey, Peter J; Morlion, Bart J; Haines, Derek

    2007-12-15

    Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks. PMID:17997224

  16. Study protocol for a pilot, randomised, double-blinded, placebo controlled trial of perineural local anaesthetics and steroids for chronic post-traumatic neuropathic pain in the ankle and foot: the PREPLANS study

    PubMed Central

    Bhatia, Anuj; Bril, Vera; Brull, Richard T; Perruccio, Anthony; Wijeysundera, Duminda; Alvi, Sabbeh; Lau, Johnny; Gandhi, Rajiv; Mahomed, Nizar; Davis, Aileen M

    2016-01-01

    Introduction Peripheral neuropathic pain (PNP) associated with trauma is often refractory to treatment. Administration of local anaesthetics (LA) and steroids around injured nerves has been proposed as an option for patients unresponsive to conventional treatments for refractory PNP following trauma. There is insufficient evidence to support a large, potentially expensive, full-scale randomised controlled trial (RCT) that involves comparison of effects of perineural steroids and LA against LA or saline injections on analgesia, physical and psychological functioning, and quality of life. There is also a lack of data that would allow estimation of analgesic efficacy or sample size for the full-scale RCT. The objective of this pilot RCT is to yield information to support planning of a full-scale RCT in this population. Methods and Analysis 30 participants with post-traumatic PNP in the ankle and foot of moderate-to-severe intensity and duration of more than 3 months will be enrolled in this pilot RCT. Participants will be randomised to receive three ultrasound-guided perineural injections of 0.9% saline, 0.25% bupivacaine (a long-acting LA) or a combination of 0.25% bupivacaine and a steroid (methylprednisolone 16 mg per nerve) at weekly intervals. The primary objectives are to determine the feasibility and sample size of a full-scale RCT in this population. The secondary objectives are to evaluate the effect of study interventions on analgesia, persistence of neuropathic pain, psychological and physical function, quality of life and participants' global impression of change at 1 and 3 months after the interventions. In addition, adverse effects associated with perineural injections and with systemic absorption of steroids will also be recorded. Ethics and Dissemination The protocol was approved by the University Health Network Research Ethics Board (UHN REB number 15-9584-A). The results will be disseminated in peer-reviewed journals and at scientific

  17. A Blinded, Randomised, Controlled Trial of Stapled Versus Tissue Glue Closure of Neck Surgery Incisions

    PubMed Central

    Ridgway, DM; Mahmood, F; Moore, L; Bramley, D; Moore, PJ

    2007-01-01

    INTRODUCTION Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery. This randomised, controlled trial compares these parameters in closures using tissue glue (Dermabond™, Ethicon, UK) and skin staples. PATIENTS AND METHODS Patients requiring a collar line incision were randomised to receiving tissue glue or staples for skin closure. Time for closure to be completed was recorded. Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery. At 6 weeks, cosmetic appearance was assessed using a linear 1–10 visual analogue scale by the patient, surgeon and an independent blinded assessor. Results were compared using appropriate statistical tests. RESULTS Glued (n = 14) and stapled (n = 15) closures were performed for hemithyroidectomy (n = 8 versus 6), sub-total thyroidectomy (n = 2 versus 4), total thyroidectomy (n = 1 versus 4) and parathyroidectomy (n = 3 versus 1). Closure with tissue glue took significantly longer than with staples (mean, 95 versus 28 s; P < 0.001). Neck mobility scores were comparable at 48 h and 1 week (mean, 4.8 versus 4.4; P = 0.552: and 2.7 versus 2.6; P = 0.886). Cosmetic appearance at 6 weeks was comparable when patient (mean, 1.7 versus 1.8; P = 0.898), surgeon (mean, 2.6 versus 2.3; P = 0.633) and independent assessment (mean, 1.4 versus 1.9; P = 0.365) was performed. CONCLUSIONS The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions. PMID:17394707

  18. GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

    PubMed Central

    2014-01-01

    Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

  19. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol

    PubMed Central

    Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V; Baandrup, Lone; Fagerlund, Birgitte; Jørgensen, Niklas R; Andersen, Ulrik B; Rostrup, Egill; Glenthøj, Birte Y; Ebdrup, Bjørn H

    2014-01-01

    Introduction Antipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight-lowering effects have also been recognised in patients with non-diabetes. The primary endpoint of this trial is weight loss after 3 months of treatment with a GLP-1 receptor agonist (exenatide once weekly) in patients with non-diabetic schizophrenia with antipsychotic-associated obesity. Secondary endpoints include physiological and metabolic measurements, various psychopathological and cognitive measures, and structural and functional brain MRI. Methods and analysis 40 obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised to subcutaneous injection of exenatide once weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. Ethics and dissemination The trial has been approved by the Danish Health and Medicines Authority, the National Committee on Health Research Ethics and the Danish Data Protection Agency. Trial participation presupposes theoral and written patient informed consent. An external, independent monitoring committee (Good Clinical Practice Unit at Copenhagen University Hospital) will monitor the study according to the GCP Guidelines. Trial data, including positive, negative and inconclusive results, will be presented at national and international scientific meetings and conferences. Papers will be submitted to peer-reviewed journals. Trial registration ClinicalTrials.gov identifier: NCT01794429; National Committee on Health Research Ethics project number: 36378; EudraCT nr: 2012-005404-17; The

  20. Lack of attentional retraining effects in cigarette smokers attempting cessation: a proof of concept double-blind randomised controlled trial

    PubMed Central

    Begh, Rachna; Munafò, Marcus R; Shiffman, Saul; Ferguson, Stuart G; Nichols, Linda; Mohammed, Mohammed A; Holder, Roger L; Sutton, Stephen; Aveyard, Paul

    2016-01-01

    Background Observational studies have shown that attentional bias for smoking-related cues is associated with increased craving and relapse. Laboratory experiments have shown that manipulating attentional bias may change craving. Interventions to reduce attentional bias could reduce relapse in smokers seeking to quit. We report a clinical trial of attentional retraining in treatment-seeking smokers. Methods This was a double-blind randomised controlled trial that took place in UK smoking cessation clinics. Smokers interested in quitting were randomised to five weekly sessions of attentional retraining (N=60) or placebo training (N=58) using a modified visual probe task from one week prior to quit day. Both groups received 21 mg nicotine patches (from quit day onwards) and behavioural support. Primary outcomes included change in attentional bias reaction times four weeks after quit day on the visual probe task and craving measured weekly using the Mood and Physical Symptoms Scale. Secondary outcomes were changes in withdrawal symptoms, time to first lapse and prolonged abstinence. Results No attentional bias towards smoking cues was found in the sample at baseline (mean difference=3 ms, 95%CI=-2, 9). Post-training bias was not significantly lower in the retraining group compared with the placebo group (mean difference=-9 ms, 95%CI=-20, 2). There was no difference between groups in change in craving (p=0.89) and prolonged abstinence at four weeks (risk ratio=1.00, 95%CI=0.70, 1.43). Conclusions Taken with one other trial, there appears to be no effect from clinic-based attentional retraining using the visual probe task. Attentional retraining conducted out of clinic may prove more effective. Clinical trial registration UK Clinical Trials ISRCTN 54375405. PMID:25697911

  1. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

    PubMed Central

    2015-01-01

    Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo

  2. Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial

    PubMed Central

    Ciliberto, Heather; Ciliberto, Michael; Briend, Andreé; Ashorn, Per; Bier, Dennis; Manary, Mark

    2005-01-01

    Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor. PMID:15851401

  3. Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

    PubMed Central

    Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.

    1995-01-01

    AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591

  4. Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

    PubMed Central

    Tiralongo, E.; Lea, R. A.; Wee, S. S.; Hanna, M. M.; Griffiths, L. R.

    2012-01-01

    Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights. PMID:22229040

  5. Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Derumeaux, Geneviève; Ernande, Laura; Serusclat, André; Servan, Evelyne; Bruckert, Eric; Rousset, Hugues; Senn, Stephen; Van Gaal, Luc; Picandet, Brigitte; Gavini, François; Moulin, Philippe

    2012-01-01

    Objectives REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. Methods Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA1c. Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. Results At baseline, patients were 59.1±10.5 years old with HbA1c 8.3±0.8%, and DM duration 7.1±6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30±0.80 to 7.77±1.31 versus pioglitazone: from 8.30±0.80 to 7.45±1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. Conclusion After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and

  6. A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients.

    PubMed Central

    Burbaud, P; Wiart, L; Dubos, J L; Gaujard, E; Debelleix, X; Joseph, P A; Mazaux, J M; Bioulac, B; Barat, M; Lagueny, A

    1996-01-01

    OBJECTIVE: To confirm the apparent effectiveness of botulinum toxin (BTX) in hemiparetic patients with ankle plantar flexors and foot invertor spasticity. METHODS: Twenty three hemiparetic patients with spasticity of the ankle plantar flexors and foot invertors were included in a randomised double blind, placebo controlled study with BTX. Patients were examined on days 0, 30, 90, and 120 and received one injection of BTX and one of placebo in a random order at day 0 and day 90. RESULTS: Patients reported a clear subjective improvement in foot spasticity after BTX (P = 0.0014) but not after placebo. Significant changes were noted in Ashworth scale values for ankle extensors (P < 0.0001) and invertors (P = 0.0002), and for active ankle dorsiflexion (P = 0.0001). Gait velocity was slightly but not significantly (P = 0.0731) improved after BTX injections. The severity of spasticity did not modify treatment efficacy, but BTX was less effective in patients with longer duration of spasticity (P = 0.0081). CONCLUSION: The efficacy of BTX injections in the treatment of spastic foot suggests that BTX may be particularly useful during the first year after a stroke. PMID:8795597

  7. A double-blind randomised comparison of intravenous patient-controlled remifentanil with intramuscular pethidine for labour analgesia.

    PubMed

    Ng, T K T; Cheng, B C P; Chan, W S; Lam, K K; Chan, M T V

    2011-09-01

    In a prospective, double-blind, randomised controlled trial, we compared the efficacy of patient-controlled analgesia using remifentanil (25-30 μg per bolus) with intramuscular pethidine (50-75 mg) for labour analgesia in 69 parturients. Parturients receiving patient-controlled analgesia reported less pain than those receiving intramuscular pethidine throughout the study period (p < 0.001), with maximal reduction in visual analogue pain score at 2 h after commencement of analgesia (mean (SD) 20 (17) in the patient-controlled analgesia group and 36 (22) in the intramuscular pethidine group. The median (95% CI) time to the first request for rescue analgesics was significantly longer with patient-controlled analgesia (8.0 (6.8-9.2) h) compared with intramuscular pethidine (4.9 (3.8-5.4) h, p < 0.001). Maternal satisfaction scores were also higher with remifentanil compared with intramuscular pethidine (p= 0.001). There was no report of sedation, aponea or oxygen desaturation in either group, and Apgar scores were similar between groups. We conclude that patient-controlled analgesia with remifentanil provides better labour analgesia and maternal satisfaction than intramuscular pethidine. At this dose, maternal and fetal side effects were uncommon. PMID:21707564

  8. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial

    PubMed Central

    Borges, Cynthia M.; Papadimitriou, Alexandros; Duarte, Diego A.; Lopes de Faria, Jacqueline M.; Lopes de Faria, José B.

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect. PMID:27320846

  9. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial.

    PubMed

    Borges, Cynthia M; Papadimitriou, Alexandros; Duarte, Diego A; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect. PMID:27320846

  10. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

    PubMed Central

    Barnes, Thomas Re; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom Kj; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

    2016-01-01

    BACKGROUND Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. OBJECTIVE To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. DESIGN A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. SETTING Adult psychiatric services, treating people with schizophrenia. PARTICIPANTS Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. INTERVENTIONS Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. MAIN OUTCOME MEASURES The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. RESULTS No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There

  11. Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial

    PubMed Central

    Wallenborn, Jan; Gelbrich, Götz; Bulst, Detlef; Behrends, Katrin; Wallenborn, Hasso; Rohrbach, Andrea; Krause, Uwe; Kühnast, Thomas; Wiegel, Martin; Olthoff, Derk

    2006-01-01

    Objectives To determine whether 10 mg, 25 mg, or 50 mg metoclopramide combined with 8 mg dexamethasone, given intraoperatively, is more effective in preventing postoperative nausea and vomiting than 8 mg dexamethasone alone, and to assess benefit in relation to adverse drug reactions. Design Four-armed, parallel group, double blind, randomised controlled clinical trial. Setting Four clinics of a university hospital and four district hospitals in Germany. Participants 3140 patients who received balanced or regional anaesthesia during surgery. Main outcome measures Postoperative nausea and vomiting within 24 hours of surgery (primary end point); occurrence of adverse reactions. Results Cumulative incidences (95% confidence intervals) of postoperative nausea and vomiting were 23.1% (20.2% to 26.0%), 20.6% (17.8% to 23.4%), 17.2% (14.6% to 19.8%), and 14.5% (12.0% to 17.0%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. In the secondary analysis, 25 mg and 50 mg metoclopramide were equally effective at preventing early nausea (0-12 hours), but only 50 mg reduced late nausea and vomiting (> 12 hours). The most frequent adverse drug reactions were hypotension and tachycardia, with cumulative incidences of 8.8% (6.8% to 10.8%), 11.2% (9.0% to 13.4%), 12.9% (10.5% to 15.3%), and 17.9% (15.2% to 20.6%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. Conclusion The addition of 50 mg metoclopramide to 8 mg dexamethasone (given intraoperatively) is an effective, safe, and cheap way to prevent postoperative nausea and vomiting. A reduced dose of 25 mg metoclopramide intraoperatively, with additional postoperative prophylaxis in high risk patients, may be equally effective and cause fewer adverse drug reactions. Trial registration Current Controlled Trials ISRCTN31625370. PMID:16861255

  12. Comparison of highly purified semi-synthetic insulin and highly purified porcine insulin in the treatment of type I diabetes: interim report of a multi-centre randomised single blind study.

    PubMed

    Birtwell, A J; Owens, D R; Jones, I R; Hayes, T M; Beale, D J; el-Shaboury, A H; Arora, P; Reeves, W G

    1984-12-01

    This is an interim report of a long term single-blind study of the effects of changing diabetic patients treated with highly purified porcine insulin to semi-synthetic human insulins of identical formulation. Twenty four insulin dependent diabetics were randomly allocated to continue with porcine insulin (n = 11) or human insulin (n = 13). There were no significant changes within the groups nor differences between the groups in mean preprandial capillary blood glucose, glycosylated haemoglobin or insulin dose during the first 24 weeks of the study. Insulin antibody levels remained low and did not differ between the groups. No local or systemic adverse reactions were observed. In this group of patients conversion to human insulin did not result in a change in diabetic control or insulin dose. PMID:6397365

  13. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study

    PubMed Central

    Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline

    2014-01-01

    Objective To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). Methods A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37–39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Results Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Conclusions Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing. PMID:23313811

  14. Diet restriction in migraine, based on IgG against foods: A clinical double-blind, randomised, cross-over trial

    PubMed Central

    Alpay, Kadriye; Ertaş, Mustafa; Orhan, Elif Kocasoy; Üstay, Didem Kanca; Lieners, Camille; Baykan, Betül

    2010-01-01

    Introduction: It is well-known that specific foods trigger migraine attacks in some patients. We aimed to investigate the effect of diet restriction, based on IgG antibodies against food antigens on the course of migraine attacks in this randomised, double blind, cross-over, headache-diary based trial on 30 patients diagnosed with migraine without aura. Methods: Following a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA. Then, the patients were randomised to a 6-week diet either excluding or including specific foods with raised IgG antibodies, individually. Following a 2-week diet-free interval after the first diet period, the same patients were given the opposite 6-week diet (provocation diet following elimination diet or vice versa). Patients and their physicians were blinded to IgG test results and the type of diet (provocation or elimination). Primary parameters were number of headache days and migraine attack count. Of 30 patients, 28 were female and 2 were male, aged 19–52 years (mean, 35 ± 10 years). Results: The average count of reactions with abnormally high titre was 24 ± 11 against 266 foods. Compared to baseline, there was a statistically significant reduction in the number of headache days (from 10.5 ± 4.4 to 7.5 ± 3.7; P < 0.001) and number of migraine attacks (from 9.0 ± 4.4 to 6.2 ± 3.8; P < 0.001) in the elimination diet period. Conclusion: This is the first randomised, cross-over study in migraineurs, showing that diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks. PMID:20647174

  15. Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo

    PubMed Central

    Gao, Y; Guo, X; Han, P; Li, Q; Yang, G; Qu, S; Yue, L; Wang, C-N; Skljarevski, V; Dueñas, H; Raskin, J; Gu, L

    2015-01-01

    Background Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. Methods This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient’s diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. Results Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: −2.40, placebo: −1.97; LS mean change difference (95% confidence interval) = −0.43 (−0.82, −0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). Conclusions Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials. PMID

  16. Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial

    PubMed Central

    McKee, Justin B; Elston, John; Evangelou, Nikos; Gerry, Stephen; Fugger, Lars; Kennard, Christopher; Kong, Yazhuo; Palace, Jacqueline; Craner, Matthew

    2015-01-01

    Introduction Neurodegeneration is a widely accepted contributor to the development of long-term disability in multiple sclerosis (MS). While current therapies in MS predominantly target inflammation and reduce relapse rate they have been less effective at preventing long-term disability. The identification and evaluation of effective neuroprotective therapies within a trial paradigm are key unmet needs. Emerging evidence supports amiloride, a licenced diuretic, as a neuroprotective agent in MS through acid sensing ion channel blockade. Optic neuritis (ON) is a common manifestation of MS with correlates of inflammation and neurodegeneration measurable within the visual pathways. Amiloride Clinical Trial In Optic Neuritis (ACTION) will utilise a multimodal approach to assess the neuroprotective efficacy of amiloride in acute ON. Methods and analysis 46 patients will be recruited within 28 days from onset of ON visual symptoms and randomised on a 1:1 basis to placebo or amiloride 10 mg daily. Double-blinded treatment groups will be balanced for age, sex and visual loss severity by a random-deterministic minimisation algorithm. The primary objective is to demonstrate that amiloride is neuroprotective in ON as assessed by scanning laser polarimetry of the peripapillary retinal nerve fibre layer (RNFL) thickness at 6 months in the affected eye compared to the unaffected eye at baseline. RNFL in combination with further retinal measures will also be assessed by optical coherence tomography. Secondary outcome measures on brain MRI will include cortical volume, diffusion-weighted imaging, resting state functional MRI, MR spectroscopy and magnetisation transfer ratio. In addition, high and low contrast visual acuity, visual fields, colour vision and electrophysiology will be assessed alongside quality of life measures. Ethics and dissemination Ethical approval was given by the south central Oxford B research ethics committee (REC reference: 13/SC/0022). The findings

  17. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

    2015-01-01

    Summary Background Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. Methods In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Findings Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1.0 [IQR 0.3–2.2]vs2.2 [1.3–3.1]; p=0.020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium

  18. A randomised, double blind comparison of tecarfarin, a novel vitamin K antagonist, with warfarin. The EmbraceAC Trial.

    PubMed

    Whitlock, Richard P; Fordyce, Christopher B; Midei, Mark G; Ellis, Dave; Garcia, David; Weitz, Jeffrey I; Canafax, Daniel M; Albrecht, Detlef; Milner, Peter G

    2016-08-01

    Tecarfarin is a novel vitamin K antagonist that is metabolised by carboxyl estererase, thereby eliminating the variability associated with cytochrome-mediated metabolism. EmbraceAC was designed to compare the quality of anticoagulation with tecarfarin and warfarin as determined by time in therapeutic range (TTR). In this phase 2/3 randomised and blinded trial, 607 patients with indications for chronic anticoagulation were assigned to warfarin (n=304) or tecarfarin (n=303). Dosing of study drugs was managed by a centralised dose control centre, which had access to genotyping. The primary analysis tested superiority of tecarfarin over warfarin for TTR. Patients were recruited between May 12, 2008 and May 12, 2009. TTR with tecarfarin and warfarin were similar (72.3 % and 71.5 %, respectively; p=0.51). In those taking CYP2C9 interacting drugs, the TTR on tecarfarin (n=92) was similar to that on warfarin (n=87, 72.2 % and 69.9 %, respectively; p=0.15). In patients with mechanical heart valves, the TTR of tecarfarin (n=42) was similar to that of warfarin (n=42, 68.4 % and 66.3 %, respectively; p=0.51). The same was true for the TTR in patients with any CYP2C9 variant allele and on CYP2C9-interacting drugs (tecarfarin, n=24, 76.5 % vs warfarin, n=31, 69.5 %; p=0.09). There was no difference in thromboembolic or bleeding events. In conclusion, superiority of tecarfarin over warfarin for TTR was not demonstrated. The TTR with tecarfarin was similar to that with well-controlled warfarin and tecarfarin appeared to be safe and well tolerated with few major bleeding and no thrombotic events. Favourable trends in certain subpopulations make tecarfarin a promising oral anticoagulant that deserves further study. PMID:27173100

  19. Lactobacillus reuteri influences regrowth of mutans streptococci after full-mouth disinfection: a double-blind, randomised controlled trial.

    PubMed

    Romani Vestman, N; Hasslöf, P; Keller, M K; Granström, E; Roos, S; Twetman, S; Stecksén-Blicks, C

    2013-01-01

    This study assessed whether the persistence of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 in saliva could delay the regrowth of mutans streptococci (MS) after a full-mouth disinfection with chlorhexidine (CHX). A randomised, double-blind, placebo-controlled study with a 6-week intervention period and 3- and 6-month follow-up was performed. 62 healthy subjects with moderate to high counts of MS were randomly assigned to a test group (n = 32) or a placebo group (n = 30). Before onset of the intervention, subjects received two sessions of professional cleaning, flossing, and application of CHX varnish and rinsed their mouth with a CHX solution between the sessions (2 days). Thereafter, the test group used probiotic lozenges (2/day) containing L. reuteri (DSM 17938 and ATCC PTA 5289; 1 × 10(8) CFU of each strain), and the placebo group used identical lozenges lacking the lactobacilli. Saliva samples were collected and cultured onto selective media, and isolates of L. reuteri as well as DNA directly extracted from saliva were tested by polymerase chain reaction (PCR) with specific primers. Presence of salivary MS was analysed with a chair-side test. L. reuteri was frequently detected by culture during the intervention period but in only 3 test group subjects at follow-ups. Regrowth of MS statistically significantly differed depending on the presence or absence of L. reuteri DSM 17938 detected by PCR. We conclude that cultivable L. reuteri strains may only sporadically be confirmed after termination of the intervention, but subjects with PCR-detected L. reuteri demonstrated slower regrowth of MS. PMID:23486236

  20. The effect of distant reiki on pain in women after elective Caesarean section: a double-blinded randomised controlled trial

    PubMed Central

    vanderVaart, Sondra; Berger, Howard; Tam, Carolyn; Goh, Y Ingrid; Gijsen, Violette M G J; de Wildt, Saskia N; Taddio, Anna

    2011-01-01

    Introduction Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. Methods In this randomised, double-blinded study, women who underwent an elective C-section were allocated to either usual care (control, n=40) or three distant reiki sessions in addition to usual care (n=40). Pain was assessed using a visual analogue scale (VAS). The primary endpoint was the Area Under the VAS-Time Curve (AUC) for days 1–3. Secondary measures included: the proportion of women who required opioid medications and dose consumed, rate of healing and vital signs. Results AUC for pain was not significantly different in the distant reiki and control groups (mean±SD; 212.1±104.7 vs 223.1±117.8; p=0.96). There were no significant differences in opioid consumption or rate of healing; however, the distant reiki group had a significantly lower heart rate (74.3±8.1 bpm vs 79.8±7.9 bpm, p=0.003) and blood pressure (106.4±9.7 mm Hg vs 111.9±11.0 mm Hg, p=0.02) post surgery. Conclusion Distant reiki had no significant effect on pain following an elective C-section. Clinical Trial Registration

  1. A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction.

    PubMed Central

    Singh, R. B.; Niaz, M. A.; Agarwal, P.; Beegum, R.; Rastogi, S. S.; Sachan, D. S.

    1996-01-01

    In a randomised, double-blind placebo-controlled trial, the effects of the administration of oral L-carnitine (2 g/day) for 28 days were compared in the management of 51 (carnitine group) and 50 (placebo group) patients with suspected acute myocardial infarction. At study entry, the extent of cardiac disease, cardiac enzymes and lipid peroxides were comparable between the groups, although both groups showed an increase in cardiac enzymes and lipid peroxides. At the end of the 28-day treatment period, the mean infarct size assessed by cardiac enzymes showed a significant reduction in the carnitine group compared to placebo. Electrocardiographic assessment of infarct size revealed that the QRS-score was significantly less in the carnitine group compared to placebo (7.4 +/- 1.2 vs 10.7 +/- 2.0), while serum aspartate transaminase and lipid peroxides showed significant reduction in the carnitine group. Lactate dehydrogenase measured on the sixth or seventh day following infarction showed a smaller rise in the carnitine group compared to placebo. Angina pectoris (17.6 vs 36.0%), New York Heart Association class III and IV heart failure plus left ventricular enlargement (23.4 vs 36.0%) and total arrhythmias (13.7 vs 28.0%) were significantly less in the carnitine group compared to placebo. Total cardiac events including cardiac deaths and nonfatal infarction were 15.6% in the carnitine group vs 26.0% in the placebo group. It is possible that L-carnitine supplementation in patients with suspected acute myocardial infarction may be protective against cardiac necrosis and complications during the first 28 days. PMID:8746285

  2. Effects of biperiden on the treatment of cocaine/crack addiction: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Dieckmann, Luiz Henrique Junqueira; Ramos, Anna Carolina; Silva, Eroy Aparecida; Justo, Luis Pereira; Sabioni, Pamela; Frade, Iracema Francisco; de Souza, Altay Lino; Galduróz, José Carlos Fernandes

    2014-08-01

    Cocaine use affects approximately 13.4 million people, or 0.3% of the world's population between 15 and 64 years of age. Several authors have described drug addiction as a disease of the brain reward system. Given that the cholinergic system impacts reward mechanisms and drug self-administration, acetylcholine (ACh) might play an important role in the cocaine addiction process. We evaluated the efficacy of biperiden (a cholinergic antagonist) in reducing craving and the amount used, and in increasing compliance with treatment for cocaine/crack addiction. It was a study double-blind, randomised, placebo-controlled, 8-week trial of 111 cocaine or crack addicted male patients between 18 and 50 years old. Two groups were compared: placebo (n=55) or biperiden (n=56) combined with weekly sessions of brief group cognitive-behavioural therapy. The efficacy of treatment was evaluated according to the patients' compliance and several instruments: the Minnesota Cocaine Craving Scale, the Beck Depression and Anxiety Scales and a questionnaire assessing the amount of drug used. All of the patients attended weekly sessions for two months. We analysed the data considering the patients' intention to treat based on our last observation. Of the 56 patients in the biperiden group, 24 completed the treatment (42.8%) compared with only 11 patients in the placebo group (20%), which was a significant difference (p=0.009). Compliance with treatment was 118% higher in the biperiden group, which was also the group that presented a statistically significant reduction in the amount of cocaine/crack use (p<0.001). There was statistically significant difference between the craving score in the biperiden group. Pharmacological blockade of the cholinergic system with biperiden is a promising alternative to treat cocaine/crack addiction, helping patients to reduce the amount used and improving compliance with psychotherapy treatment. PMID:24974353

  3. A blinded randomised controlled trial to determine the effect of enteric coating on enzyme treatment for canine exocrine pancreatic efficiency

    PubMed Central

    2012-01-01

    Background Enzyme treatment is the mainstay for management of exocrine pancreatic insufficiency (EPI) in dogs. ‘Enteric-coated’ preparations have been developed to protect the enzyme from degradation in the stomach, but their efficacy has not been critically evaluated. The hypothesis of the current study was that enteric coating would have no effect on the efficacy of pancreatic enzyme treatment for dogs with EPI. Thirty-eight client-owned dogs with naturally occurring EPI were included in this multicentre, blinded, randomised controlled trial. Dogs received either an enteric-coated enzyme preparation (test treatment) or an identical preparation without the enteric coating (control treatment) over a period of 56 days. Results There were no significant differences in either signalment or cobalamin status (where cobalamin deficient or not) between the dogs on the test and control treatments. Body weight and body condition score increased in both groups during the trial (P<0.001) but the magnitude of increase was greater for the test treatment compared with the control treatment (P<0.001). By day 56, mean body weight increase was 17% (95% confidence interval 11-23%) in the test treatment group and 9% (95% confidence interval 4-15%) in the control treatment group. The dose of enzyme required increased over time (P<0.001) but there was no significant difference between treatments at any time point (P=0.225). Clinical disease severity score decreased over time for both groups (P=0.011) and no difference was noted between groups (P=0.869). No significant adverse effects were reported, for either treatment, for the duration of the trial. Conclusions Enteric coating a pancreatic enzyme treatment improves response in canine EPI. PMID:22839732

  4. Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: Randomised, Investigator Blinded, Controlled Trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. A randomised, investigator blinded, controlled trial was used in a large, public clinic associated with a referral hospital in Blantyre, M...

  5. Differential effects of cathodal transcranial direct current stimulation of prefrontal, motor and somatosensory cortices on cortical excitability and pain perception - a double-blind randomised sham-controlled study.

    PubMed

    Vaseghi, B; Zoghi, M; Jaberzadeh, S

    2015-10-01

    The primary aim of this study was to assess the effects of cathodal transcranial direct current stimulation (c-tDCS) over cortical regions of the pain neuromatrix, including the primary motor (M1), sensory (S1) and dorsolateral prefrontal (DLPFC) cortices on M1/S1 excitability, sensory (STh), and pain thresholds (PTh) in healthy adults. The secondary aim was to evaluate the placebo effects of c-tDCS on induced cortical and behavioural changes. Before, immediately after and 30 min after c-tDCS the amplitude of N20-P25 components of somatosensory evoked potentials (SEPs) and peak-to-peak amplitudes of motor evoked potentials (MEPs) were measured under four different experimental conditions. STh and PTh for peripheral electrical and mechanical stimulation were also evaluated. c-tDCS of 0.3 mA was applied for 20 min. A blinded assessor evaluated all outcome measures. c-tDCS of M1, S1 and DLPFC significantly decreased the corticospinal excitability of M1 (P < 0.05) for at least 30 min. Following the application of c-tDCS over S1, M1 and DLPFC, the amplitude of the N20-P25 component of SEPs decreased for at least 30 min (P < 0.05). Compared with baseline values, significant STh and PTh increases were observed after c-tDCS of these three sites. Decreasing the level of S1 and M1 excitability, following S1, M1 and DLPFC stimulation, confirmed the functional connectivities between these cortical sites involved in pain processing. Furthermore, increasing the level of STh/PTh after c-tDCS of these sites indicated that stimulation of not only M1 but also S1 and DLPFC could be considered a technique to decrease the level of pain in patients. PMID:26275236

  6. Urinary Excretion of Phenolic Acids by Infants and Children: A Randomised Double-Blind Clinical Assay

    PubMed Central

    Uberos, J.; Fernández-Puentes, V.; Molina-Oya, M.; Rodríguez-Belmonte, R.; Ruíz-López, A.; Tortosa-Pinto, P.; Molina-Carballo, A.; Muñoz-Hoyos, A.

    2012-01-01

    Objectives: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. Methods: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. Results: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024–1.1; P = 0.001). Conclusions: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options. PMID:23641168

  7. Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Evans, Malkanthi; Salewski, Ryan P; Christman, Mary C; Girard, Stephanie-Anne; Tompkins, Thomas A

    2016-07-01

    Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics. PMID:27169634

  8. Assessing the effect of an interactive decision-aid smartphone smoking cessation application (app) on quit rates: a double-blind automated randomised control trial protocol

    PubMed Central

    BinDhim, Nasser F; McGeechan, Kevin; Trevena, Lyndal

    2014-01-01

    Introduction In a previous study exploring the feasibility of a smoking cessation application (app), we found that about 77% of the respondents from three countries were ready to quit in the next 30 days without significant differences between countries in terms of age, operating system and number of quitting attempts. However, the efficacy of smartphone apps for smoking cessation has not yet been established. This study tests the efficacy of a smartphone smoking cessation decision-aid app compared with an app that contains only smoking cessation information. Methods and analysis This is an automated double-blind, randomised controlled trial of a smoking cessation app that contains the eligibility requirements and baseline questionnaire and will randomise the participants into one of the two subapps (the intervention and the control). Participants will be recruited directly from the Apple app stores in Australia, Singapore, the UK and the USA. Daily smokers aged 18 and above will be randomised into one of the subapps after completing the baseline questionnaire. Abstinence rates will be measured at 10 days, 1 month, 3 months and 6 months, with the 1-month follow-up abstinence rate as the primary outcome. Logistic regression mixed models will be used to analyse the primary outcome. Ethics and dissemination This study was approved by the University of Sydney's Human Ethics Committee. The results of the trial will be published in peer-reviewed journals according to the CONSORT statement. Trial registration number Australian New Zealand ClinicalTrial RegistryACTRN12613000833763. PMID:25037644

  9. A double blind, randomised controlled trial of glycerol adjuvant therapy in adult bacterial meningitis in a high HIV seroprevalence setting in Malawi

    PubMed Central

    Ajdukiewicz, Katherine M.B.; Cartwright, Katharine E.; Scarborough, Matthew; Mwambene, James B.; Goodson, Patrick; Molyneux, Malcolm E.; Zijlstra, Eduard E.; French, Neil; Whitty, Christopher J.M.; Lalloo, David G.

    2014-01-01

    Summary Background Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Even with appropriate antibiotic therapy, mortality exceeds 50% and is not improved with corticosteroids. Glycerol adjuvant therapy reduced mortality and long-term morbidity (deafness) in bacterial meningitis in children and is being promoted. If similarly effective in adults, glycerol would provide a cheap, available adjuvant therapy in Africa. Methods Following a dose-finding study, we conducted a randomised double-blind placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and CSF findings suggestive of bacterial meningitis were randomised either to glycerol or an equivalent volume of sugar solution. The primary outcome was mortality at 40 days with secondary outcomes including disability and mortality restricted to pneumococcal disease. Findings 75ml glycerol QDS was best tolerated and was used for the main study. 265 patients were randomised to receive glycerol or placebo. The trial was stopped early on the advice of the Data and Safety Monitoring Board (DSMB) following a planned interim analysis. Mortality by day 40 was 61/125 (49%) in the placebo and 86/136 (69%) in the glycerol arms, Adjusted Odds Ratio 2·4 (95% CI 1·3-4·2 p0·003). There was no benefit from glycerol for death and disability by day 40 by intention to treat or in predefined subgroups. Two serious adverse events occurred possibly due to study drug. Interpretation Oral glycerol therapy did not improve mortality in adults with bacterial meningitis and cannot be recommended as a suitable adjuvant therapy in resource-poor settings with a high HIV prevalence. PMID:21334262

  10. Efficacy of a strategy for implementing a guideline for the control of cardiovascular risk in a primary healthcare setting: the SIRVA2 study a controlled, blinded community intervention trial randomised by clusters

    PubMed Central

    2011-01-01

    This work describes the methodology used to assess a strategy for implementing clinical practice guidelines (CPG) for cardiovascular risk control in a health area of Madrid. Background The results on clinical practice of introducing CPGs have been little studied in Spain. The strategy used to implement a CPG is known to influence its final use. Strategies based on the involvement of opinion leaders and that are easily executed appear to be among the most successful. Aim The main aim of the present work was to compare the effectiveness of two strategies for implementing a CPG designed to reduce cardiovascular risk in the primary healthcare setting, measured in terms of improvements in the recording of calculated cardiovascular risk or specific risk factors in patients' medical records, the control of cardiovascular risk factors, and the incidence of cardiovascular events. Methods This study involved a controlled, blinded community intervention in which the 21 health centres of the Number 2 Health Area of Madrid were randomly assigned by clusters to be involved in either a proposed CPG implementation strategy to reduce cardiovascular risk, or the normal dissemination strategy. The study subjects were patients ≥ 45 years of age whose health cards showed them to belong to the studied health area. The main variable examined was the proportion of patients whose medical histories included the calculation of their cardiovascular risk or that explicitly mentioned the presence of variables necessary for its calculation. The sample size was calculated for a comparison of proportions with alpha = 0.05 and beta = 0.20, and assuming that the intervention would lead to a 15% increase in the measured variables. Corrections were made for the design effect, assigning a sample size to each cluster proportional to the size of the population served by the corresponding health centre, and assuming losses of 20%. This demanded a final sample size of 620 patients. Data were analysed

  11. Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

    PubMed Central

    Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

    2015-01-01

    Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

  12. Doubly blind: a systematic review of gender in randomised controlled trials

    PubMed Central

    Phillips, Susan P; Hamberg, Katarina

    2016-01-01

    Background Although observational data show social characteristics such as gender or socio-economic status to be strong predictors of health, their impact is seldom investigated in randomised controlled studies (RCTs). Objective & design Using a random sample of recent RCTs from high-impact journals, we examined how the most often recorded social characteristic, sex/gender, is considered in design, analysis, and interpretation. Of 712 RCTs published from September 2008 to 31 December 2013 in the Annals of Internal Medicine, British Medical Journal, Lancet, Canadian Medical Association Journal, or New England Journal of Medicine, we randomly selected 57 to analyse funding, methods, number of centres, documentation of social circumstances, inclusion/exclusion criteria, proportions of women/men, and reporting about sex/gender in analyses and discussion. Results Participants’ sex was recorded in most studies (52/57). Thirty-nine percent included men and women approximately equally. Overrepresentation of men in 43% of studies without explicit exclusions for women suggested interference in selection processes. The minority of studies that did analyse sex/gender differences (22%) did not discuss or reflect upon these, or dismissed significant findings. Two studies reinforced traditional beliefs about women's roles, finding no impact of breastfeeding on infant health but nevertheless reporting possible benefits. Questionable methods such as changing protocols mid-study, having undefined exclusion criteria, allowing local researchers to remove participants from studies, and suggesting possible benefit where none was found were evident, particularly in industry-funded research. Conclusions Social characteristics like sex/gender remain hidden from analyses and interpretation in RCTs, with loss of information and embedding of error all along the path from design to interpretation, and therefore, to uptake in clinical practice. Our results suggest that to broaden external

  13. Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial

    PubMed Central

    Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alström, Katarina; Andersson, Gerhard; Ljótsson, Brjánn; Rück, Christian

    2016-01-01

    Objectives To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. Design A 12 week single blind parallel group randomised controlled trial. Setting Academic medical centre. Participants 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. Interventions Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. Main outcome measures The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a ≥30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. Results BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference −7.1 points, 95% confidence interval −9.8 to −4.4), depression (MADRS-S group difference −4.5 points, −7.5 to −1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self

  14. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome.

    PubMed

    Klupp, Nerida L; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z; Chang, Dennis H

    2016-01-01

    This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [-0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [-0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742

  15. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome

    PubMed Central

    Klupp, Nerida L.; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z.; Chang, Dennis H.

    2016-01-01

    This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [−0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [−0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742

  16. Topical nonsteroidal anti-inflammatory gel for the prevention of peripheral vein thrombophlebitis. A double-blind, randomised, placebo-controlled trial in normal subjects.

    PubMed

    Payne-James, J J; Bray, M J; Kapadia, S; Rana, S K; McSwiggan, D; Silk, D B

    1992-04-01

    A double-blind, randomised, placebo-controlled study was undertaken to determine whether topical application of a nonsteroidal anti-inflammatory gel to skin overlying peripheral vein cannula sites has a role in reducing the incidence or delaying the onset of peripheral vein thrombophlebitis. Fifty normal subjects had intravenous cannulae placed in right and left arms. Subjects were randomised to receive twice daily application of either active nonsteroidal anti-inflammatory gel or placebo gel to each cannula site. Cannula sites were observed and signs and symptoms of inflammation recorded up to 108 h. If any site had signs extending beyond 2 cm then the cannula was removed. Cannula sites that had 'active' gel applied had half the incidence of marked signs at 108 h (44% vs 22%, p less than 0.05). These results suggest that local application of topical nonsteroidal anti-inflammatory gel to cannula sites may have a significant role to play in the prevention of peripheral vein thrombophlebitis. PMID:1519685

  17. Efficacy of autologous platelet-rich plasma for the treatment of muscle rupture with haematoma: a multicentre, randomised, double-blind, placebo-controlled clinical trial

    PubMed Central

    Martinez-Zapata, Ma José; Orozco, Lluís; Balius, Ramon; Soler, Robert; Bosch, Alba; Rodas, Gil; Til, Lluís; Peirau, Xavier; Urrútia, Gerard; Gich, Ignasi; Bonfill, Xavier

    2016-01-01

    Background The goals of the treatment of muscle injuries are to shorten the time of healing and to avoid relapses. The aim of this study was to assess the efficacy of autologous platelet-rich plasma (PRP) in the healing of muscle injuries. Materials and methods A multicentre, randomised, double-blind, parallel, controlled clinical trial was conducted in 71 patients (81.8% males) aged 45.6 (SD=10.0) years with muscle tears in the legs and haematoma. The haematoma was evacuated in all patients. Thirty-three patients were randomised to a single dose of autologous PRP and 38 patients to simulation of PRP administration. The primary end-point was time to complete recovery of muscle injury. Secondary end-points were pain, relapses, ultrasound parameters, and adverse events. The total follow-up per patient was 12 months. Results Time to complete recovery after the treatment was 31.63 days (SD=15.38) in the PRP group, and 38.43 days (SD=18.58) in the control group (p=0.261). Pain decreased over time in both groups without statistical differences between them. Eight patients relapsed (seven in the control group, and one in the PRP group). There were no adverse effects related to the interventions. Discussion Autologous PRP did not significantly improve the time to healing compared to that in the control group. PMID:26509827

  18. The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

    PubMed Central

    2014-01-01

    Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

  19. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study

    PubMed Central

    Landewé, R; Braun, J; Deodhar, A; Dougados, M; Maksymowych, W P; Mease, P J; Reveille, J D; Rudwaleit, M; van der Heijde, D; Stach, C; Hoepken, B; Fichtner, A; Coteur, G; de Longueville, M; Sieper, J

    2014-01-01

    Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Methods Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. Results Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (−2.28 vs −0.40), BASDAI (−3.05 vs −1.05), and BASMI (−0.52 vs −0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. Conclusions CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients. PMID:24013647

  20. Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial

    PubMed Central

    MacDonald, Thomas M; Williams, Bryan; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Mackenzie, Isla S; Salsbury, Jackie; Morant, Steve; Ford, Ian; Brown, Morris J

    2015-01-01

    Introduction Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. Methods and analysis The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. Ethics and dissemination PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the

  1. Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

    PubMed Central

    2012-01-01

    Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor

  2. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Ralph, Anna P.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B.; Yeo, Tsin W.; Chatfield, Mark D.; Soemanto, Retno K.; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P.; Eisman, John; Price, Ric N.; Morris, Peter S.; Kelly, Paul M.; Anstey, Nicholas M.

    2013-01-01

    Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained

  3. Antifatigue Effects of Panax ginseng C.A. Meyer: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Yoo, Sa-Ra; Lee, Jin-Seok; Han, Jong-Min; Lee, Nam-Hun; Ahn, Yo-Chan; Son, Chang-Gue

    2013-01-01

    The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day–1) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4±5.0 to 15.1±6.5 [95% CI 2.3∼8.2] for 1 g and 20.7±6.3 to 13.8±6.2 [95% CI −0.1∼4.2] for 2 g compared with placebo 20.9±4.5 to 18.8±2.9 [95% CI 4.1∼9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3±1.3 to 4.4±1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1±1.0 to 5.8±1.3 [95% CI 2.2 ∼3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. Trial Registration Clinical Research Information Service (CRIS) KCT0000048 PMID:23613825

  4. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial

    PubMed Central

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-01-01

    Summary Background Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10–2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87–2·38, p=0·151

  5. Effect of Triticum turgidum subsp. turanicum wheat on irritable bowel syndrome: a double-blinded randomised dietary intervention trial.

    PubMed

    Sofi, Francesco; Whittaker, Anne; Gori, Anna Maria; Cesari, Francesca; Surrenti, Elisabetta; Abbate, Rosanna; Gensini, Gian Franco; Benedettelli, Stefano; Casini, Alessandro

    2014-06-01

    The aim of the present study was to examine the effect of a replacement diet with organic, semi-whole-grain products derived from Triticum turgidum subsp. turanicum (ancient) wheat on irritable bowel syndrome (IBS) symptoms and inflammatory/biochemical parameters. A double-blinded randomised cross-over trial was performed using twenty participants (thirteen females and seven males, aged 18-59 years) classified as having moderate IBS. Participants received products (bread, pasta, biscuits and crackers) made either from ancient or modern wheat for 6 weeks in a random order. Symptoms due to IBS were evaluated using two questionnaires, which were compiled both at baseline and on a weekly basis during the intervention period. Blood analyses were carried out at the beginning and end of each respective intervention period. During the intervention period with ancient wheat products, patients experienced a significant decrease in the severity of IBS symptoms, such as abdominal pain (P< 0·0001), bloating (P= 0·004), satisfaction with stool consistency (P< 0·001) and tiredness (P< 0·0001). No significant difference was observed after the intervention period with modern wheat products. Similarly, patients reported significant amelioration in the severity of gastrointestinal symptoms only after the ancient wheat intervention period, as measured by the intensity of pain (P= 0·001), the frequency of pain (P< 0·0001), bloating (P< 0·0001), abdominal distension (P< 0·001) and the quality of life (P< 0·0001). Interestingly, the inflammatory profile showed a significant reduction in the circulating levels of pro-inflammatory cytokines, including IL-6, IL-17, interferon-γ, monocyte chemotactic protein-1 and vascular endothelial growth factor after the intervention period with ancient wheat products, but not after the control period. In conclusion, significant improvements in both IBS symptoms and the inflammatory profile were reported after the ingestion of ancient

  6. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial

    PubMed Central

    Paulsen, Gøran; Cumming, Kristoffer T; Holden, Geir; Hallén, Jostein; Rønnestad, Bent Ronny; Sveen, Ole; Skaug, Arne; Paur, Ingvild; Bastani, Nasser E; Østgaard, Hege Nymo; Buer, Charlotte; Midttun, Magnus; Freuchen, Fredrik; Wiig, Håvard; Ulseth, Elisabeth Tallaksen; Garthe, Ina; Blomhoff, Rune; Benestad, Haakon B; Raastad, Truls

    2014-01-01

    In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4–6 × 4–6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30–60 min; 70–90% of HRmax). Maximal oxygen uptake (), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: −13 ± 54%; PGC-1α: −13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to

  7. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    Summary Background The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). Methods In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per

  8. Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial

    PubMed Central

    Cunningham, Steve; Rodriguez, Aryelly; Adams, Tim; Boyd, Kathleen A; Butcher, Isabella; Enderby, Beth; MacLean, Morag; McCormick, Jonathan; Paton, James Y; Wee, Fiona; Thomas, Huw; Riding, Kay; Turner, Steve W; Williams, Chris; McIntosh, Emma; Lewis, Steff C

    2015-01-01

    Summary Background The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. Methods We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study [BIDS]). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation [SpO2] <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. Findings Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference −1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged

  9. Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial–a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Chronic kidney disease (CKD) is common and increasing in prevalence. Cardiovascular disease (CVD) is a major cause of morbidity and death in CKD, though of a different phenotype to the general CVD population. Few therapies have proved effective in modifying the increased CVD risk or rate of renal decline in CKD. There are accumulating data that aldosterone receptor antagonists (ARA) may offer cardio-protection and delay renal impairment in patients with the CV phenotype in CKD. The use of ARA in CKD has therefore been increasingly advocated. However, no large study of ARA with renal or CVD outcomes is underway. Methods The study is a prospective randomised open blinded endpoint (PROBE) trial set in primary care where patients will mainly be identified by their GPs or from existing CKD lists. They will be invited if they have been formally diagnosed with CKD stage 3b or there is evidence of stage 3b CKD from blood results (eGFR 30–44 mL/min/1.73 m2) and fulfil the other inclusion/exclusion criteria. Patients will be randomised to either spironolactone 25 mg once daily in addition to routine care or routine care alone and followed-up for 36 months. Discussion BARACK D is a PROBE trial to determine the effect of ARA on mortality and cardiovascular outcomes (onset or progression of CVD) in patients with stage 3b CKD. Trial registration EudraCT: 2012-002672-13 ISRTN: ISRCTN44522369 PMID:24886488

  10. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

    PubMed Central

    Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

    1999-01-01

    BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

  11. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Summary Background Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. Methods The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. Findings Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ2 on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40–1·24). 56 patients in the placebo group and 61 in the lithium

  12. Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial

    PubMed Central

    van Samkar, Ganapathy; Eshuis, Wietse J.; Bennink, Roelof J.; van Gulik, Thomas M.; Dijkgraaf, Marcel G. W.; Preckel, Benedikt; de Hert, Stefan; Gouma, Dirk J.; Hollmann, Markus W.; Busch, Olivier R. C.

    2015-01-01

    Background Perioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function. Methods In this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. Primary endpoint: gastric emptying scintigraphically assessed on postoperative day 7. Results In 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74–369) versus 159 minutes (R-group, 95% confidence interval: 61–204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups. Conclusion A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery. Trial registration ISRCTN62621488 PMID:26465290

  13. Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial

    PubMed Central

    Kruis, W; Kiudelis, G; Rácz, I; Gorelov, I A; Pokrotnieks, J; Horynski, M; Batovsky, M; Kykal, J; Boehm, S; Greinwald, R; Mueller, R

    2009-01-01

    Objectives: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. Design: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. Setting: 54 centres in 13 countries. Patients: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index ⩾4 at baseline) were randomised and treated. Interventions: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. Main outcome measures: Clinical remission (CAI⩽4) at study end. Results: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. Conclusions: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis. ClinicalTrials.gov Identifier: NCT00449722 PMID:18832520

  14. Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial

    PubMed Central

    Maes, Michael; Ashton, Melanie; Berk, Lesley; Kanchanatawan, Buranee; Sughondhabirom, Atapol; Tangwongchai, Sookjareon; Ng, Chee; Dowling, Nathan; Malhi, Gin S.; Berk, MIchael

    2014-01-01

    While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression. PMID:25598820

  15. Blindness

    MedlinePlus

    ... Prevalent Cases of Blindness (in thousands) by Age, Gender, and Race/Ethnicity Table for 2010 U.S. Prevalent ... Prevalent Cases of Blindness (in thousands) by Age, Gender, and Race/Ethnicity Table for 2000 U.S. Prevalent ...

  16. Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial

    PubMed Central

    Hanley, Janet; McCloughan, Lucy; Todd, Allison; Krishan, Ashma; Lewis, Stephanie; Stoddart, Andrew; van der Pol, Marjon; MacNee, William; Sheikh, Aziz; Pagliari, Claudia; McKinstry, Brian

    2013-01-01

    Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care. Design Researcher blind, multicentre, randomised controlled trial. Setting UK primary care (Lothian, Scotland). Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation. We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems. Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring. Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments. Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds. Both groups received similar care from existing clinical services. Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation. Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment. Analysis was intention to treat. Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar. The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44). Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person

  17. Traumeel vs. diclofenac for reducing pain and improving ankle mobility after acute ankle sprain: A multicentre, randomised, blinded, controlled and non-inferiority trial

    PubMed Central

    González de Vega, C; Speed, C; Wolfarth, B; González, J

    2013-01-01

    Background Acute ankle sprains are common and activity limiting injuries, and topical diclofenac gel has proven efficacy in alleviating pain and restoring function. This trial aimed to compare a topical natural agent, Traumeel with topical diclofenac gel (1%) in the management of acute ankle sprain. Methods This prospective, multicentre, randomised, blinded, active-control and non-inferiority study involved 449 physically active adults sustaining unilateral grade 1 or 2 ankle sprain within the past 24 h. Participants were randomised to receive 2 g of Traumeel ointment (T-O) (n = 152) or Traumeel gel (T-G) (n = 150) or diclofenac gel (D-G) (n = 147), administered topically to the ankle three times a day for 14 days, with 6-weeks follow up. Results Day 7 median percentage reductions in Visual Analogue Scale pain score were 60.6%, 71.1% and 68.9% for the T-O, T-G and D-G groups, respectively. Total pain relief was reported by 12 (8.5%), 7 (5.0%) and 8 (5.9%) participants in each group, respectively. Median improvements in Foot and Ankle Ability Measure Activities of Daily Living subscale score were 26.2, 26.2 and 25.0 points for T-O, T-G and D-G groups, respectively. Mann–Whitney effect sizes and lower bound confidence intervals demonstrated non-inferiority of Traumeel vs. diclofenac for reducing pain and functional improvement. At 6 weeks, participants reported total pain relief and normal functioning. Adverse events (n = 43) were reported by 31/447 participants (6.9%). Treatments were equally well tolerated. Conclusions T-O and T-G decreased pain and improved joint function to the same extent as D-G in acute ankle sprain, and were well tolerated. PMID:23889885

  18. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

    PubMed Central

    Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

    2014-01-01

    Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

  19. How to improve walking, balance and social participation following stroke: a comparison of the long term effects of two walking aids--canes and an orthosis TheraTogs--on the recovery of gait following acute stroke. A study protocol for a multi-centre, single blind, randomised control trial

    PubMed Central

    2012-01-01

    Background Annually, some 9000 people in Switzerland suffer a first time stroke. Of these 60% are left with moderate to severe walking disability. Evidence shows that rehabilitation techniques which emphasise activity of the hemiplegic side increase ipsilesional cortical plasticity and improve functional outcomes. Canes are commonly used in gait rehabilitation although they significantly reduce hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset with elasticated strapping) significantly increases hemiplegic muscle activity during gait. The aim of the present study is to investigate the long term effects on the recovery of gait, balance and social participation of gait rehabilitation with TheraTogs compared to gait rehabilitation with a cane following first time acute stroke. Methods/Design Multi-centre, single blind, randomised trial with 120 patients after first stroke. When subjects have reached Functional Ambulation Category 3 they will be randomly allocated into TheraTogs or cane group. TheraTogs will be applied to support hip extensor and abductor musculature according to a standardised procedure. Cane walking held at the level of the radial styloid of the sound wrist. Subjects will walk throughout the day with only the assigned walking aid. Standard therapy treatments and usual care will remain unchanged and documented. The intervention will continue for five weeks or until patients have reached Functional Ambulation category 5. Outcome measures will be assessed the day before begin of intervention, the day after completion, 3 months, 6 months and 2 years. Primary outcome: Timed "up and go" test, secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius, activation patterns of hemiplegic leg musculature, temporo-spatial gait parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic balance, daily activity measured by accelerometry, Stroke Impact Scale. Significance levels will be 5% with 95

  20. Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment. There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease: some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement (TKR); whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement (UKR). Both interventions are established and well-documented procedures. Little evidence exists to prove the clinical and cost-effectiveness of either management option. This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology. The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis. Methods/Design The design of the study is a single layer multicentre superiority type randomised controlled trial of unilateral knee replacement patients. Blinding will not be possible as the surgical scars for each procedure differ. We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals. Participants will be randomised to either UKR or TKR. Randomisation will occur using a web-based randomisation system. The study is pragmatic in terms of implant selection for the knee replacement operation. Participants will be followed up for 5 years. The primary outcome is the Oxford Knee Score, which will be collected via questionnaires at 2 months, 1 year and then annually to 5 years. Secondary outcomes will include cost-effectiveness, patient satisfaction and complications data. Trial registration Current Controlled Trials ISRCTN03013488; ClinicalTrials.gov Identifier: NCT01352247 PMID:24028414

  1. High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults

    PubMed Central

    2014-01-01

    Background Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection. Methods In a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat. Results 18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7–95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818–11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3–146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM. Conclusions MM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional

  2. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial

    PubMed Central

    Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group

    2010-01-01

    Summary Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. Methods We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88–1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. Interpretation The 6% (SE 3·5%) reduction in major

  3. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial

    PubMed Central

    2010-01-01

    Background Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage. Methods The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not

  4. Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Bennell, Kim; Coburn, Sally; Wee, Elin; Green, Sally; Harris, Anthony; Forbes, Andrew; Buchbinder, Rachelle

    2007-01-01

    Background Chronic rotator cuff pathology (CRCP) is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI), average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36), Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log

  5. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial

    PubMed Central

    Brunner, Hermine I; Ruperto, Nicolino; Zuber, Zbigniew; Keane, Caroline; Harari, Olivier; Kenwright, Andrew; Lu, Peng; Cuttica, Ruben; Keltsev, Vladimir; Xavier, Ricardo M; Calvo, Inmaculada; Nikishina, Irina; Rubio-Pérez, Nadina; Alexeeva, Ekaterina; Chasnyk, Vyacheslav; Horneff, Gerd; Opoka-Winiarska, Violetta; Quartier, Pierre; Silva, Clovis A; Silverman, Earl; Spindler, Alberto; Baildam, Eileen; Gámir, M Luz; Martin, Alan; Rietschel, Christoph; Siri, Daniel; Smolewska, Elzbieta; Lovell, Daniel; Martini, Alberto; De Benedetti, Fabrizio

    2015-01-01

    Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221. PMID:24834925

  6. Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold

    PubMed Central

    2012-01-01

    Background Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. Methods We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. Results The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. Conclusion In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. Trial registration ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/ PMID:22950667

  7. Impact of peer review on reports of randomised trials published in open peer review journals: retrospective before and after study

    PubMed Central

    Collins, Gary S; Boutron, Isabelle; Yu, Ly-Mee; Cook, Jonathan; Shanyinde, Milensu; Wharton, Rose; Shamseer, Larissa; Altman, Douglas G

    2014-01-01

    Objective To investigate the effectiveness of open peer review as a mechanism to improve the reporting of randomised trials published in biomedical journals. Design Retrospective before and after study. Setting BioMed Central series medical journals. Sample 93 primary reports of randomised trials published in BMC-series medical journals in 2012. Main outcome measures Changes to the reporting of methodological aspects of randomised trials in manuscripts after peer review, based on the CONSORT checklist, corresponding peer reviewer reports, the type of changes requested, and the extent to which authors adhered to these requests. Results Of the 93 trial reports, 38% (n=35) did not describe the method of random sequence generation, 54% (n=50) concealment of allocation sequence, 50% (n=46) whether the study was blinded, 34% (n=32) the sample size calculation, 35% (n=33) specification of primary and secondary outcomes, 55% (n=51) results for the primary outcome, and 90% (n=84) details of the trial protocol. The number of changes between manuscript versions was relatively small; most involved adding new information or altering existing information. Most changes requested by peer reviewers had a positive impact on the reporting of the final manuscript—for example, adding or clarifying randomisation and blinding (n=27), sample size (n=15), primary and secondary outcomes (n=16), results for primary or secondary outcomes (n=14), and toning down conclusions to reflect the results (n=27). Some changes requested by peer reviewers, however, had a negative impact, such as adding additional unplanned analyses (n=15). Conclusion Peer reviewers fail to detect important deficiencies in reporting of the methods and results of randomised trials. The number of these changes requested by peer reviewers was relatively small. Although most had a positive impact, some were inappropriate and could have a negative impact on reporting in the final publication. PMID:24986891

  8. Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study.

    PubMed

    Childs, Caroline E; Röytiö, Henna; Alhoniemi, Esa; Fekete, Agnes A; Forssten, Sofia D; Hudjec, Natasa; Lim, Ying Ni; Steger, Cara J; Yaqoob, Parveen; Tuohy, Kieran M; Rastall, Robert A; Ouwehand, Arthur C; Gibson, Glenn R

    2014-06-01

    Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of

  9. Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study).

    PubMed

    Putet, Guy; Labaune, Jean-Marc; Mace, Katherine; Steenhout, Philippe; Grathwohl, Dominik; Raverot, Veronique; Morel, Yves; Picaud, Jean-Charles

    2016-01-28

    The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity. PMID:26586096

  10. A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia.

    PubMed

    Karlsson, I; Godderis, J; Augusto De Mendonça Lima, C; Nygaard, H; Simányi, M; Taal, M; Eglin, M

    2000-04-01

    Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning. Depression in old age has been shown to be associated with degenerative changes in the brain. It is, therefore, important that in this patient population antidepressants with a favourable tolerability profile, such as the selective serotonin reuptake inhibitors (SSRIs), are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment. This randomised, double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly, depressed patients with or without dementia. Patients received either citalopram 20-40 mg/day or mianserin 30-60 mg/day for 12 weeks. The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale (MADRS) total score; patients in both treatment groups responded well. Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia. Both treatments were well tolerated with a relatively low incidence of adverse events. Fatigue and somnolence were more frequent with mianserin, while insomnia was more frequent with citalopram. Overall, this study showed that the two treatments were equivalent in efficacy, and that citalopram is an effective, well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia. PMID:10767728

  11. Comparison of lidocaine spray and paracervical block application for pain relief during first-trimester surgical abortion: A randomised, double-blind, placebo-controlled trial.

    PubMed

    Aksoy, Huseyin; Aksoy, Ulku; Ozyurt, Sezin; Ozoglu, Nil; Acmaz, Gokhan; Aydın, Turgut; İdem Karadağ, Özge; Tayyar, Ahter Tanay

    2016-07-01

    Surgical abortion is one of the most frequently performed gynaecological procedures and its associated pain has always been a problem in gynaecology. Here we studied the analgesic efficacy of lidocaine spray and paracervical block (PCB) in patients undergoing first-trimester surgical abortion. A randomised double-blind placebo-controlled study was conducted on 108 women requesting pregnancy termination. The subjects were randomly assigned into four groups: Group 1 (PCB plus lidocaine spray) (n=27), Group 2 (PCB) (n=27), Group 3 (lidocaine spray) (n=27) and Group 4 (placebo) (n=27). Intra-procedural and post-procedural pain scores were measured with a standard visual analogue scale (VAS). The median VAS scores during procedure in placebo, lidocaine spray, PCB plus lidocaine spray and PCB groups were 8 (7-9), 5 (4-8), 4 (3-4) and 5 (3-5), respectively. The most effective method of pain relief during first-trimester abortion can be achieved through a combined use of PCB plus lidocaine spray. Therefore, lidocaine spray is a non-invasive complementary anaesthetic method versus traditional PCB for first-trimester surgical abortion. PMID:26926158

  12. Effect of caudal epidural steroid or saline injection in chronic lumbar radiculopathy: multicentre, blinded, randomised controlled trial

    PubMed Central

    Solberg, Tore K; Romner, Bertil; Wilsgaard, Tom; Twisk, Jos; Anke, Audny; Nygaard, Øystein; Hasvold, Toralf; Ingebrigtsen, Tor

    2011-01-01

    Objective To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short (6 weeks), intermediate (12 weeks), and long term (52 weeks). Design Multicentre, blinded, randomised controlled trial. Setting Outpatient multidisciplinary back clinics of five Norwegian hospitals. Participants Between October 2005 and February 2009, 461 patients assessed for inclusion (presenting with lumbar radiculopathy >12 weeks). 328 patients excluded for cauda equina syndrome, severe paresis, severe pain, previous spinal injection or surgery, deformity, pregnancy, ongoing breast feeding, warfarin therapy, ongoing treatment with non-steroidal anti-inflammatory drugs, body mass index >30, poorly controlled psychiatric conditions with possible secondary gain, and severe comorbidity. Interventions Subcutaneous sham injections of 2 mL 0.9% saline, caudal epidural injections of 30 mL 0.9% saline, and caudal epidural injections of 40 mg triamcinolone acetonide in 29 mL 0.9% saline. Participants received two injections with a two week interval. Main outcome measures Primary: Oswestry disability index scores. Secondary: European quality of life measure, visual analogue scale scores for low back pain and for leg pain. Results Power calculations required the inclusion of 41 patients per group. We did not allocate 17 of 133 eligible patients because their symptoms improved before randomisation. All groups improved after the interventions, but we found no statistical or clinical differences between the groups over time. For the sham group (n=40), estimated change in the Oswestry disability index from the adjusted baseline value was −4.7 (95% confidence intervals −0.6 to −8.8) at 6 weeks, −11.4 (−6.3 to −14.5) at 12 weeks, and −14.3 (−10.0 to −18.7) at 52 weeks. For the epidural saline intervention group (n=39) compared with the sham group, differences in primary outcome were −0.5 (−6.3 to 5.4) at 6 weeks, 1.4 (−4.5 to 7

  13. Randomised, Double Blind, Controlled Trial of the Provision of Information about the Benefits of Organ Donation during a Family Donation Conversation

    PubMed Central

    Aranha, Sarah; Pilcher, David V.; Bailey, Michael

    2016-01-01

    Introduction It is unclear how much information should be provided to families of potential organ donors about the benefits of organ donation. Whilst this information is material to the donation decision, it may also be perceived as coercive. Methods Randomised, double blind, controlled trial in which community members watched one of two videos of a simulated organ donation conversation that differed only in the amount of information provided about the benefits of donation. Participants then completed a questionnaire about the adequacy of the information provided and the degree to which they felt the doctor was trying to convince the family member to say yes to donation. Results There was a wide variability in what participants considered was the “right” amount of information about organ donation. Those who watched the conversation that included information about the benefits of donation were more likely to feel that the information provided to the family was sufficient. They were more likely to report that the doctor was trying to convince the family member to say yes to donation, yet were no more likely to feel uncomfortable or to feel that the doctor was uncaring or cared more about transplant recipients than he did for the patient and their family. Conclusions This study suggests that community members are comfortable with health care staff providing information to family members that may be influential in supporting them to give consent for donation. PMID:27322832

  14. Cost analysis of cataract surgery with intraocular lens implantation: a single blind randomised clinical trial comparing extracapsular cataract extraction and phacoemulsification.

    PubMed

    Rizal, A M; Aljunid, S M; Normalina, M; Hanom, A Faridah; Chuah, K L; Suzainah, Y; Zainal, M; Azman, A B

    2003-08-01

    A randomised single blinded clinical trial to compare the cost of cataract surgery between extracapsular cataract extraction (ECCE) and phacoemulsification (PEA) was conducted at Hospital Universiti Kebangsaan Malaysia (HUKM) between March and December 2000. A total of 60 patients were included in this study. The cost of a cataract surgery incurred by hospital, patients and households up to two months after discharge were included. The costs of training, loss of patients' income after discharge and intangible costs were excluded. Results showed that the average cost for one ECCE operation is RM1,664.46 (RM1,233.04-RM2,377.64) and for PEA is RM1,978.00 (RM1,557.87-RM3,334.50). During this short period of follow up, it can be concluded that ECCE is significantly cheaper than PEA by an average difference of RM 313.54 per patient (p < 0.001). Cost of equipment and low frequency of PEA technique done in HUKM were the two main reasons for the high unit cost of PEA as compared to ECCE. PMID:14750378

  15. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial

    PubMed Central

    Takwale, A; Tan, E; Agarwal, S; Barclay, G; Ahmed, I; Hotchkiss, K; Thompson, J R; Chapman, T; Berth-Jones, J

    2003-01-01

    Objective To study the efficacy and tolerability of borage oil, which contains a high concentration of γ linolenic acid, in children and adults with atopic eczema. Design Single centre, randomised, double blind, placebo controlled, parallel group trial. Setting Acute district general hospital in Nuneaton, England. Participants 151 patients, of whom 11 failed to return for assessment, leaving an evaluable population of 140 (including 69 children). Intervention Adults received four capsules of borage oil twice daily (920 mg γ linolenic acid), and children received two capsules twice daily, for 12 weeks. Main outcome measures Change in total sign score at 12 weeks measured with the six area, six sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores, assessed on visual analogue scales; topical corticosteroid requirement, assessed on a five point scale; global assessment of response by participants; adverse events and tolerability. Results The mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to 5.0) points in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in the other assessments. Subset analysis of adults and children did not indicate any difference in response. The treatments were well tolerated. Conclusion γ linolenic acid is not beneficial in atopic dermatitis. PMID:14670885

  16. Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo-controlled, double-blind pilot clinical trial.

    PubMed

    Whitmont, Kaley; McKelvey, Kelly J; Fulcher, Gregory; Reid, Ian; March, Lyn; Xue, Meilang; Cooper, Alan; Jackson, Christopher J

    2015-08-01

    Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo-controlled, double-blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC-treated wounds (p = 0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one saline-treated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p < 0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial. PMID:23848141

  17. P3MC: A double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children

    PubMed Central

    2010-01-01

    Background A recent Cochrane Review demonstrated the remarkable lack of reliable clinical trials of migraine treatments for children, especially for the two most prescribed preventative treatments in the UK, Propranolol and Pizotifen. Migraine trials in both children and adults have high placebo responder rates, e.g. of 23%, but for a trial's results to be generalisable "placebo responders" should not be excluded and for a drug to be worthwhile it should be clearly superior, both clinically and statistically, to placebo. Methods/Design Two multicentre, two arm double blind parallel group randomised controlled trials, with allocation ratio of 2:1 for each comparison, Propranolol versus placebo and Pizotifen versus placebo. The trial is designed to test whether Propranolol is superior to placebo and whether Pizotifen is superior to placebo for the prevention of migraine attacks in children aged 5 - 16 years referred to secondary care out-patient settings with frequent migraine (2-6/4 weeks). The primary outcome measure is the number of migraine attacks during trial weeks 11 to 14. Discussion A strength of this trial is the participation of clinically well defined migraine patients who will also be approached to help with future longer-term follow-up studies. Trial Registration ISRCTN97360154 PMID:20553601

  18. Blindness

    MedlinePlus

    ... The problem may affect one eye or both eyes. When you think of being blind, you might imagine total darkness. But most people who are blind can still see a little light or shadows. They just can't see things clearly. People who have some sight, but still need a lot of help, are ...

  19. Crotaline snake bite in the Ecuadorian Amazon: randomised double blind comparative trial of three South American polyspecific antivenoms

    PubMed Central

    Smalligan, Roger; Cole, Judy; Brito, Narcissa; Laing, Gavin D; Mertz, Bruce L; Manock, Steven; Maudlin, Jeffrey; Quist, Brad; Holland, Gary; Nelson, Stephen; Lalloo, David G; Rivadeneira, Gonzalo; Barragan, Maria Elena; Dolley, Daniel; Eddleston, Michael; Warrell, David A; Theakston, R David G

    2004-01-01

    Objective To compare the efficacy and safety of three polyspecific antivenoms for bites by pit vipers. Design Randomised double blind comparative trial of three antivenoms. Setting Shell, Pastaza, southeastern Ecuador. Participants 210 patients with incoagulable blood were recruited from 221 consecutive patients admitted with snake bite between January 1997 and December 2001. Intervention One of three antivenoms manufactured in Brazil, Colombia, and Ecuador, chosen for their preclinical potency against Ecuadorian venoms. Main outcome measures Permanent restoration of blood coagulability after 6 and 24 hours. Results The snakes responsible for the bites were identified in 187 cases: 109 patients (58%) were bitten by Bothrops atrox, 68 (36%) by B bilineatus, and 10 (5%) by B taeniatus, B brazili, or Lachesis muta. Eighty seven patients (41%) received Colombian antivenom, 82 (39%) received Brazilian antivenom, but only 41 (20%) received Ecuadorian antivenom because the supply was exhausted. Two patients died, and 10 developed local necrosis. All antivenoms achieved the primary end point of permanently restoring blood coagulability by 6 or 24 hours after the start of treatment in > 40% of patients. Colombian antivenom, however, was the most effective after initial doses of 20 ml (two vials), < 70 ml, and any initial dose at both 6 and 24 hours. An initial dose of 20 ml of Colombian antivenom permanently restored blood coagulability in 64% (46/72) of patients after 6 hours (P = 0.054 compared with the other two antivenoms) and an initial dose of < 70 ml was effective at 6 hours (65%, P = 0.045) and 24 hours (99%, P = 0.06). Early anaphylactoid reactions were common (53%, 73%, and 19%, respectively, for Brazilian, Colombian, and Ecuadorian antivenoms, P < 0.0001) but only three reactions were severe and none was fatal. Conclusions All three antivenoms can be recommended for the treatment of snakebites in this region, though the reactogenicity of Brazilian and Colombian

  20. The Explorer study: the first double-blind RCT to assess the efficacy of TLC-NOSF on DFUs.

    PubMed

    Shanahan, D R

    2013-02-01

    Urgo Medical recently announced the launch of the Explorer study, a large, Europe-wide, clinical study on the efficacy and tolerability of UrgoStart Contact, a lipidocolloid technology dressing impregnated with nano-oligosaccharide factor, in the treatment of diabetic foot ulceration. The number of patients, investigating centres and countries involved, as well as the length of treatment and patient follow-up, make this an ambitious, double-blind, randomised controlled trial. PMID:23665662

  1. Intravenous immunoglobulins for the treatment of mild to moderate Alzheimer’s disease: a phase II, randomised, double-blind, placebo-controlled dose-finding trial

    PubMed Central

    Dodel, Richard; Rominger, Axel; Bartenstein, Peter; Barkhof, Frederik; Blennow, Kai; Förster, Stefan; Winter, Yaroslav; Bach, Jan-Philipp; Popp, Julius; Alferink, Judith; Wiltfang, Jens; Buerger, Katharina; Otto, Markus; Antuono, Piero; Jacoby, Michael; Richter, Ralph; Stevens, James; Melamed, Isaac; Goldstein, Jerome; Haag, Stefan; Wietek, Stefan; Farlow, Martin; Jessen, Frank

    2016-01-01

    Background Three small trials have suggested effects of intravenous immunoglobulins (IVIG) on biomarkers and symptoms of mild-to-moderate Alzheimer’s disease (AD). We explored the safety, the effective dose, and the infusion interval for Octagam®10% in this patients’ group. Methods The study was a 24-week multicentre, double-blind, placebo-controlled phase II trial with 8 treatment arms at 7 sites in the USA and 5 sites in Germany. Participants aged 50–85 years were randomised (using a computer-generated randomisation sequence) to either 4 weekly infusions (n=22) (0.2 g/0.5 g/0.8 g/kg body weight), 2 weekly infusions (0.1g/0.25 g/0.4 g/kg) (n=21) or to placebo (n=7, 4-weekly, n=8, 2 weekly). The primary endpoint was the mean area under the curve (AUC) of plasma Aβ1–40 after the last infusion for one infusion interval. We considered the AUC of plasma Aβ1–40 being more representative of the potential effect of IVIG than a single time point measurement. Secondary outcomes included changes in (a) the concentrations of Aβ1–40, Aβ1–42, anti-Aβ autoantibodies in CSF/plasma and tau/ptau181 in CSF, (b) cognitive and functional scales, and (c) brain imaging (MRI/FDG-PET). Patients’ safety was assessed by recording of adverse events, clinical examinations, MRI investigations, electrocardiography and laboratory tests. The infusions were performed by site personnel who were otherwise not involved in any other assessments; therefore, the patients, caregivers, and investigators were blinded to the treatment allocations. The study medication was blinded by using intransparent overpouches and infusion lines. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). Findings Fifty-six patients were randomized. AUC of plasma Aβ1–40, was not significantly different from the placebo for five of the six IVIG arms (median with range: −18.00 [−1347.0; 1068.5] for 0.2 g/kg; 364.25 [−5834.5; 1953.5] for 0.5 g

  2. Internet-based treatment for older adults with depression and co-morbid cardiovascular disease: protocol for a randomised, double-blind, placebo controlled trial

    PubMed Central

    2011-01-01

    Background Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. Methods/Design This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Discussion Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on depressive symptoms and

  3. Feasibility, double-blind, randomised, placebo-controlled, multi-centre trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home (HI-Light trial: Home Intervention of Light therapy)

    PubMed Central

    2014-01-01

    Background Hand-held NB-UVB units are lightweight devices that may overcome the need to treat vitiligo in hospital-based phototherapy cabinets, allowing early treatment at home that may enhance the likelihood of successful repigmentation. The pilot Hi-Light trial examined the feasibility of conducting a large multi-centre randomised controlled trial (RCT) on the use of such devices by exploring recruitment, adherence, acceptability, and patient education. Methods This was a feasibility, double-blind, multi-centre, parallel group randomised placebo-controlled trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home. The overall duration of the trial was seven months; three months recruitment and four months treatment. Participants were randomly allocated to active or placebo groups (2:1 ratio). The primary outcome measure was the proportion of eligible participants who were willing to be randomised. The secondary outcomes included proportion of participants expressing interest in the trial and fulfilling eligibility criteria, withdrawal rates and missing data, proportion of participants adhering to and satisfied with the treatment, and incidence of NB-UVB short-term adverse events. Results Eighty-three percent (45/54) of vitiligo patients who expressed interest in the trial were willing to be randomised. Due to time and financial constraints, only 29/45 potential participants were booked to attend a baseline hospital visit. All 29 (100%) potential participants were confirmed as being eligible and were subsequently randomised. Willingness to participate in the study for General Practice (family physicians) surgeries and hospitals were 40% and 79%, respectively; 86% (25/29) of patients adhered to the treatment and 65% (7/11) of patients in the active group had some degree of repigmentation. Only one patient in the active group reported erythema grade 3 (3%). Both devices (Dermfix 1000 NB-UVB and Waldmann NB-UVB 109) were acceptable to participants

  4. Corticosteroids in peri-radicular infiltration for radicular pain: a randomised double blind controlled trial. One year results and subgroup analysis

    PubMed Central

    Ng, Leslie; Chaudhary, Neeraj; Sell, Philip

    2009-01-01

    The objective of this study is to evaluate the efficacy of corticosteroids in patients with radicular pain due to lumbar disc herniation or lumbar spinal stenosis through a prospective randomised, double blind controlled trial, and whether there was an effect on subsequent interventions such as additional root blocks or surgery. Peri-radicular infiltration of corticosteroids has previously been shown to offer no additional benefit in patients with sciatica compared to local anaesthetic alone. It is not known if the response to peri-radicular infiltration is less marked in certain subgroups of patients such as those with radicular pain due to lumbar spinal stenosis. Previous studies have suggested that peri-radicular infiltration of corticosteroids may obviate the need for subsequent interventions and we therefore further investigated this in the current study. We randomised 150 patients to receive a single injection with either bupivacaine alone or bupivacaine and methylprednisolone. Patients were assessed at 6 weeks and 3 months after the injection using standard outcome measures including Oswestry Disability Index (ODI), visual analogue score for leg pain and patient’s subjective assessment of outcome. At 1-year follow-up, we looked at the outcome in terms of the need for subsequent interventions such as additional root blocks or surgery. At 3-month follow-up, there was no statistically significant difference in the standard outcome measures between the two injection groups. At a minimum 1-year post injection, there was no difference in the need for subsequent interventions in either group. Patients with lumbar spinal stenosis had a less marked reduction in the ODI at 3 months with a mean change of 3.3 points when compared with 15 points for patients with lumbar disc herniation. In conclusion, peri-radicular infiltration of corticosteroids for sciatica does not provide any additional benefit when compared to local anaesthetic injection alone. Corticosteroids

  5. A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

    PubMed Central

    Vischer, T L

    1988-01-01

    The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

  6. Sleeve gastrectomy versus Roux-en-Y gastric bypass for type 2 diabetes and morbid obesity: double-blind randomised clinical trial protocol

    PubMed Central

    Murphy, Rinki; Evennett, Nicholas J; Clarke, Michael G; Robinson, Steven J; Humphreys, Lee; Jones, Bronwen; Kim, David D; Cutfield, Richard; Plank, Lindsay D; Hammodat, Hisham; Booth, Michael W C

    2016-01-01

    Introduction Type 2 diabetes (T2D) in association with obesity is an increasing disease burden. Bariatric surgery is the only effective therapy for achieving remission of T2D among those with morbid obesity. It is unclear which of the two most commonly performed types of bariatric surgery, laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), is most effective for obese patients with T2D. The primary objective of this study is to determine whether LSG or LRYGB is more effective in achieving HbA1c<6% (<42 mmol/mol) without the use of diabetes medication at 5 years. Methods and analysis Single-centre, double-blind (assessor and patient), parallel, randomised clinical trial (RCT) conducted in New Zealand, targeting 106 patients. Eligibility criteria include age 20–55 years, T2D of at least 6 months duration and body mass index 35–65 kg/m2 for at least 5 years. Randomisation 1:1 to LSG or LRYGB, used random number codes disclosed to the operating surgeon after induction of anaesthesia. A standard medication adjustment schedule will be used during postoperative metabolic assessments. Secondary outcomes include proportions achieving HbA1c<5.7% (39 mmol/mol) or HbA1c<6.5% (48 mmol/mol) without the use of diabetes medication, comparative weight loss, obesity-related comorbidity, operative complications, revision rate, mortality, quality of life, anxiety and depression scores. Exploratory outcomes include changes in satiety, gut hormone and gut microbiota to gain underlying mechanistic insights into T2D remission. Ethics and dissemination Ethics approval was obtained from the New Zealand regional ethics committee (NZ93405) who also provided independent safety monitoring of the trial. Study commenced in September 2011. Recruitment completed in October 2014. Data collection is ongoing. Results will be reported in manuscripts submitted to peer-reviewed journals and in presentations at national and international meetings

  7. Effects of needs-based patient education on self-efficacy and health outcomes in people with rheumatoid arthritis: a multicentre, single blind, randomised controlled trial

    PubMed Central

    Ndosi, M; Johnson, D; Young, T; Hardware, B; Hill, J; Hale, C; Maxwell, J; Roussou, E; Adebajo, A

    2016-01-01

    Objectives The Educational Needs Assessment Tool (ENAT) is a self-completed questionnaire, which allows patients with arthritis to prioritise their educational needs. The aim of this study was to evaluate the effects of needs-based patient education on self-efficacy, health outcomes and patient knowledge in people with rheumatoid arthritis (RA). Methods Patients with RA were enrolled into this multicentre, single-blind, parallel-group, pragmatic randomised controlled trial. Patients were randomised to either the intervention group (IG) where patients completed ENAT, responses of which were used by the clinical nurse specialist to guide patient education; or control group (CG) in which they received patient education without the use of ENAT. Patients were seen at weeks 0, 16 and 32. The primary outcome was self-efficacy (Arthritis Self Efficacy Scale (ASES)-Pain and ASES-Other symptoms). Secondary outcomes were health status (short form of Arthritis Impact Measurement Scale 2, AIMS2-SF) and patient knowledge questionnaire-RA. We investigated between-group differences using analysis of covariance, adjusting for baseline variables. Results A total of 132 patients were recruited (IG=70 and CG=62). Their mean (SD) age was 54 (12.3) years, 56 (13.3)  years and disease duration 5.2 (4.9) years, 6.7 (8.9) years for IG and CG, respectively. There were significant between-group differences, in favour of IG at week 32 in the primary outcomes, ASES-Pain, mean difference (95% CI) −4.36 (1.17 to 7.55), t=−2.72, p=0.008 and ASES-Other symptoms, mean difference (95% CI) −5.84 (2.07 to 9.62), t=−3.07, p=0.003. In secondary outcomes, the between-group differences favoured IG in AIMS2-SF Symptoms and AIMS2-SF Affect. There were no between-group differences in other secondary outcomes. Conclusions The results suggest that needs-based education helps improve patients’ self-efficacy and some aspects of health status. Trial registration number ISRCTN51523281. PMID:26162769

  8. Effect on skin hydration of using baby wipes to clean the napkin area of newborn babies: assessor-blinded randomised controlled equivalence trial

    PubMed Central

    2012-01-01

    Background Some national guidelines recommend the use of water alone for napkin cleansing. Yet, there is a readiness, amongst many parents, to use baby wipes. Evidence from randomised controlled trials, of the effect of baby wipes on newborn skin integrity is lacking. We conducted a study to examine the hypothesis that the use of a specifically formulated cleansing wipe on the napkin area of newborn infants (<1 month) has an equivalent effect on skin hydration when compared with using cotton wool and water (usual care). Methods A prospective, assessor-blinded, randomised controlled equivalence trial was conducted during 2010. Healthy, term babies (n = 280), recruited within 48 hours of birth, were randomly assigned to have their napkin area cleansed with an alcohol-free baby wipe (140 babies) or cotton wool and water (140 babies). Primary outcome was change in hydration from within 48 hours of birth to 4 weeks post-birth. Secondary outcomes comprised changes in trans-epidermal water loss, skin surface pH and erythema, presence of microbial skin contaminants/irritants at 4 weeks and napkin dermatitis reported by midwife at 4 weeks and mother during the 4 weeks. Results Complete hydration data were obtained for 254 (90.7 %) babies. Wipes were shown to be equivalent to water and cotton wool in terms of skin hydration (intention-to-treat analysis: wipes 65.4 (SD 12.4) vs. water 63.5 (14.2), p = 0.47, 95 % CI -2.5 to 4.2; per protocol analysis: wipes 64.6 (12.4) vs. water 63.6 (14.3), p = 0.53, 95 % CI -2.4 to 4.2). No significant differences were found in the secondary outcomes, except for maternal-reported napkin dermatitis, which was higher in the water group (p = 0.025 for complete responses). Conclusions Baby wipes had an equivalent effect on skin hydration when compared with cotton wool and water. We found no evidence of any adverse effects of using these wipes. These findings offer reassurance to parents who choose to use baby

  9. Effect of Household-Based Drinking Water Chlorination on Diarrhoea among Children under Five in Orissa, India: A Double-Blind Randomised Placebo-Controlled Trial

    PubMed Central

    Boisson, Sophie; Stevenson, Matthew; Shapiro, Lily; Kumar, Vinod; Singh, Lakhwinder P.; Ward, Dana; Clasen, Thomas

    2013-01-01

    Background Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. Methods and Findings We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating

  10. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Chiswick, Carolyn; Reynolds, Rebecca M; Denison, Fiona; Drake, Amanda J; Forbes, Shareen; Newby, David E; Walker, Brian R; Quenby, Siobhan; Wray, Susan; Weeks, Andrew; Lashen, Hany; Rodriguez, Aryelly; Murray, Gordon; Whyte, Sonia; Norman, Jane E

    2015-01-01

    Summary Background Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. Methods We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30–39 vs ≥40 kg/m2). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Findings Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference −0·029, 95% CI −0·217 to 0·158; p=0·7597). The difference in the number of women reporting the

  11. Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial

    PubMed Central

    Freeman, Daniel; Waite, Felicity; Startup, Helen; Myers, Elissa; Lister, Rachel; McInerney, Josephine; Harvey, Allison G; Geddes, John; Zaiwalla, Zenobia; Luengo-Fernandez, Ramon; Foster, Russell; Clifton, Lei; Yu, Ly-Mee

    2015-01-01

    Summary Background Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)—the best evidence-based treatment for insomnia—has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. Methods We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18–65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post-treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. Findings Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large

  12. Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial

    PubMed Central

    Veysey, M; Malcolm, P; Mallet, A; Jenkins, P; Besser, G; Murphy, G; Dowling, R

    2001-01-01

    BACKGROUND—Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones.
AIMS—To see if an intestinal prokinetic, cisapride, could overcome these adverse effects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones.
METHODS—A randomised, double blind, placebo controlled, crossover design was used to examine the effects of cisapride (10 mg four times daily) on gall bladder emptying, mouth to caecum and large bowel transit times, and the proportions of deoxycholic acid and other bile acids, in fasting serum from: (i) control subjects (n=6), (ii) acromegalic patients not treated with octreotide (n=6), (iii) acromegalics on long term octreotide (n=8), and (iv) patients with constipation (n=8).
RESULTS—Cisapride had no prokinetic effect on the gall bladder. In fact, it significantly increased both fasting and postprandial gall bladder volumes. However, it shortened mouth to caecum (from 176 (13) to 113 (11) minutes; p<0.001) and large bowel (from 50 (3.0) to 31 (3.4) h; p<0.001) transit times. It also reduced the proportion of deoxycholic acid in serum from 26 (2.3) to 15 (1.8)% (p<0.001), with a reciprocal increase in the proportion of cholic acid from 40 (3.5) to 51 (3.8)% (p<0.01). There were significant linear relationships between large bowel transit time and the proportions of deoxycholic acid (r=0.81; p<0.001) and cholic acid (r=−0.53; p<0.001) in fasting serum.
INTERPRETATION/SUMMARY—Cisapride failed to overcome the adverse effects of octreotide on gall bladder emptying but it countered octreotide induced prolongation of small and large bowel transit. Therefore, if changes in intestinal transit contribute to the development of octreotide induced gall bladder stones

  13. Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

    PubMed Central

    2014-01-01

    Background The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. Discussion Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. Trial registration ClinicalTrials.gov: NCT01119014 PMID:25015535

  14. Comparison of phenothrin mousse, phenothrin lotion, and wet-combing for treatment of head louse infestation in the UK: a pragmatic randomised, controlled, assessor blind trial

    PubMed Central

    Burgess, Ian F.; Brown, Christine M.; Nair, Pat

    2014-01-01

    In this investigation of effectiveness of an alternative pediculicide dosage form, we recruited 228 children and 50 adult participants from Bedfordshire, UK, to a randomised, controlled, assessor blind trial comparing two insecticide products with mechanical removal of lice as a control group.  Participants using insecticide were treated with either the investigative 0.5% phenothrin mousse, for 30 minutes, or 0.2% phenothrin lotion, for 2 hours as the reference product.  Both treatments were applied only once, followed by shampoo washing.  Those treated by wet-combing with conditioner were combed 4 times over 12 days.  Parents/carers carried out the treatments to mimic normal consumer use.  The outcome measure was the absence of lice, 14 days after treatment for the insecticides, and up to 14 days after completion of combing.  Intention to treat analysis of the outcomes for 275 participants showed success for phenothrin mousse in 21/105 (20.0%), in 23/107 (21.5%) for phenothrin lotion, and in 12/63 (19.1%) for wet-combing.  People receiving mousse were 1.07 (95% CI, 0.63 to 1.81) times more likely to still have lice after treatment compared with those treated with lotion. The group of participants who received the wet combing treatment were 1.13 (95% CI, 0.61 to 2.11) times more likely to still have lice after the treatment.  None of the treatments was significantly (p < 0.05) more effective than any other. This study was carried out in an area where moderate resistance to phenothrin was demonstrated after the study by using a bioassay.  Analysis of post treatment assessments found that failure of insecticides to kill louse eggs had influenced the outcome. PMID:25254106

  15. Prevention of oxaliplatin-induced peripheral neuropathy by a polyamine-reduced diet—NEUROXAPOL: protocol of a prospective, randomised, controlled, single-blind and monocentric trial

    PubMed Central

    Balayssac, David; Ferrier, Jérémy; Pereira, Bruno; Gillet, Brigitte; Pétorin, Caroline; Vein, Julie; Libert, Frédéric; Eschalier, Alain; Pezet, Denis

    2015-01-01

    Introduction Oxaliplatin remains the most widely used chemotherapeutic agent for treating advanced colorectal cancer but its efficacy is hampered by dose-limiting neurotoxicity manifested by a painful polyneuropathy. Oxaliplatin-induced peripheral neuropathy (OIPN) is characterised by acute and transient cold hyperaesthesia in the hours and days following oxaliplatin infusion (>90% of patients), but also by retarded chronic neuropathy due to the repetition of chemotherapy cycles (30–50% of patients). OIPN impairs the health-related quality of life (HRQOL) of patients and no preventive or curative strategies have as yet proven effective. A polyamine-reduced diet (PRD) has recently demonstrated its efficacy to prevent OIPN in animals without adverse effects. Methods and analysis The NEUROXAPOL trial is a prospective, randomised, controlled, single-blind, monocentric and interventional study. This trial is aimed at evaluating the efficacy and feasibility of a PRD compared to a normal polyamine containing diet to prevent OIPN in patients treated by oxaliplatin-based chemotherapy. Patients (n=40 per group) will be randomly assigned to receive either a PRD or a normal diet before and during the chemotherapy regimen. The main objectives are to improve the cold pain thresholds, neuropathic pain symptoms, comorbidities (anxiety and depression) and HRQOL of patients. The primary end point is the assessment of cold pain thresholds 2 weeks after the third cycle of chemotherapy. The secondary end points are the evaluation of thermal pain thresholds, the grade of neuropathy, neuropathic pain, symptoms of anxiety and depression and HRQOL, until the 12th cycle of chemotherapy. Ethics and dissemination The study was approved by an independent medical ethics committee 1 (CPP Sud Est 1, Saint Etienne, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international

  16. Comparative electrocardiographic effects of intravenous ondansetron and granisetron in patients undergoing surgery for carcinoma breast: A prospective single-blind randomised trial

    PubMed Central

    Ganjare, Ashish; Kulkarni, Atul P

    2013-01-01

    Background: Postoperative nausea and vomiting (PONV) are common and distressing symptoms after surgery performed under general anaesthesia. 5-hydroxytryptamine3 antagonists are routinely used for prevention and treatment of PONV. The aim of our study was to compare the incidence of QTc prolongation and quantify the amount of QTc prolongation with ondansetron and granisetron. Methods: This prospective, randomised, single-blind study was carried out in the OT and Recovery Room (RR) of a tertiary referral cancer centre. After obtaining Institutional Review Board approval and written informed consent from the patients, 70 patients undergoing elective surgery for carcinoma breast were included. In the RR, patients randomly received 8 mg of ondansetron or 1 mg of granisetron intravenously. Serial ECGs were recorded at various intervals, Non-invasive blood pressure and SpO2 were also recorded. Chi-square test and Mann-Whiteny test were used for statistical analysis. Results: The demographics were similar in both groups. The incidence of significant QTc prolongation was significantly higher in the ondansetron group (22 of 37 (59.4%) vs. 11 of 33 patients (33.33%) (P<0.05)). There was an increase in the QTc interval in both the groups as compared to the baseline. The median prolongation in QTc interval from baseline was much more in the ondansetron group; this was statistically significant only at 5 and 15 min. Conclusion: Granisetron may be a safer option than ondanasetron for prevention and treatment of PONV due to lesser prolongation QTc interval. (ClinicalTrials.gov ID: NCT01352130) PMID:23716765

  17. Comparison of phenothrin mousse, phenothrin lotion, and wet-combing for treatment of head louse infestation in the UK: a pragmatic randomised, controlled, assessor blind trial.

    PubMed

    Burgess, Ian F; Brown, Christine M; Nair, Pat

    2014-01-01

    In this investigation of effectiveness of an alternative pediculicide dosage form, we recruited 228 children and 50 adult participants from Bedfordshire, UK, to a randomised, controlled, assessor blind trial comparing two insecticide products with mechanical removal of lice as a control group.  Participants using insecticide were treated with either the investigative 0.5% phenothrin mousse, for 30 minutes, or 0.2% phenothrin lotion, for 2 hours as the reference product.  Both treatments were applied only once, followed by shampoo washing.  Those treated by wet-combing with conditioner were combed 4 times over 12 days.  Parents/carers carried out the treatments to mimic normal consumer use.  The outcome measure was the absence of lice, 14 days after treatment for the insecticides, and up to 14 days after completion of combing.  Intention to treat analysis of the outcomes for 275 participants showed success for phenothrin mousse in 21/105 (20.0%), in 23/107 (21.5%) for phenothrin lotion, and in 12/63 (19.1%) for wet-combing.  People receiving mousse were 1.07 (95% CI, 0.63 to 1.81) times more likely to still have lice after treatment compared with those treated with lotion. The group of participants who received the wet combing treatment were 1.13 (95% CI, 0.61 to 2.11) times more likely to still have lice after the treatment.  None of the treatments was significantly (p < 0.05) more effective than any other. This study was carried out in an area where moderate resistance to phenothrin was demonstrated after the study by using a bioassay.  Analysis of post treatment assessments found that failure of insecticides to kill louse eggs had influenced the outcome. PMID:25254106

  18. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT)

    PubMed Central

    Gertsch, Jeffrey H; Basnyat, Buddha; Johnson, E William; Onopa, Janet; Holck, Peter S

    2004-01-01

    Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness. Design Prospective, double blind, randomised, placebo controlled trial. Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002. Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent. Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache. Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70). Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness. PMID:15070635

  19. Low-intensity case management increases contact with primary care in recently released prisoners: a single-blinded, multisite, randomised controlled trial

    PubMed Central

    Alati, Rosa; Longo, Marie; Spittal, Matthew J; Boyle, Frances M; Williams, Gail M; Lennox, Nicholas G

    2016-01-01

    Background The world prison population is large and growing. Poor health outcomes after release from prison are common, but few programmes to improve health outcomes for ex-prisoners have been rigorously evaluated. The aim of this study was to evaluate the impact of individualised case management on contact with health services during the first 6 months post-release. Methods Single-blinded, randomised, controlled trial. Baseline assessment with N=1325 adult prisoners in Queensland, Australia, within 6 weeks of expected release; follow-up interviews 1, 3 and 6 months post-release. The intervention consisted of provision of a personalised booklet (‘Passport’) at the time of release, plus up to four brief telephone contacts in the first 4 weeks post-release. Results Of 1179 eligible participants, 1003 (85%) completed ≥1 follow-up interview. In intention-to-treat analyses, 53% of the intervention group and 41% of the control group reported contacting a general practitioner (GP) at 1 month post-release (difference=12%, 95% CI 5% to 19%). Similar effects were observed for GP contact at 3 months (difference=9%, 95% CI 2% to 16%) and 6 months (difference=8%, 95% CI 1% to 15%), and for mental health (MH) service contact at 6 months post release (difference=8%, 95% CI 3% to 14%). Conclusions Individualised case management in the month after release from prison increases usage of primary care and MH services in adult ex-prisoners for at least 6 months post-release. Given the poor health profile of ex-prisoners, there remains an urgent need to develop and rigorously evaluate interventions to increase health service contact in this profoundly marginalised population. Trial registration number ACTRN12608000232336. PMID:26787201

  20. The value of herbal medicines in the treatment of acute non-purulent rhinosinusitis. Results of a double-blind, randomised, controlled trial.

    PubMed

    Tesche, Stefan; Metternich, Frank; Sonnemann, Uwe; Engelke, Jan-Christian; Dethlefsen, Uwe

    2008-11-01

    In a prospective, randomised, double-blinded controlled study, we compared the efficacy and safety of two different treatment options with the herbal medicines cineole and a combination of five different components for acute viral rhinosinusitis. One hundred and fifty patients with acute and viral rhinosinusitis (75 patients in each treatment group) were enrolled. The diagnosis rhinosinusitis was made according to a defined symptoms-sum-score which was based on rhinoscopic and clinical signs which are characteristic for rhinosinusitis. The primary endpoint was the amelioration of the symptoms-sum-score, which includes all relevant characteristics for rhinosinusitis as headache on bending, frontal headache, sensitivity of pressure points of trigeminal nerve, impairment of general condition, nasal obstruction, rhino-secretion, secretion quantity, secretion viscosity and fever in a treatment period of 7 days. The mean reduction of the symptoms-sum-score after 4 days was 6.7 (+/-3.4) and after 7 days 11.0 (+/-3.3) in the cineole group and 3.6 (+/-2.8) after 4 days and 8.0 (+/-3.0) after 7 days in the control group. The differences between both groups were clinically relevant and statistically significant after 4 and 7 days (P < 0.0001). This result is validated by the amelioration of the secondary endpoints headache on bending, frontal headache, sensitivity of pressure points of trigeminal nerve, impairment of general condition, nasal obstruction and rhino-secretion. These findings correlate with the statistically significant difference of the estimation of B-scan ultrasonography. It is safe to use both medications for 7 days in patients with acute viral rhinosinusitis. Treatment with cineole is clinically relevant and statistically significant, more effective in comparison to the alternative herbal preparation with five different components. PMID:18437408

  1. Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial

    PubMed Central

    Junquera, F; Lopez-Talavera, J; Mearin, F; Saperas, E; Videla, S; Armengol, J; Esteban, R; Malagelada, J

    2000-01-01

    BACKGROUND—Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure.
AIM—To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis.
METHODS—A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 µg/hour) plus oral isosorbide 5-mononitrate (40 mg/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours.
RESULTS—The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p<0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2) v 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p<0.05).
CONCLUSION—In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.


Keywords: gastro-oesophageal bleeding; haemorrhage; portal hypertension; clinical trial; isosorbide 5-mononitrate; somatostatin PMID:10601068

  2. Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study

    PubMed Central

    Ghert, Michelle; Deheshi, Benjamin; Holt, Ginger; Randall, R Lor; Ferguson, Peter; Wunder, Jay; Turcotte, Robert; Werier, Joel; Clarkson, Paul; Damron, Timothy; Benevenia, Joseph; Anderson, Megan; Gebhardt, Mark; Isler, Marc; Mottard, Sophie; Healey, John; Evaniew, Nathan; Racano, Antonella; Sprague, Sheila; Swinton, Marilyn; Bryant, Dianne; Thabane, Lehana; Guyatt, Gordon; Bhandari, Mohit

    2012-01-01

    Introduction Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours. Methods and analysis This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05. Ethics and dissemination This study has ethics approval from the McMaster University

  3. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression.

    PubMed

    Silvers, Karen M; Woolley, Cheryl C; Hamilton, Frances C; Watts, Peter M; Watson, Rosemary A

    2005-03-01

    Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression. To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting, 77 participants were randomly assigned to receive 8 g of either fish or olive oil per day in addition to their existing therapy. Fifty-nine (77%) participants completed 12 weeks of treatment. Dietary, biochemical and lifestyle factors were measured throughout the study. Mood was assessed using the Short Form Hamilton Depression Rating Scale (HDRS-SF) and the Beck Depression Inventory II. Sample size calculations were based on the HDRS-SF. Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood. There was no evidence that fish oil improved mood when compared to the placebo oil, despite an increase in circulating omega-3 polyunsaturated fatty acids. However, mood improved significantly in both groups within the first 2 weeks of the study (P<0.001) and this improvement was sustained throughout. In conclusion, fish oil was no more effective than the control as an add-on therapy for depression in this setting. PMID:15664306

  4. Prebiotic and Synbiotic Treatment before Colorectal Surgery--Randomised Double Blind Trial.

    PubMed

    Krebs, Bojan

    2016-04-01

    The aim of our study was to demonstrate higher concentrations of lactic acid bacteria (LAB) on the colonic mucosa in operated colorectal cancer patients treated with oral intake of synbiotics or prebiotics preoperatively. We also tried to prove that the systemic inflammatory response after surgery is not so severe in patients who took synbiotics or prebiotics, furthermore these patients have less postoperative complications and a favorable postoperative course. 73 patients with preceding colorectal operations were recruited. They were randomized into three groups. One group received preoperatively prebiotics, the second synbiotics in and third was preoperatively cleansed. We have defined the number of four different probiotic bacteria on colonic mucosa with polymerase chain reaction (PCR). Serum levels of interleukin-6, CRP, fibrinogen, white cell count and differential blood count were measured pre- and postoperatively to determine systemic inflammatory response. We succeed in confirming that in the synbiotic group there were considerably more LAB presented on the mucosa. They did pass the upper gastrointestinal tract and were isolated in colonic mucosa. On the other hand, we did not find any statistical differences in systemic inflammatory response measured by upper factors and no differences in postoperative course and complications rate between all three groups. PMID:27301235

  5. Effect of 0.1% pilocarpine mouthwash on xerostomia: double-blind, randomised controlled trial.

    PubMed

    Kim, J H; Ahn, H-J; Choi, J-H; Jung, D W; Kwon, J-S

    2014-03-01

    The objective of this study was to evaluate the effect of 0.1% pilocarpine mouthwash in xerostomic patients. Sixty volunteers were randomly allocated to two groups. The experimental group used 0.1% pilocarpine solution, and the control group used 0.9% saline. The short- and long-term effects of pilocarpine were investigated by measuring the severity of oral dryness, minor salivary flow rates and unstimulated whole salivary flow rate at predetermined times. The severity of oral dryness was decreased in both groups at 0, 30 and 60 min after mouthwashing, with no significant difference between the groups. Buccal and labial secretions were increased in both groups, but only the experimental group exhibited increased palatal secretion. Labial and palatal secretions, but not buccal secretion, differed between the groups. The unstimulated whole salivary flow rate was increased in the experimental group and differed from that in the control group. After 4 weeks, the severity of oral dryness was decreased in both groups and did not differ between them. The oral dryness at night or on awakening significantly decreased in both groups, with no significant difference between them, but the oral dryness at other times of the day and the difficulty in swallowing foods were not significantly changed in both groups. Minor salivary and unstimulated whole salivary flow rates did not increase in both groups. Until 1 h after mouthwashing, 0.1% pilocarpine mouthwash increased minor salivary and unstimulated whole salivary secretions, but was not superior compared with 0.9% saline at relieving subjective oral dryness. PMID:24527846

  6. Development of thrombophlebitis in peripheral veins with Vialon and PTFE-Teflon cannulas: a double-blind, randomised, controlled trial.

    PubMed Central

    Payne-James, J. J.; Rogers, J.; Bray, M. J.; Rana, S. K.; McSwiggan, D.; Silk, D. B.

    1991-01-01

    A series of 54 normal subjects were randomised to have either a Vialon or a PTFE-Teflon peripheral vein cannula inserted in a vein in each forearm to observe the development of thrombophlebitis. Cannulas were inspected twice daily for up to 5 days to observe the development of three signs, erythema, oedema or hardness and one symptom, pain. Each sign and symptom was recorded twice daily at three points, the cannula insertion site, the mid-point of the cannula and the cannula tip. The degree of change was recorded as less than 1, 1-2 and greater than 2 cm. Any cannula causing any sign greater than 2 cm was removed. By the end of the study over 40% of both types of cannula had been removed. There were no significant differences between the numbers of each type of cannula removed at any time point throughout the duration of the study. There were no significant differences in the amounts of erythema or hardness, but minimally increased swelling was observed at the mid-point of the PTFE-Teflon cannulas (P = 0.022). Despite the theoretical superiority of Vialon as a cannula material, under controlled conditions there appears to be little difference in its inherent capacity to cause the thrombophlebitis. PMID:1929137

  7. Development of thrombophlebitis in peripheral veins with Vialon and PTFE-Teflon cannulas: a double-blind, randomised, controlled trial.

    PubMed

    Payne-James, J J; Rogers, J; Bray, M J; Rana, S K; McSwiggan, D; Silk, D B

    1991-09-01

    A series of 54 normal subjects were randomised to have either a Vialon or a PTFE-Teflon peripheral vein cannula inserted in a vein in each forearm to observe the development of thrombophlebitis. Cannulas were inspected twice daily for up to 5 days to observe the development of three signs, erythema, oedema or hardness and one symptom, pain. Each sign and symptom was recorded twice daily at three points, the cannula insertion site, the mid-point of the cannula and the cannula tip. The degree of change was recorded as less than 1, 1-2 and greater than 2 cm. Any cannula causing any sign greater than 2 cm was removed. By the end of the study over 40% of both types of cannula had been removed. There were no significant differences between the numbers of each type of cannula removed at any time point throughout the duration of the study. There were no significant differences in the amounts of erythema or hardness, but minimally increased swelling was observed at the mid-point of the PTFE-Teflon cannulas (P = 0.022). Despite the theoretical superiority of Vialon as a cannula material, under controlled conditions there appears to be little difference in its inherent capacity to cause the thrombophlebitis. PMID:1929137

  8. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    White, David J.; Cox, Katherine H. M.; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B.

    2015-01-01

    This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults. PMID:26529011

  9. A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old.

    PubMed

    2015-09-01

    This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were titered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose. PMID:26517656

  10. A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

    PubMed Central

    2015-01-01

    This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose. PMID:26517656

  11. Alcohol intake and cardiovascular risk factors: A Mendelian randomisation study

    PubMed Central

    Cho, Yoonsu; Shin, So-Youn; Won, Sungho; Relton, Caroline L; Davey Smith, George; Shin, Min-Jeong

    2015-01-01

    Mendelian randomisation studies from Asia suggest detrimental influences of alcohol on cardiovascular risk factors, but such associations are observed mainly in men. The absence of associations of genetic variants (e.g. rs671 in ALDH2) with such risk factors in women – who drank little in these populations – provides evidence that the observations are not due to genetic pleiotropy. Here, we present a Mendelian randomisation study in a South Korean population (3,365 men and 3,787 women) that 1) provides robust evidence that alcohol consumption adversely affects several cardiovascular disease risk factors, including blood pressure, waist to hip ratio, fasting blood glucose and triglyceride levels. Alcohol also increases HDL cholesterol and lowers LDL cholesterol. Our study also 2) replicates sex differences in associations which suggests pleiotropy does not underlie the associations, 3) provides further evidence that association is not due to pleiotropy by showing null effects in male non-drinkers, and 4) illustrates a way to measure population-level association where alcohol intake is stratified by sex. In conclusion, population-level instrumental variable estimation (utilizing interaction of rs671 in ALDH2 and sex as an instrument) strengthens causal inference regarding the largely adverse influence of alcohol intake on cardiovascular health in an Asian population. PMID:26687910

  12. Analgesic efficacy of three different dosages of intra-articular morphine in arthroscopic knee surgeries: Randomised double-blind trial

    PubMed Central

    Gupta, Babita; Banerjee, Sumantra; Prasad, Arunima; Farooque, Kamran; Sharma, Vijay; Trikha, Vivek

    2015-01-01

    Background and Aims: Arthroscopic knee surgery is a common procedure and may cause enough pain to delay rehabilitation. Intra-articular (IA) morphine is a known modality for post-operative pain relief. However, the optimal dose of IA morphine has not been studied. The current study has been conducted to find out the optimal dosage of IA morphine when administered with 0.25% bupivacaine. Methods: Sixty adult patients of either sex, aged between 18 and 60 years, undergoing diagnostic/therapeutic knee arthroscopic surgery were included in the study and randomised into three groups. All patients underwent surgery under subarachnoid block. After the surgical closure, 20 ml of 0.25% bupivacaine with 1 mg, 3 mg and 5 mg of morphine as additive was injected intra-articularly in Group A, B and C patients, respectively. Post-operative pain assessment was performed with visual analogue scale score in the 1st, 2nd, 6th, 12th and 24th post-operative hour. The common complications were also recorded. Results: There was statistically significant analgesia in Group B and C than Group A in the 1st and 2nd post-operative hour; while at the 24th post-operative hour, Group C had statistically significant analgesia than the other two groups. Time to first rescue analgesia was statistically significantly less and consumption of supplemental analgesia was significantly higher in Group A than the other two groups. Conclusion: IA dose of 3 mg and 5 mg morphine with 20 ml of 0.25% bupivacaine provided adequate analgesia. However, 3 mg morphine group patients had fewer side effects than 5 mg group patients although the difference was not statistically significant. PMID:26644611

  13. CT scan-evaluated outcome of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a randomised, multicentre, double-blind, placebo-controlled trial.

    PubMed

    Hannemann, P F W; van Wezenbeek, M R; Kolkman, K A; Twiss, E L L; Berghmans, C H J; Dirven, P A M G M; Brink, P R G; Poeze, M

    2014-08-01

    We hypothesised that the use of pulsed electromagnetic field (PEMF) bone growth stimulation in acute scaphoid fractures would significantly shorten the time to union and reduce the number of nonunions in a randomised, double-blind, placebo-controlled multicentre trial. A total of 102 patients (78 male, 24 female; mean age 35 years (18 to 77)) from five different medical centres with a unilateral undisplaced acute scaphoid fracture were randomly allocated to PEMF (n = 51) or placebo (n = 51) and assessed with regard to functional and radiological outcomes (multiplanar reconstructed CT scans) at 6, 9, 12, 24 and 52 weeks. The overall time to clinical and radiological healing did not differ significantly between the active PEMF group and the placebo group. We concluded that the addition of PEMF bone growth stimulation to the conservative treatment of acute scaphoid fractures does not accelerate bone healing. PMID:25086123

  14. Interventions to increase immunisation coverage among children 12–23 months of age in India through participatory learning and community engagement: pilot study for a cluster randomised trial

    PubMed Central

    Johri, Mira; Chandra, Dinesh; Koné, Georges K; Dudeja, Sakshi; Sylvestre, Marie-Pierre; Sharma, Jitendar K; Pahwa, Smriti

    2015-01-01

    Objective With the aim of conducting a future cluster randomised trial to assess intervention impact on child vaccination coverage, we designed a pilot study to assess feasibility and aid in refining methods for the larger study. Trial design Cluster-randomised design with a 1:1 allocation ratio. Methods Clusters were 12 villages in rural Uttar Pradesh. All women residing in a selected village who were mothers of a child 0–23 months of age were eligible; participants were chosen at random. Over 4 months, intervention group (IG) villages received: (1) home visits by volunteers; (2) community mobilisation events to promote immunisation. Control group (CG) villages received community mobilisation to promote nutrition. A toll-free number for immunisation was offered to all IG and CG village residents. Primary outcomes were ex-ante criteria for feasibility of the main study related to processes for recruitment and randomisation (50% of villages would agree to participate and accept randomisation; 30 women could be recruited in 70% of villages), and retention of participants (50% of women retained from baseline to endline). Clusters were assigned to IG or CG using a computer-generated randomisation schedule. Neither participants nor those delivering interventions were blinded, but those assessing outcomes were blinded to group assignment. Results All villages contacted agreed to participate and accepted randomisation. 36 women were recruited per village; 432 participants were randomised (IG n=216; CG n=216). No clusters were lost to follow-up. The main analysis included 86% (373/432) of participants, 90% (195/216) from the IG and 82% (178/216) from the CG. Conclusions Criteria related to feasibility were satisfied, giving us confidence that we can successfully conduct a larger cluster randomised trial. Methodological lessons will inform design of the main study. Trial registration number ISRCTN16703097 PMID:26384721

  15. Ergocalciferol and Microcirculatory Function in Chronic Kidney Disease and Concomitant Vitamin D Deficiency: An Exploratory, Double Blind, Randomised Controlled Trial

    PubMed Central

    Dreyer, Gavin; Tucker, Arthur T.; Harwood, Steven M.; Pearse, Rupert M.; Raftery, Martin J.; Yaqoob, Muhammad M.

    2014-01-01

    Background and Objectives Vitamin D deficiency and endothelial dysfunction are non-traditional risk factors for cardiovascular events in chronic kidney disease. Previous studies in chronic kidney disease have failed to demonstrate a beneficial effect of vitamin D on arterial stiffness, left ventricular mass and inflammation but none have assessed the effect of vitamin D on microcirculatory endothelial function. Study Design We conducted a randomised controlled trial of 38 patients with non diabetic chronic kidney disease stage 3–4 and concomitant vitamin D deficiency (<16 ng/dl) who received oral ergocalciferol (50,000 IU weekly for one month followed by 50,000 IU monthly) or placebo over 6 months. The primary outcome was change in microcirculatory function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Secondary endpoints were tissue advanced glycation end products, sublingual functional capillary density and flow index as well as macrovascular parameters. Parallel in vitro experiments were conducted to determine the effect of ergocalciferol on cultured human endothelial cells. Results Twenty patients received ergocalciferol and 18 patients received placebo. After 6 months, there was a significant improvement in the ergocalciferol group in both endothelium dependent microcirculatory vasodilatation after iontophoresis of acetylcholine (p = 0.03) and a reduction in tissue advanced glycation end products (p = 0.03). There were no changes in sublingual microcirculatory parameters. Pulse pressure (p = 0.01) but not aortic pulse wave velocity was reduced. There were no significant changes in bone mineral parameters, blood pressure or left ventricular mass index suggesting that ergocalciferol improved endothelial function independently of these parameters. In parallel experiments, expression of endothelial nitric oxide synthase and activity were increased in human endothelial cells in a dose dependent manner. Conclusions

  16. Randomised Controlled Trials in Education Research: A Case Study of an Individually Randomised Pragmatic Trial

    ERIC Educational Resources Information Center

    Torgerson, Carole J.

    2009-01-01

    The randomised controlled trial (RCT) is an evaluative method used by social scientists in order to establish whether or not an intervention is effective. This contribution discusses the fundamental aspects of good RCT design. These are illustrated through the use of a recently completed RCT which evaluated an information and communication…

  17. Acupuncture for post anaesthetic recovery and postoperative pain: study protocol for a randomised controlled trial

    PubMed Central

    2014-01-01

    Background We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain. Methods/Design The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to ‘ready for discharge’ from the post anaesthesia care unit (in minutes). The ‘ready for discharge’ end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication). Discussion The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques. Trial registration NCT01816386 (First received: 28 October 2012) PMID:25047046

  18. Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

    PubMed Central

    Symonds, R Paul; Gourley, Charlie; Davidson, Susan; Carty, Karen; McCartney, Elaine; Rai, Debbie; Banerjee, Susana; Jackson, David; Lord, Rosemary; McCormack, Mary; Hudson, Emma; Reed, Nicholas; Flubacher, Maxine; Jankowska, Petra; Powell, Melanie; Dive, Caroline; West, Catharine M L; Paul, James

    2015-01-01

    Summary Background Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median

  19. Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE)

    PubMed Central

    O'Gorman, Neil; Wright, David; Rolnik, Daniel L; Nicolaides, Kypros H; Poon, Liona C

    2016-01-01

    Introduction Pre-eclampsia (PE) affects 2–3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Prophylactic use of low-dose aspirin in women at risk for PE may substantially reduce the prevalence of the disease. Effective screening for PE requiring delivery before 37 weeks (preterm PE) can be provided by a combination of maternal factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein A and placental growth factor at 11–13 weeks' gestation, with a detection rate of 75% at a false-positive rate of 10%. We present a protocol (V.6, date 25 January 2016) for the ASpirin for evidence-based PREeclampsia prevention (ASPRE) trial, which is a double-blinded, placebo-controlled, randomised controlled trial (RCT) that uses an effective PE screening programme to determine whether low-dose aspirin given to women from 11 to 13 weeks' gestation will reduce the incidence of preterm PE. Methods and analysis All eligible women attending for their first trimester scan will be invited to participate in the screening study for preterm PE. Those found to be at high risk of developing preterm PE will be invited to participate in the RCT. Further scans will be conducted for assessment of fetal growth and biomarkers. Pregnancy and neonatal outcomes will be collected and analysed. The first enrolment for the pilot study was in April 2014. As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Trial registration number ISRCTN13633058. PMID:27354081

  20. Preventive effects of oral probiotic on infantile colic: a prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938.

    PubMed

    Savino, F; Ceratto, S; Poggi, E; Cartosio, M E; Cordero di Montezemolo, L; Giannattasio, A

    2015-01-01

    Infants were recruited in four centres in North-West Italy. 138 infants were assessed for eligibility, 113 ones underwent randomisation and 105 completed the study. Newborns aged less than 10 days of life, with gestational age between 37 and 42 weeks, birth weight from 2,500 to 4,300 g and normal physical examination were recruitable. Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded. Patients were randomly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 (108 cfu) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily. The primary endpoints concern the administration of pain relieving agents (cimetropium bromide at least three times per week or simethicone at least five times per week) from baseline to 12 weeks. Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks. Data concerning the number of calls to the paediatricians and the number of visits at paediatricians' ambulatories due to infantile colic have been collected by paediatrician and analysed. Comparing the two groups, the relative risk was 0.04 (95% confidence interval (CI)=0.01-0.31) for cimetropium bromide, 0.24 (95% CI=0.14-0.41) for simethicone and 0.37 (95% CI=0.17-0.80) for the administration of infant formula, showing a protective action of L. reuteri. The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group (P<0.0001). L. reuteri DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic. The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic, as well as use of pain relieving agents and of infant formula. PMID:25488262

  1. Comparison of driving simulator performance with real driving after alcohol intake: a randomised, single blind, placebo-controlled, cross-over trial.

    PubMed

    Helland, Arne; Jenssen, Gunnar D; Lervåg, Lone-Eirin; Westin, Andreas Austgulen; Moen, Terje; Sakshaug, Kristian; Lydersen, Stian; Mørland, Jørg; Slørdal, Lars

    2013-04-01

    The purpose of this study was to establish and validate a driving simulator method for assessing drug effects on driving. To achieve this, we used ethanol as a positive control, and examined whether ethanol affects driving performance in the simulator, and whether these effects are consistent with performance during real driving on a test track, also under the influence of ethanol. Twenty healthy male volunteers underwent a total of six driving trials of 1h duration; three in an instrumented vehicle on a closed-circuit test track that closely resembled rural Norwegian road conditions, and three in the simulator with a driving scenario modelled after the test track. Test subjects were either sober or titrated to blood alcohol concentration (BAC) levels of 0.5g/L and 0.9g/L. The study was conducted in a randomised, cross-over, single-blind fashion, using placebo drinks and placebo pills as confounders. The primary outcome measure was standard deviation of lateral position (SDLP; "weaving"). Eighteen test subjects completed all six driving trials, and complete data were acquired from 18 subjects in the simulator and 10 subjects on the test track, respectively. There was a positive dose-response relationship between higher ethanol concentrations and increases in SDLP in both the simulator and on the test track (p<0.001 for both). In the simulator, this dose-response was evident already after 15min of driving. SDLP values were higher and showed a larger inter-individual variability in the simulator than on the test track. Most subjects displayed a similar relationship between BAC and SDLP in the simulator and on the test track; however, a few subjects showed striking dissimilarities, with very high SDLP values in the simulator. This may reflect the lack of perceived danger in the simulator, causing reckless driving in a few test subjects. Overall, the results suggest that SDLP in the driving simulator is a sensitive measure of ethanol impaired driving. The comparison

  2. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial

    PubMed Central

    Müller, Olaf; Becher, Heiko; van Zweeden, Anneke Baltussen; Ye, Yazoume; Diallo, Diadier A; Konate, Amadou T; Gbangou, Adjima; Kouyate, Bocar; Garenne, Michel

    2001-01-01

    Objective To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa. Design Randomised, double blind, placebo controlled efficacy trial. Setting 18 villages in rural northwestern Burkina Faso. Participants 709 children were enrolled; 685 completed the trial. Intervention Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for six days a week for six months. Main outcome measures The primary outcome was the incidence of symptomatic falciparum malaria. Secondary outcomes were the severity of malaria episodes, prevalence of malaria parasite, mean parasite densities, mean packed cell volume, prevalence of other morbidity, and all cause mortality. Results The mean number of malaria episodes per child (defined as a temperature ⩾37.5°C with ⩾5000 parasites/μl) was 1.7, 99.7% due to infection with Plasmodium falciparum. No difference was found between the zinc and placebo groups in the incidence of falciparum malaria (relative risk 0.98, 95% confidence interval 0.86 to 1.11), mean temperature, and mean parasite densities during malaria episodes, nor in malaria parasite rates, mean parasite densities, and mean packed cell volume during cross sectional surveys. Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause mortality was non-significantly lower in children given zinc compared with those given placebo (5 v 12, P=0.1). Conclusions Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa, but it does reduce morbidity associated with diarrhoea. What is already known on this topicZinc deficiency is common in infants in developing countriesZinc supplementation has been shown to reduce morbidity from infectious disease in such populations, particularly through reductions in morbidity from diarrhoea and respiratory infectionsLimited evidence

  3. Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial

    PubMed Central

    Gault, Emma Jane; Perry, Rebecca J; Cole, Tim J; Casey, Sarah; Paterson, Wendy F; Hindmarsh, Peter C; Betts, Peter; Dunger, David B

    2011-01-01

    Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14. Main outcome measure Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P=0.001, n=82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P=0.05, n=48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P<0.001). No cases of virilisation were reported. Conclusion Oxandrolone had a positive effect on final height in girls with Turner’s syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner’s syndrome. Trial registration Current

  4. Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?

    PubMed

    Lanini, Simone; Zumla, Alimuddin; Ioannidis, John P A; Di Caro, Antonino; Krishna, Sanjeev; Gostin, Lawrence; Girardi, Enrico; Pletschette, Michel; Strada, Gino; Baritussio, Aldo; Portella, Gina; Apolone, Giovanni; Cavuto, Silvio; Satolli, Roberto; Kremsner, Peter; Vairo, Francesco; Ippolito, Giuseppe

    2015-06-01

    The Ebola outbreak that has devastated parts of west Africa represents an unprecedented challenge for research and ethics. Estimates from the past three decades emphasise that the present effort to contain the epidemic in the three most affected countries (Guinea, Liberia, and Sierra Leone) has been insufficient, with more than 24,900 cases and about 10,300 deaths, as of March 25, 2015. Faced with such an exceptional event and the urgent response it demands, the use of randomised controlled trials (RCT) for Ebola-related research might be both unethical and infeasible and that potential interventions should be assessed in non-randomised studies on the basis of compassionate use. However, non-randomised studies might not yield valid conclusions, leading to large residual uncertainty about how to interpret the results, and can also waste scarce intervention-related resources, making them profoundly unethical. Scientifically sound and rigorous study designs, such as adaptive RCTs, could provide the best way to reduce the time needed to develop new interventions and to obtain valid results on their efficacy and safety while preserving the application of ethical precepts. We present an overview of clinical studies registered at present at the four main international trial registries and provide a simulation on how adaptive RCTs can behave in this context, when mortality varies simultaneously in either the control or the experimental group. PMID:25881871

  5. Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial

    PubMed Central

    Zimmer, Robert; Scherbarth, Hugo R; Rillo, Oscar Luis; Gomez-Reino, Juan Jesus; Muller, Sylviane

    2013-01-01

    Objectives To evaluate treatment with the peptide-based agent, Lupuzor, in a double-blind, randomised, placebo-controlled study of patients with systemic lupus erythematosus. Methods Patients who met ≥4 of the American College of Rheumatology criteria, had a score of ≥6 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and did not have an A score on the British Isles Lupus Assessment Group (BILAG)-2004 scale were eligible. 149 intention-to-treat (ITT) patients were randomly assigned to receive Lupuzor (200 μg) subcutaneously every 4 weeks (n=49; group 1) or every 2 weeks (n=51; group 2) or placebo (n=49; group 3) in addition to standard of care (SOC). A target population (136 ITT patients) consisting of patients having a clinical SLEDAI score ≥6 at week 0 was considered. The clinical SLEDAI score is the SLEDAI-2K score obtained by omitting low complement and increased DNA binding components. Results In the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in group 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index (SRI) response at week 12. In the target population, the results were more impressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in the placebo group achieved an SRI response at week 12. An interim analysis including 114 patients from the target population demonstrated an even better efficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs 41.5% (p<0.025) at week 12 and 84.2% vs 45.8% (p<0.025) at week 24). The most common adverse event was a mild injection-site erythema. Conclusions Lupuzor/200 µg given three times at 4-week intervals during 12 weeks in addition to SOC is efficacious and generally well tolerated. PMID:23172751

  6. The effects of different levels of calcium supplementation on the bone mineral status of postpartum lactating Chinese women: a 12-month randomised, double-blinded, controlled trial.

    PubMed

    Zhang, Zhe-Qing; Chen, Yu-Ming; Wang, Ruo-Qin; Huang, Zhen-Wu; Yang, Xiao-Guang; Su, Yi-Xiang

    2016-01-14

    Increasing dietary Ca intake may prevent the excessive mobilisation of bone mineral in nursing mothers. We aimed to investigate whether higher Ca intake could positively modulate the bone mineral changes in Chinese postpartum lactating women. The study was a 12-month randomised, double-blinded, parallel group trial conducted over 12 months. A total of 150 postpartum women were randomly selected to receive either 40 g of milk powder containing 300 mg of Ca and 5 μg of vitamin D (Low-Ca group) or same milk powder additionally fortified with 300 mg of Ca (Mid-Ca group) or 600 mg of Ca (High-Ca group). Bone mineral density (BMD) for the whole body, the lumbar spine, the total left hip and its sub-regions was measured using dual-energy X-ray absorptiometry. A total of 102 subjects completed the whole trial. The duration of total lactating time was 7·9 (SD 2·8) months on average. The intention-to-treat analysis yielded the following mean percentage changes in BMD for the whole body, the lumbar spine and the total left hip, respectively: -0·93 (SD 1·97), 2·11 (SD 4·90) and -1·60 (SD 2·65)% for the Low-Ca group; -0·56 (SD 1·89), 2·21 (SD 3·77) and -1·43 (SD 2·30)% for the Mid-Ca group; and -0·44 (SD 1·67), 2·32 (SD 4·66) and -0·95 (SD 4·08)% for the High-Ca group. The differences between the groups were not statistically significant (P: 0·5-0·9). The results of the complete case analysis were similar. In sum, we found no significant differences in the bone mineral changes from baseline to 12 months in postpartum lactating women consuming milk powder fortified with different levels of Ca. PMID:26522081

  7. Acupuncture for menopausal vasomotor symptoms: study protocol for a randomised controlled trial

    PubMed Central

    2014-01-01

    Background Hot flushes and night sweats (vasomotor symptoms) are common menopausal symptoms, often causing distress, sleep deprivation and reduced quality of life. Although hormone replacement therapy is an effective treatment, there are concerns about serious adverse events. Non-hormonal pharmacological therapies are less effective and can also cause adverse effects. Complementary therapies, including acupuncture, are commonly used for menopausal vasomotor symptoms. While the evidence for the effectiveness of acupuncture in treating vasomotor symptoms is inconclusive, acupuncture has a low risk of adverse effects, and two small studies suggest it may be more effective than non-insertive sham acupuncture. Our objective is to assess the efficacy of needle acupuncture in improving hot flush severity and frequency in menopausal women. Our current study design is informed by methods tested in a pilot study. Methods/design This is a stratified, parallel, randomised sham-controlled trial with equal allocation of participants to two trial groups. We are recruiting 360 menopausal women experiencing a minimum average of seven moderate hot flushes a day over a seven-day period and who meet diagnostic criteria for the Traditional Chinese Medicine diagnosis of Kidney Yin deficiency. Exclusion criteria include breast cancer, surgical menopause, and current hormone replacement therapy use. Eligible women are randomised to receive either true needle acupuncture or sham acupuncture with non-insertive (blunt) needles for ten treatments over eight weeks. Participants are blinded to treatment allocation. Interventions are provided by Chinese medicine acupuncturists who have received specific training on trial procedures. The primary outcome measure is hot flush score, assessed using the validated Hot Flush Diary. Secondary outcome measures include health-related quality of life, anxiety and depression symptoms, credibility of the sham treatment, expectancy and beliefs about

  8. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis

    PubMed Central

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Background Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Methods Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. Results The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Conclusions Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Trial registration number Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40. PMID:26688732

  9. Color-Blindness Study: Color Discrimination on the TICCIT System.

    ERIC Educational Resources Information Center

    Asay, Calvin S.; Schneider, Edward W.

    The question studied whether the specific seven TICCIT system colors used within color coding schemes can be a source of confusion, or not seen at all, by the color-blind segment of target populations. Subjects were 11 color-blind and three normally sighted students at Brigham Young University. After a preliminary training exercise to acquaint the…

  10. The Institute for Deaf-Blind Studies: Proceedings.

    ERIC Educational Resources Information Center

    Scheffler, Joye A.; And Others

    The document contains 16 papers from the Institute for Deaf Blind Studies, a program to bring together many disciplines and to place emphasis on every aspect of the learning and teaching activity involved in the development of deaf-blind children. The following titles and authors are included: "Current Status of the Rubella Problem" (P. Ziring);…

  11. A Randomised Controlled Single-Blind Trial of the Efficacy of Reiki at Benefitting Mood and Well-Being

    PubMed Central

    Bowden, Deborah; Goddard, Lorna; Gruzelier, John

    2011-01-01

    This is a constructive replication of a previous trial conducted by Bowden et al. (2010), where students who had received Reiki demonstrated greater health and mood benefits than those who received no Reiki. The current study examined impact on anxiety/depression. 40 university students—half with high depression and/or anxiety and half with low depression and/or anxiety—were randomly assigned to receive Reiki or to a non-Reiki control group. Participants experienced six 30-minute sessions over a period of two to eight weeks, where they were blind to whether noncontact Reiki was administered as their attention was absorbed in a guided relaxation. The efficacy of the intervention was assessed pre-post intervention and at five-week follow-up by self-report measures of mood, illness symptoms, and sleep. The participants with high anxiety and/or depression who received Reiki showed a progressive improvement in overall mood, which was significantly better at five-week follow-up, while no change was seen in the controls. While the Reiki group did not demonstrate the comparatively greater reduction in symptoms of illness seen in our earlier study, the findings of both studies suggest that Reiki may benefit mood. PMID:21584234

  12. A randomised controlled single-blind trial of the efficacy of reiki at benefitting mood and well-being.

    PubMed

    Bowden, Deborah; Goddard, Lorna; Gruzelier, John

    2011-01-01

    This is a constructive replication of a previous trial conducted by Bowden et al. (2010), where students who had received Reiki demonstrated greater health and mood benefits than those who received no Reiki. The current study examined impact on anxiety/depression. 40 university students-half with high depression and/or anxiety and half with low depression and/or anxiety-were randomly assigned to receive Reiki or to a non-Reiki control group. Participants experienced six 30-minute sessions over a period of two to eight weeks, where they were blind to whether noncontact Reiki was administered as their attention was absorbed in a guided relaxation. The efficacy of the intervention was assessed pre-post intervention and at five-week follow-up by self-report measures of mood, illness symptoms, and sleep. The participants with high anxiety and/or depression who received Reiki showed a progressive improvement in overall mood, which was significantly better at five-week follow-up, while no change was seen in the controls. While the Reiki group did not demonstrate the comparatively greater reduction in symptoms of illness seen in our earlier study, the findings of both studies suggest that Reiki may benefit mood. PMID:21584234

  13. CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients

    PubMed Central

    Molloy, Alexander J; Clarke, France; Herridge, Margaret S; Koo, Karen K Y; Rudkowski, Jill; Seely, Andrew J E; Pellizzari, Joseph R; Tarride, Jean-Eric; Mourtzakis, Marina; Karachi, Timothy; Cook, Deborah J

    2016-01-01

    Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. Trial registration number NCT02377830; Pre

  14. PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

    PubMed Central

    Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E; Atik, Ruth Bender; Bloemenkamp, Kitty Wm; Brady, Rebecca; Briley, Annette; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin; Eapen, Abey; Essex, Holly; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Parrott, Steve; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Trépel, Dominic; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark David; Khalaf, Yacoub; Goddijn, Mariëtte; Regan, Lesley; Rai, Rajendra

    2016-01-01

    BACKGROUND AND OBJECTIVES Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body

  15. Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220

    PubMed Central

    Vas, Jorge; Perea-Milla, Emilio; Mendez, Camila; Galante, Antonia Herrera; Madrazo, Fernando; Medina, Ivan; Ortega, Caridad; Olmo, Victoria; Fernandez, Francisco Perez; Hernandez, Luz; Seminario, Jose Maria; Brioso, Mauricio; Luna, Francisco; Gordo, Isabel; Godoy, Ana Maria; Jimenez, Carmen; Ruiz, Manuel Anselmo; Montes, Joaquin; Hidalgo, Alonso; Gonzalez-Quevedo, Rosa; Bosch, Pablo; Vazquez, Antonio; Lozano, Juan Vicente

    2005-01-01

    Background Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). Methods/design Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary

  16. Exploring the effect of space and place on response to exercise therapy for knee and hip pain—a protocol for a double-blind randomised controlled clinical trial: the CONEX trial

    PubMed Central

    Thorlund, Jonas Bloch; Ulrich, Roger S; Dieppe, Paul A; Roos, Ewa M

    2015-01-01

    Introduction Context effects are described as effects of a given treatment, not directly caused by the treatment itself, but rather caused by the context in which treatment is delivered. Exercise is a recommended core treatment in clinical guidelines for musculoskeletal disorders. Although moderately effective overall, variation is seen in size of response to exercise across randomised controlled trial (RCT) studies. Part of this variation may be related to the fact that exercise interventions are performed in different physical environments, which may affect participants differently. The study aims to investigate the effect of exercising in a contextually enhanced physical environment for 8 weeks in people with knee or hip pain. Methods and analysis The study is a double-blind RCT. Eligible participants are 35 years or older with persisting knee and/or hip pain for 3 months. Participants are randomised to one of three groups: (1) exercise in a contextually enhanced environment, (2) exercise in a standard environment and (3) waiting list. The contextually enhanced environment is located in a newly built facility, has large windows providing abundant daylight and overlooks a recreational park. The standard environment is in a basement, has artificial lighting and is marked by years of use; that is, resembling many clinical environments. The primary outcome is the participant's global perceived effect rated on a seven-point Likert scale after 8 weeks exercise. Patient-reported and objective secondary outcomes are included. Ethics and dissemination The Regional Scientific Ethical Committee for Southern Denmark has approved the study. Study findings will be disseminated in peer-reviewed publications and presented at national and international conferences. Trial registration number NCT02043613. PMID:25818278

  17. Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial

    PubMed Central

    Zheng, Ju-Sheng; Lin, Mei; Imamura, Fumiaki; Cai, Wenwen; Wang, Ling; Feng, Jue-Ping; Ruan, Yue; Tang, Jun; Wang, Fenglei; Yang, Hong; Li, Duo

    2016-01-01

    We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10−7) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10−6), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10−4), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10−7). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation. PMID:27404516

  18. Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

    PubMed

    Zheng, Ju-Sheng; Lin, Mei; Imamura, Fumiaki; Cai, Wenwen; Wang, Ling; Feng, Jue-Ping; Ruan, Yue; Tang, Jun; Wang, Fenglei; Yang, Hong; Li, Duo

    2016-01-01

    We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation. PMID:27404516

  19. Causes of childhood blindness in Malaysia: results from a national study of blind school students.

    PubMed

    Reddy, S C; Tan, B C

    2001-01-01

    A national study was conducted in children attending six schools for the blind in Malaysia to identify the anatomical site and underlying causes of blindness (BL) and severe visual impairment (SVI), with a view to determine the potentially preventable and treatable causes so that appropriate control measures can be implemented in the future. The standardized clinical examination of eyes was performed and the findings were recorded on the WHO Prevention of Blindness Programme eye examination record form for children with blindness and low vision. A total of 358 children aged between 7 and 17 years were examined, of whom 332 (92.7%) were blind or severely visually impaired. The results relate to these 332 children. Lens was the major anatomical site (22.3%) of visual loss followed by retina (20.8%), whole globe (17.2%), cornea (15.1%), optic nerve (8.7%) and uvea (5.1%). Glaucoma was responsible for BL/SVI in 7.2% and others in 3.6% of cases. Hereditary diseases were responsible for visual loss in 29.5%, intrauterine factors in 4.5%, perinatal factors in 9% and childhood factors in 7.8% of cases. However, the aetiology was unknown in 49.1% of cases which included congenital anomalies of the globe. Childhood cataract and corneal scarring are major treatable causes of BL/SVI that can benefit from future intervention strategies. Perinatal screening for intrauterine factors and hereditary eye diseases, and appropriate interventional therapy will help in reducing the prevalence of childhood blindness. PMID:11998890

  20. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

    PubMed Central

    2013-01-01

    Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively

  1. High-dose albumin treatment for acute ischaemic stroke (ALIAS): a phase 3, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Ginsberg, Myron D.; Palesch, Yuko Y.; Hill, Michael D.; Martin, Renee H.; Moy, Claudia S.; Barsan, William G.; Waldman, Bonnie D.; Tamariz, Diego; Ryckborst, Karla J.

    2014-01-01

    Background In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioral outcome. In a pilot clinical trial, albumin doses as high as 2 g per kg were safely tolerated. Trial Design and Methods This was a randomised, parallel-group, double-blind trial to test the superiority of 25% albumin (dose 2 g [8 ml] per kg; maximum, 750 ml) over an equivalent volume of isotonic saline in improving the outcome of acute ischaemic stroke. Eligibility criteria were an ischaemic (i.e., non-haemorrhagic) stroke with baseline National Institutes of Health Stroke Scale (NIHSS) score of 6 or above, ability to treat within 5 hours of onset, age 18 through 83 years, and written informed consent. The major exclusion criteria were cardiovascular. The objective was to test the hypothesis that the primary outcome (defined as either a modified Rankin Scale score of 0 or 1, or a NIHSS score of 0 or 1, or both, at 90 days) with albumin treatment was superior to saline by an absolute margin of 10 percentage points. Centralised web-based randomisation was by a minimisation-plus-biased-coin algorithm. Thrombolytic therapies were permitted. The trial is registered with ClinicalTrials.gov, Identifier: NCT00235495. Findings The trial was stopped prematurely for futility after 841 participants were randomised (422 patients to albumin and 419 to saline). The primary outcome did not differ by treatment assignment (albumin, 44.1%; saline, 44.2%; relative benefit, 0.96; 95% confidence interval [CI] 0.84 – 1.10 adjusted for baseline NIHSS score and thrombolysis stratum). Secondary outcomes were also neutral. The chief adverse event was mild-to-moderate pulmonary edema, which was more common with albumin than saline (13.1% and 1.2%, respectively), as was symptomatic intracranial haemorrhage within 24 hours (albumin, 4.1%; saline, 1.7%). While the favourable outcome rate in albumin-treated subjects remained consistent at 44–45% over the course of the trial, the

  2. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

    PubMed Central

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-01-01

    Summary Background Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of

  3. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

    PubMed Central

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Ishiguro, Naoki; Yamanaka, Hisashi; Yoneda, Toshiyuki; Ohira, Takeshi; Okubo, Naoki; Genant, Harry K

    2016-01-01

    Objectives To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number JapicCTI-101263. PMID:26585988

  4. Double blind, cluster randomised trial of low dose supplementation with vitamin A or β carotene on mortality related to pregnancy in Nepal

    PubMed Central

    West, Keith P; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Pradhan, Elizabeth K; Shrestha, Sharada R; Connor, Paul B; Dali, Sanu M; Christian, Parul; Pokhrel, Ram P; Sommer, Alfred

    1999-01-01

    Objective To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as β carotene. Design Double blind, cluster randomised, placebo controlled field trial. Setting Rural southeast central plains of Nepal (Sarlahi district). Subjects 44 646 married women, of whom 20 119 became pregnant 22 189 times. Intervention 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 μg retinol equivalents) or β carotene (42 mg, or 7000 μg retinol equivalents) for over 3½ years. Main outcome measures All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). Results Mortality related to pregnancy in the placebo, vitamin A, and β carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and β carotene. Combined, vitamin A or β carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. Conclusion Supplementation of women with either vitamin A or β carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia. Key messagesMaternal vitamin A deficiency, evident as night blindness or low serum retinol concentration during pregnancy, is widely prevalent in rural south AsiaIn Nepal, women of

  5. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials

    PubMed Central

    2010-01-01

    Background Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Methods These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day). Results No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively). Conclusions Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy. Trial registration numbers ClinicalTrials.gov identifier: NCT00412100 and NCT00412152 PMID:20920236

  6. The combination of oligo- and polysaccharides and reticulated protein for the control of symptoms in patients with irritable bowel syndrome: Results of a randomised, placebo-controlled, double-blind, parallel group, multicentre clinical trial

    PubMed Central

    Alexea, Octavian; Bacarea, Vlad

    2015-01-01

    Background A medical device containing the film-forming agent reticulated protein and a prebiotic mixture of vegetable oligo- and polysaccharides has been developed, recently receiving European approval as MED class III for the treatment of chronic/functional or recidivant diarrhoea due to different causes including irritable bowel syndrome (IBS). In the present paper, we evaluate a protein preparation containing these components in comparison with placebo in adult patients with diarrhoea-predominant IBS. Methods In a randomised, placebo-controlled, double-blind, parallel group, multicentre clinical trial, patients were randomly assigned to receive the combination of oligo- and polysaccharides and reticulated protein and placebo (four oral tablets/day for 56 days). Demographic, clinical and quality of life characteristics and presence and intensity of abdominal pain and flatulence (seven-point Likert scale) were assessed at three study visits (baseline and at 28 and 56 days). Stool emissions were recorded on the diary card using the seven-point Bristol Stool Scale. Results A total of 128 patients were randomised to receive either tablets containing the combination (n = 63) or placebo (n = 65). Treatment with oligo- and polysaccharides and reticulated protein was safe and well tolerated. A significant improvement in symptoms across the study was observed in patients treated with oligo- and polysaccharides and reticulated protein between visit 2 and visit 3 in abdominal pain (p = 0.0167) and flatulence (p = 0.0373). We also detected a statistically significant increase in the quality of life of patients receiving the active treatment from baseline to visit 3 (p < 0.0001). Conclusions Treatment with oligo- and polysaccharides and reticulated protein is safe, improving IBS symptoms and quality of life of patients with diarrhoea-predominant IBS. PMID:27403313

  7. Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

    PubMed Central

    2011-01-01

    Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of

  8. Effect of the probiotic strain Bifidobacterium animalis subsp. lactis, BB-12®, on defecation frequency in healthy subjects with low defecation frequency and abdominal discomfort: a randomised, double-blind, placebo-controlled, parallel-group trial.

    PubMed

    Eskesen, Dorte; Jespersen, Lillian; Michelsen, Birgit; Whorwell, Peter J; Müller-Lissner, Stefan; Morberg, Cathrine M

    2015-11-28

    The aim of the present study was to investigate the effect of Bifidobacterium animalis subsp. lactis, BB-12®, on two primary end points - defecation frequency and gastrointestinal (GI) well-being - in healthy adults with low defecation frequency and abdominal discomfort. A total of 1248 subjects were included in a randomised, double-blind, placebo-controlled trial. After a 2-week run-in period, subjects were randomised to 1 or 10 billion colony-forming units/d of the probiotic strain BB-12® or a matching placebo capsule once daily for 4 weeks. Subjects completed a diary on bowel habits, relief of abdominal discomfort and symptoms. GI well-being, defined as global relief of abdominal discomfort, did not show significant differences. The OR for having a defecation frequency above baseline for ≥50% of the time was 1·31 (95% CI 0·98, 1·75), P=0·071, for probiotic treatment overall. Tightening the criteria for being a responder to an increase of ≥1 d/week for ≥50 % of the time resulted in an OR of 1·55 (95% CI 1·22, 1·96), P=0·0003, for treatment overall. A treatment effect on average defecation frequency was found (P=0·0065), with the frequency being significantly higher compared with placebo at all weeks for probiotic treatment overall (all P<0·05). Effects on defecation frequency were similar for the two doses tested, suggesting that a ceiling effect was reached with the one billion dose. Overall, 4 weeks' supplementation with the probiotic strain BB-12® resulted in a clinically relevant benefit on defecation frequency. The results suggest that consumption of BB-12® improves the GI health of individuals whose symptoms are not sufficiently severe to consult a doctor (ISRCTN18128385). PMID:26382580

  9. The effects of vitamin D2 or D3 supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial

    PubMed Central

    2013-01-01

    Background The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes. Methods/design In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitamin D3 (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited. Discussion Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D2 and D3 and an evidence based approach to determination of the dose of supplementation. Trial registration EudraCT2009-011264-11; ISRCTN86515510 PMID:24152375

  10. Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A Randomised Study Comparing Efficacy and Tolerability versus Clindamycin

    PubMed Central

    Tancawan, Archiel Launch; Pato, Maria Noemi; Abidin, Khamiza Zainol; Asari, A. S. Mohd; Thong, Tran Xuan; Kochhar, Puja; Muganurmath, Chandra; Twynholm, Monique; Barker, Keith

    2015-01-01

    Background. Treatment of odontogenic infections includes surgical drainage and adjunctive antibiotics. This study was designed to generate efficacy and safety data to support twice daily dosing of amoxicillin/clavulanic acid compared to clindamycin in odontogenic infections. Methods. This was a phase IV, randomised, observer blind study; 472 subjects were randomised to receive amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint was percentage of subjects achieving clinical success (composite measure of pain, swelling, fever, and additional antimicrobial therapy required) at the end of treatment. Results. The upper limit of two-sided 95% confidence interval for the treatment difference between the study arms (7.7%) was within protocol specified noninferiority margin of 10%, thus demonstrating noninferiority of amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm. Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar across both arms and were of mild to moderate intensity. Conclusion. Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical success (88.2% versus 89.7%) in acute odontogenic infections and the safety profile was consistent with the known side effects of both drugs. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT02141217. PMID:26300919

  11. Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A Randomised Study Comparing Efficacy and Tolerability versus Clindamycin.

    PubMed

    Tancawan, Archiel Launch; Pato, Maria Noemi; Abidin, Khamiza Zainol; Asari, A S Mohd; Thong, Tran Xuan; Kochhar, Puja; Muganurmath, Chandra; Twynholm, Monique; Barker, Keith

    2015-01-01

    Background. Treatment of odontogenic infections includes surgical drainage and adjunctive antibiotics. This study was designed to generate efficacy and safety data to support twice daily dosing of amoxicillin/clavulanic acid compared to clindamycin in odontogenic infections. Methods. This was a phase IV, randomised, observer blind study; 472 subjects were randomised to receive amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint was percentage of subjects achieving clinical success (composite measure of pain, swelling, fever, and additional antimicrobial therapy required) at the end of treatment. Results. The upper limit of two-sided 95% confidence interval for the treatment difference between the study arms (7.7%) was within protocol specified noninferiority margin of 10%, thus demonstrating noninferiority of amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm. Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar across both arms and were of mild to moderate intensity. Conclusion. Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical success (88.2% versus 89.7%) in acute odontogenic infections and the safety profile was consistent with the known side effects of both drugs. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT02141217. PMID:26300919

  12. Curved versus Straight Stem Uncemented Total Hip Arthroplasty Osteoarthritis Multicenter trial (CUSTOM): design of a prospective blinded randomised controlled multicentre trial

    PubMed Central

    van Beers, Loes W A H; van Oldenrijk, Jakob; Scholtes, Vanessa A B; Geerdink, Carel H; Niers, Bob B A M; Runne, Wouter; Bhandari, Mohit; Poolman, Rudolf W

    2016-01-01

    Introduction Answering the demands of an increasingly young and active patient population, recent developments in total hip arthroplasty (THA) have shifted towards minimising tissue damage. The Collum Femoris Preserving (CFP) stem was developed to preserve the trochanteric region of the femur, which potentially preserves the insertion of the gluteus musculature. This might accelerate early postoperative rehabilitation and improve functional outcome. Currently the functional results of the CFP stem have not been compared with conventional straight stems in a randomised controlled trial (RCT). The primary purpose of this trial is to compare the functional result of CFP stem THA with conventional uncemented straight stem THA, measured by the Dutch Hip disability and Osteoarthritis Outcome Score (HOOS) at 3-month follow-up. Methods A prospective blinded multicentre RCT will be performed. We aim to recruit 150 patients. The patients will be randomly allocated to a THA with a straight or a curved stem. All patients, research assistants, clinical assessors and investigators will be blinded for the type of prosthesis for 5 years. Clinical assessments and roentgenograms will be taken preoperative, at 6 weeks after surgery, at 1, 2, 3, 4 and 5 years after surgery. Patient reported outcome measures (PROMs) will be obtained at the same follow-up moments. In addition, the PROMs will also be sent to the patients at 3 and 6 months after surgery. The HOOS at 3-month follow-up will be our primary outcome. Ethics and dissemination This trial will be performed in accordance with the Declaration of Helsinki. A local ethics committee has approved this trial. Written informed consent will be obtained from all participating patients. All serious adverse events will be reported to the ethics committee. Results Results will be submitted for publication to an orthopaedics related journal. Trial registration number NTR1560. PMID:27009147

  13. Improving Well-being and Health for People with Dementia (WHELD): study protocol for a randomised controlled trial

    PubMed Central

    2014-01-01

    Background People with dementia living in care homes often have complex mental health problems, disabilities and social needs. Providing more comprehensive training for staff working in care home environments is a high national priority. It is important that this training is evidence based and delivers improvement for people with dementia residing in these environments. Well-being and Health for People with Dementia (WHELD) combines the most effective elements of existing approaches to develop a comprehensive but practical staff training intervention. This optimised intervention is based on a factorial study and qualitative evaluation, to combine: training on person-centred care, promoting person-centred activities and interactions, and providing care home staff and general practitioners with updated knowledge regarding the optimal use of psychotropic medications for persons with dementia in care homes. Design The trial will be a randomised controlled two-arm cluster single blind trial that will take place for nine months across 80 care homes in the United Kingdom. Discussion The overarching goal of this trial is to determine whether this optimised WHELD intervention is more effective in improving the quality of life and mental health than the usual care provided to people with dementia living in nursing homes. This study will be the largest and best powered randomised controlled trial (RCT) evaluating the benefits of an augmented person-centred care training intervention in care homes worldwide. Trial registration Current controlled trials ISRCTN62237498 Date registered: 5 September 2013 PMID:25016303

  14. Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis

    PubMed Central

    Freeman, Daniel; Dunn, Graham; Startup, Helen; Pugh, Katherine; Cordwell, Jacinta; Mander, Helen; Černis, Emma; Wingham, Gail; Shirvell, Katherine; Kingdon, David

    2015-01-01

    Summary Background Worry might be a contributory causal factor in the occurrence of persecutory delusions in patients with psychotic disorders. Therefore we postulated that reducing worry with cognitive behaviour therapy (CBT) would reduce persecutory delusions. Methods For our two-arm, assessor-blinded, randomised controlled trial (Worry Intervention Trial [WIT]), we recruited patients aged 18–65 years with persistent persecutory delusions but non-affective psychosis from two centres: the Oxford Health National Health Service (NHS) Foundation Trust (Oxford, UK) and the Southern Health NHS Foundation Trust (Southampton, UK). The key inclusion criteria for participants were a score of at least 3 on the Psychotic Symptoms Rating Scale (PSYRATS) denoting a current persecutory delusion; that the delusion had persisted for at least 3 months; a clinical diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder; and a clinically significant level of worry. We randomly assigned (1:1) eligible patients, using a randomly permuted block procedure with variable block sizes and division by four strata, to either six sessions of worry-reduction CBT intervention done over 8 weeks added to standard care (the CBT-intervention group), or to standard care alone (the control group). The assessors were masked to patient allocations and did their assessments at week 0 (baseline), 8 weeks (end of treatment), and 24 weeks, follow-up. The primary outcomes were worry measured by the Penn State Worry Questionnaire (PSWQ) and delusions measured by the PSYRATS-delusion scale; we did the analyses in the intention-to-treat population, and also did a planned mediation analysis. This trial is registered with the ISRCTN Registry (number ISRCTN23197625) and is closed to new participants. Findings From Nov 1, 2011, to Sept 9, 2013, we recruited 150 eligible participants and randomly assigned 73 to the CBT intervention group, and 77 to the control group. 143 patients (95

  15. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial.

    PubMed

    Zenico, T; Cicero, A F G; Valmorri, L; Mercuriali, M; Bercovich, E

    2009-04-01

    Lepidium meyenii (Maca) is a cultivated root belonging to the brassica family used in the Andean region for its supposed aphrodisiac properties. We carried out a double-blind clinical trial on 50 Caucasian men affected by mild erectile dysfunction (ED), randomised to treatment with Maca dry extract, 2400 mg, or placebo. The treatment effect on ED and subjective well-being was tested administrating before and after 12 weeks the International Index of Erectile Function (IIEF-5) and the Satisfaction Profile (SAT-P). After 12 weeks of treatment, both Maca- and placebo-treated patients experienced a significant increase in IIEF-5 score (P < 0.05 for both). However, patients taking Maca experienced a more significant increase than those taking placebo (1.6 +/- 1.1 versus 0.5 +/- 0.6, P < 0.001). Both Maca- and placebo-treated subjects experienced a significant improvement in psychological performance-related SAT-P score, but the Maca group higher than that of placebo group (+9 +/- 6 versus +6 +/- 5, P < 0.05). However, only Maca-treated patients experienced a significant improvement in physical and social performance-related SAT-P score compared with the baseline (+7 +/- 6 and +7 +/- 6, both P < 0.05). In conclusion, our data support a small but significant effect of Maca supplementation on subjective perception of general and sexual well-being in adult patients with mild ED. PMID:19260845

  16. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial.

    PubMed

    Shi, Yuanlu; Williamson, Gary

    2016-03-14

    Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19-60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (SD 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95% CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males. PMID:26785820

  17. Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial

    PubMed Central

    Ried-Larsen, Mathias; Hansen, Katrine B; Johansen, Mette Y; Pedersen, Maria; Zacho, Morten; Hansen, Louise S; Kofoed, Katja; Thomsen, Katja; Jensen, Mette S; Nielsen, Rasmus O; MacDonald, Chris; Langberg, Henning; Vaag, Allan A; Pedersen, Bente K; Karstoft, Kristian

    2015-01-01

    Introduction Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications. Methods and analysis The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment. Ethics and dissemination This study has been approved by the Scientific Ethical Committee at the

  18. Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial

    PubMed Central

    Glover, Mark; Smerdon, Gary R; Andreyev, H Jervoise; Benton, Barbara E; Bothma, Pieter; Firth, Oliver; Gothard, Lone; Harrison, John; Ignatescu, Mihaela; Laden, Gerard; Martin, Sue; Maynard, Lauren; McCann, Des; Penny, Christine E L; Phillips, Spencer; Sharp, Grace; Yarnold, John

    2016-01-01

    Summary Background Hyperbaric oxygen has been used as a therapy for patients experiencing chronic intestinal syndromes after pelvic radiotherapy for decades, yet the evidence to support the use of this therapy is based almost exclusively on non-randomised studies. We aimed to provide conclusive results for the clinical benefits of hyperbaric oxygen in patients with chronic bowel dysfunction after radiotherapy for pelvic malignancies. Methods HOT2 was a double-blind, sham-controlled, phase 3 randomised study of patients (≥18 years) with chronic gastrointestinal symptoms for 12 months or more after radiotherapy and which persisted despite at least 3 months of optimal medical therapy and no evidence of cancer recurrence. Participants were stratified by participating hyperbaric centre and randomly assigned (2:1) by a computer-generated list (block size nine or 12) to receive treatment with hyperbaric oxygen therapy or sham. Participants in the active treatment group breathed 100% oxygen at 2·4 atmospheres of absolute pressure (ATA) and the control group breathed 21% oxygen at 1·3 ATA; both treatment groups received 90-min air pressure exposures once daily for 5 days per week for a total of 8 weeks (total of 40 exposures). Staff at the participating hyperbaric medicine facilities knew the allocated treatment, but patients, clinicians, nurse practitioners, and other health-care professionals associated with patients' care were masked to treatment allocation. Primary endpoints were changes in the bowel component of the modified Inflammatory Bowel Disease Questionnaire (IBDQ) score and the IBDQ rectal bleeding score 12 months after start of treatment relative to baseline. The primary outcome was analysed in a modified intention-to-treat population, excluding patients who did not provide IBDQ scores within a predetermined time-frame. All patients have completed 12 months of follow-up and the final analysis is complete. The trial is registered with the ISRCTN registry

  19. Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

    PubMed Central

    Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

    2015-01-01

    Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

  20. A preliminary randomised double-blind placebo-controlled clinical trial of hydroxyzine for treating sleep bruxism in children.

    PubMed

    Ghanizadeh, A; Zare, S

    2013-06-01

    This is a randomised placebo-controlled clinical trial investigating the efficacy of hydroxyzine for treating parent-reported sleep bruxism in children. Participants of this trial were 30 patients randomly allocated to one of the two groups in a ratio of 1:2. One group received hydroxyzine and the other group received placebo. The outcome measures were Visual Analogue Scale test and Clinical Global Severity scale. Assessments occurred at baseline and at the end of week 4. The side effects of drugs were assessed using a checklist. The number of children in the hydroxyzine and placebo groups was 21 and 9, respectively. The mean age of children in the hydroxyzine and placebo groups was 8·4(s.d. = 3·3) and 6·5(s.d. = 1·5) years, respectively. Hydroxyzine more than placebo decreased bruxism score (3·8 versus 2·2). No serious adverse effect was reported. Current evidence support that hydroxyzine is effective and well tolerated for treating bruxism in children. PMID:23550945

  1. Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial

    PubMed Central

    Wildes, T S; Winter, A C; Maybrier, H R; Mickle, A M; Lenze, E J; Stark, S; Lin, N; Inouye, S K; Schmitt, E M; McKinnon, S L; Muench, M R; Murphy, M R; Upadhyayula, R T; Fritz, B A; Escallier, K E; Apakama, G P; Emmert, D A; Graetz, T J; Stevens, T W; Palanca, B J; Hueneke, R L; Melby, S; Torres, B; Leung, J; Jacobsohn, E; Avidan, M S

    2016-01-01

    Introduction Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. Methods and analysis This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. Ethics and dissemination Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences

  2. Case management for frequent users of the emergency department: study protocol of a randomised controlled trial

    PubMed Central

    2014-01-01

    Background We devised a randomised controlled trial to evaluate the effectiveness and efficiency of an intervention based on case management care for frequent emergency department users. The aim of the intervention is to reduce such patients’ emergency department use, to improve their quality of life, and to reduce costs consequent on frequent use. The intervention consists of a combination of comprehensive case management care and standard emergency care. It uses a clinical case management model that is patient-identified, patient-directed, and developed to provide high intensity services. It provides a continuum of hospital- and community-based patient services, which include clinical assessment, outreach referral, and coordination and communication with other service providers. Methods/Design We aim to recruit, during the first year of the study, 250 patients who visit the emergency department of the University Hospital of Lausanne, Switzerland. Eligible patients will have visited the emergency department 5 or more times during the previous 12 months. Randomisation of the participants to the intervention or control groups will be computer generated and concealed. The statistician and each patient will be blinded to the patient’s allocation. Participants in the intervention group (N = 125), additionally to standard emergency care, will receive case management from a team, 1 (ambulatory care) to 3 (hospitalization) times during their stay and after 1, 3, and 5 months, at their residence, in the hospital or in the ambulatory care setting. In between the consultations provided, the patients will have the opportunity to contact, at any moment, the case management team. Participants in the control group (N = 125) will receive standard emergency care only. Data will be collected at baseline and 2, 5.5, 9, and 12 months later, including: number of emergency department visits, quality of life (EuroQOL and WHOQOL), health services use, and relevant costs

  3. A Randomised Controlled Trial of Intravenous Zoledronic Acid in Malignant Pleural Disease: A Proof of Principle Pilot Study

    PubMed Central

    Clive, Amelia O.; Hooper, Clare E.; Edey, Anthony J.; Morley, Anna J.; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P.; Sequeiros, Iara; Lyen, Stephen M.; Milton, Tim; Kahan, Brennan C.; Maskell, Nick A.

    2015-01-01

    Introduction Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI −4.7 to 13.0)) or change in DCE-MRI iAUC (AMD −15.4 (95%CI −58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration UK Clinical

  4. GaPP: a pilot randomised controlled trial of the efficacy of action of gabapentin for the management of chronic pelvic pain in women: study protocol

    PubMed Central

    Critchley, Hilary O D; Doust, Ann; Fehr, Daniel; Wilson, John; Wu, Olivia; Jack, S; Porter, Maureen; Lewis, Steff; Bhattacharya, Siladitya

    2012-01-01

    Introduction Chronic pelvic pain (CPP) affects >1 million UK women. Annual healthcare costs are estimated at >£150 million. Proven interventions for CPP are limited, and treatment is often unsatisfactory. Gabapentin is increasingly prescribed due to reports of effectiveness in other chronic pain conditions, but there are insufficient data supporting value in CPP specifically. The mechanism by which gabapentin exerts its analgesic action is unknown. Given the prevalence and costs of CPP, the authors believe that a large, multicentre, placebo-controlled, double-blind randomised controlled trial to evaluate the efficacy of gabapentin in management of CPP is required. The focus of this study is a pilot to inform planning of a future randomised controlled trial. Methods and analysis The authors plan to perform a two-arm, parallel, randomised controlled pilot trial. The authors aim to recruit 60 women with CPP in NHS Lothian and NHS Grampian (UK) and randomise them to gabapentin or placebo. Response to treatment will be monitored by questionnaire compared at 0, 3 and 6 months. The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness and acceptability to participants of the proposed methods of recruitment, randomisation, drug treatments and assessment tools and to perform a pretrial cost-effectiveness assessment of treatment with gabapentin. Ethics and dissemination Ethical approval has been obtained from the Scotland A Research Ethics Committee (LREC 12/SS/0005). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ISRCTN70960777. PMID:22685224

  5. Physical fitness training in Subacute Stroke (PHYS-STROKE) - study protocol for a randomised controlled trial

    PubMed Central

    2014-01-01

    Background Given the rising number of strokes worldwide, and the large number of individuals left with disabilities after stroke, novel strategies to reduce disability, increase functions in the motor and the cognitive domains, and improve quality of life are of major importance. Physical activity is a promising intervention to address these challenges but, as yet, there is no study demonstrating definite outcomes. Our objective is to assess whether additional treatment in the form of physical fitness-based training for patients early after stroke will provide benefits in terms of functional outcomes, in particular gait speed and the Barthel Index (co-primary outcome measures) reflecting activities of daily living (ADL). We will gather secondary functional outcomes as well as mechanistic parameters in an exploratory approach. Methods/Design Our phase III randomised controlled trial will recruit 215 adults with moderate to severe limitations of walking and ADL 5 to 45 days after stroke onset. Participants will be stratified for the prognostic variables of “centre”, “age”, and “stroke severity”, and randomly assigned to one of two groups. The interventional group receives physical fitness training delivered as supported or unsupported treadmill training (cardiovascular active aerobic training; five times per week, over 4 weeks; each session 50 minutes; total of 20 additional physical fitness training sessions) in addition to standard rehabilitation treatment. The control intervention consists of relaxation sessions (non-cardiovascular active; five times per week week, over 4 weeks; each session 50 minutes) in addition to standard rehabilitation treatment. Co-primary efficacy endpoints will be gait speed (in m/s, 10 m walk) and the Barthel Index (100 points total) at 3 months post-stroke, compared to baseline measurements. Secondary outcomes include standard measures of quality of life, sleep and mood, cognition, arm function, maximal oxygen uptake

  6. Injury risk in runners using standard or motion control shoes: a randomised controlled trial with participant and assessor blinding

    PubMed Central

    Malisoux, Laurent; Chambon, Nicolas; Delattre, Nicolas; Gueguen, Nils; Urhausen, Axel; Theisen, Daniel

    2016-01-01

    Background/aim This randomised controlled trial investigated if the usage of running shoes with a motion control system modifies injury risk in regular leisure-time runners compared to standard shoes, and if this influence depends on foot morphology. Methods Recreational runners (n=372) were given either the motion control or the standard version of a regular running shoe model and were followed up for 6 months regarding running activity and injury. Foot morphology was analysed using the Foot Posture Index method. Cox regression analyses were used to compare injury risk between the two groups, based on HRs and their 95% CIs, controlling for potential confounders. Stratified analyses were conducted to evaluate the effect of motion control system in runners with supinated, neutral and pronated feet. Results The overall injury risk was lower among the participants who had received motion control shoes (HR=0.55; 95% CI 0.36 to 0.85) compared to those receiving standard shoes. This positive effect was only observed in the stratum of runners with pronated feet (n=94; HR=0.34; 95% CI 0.13 to 0.84); there was no difference in runners with neutral (n=218; HR=0.78; 95% CI 0.44 to 1.37) or supinated feet (n=60; HR=0.59; 95% CI 0.20 to 1.73). Runners with pronated feet using standard shoes had a higher injury risk compared to those with neutral feet (HR=1.80; 95% CI 1.01 to 3.22). Conclusions The overall injury risk was lower in participants who had received motion control shoes. Based on secondary analysis, those with pronated feet may benefit most from this shoe type. PMID:26746907

  7. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    PubMed Central

    2012-01-01

    Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in

  8. Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

    PubMed

    Lockyer, Stacey; Corona, Giulia; Yaqoob, Parveen; Spencer, Jeremy P E; Rowland, Ian

    2015-07-14

    The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health. PMID:26051429

  9. Local heating of the wound with dressings soaked in saline at 42°C can reduce postoperative bleeding: a single-blind, split-mouth, randomised controlled clinical trial.

    PubMed

    Haraji, Afshin; Rakhshan, Vahid; Hosseini, Vasim

    2016-04-01

    Control of bleeding is essential during oral procedures. Although various chemical agents have been introduced and tested, hot water dressing has not to our knowledge been assessed before. Studies of operations for epistaxis or sinus conditions have suggested that irrigation with hot water can reduce bleeding, so we hypothesised that it might be effective in reducing bleeding after extraction too. Ten patients who required bilateral extractions took part in this split-mouth, randomised, single-blind, controlled clinical trial. After extraction, sockets were packed with similar gauze dressings soaked in normal saline 4ml at room temperature (control) and warmed to 42°C (experimental). The extent of bleeding on each side was measured by subtracting the original weight of the gauze from its weight after absorption of blood. The difference between the weights was compared using Student's paired t test (α=0.05, β<0.05). Mean (SD) weights were 22.1(2.2) g and 18.4 (2.5) g in the control and experimental groups, respectively, indicating an 18% reduction in the experimental group (p=0.002). Soaking gauze in normal saline heated to 42°C can reduce bleeding after extraction. PMID:26872898

  10. Topical treatment of major omphalocoele: Acacia nilotica versus povidone-iodine: A randomised controlled study

    PubMed Central

    Eltayeb, Almoutaz A.; Mostafa, Mahmoud M.

    2015-01-01

    Background: Conservative management for major omphalocoele with topical agents as escharotics therapy is well established in practice. Different agents have been used in the past, including mercurochrome and alcohol, proved later to be unsafe. The aim of this study is to evaluate the efficacy and safety of the application of Acacia nilotica paste compared to povidone-iodine solution as a primary non-surgical treatment of major omphalocoele. Patients and Methods: A double-blind, randomised study was conducted on 24 cases of major omphalocoele where they were randomly divided into two equal groups; Group A treated with topical application of A. nilotica paste and Group B treated with topical application of povidone-iodine solution. Cases with gastroschisis, ruptured major omphalocoele or minor omphalocoele were excluded from the study. The evaluating parameters were size of the fascial defect in cm, period of mechanical ventilation if needed, time required for full oral feeding tolerance, duration of hospital stay and any short- or long-term complications. Results: There was no statistical significant difference between both groups regarding their gestational or post-natal age, weight and the mean umbilical port defect. Patients from Group A tolerated full oral feeding earlier and had shorter total hospital stay duration than those from Group B, but without a statistical significant difference (P = 0.347 and 0.242, respectively). The overall mortality rate was 33.3% without a statistical significant difference between both groups (P = 0.667). Conclusions: Application of A. nilotica is a safe and effective treatment of major omphalocoele as it was associated with rapid full enteral feeding tolerance, short duration of hospital stay and low mortality rate. PMID:26712288

  11. Neonatal ECMO Study of Temperature (NEST) - a randomised controlled trial

    PubMed Central

    2010-01-01

    Background Existing evidence indicates that once mature neonates with severe cardio-respiratory failure become eligible for Extra Corporeal Membrane Oxygenation (ECMO) their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a multi-centre randomised controlled trial designed to test whether, in neonates requiring ECMO, cooling to 34°C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Infants allocated to the control group will receive ECMO at 37°C throughout their course, which is currently standard practice around the world. Health status of both groups will be assessed formally at 2 years corrected age. Methods/Design All infants recruited to the study will be cared for in one of the four United Kingdom (UK) ECMO centres. Babies who are thought to be eligible will be assessed by the treating clinician who will confirm eligibility, ensure that consent has been obtained and then randomise the baby using a web based system, based at the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit. Trial registration. Babies allocated ECMO without cooling will receive ECMO at 37°C ± 0.2°C. Babies allocated ECMO with cooling will be managed at 34°C ± 0.2°C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling will be 48 hours. Rewarming (to 37°C) will occur at a rate of no more than 0.5°C per hour. All other aspects of ECMO management will be identical. Primary outcome: Cognitive score from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at age of 2 years (24 - 27 months). Discussion For the primary analysis, children will be analysed in the groups to which they are assigned, comparing the outcome of all babies allocated to "ECMO with cooling" with all those allocated to "ECMO" alone, regardless of deviation from the protocol or treatment received. For the primary outcome the

  12. Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention – IMPRINT study

    PubMed Central

    2013-01-01

    Background Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm. In a cohort of extremely preterm (<28 weeks’ gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years’ post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks’, 12 months’ and 24 months’ post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks’ post-intervention. Methods/Design This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child’s home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks’, 12

  13. Assessment of CAOS as a training model in spinal surgery: a randomised study.

    PubMed

    Richards, P J; Kurta, I C; Jasani, V; Jones, C H Wynn; Rahmatalla, A; Mackenzie, G; Dove, J

    2007-02-01

    The objectives of this study were (1) to quantify the benefit of computer assisted orthopaedic surgery (CAOS) pedicle screw insertion in a porcine cadaver model evaluated by dissection and computed tomography (CT); (2) to compare the effect on performance of four surgeons with no experience of CAOS, and varying experience of pedicle screw insertion; (3) to see if CT with extended windows was an acceptable method to evaluate the position of the pedicle screws in the porcine cadaver model, compared to dissection. This was a prospective, randomised, controlled and blinded porcine cadaver study. Twelve 6-month-old porcine (white skinned Landrace) lumbar spines were scanned pre-operatively by spiral CT, as required for the CAOS computer data set. Computer randomisation allocated the specimens to one of four surgeons, all new to CAOS but with different levels of experience in spinal surgery. The usual anatomical landmarks for the freehand technique were known to all four surgeons. Two pedicles at each vertebral level were randomly allocated between conventional free hand insertion and an electromagnetic image guided surgery (NAVITRAK) and 6.5 mm cancellous AO screws inserted. Post-operatively, spiral CT was blindly evaluated by an independent radiologist and the spine fellow to assess the accuracy of pedicle screw placement, by each method. The inter- and intra-observer reliability of CT was evaluated compared to dissection. The pedicle screw placement was assessed as perfect if within the pedicle along its central axis, or acceptable (within < 2 mm from perfect), and measured in millimetres from perfect thereafter. One hundred and sixty-six of 168 pedicles in 12 porcine spines were operated on. Complete data were present for 163 pedicles (81 CAOS, 82 freehand). In the CAOS group 84% of screws were deemed acceptable or perfect, compared to 75.6% with the freehand technique. Screw misplacement was significantly reduced using CAOS (P = 0.049). Seventy-nine percent of CAOS

  14. A randomised double-blind placebo-controlled trial investigating the behavioural effects of vitamin, mineral and n-3 fatty acid supplementation in typically developing adolescent schoolchildren.

    PubMed

    Tammam, Jonathan D; Steinsaltz, David; Bester, D W; Semb-Andenaes, Turid; Stein, John F

    2016-01-28

    Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13-16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners' teacher ratings and school disciplinary records. At baseline, the children's PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour. PMID:26573368

  15. Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial

    PubMed Central

    Eichenseer, M.; Johansen, C.; Mueller, R. S.

    2013-01-01

    Antihistaminic drugs are commonly used as symptomatic therapy of atopic dermatitis in dogs. Unfortunately, their clinical benefit is largely unsubstantiated. In a double-blinded, placebo-controlled, cross-over trial, the influence of dimetinden and of a combination of chlorpheniramine and hydroxyzine on pruritus and lesions was evaluated in 19 dogs. They were treated with either product or a placebo orally for 14 days, each time followed by a 14-day washout period. Before and after each period, the dogs were examined and the Canine Atopic Dermatitis Extent and Severity Index (CADESI) determined by a clinician, and the pruritus and general condition by the owner. Dimetinden improved the pruritus significantly (P=0.014) but not the CADESI (P=0.087), the combination of hydroxyzine and chlorpheniramine improved the CADESI (P=0.049) and pruritus (P=0.05) significantly. Ten of 17 dogs improved by more than 25 per cent in pruritus with the combination of hydroxyzine and chlorpheniramine, 12 of 18 with dimetindenmaleate and only 2 of 19 with placebo. Antihistamines can help to reduce pruritus in atopic dogs, but in most cases, the improvement is limited and additional treatment may be needed. PMID:24114734

  16. Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial

    PubMed Central

    Fang, Jianqiao; Chen, Lifang; Chen, Luni; Wang, Chao; Keeler, Crystal Lynn; Ma, Ruijie; Xu, Shouyu; Shen, Laihua; Bao, Yehua; Ji, Conghua

    2014-01-01

    Introduction Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. Methods and analysis 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks’ follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. Ethics and dissemination Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. Trial registration number Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561 PMID:25475247

  17. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial.

    PubMed

    Knapen, Marjo H J; Braam, Lavienja A J L M; Drummen, Nadja E; Bekers, Otto; Hoeks, Arnold P G; Vermeer, Cees

    2015-05-01

    Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. PMID:25694037

  18. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis

    PubMed Central

    Miehlke, Stephan; Hruz, Petr; Vieth, Michael; Bussmann, Christian; von Arnim, Ulrike; Bajbouj, Monther; Schlag, Christoph; Madisch, Ahmed; Fibbe, Christiane; Wittenburg, Henning; Allescher, Hans Dieter; Reinshagen, Max; Schubert, Stefan; Tack, Jan; Müller, Michaela; Krummenerl, Patrick; Arts, Joris; Mueller, Ralph; Dilger, Karin; Greinwald, Roland; Straumann, Alex

    2016-01-01

    Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm2 hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation. Results Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. Conclusions BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. ClinicalTrials.gov number NCT02280616; EudraCT number, 2009-016692-29. PMID:25792708

  19. Clinical and biometrological efficacy of a hyaluronic acid-based mesotherapy product: a randomised controlled study.

    PubMed

    Baspeyras, Martine; Rouvrais, Céline; Liégard, Laetitia; Delalleau, Alexandre; Letellier, Sandrine; Bacle, Irène; Courrech, Laetitia; Murat, Pascale; Mengeaud, Valérie; Schmitt, Anne-Marie

    2013-10-01

    Data demonstrating the efficacy of hyaluronic acid (HA)-based mesotherapy for skin rejuvenation are scarce. The aim of the study is to assess the efficacy of non-reticulated HA-based mesotherapy on skin elasticity and complexion radiance. 55 women with cutaneous ageing signs included in the Full Analysis Set (FAS) population blindly received intradermal micro-injections (50 × 0.02 mL) of non-cross-linked HA filler with mannitol (Glytone 1, HA concentration: 14 mg/g) in one cheek and saline physiological solution in the other according to hemifacial randomisation in 3 monthly sessions. Elasticity (E1 and E2 stiffness parameters) and dermis thickness were measured by cutometry and 20 MHz echography, before (D0) treatment and 1 (1M) and 3 months (3M) after the last injection. A trained panel blindly scored skin complexion radiance from standardised and calibrated photographs, using 100 mm analogue scales. In the FAS population, only HA filler significantly decreased E1 at 1M (-10.9 %, p = 0.026) and 3M (-10.5 %, p = 0.035) compared with D0; its effect versus the control tended to be more persistent, with a difference between treatments at 3M close to significance (p = 0.063). E2 also decreased at 1M (-8.2 %, p = 0.027 in the per protocol population, n = 53) and 3M after HA-treatment only. Dermis thickness significantly increased after HA-treatment at 1M (+3.4 %, p = 0.028) and 3M (+4 %, p = 0.008), and after control-treatment at 1M only (+2.5 %, p = 0.015). The HA filler significantly improved complexion radiance at 3M compared with the control (p = 0.012) and for 51 % of subjects, their skin status. Non-reticulated HA-based mesotherapy significantly and sustainably improves skin elasticity and complexion radiance. PMID:23715889

  20. Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes

    PubMed Central

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Pieters, Indra C; Cahen, Djuna L; Diamant, Michaela; van Raalte, Daniël H

    2015-01-01

    Introduction Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. Methods and analyses 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention

  1. Missouri Annual Blind/Visually Impaired Literacy Study, December 2009

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2009

    2009-01-01

    The Missouri Department of Elementary and Secondary Education (DESE) Division of Special Education (DSE), per Section 162.1136 RSMo, conducts an annual study of the educational status of eligible blind/visually impaired students and reports the findings to the Missouri Legislature on December 1st each year. The information contained in this report…

  2. Missouri Annual Blind/Visually Impaired Literacy Study, December 2008

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2008

    2008-01-01

    The Missouri Department of Elementary and Secondary Education (DESE) Division of Special Education (DSE), per Missouri Revised Statute 162.1136, conducts an annual study of the educational status of eligible blind/visually impaired students and reports the findings to the Missouri Legislature on December 1st each year. The information contained in…

  3. Missouri Annual Blind/Visually Impaired Literacy Study, December 2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2012

    2012-01-01

    The Missouri Department of Elementary and Secondary Education, per Section 162.1136 RSMo, conducts an annual study of the educational status of eligible blind/visually impaired students and reports the findings to the Missouri Legislature on December 1st each year. The information contained in this report pertains to the twelve data elements…

  4. Missouri Annual Blind/Visually Impaired Literacy Study, December 2010

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2010

    2010-01-01

    The Missouri Department of Elementary and Secondary Education, per Section 162.1136 RSMo, conducts an annual study of the educational status of eligible blind/visually impaired students and reports the findings to the Missouri Legislature on December 1st each year. The information contained in this report pertains to the twelve data elements…

  5. Missouri Annual Blind/Visually Impaired Literacy Study, December 2011

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The Missouri Department of Elementary and Secondary Education, per Section 162.1136 RSMo, conducts an annual study of the educational status of eligible blind/visually impaired students and reports the findings to the Missouri Legislature on December 1st each year. The information contained in this report pertains to the twelve data elements…

  6. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial.

    PubMed

    Park, Eunyoung; Edirisinghe, Indika; Choy, Ying Yng; Waterhouse, Andrew; Burton-Freeman, Britt

    2016-01-28

    The aim of the present study was to test grape seed extract (GSE) as a functional ingredient to lower blood pressure (BP) in individuals with pre-hypertension. A single-centre, randomised, two-arm, double-blinded, placebo-controlled, 12-week, parallel study was conducted in middle-aged adults with pre-hypertension. A total of thirty-six subjects were randomised (1:1) to Placebo (n 18) or GSE (n 18) groups; twenty-nine of them completed all the protocol-specified procedures (Placebo, n 17; GSE, n 12). Subjects consumed a juice (167 kJ (40 kcal)) containing 0 mg (Placebo) or 300 mg/d GSE (150 mg) twice daily for 6 weeks preceded by a 2-week Placebo run-in and followed by 4-week no-beverage follow-up. Compliance was monitored. BP was measured at screening, 0, 6 and 10 weeks of intervention and blood samples were collected at 0, 3, 6 and 10 weeks of intervention. GSE significantly reduced systolic BP (SBP) by 5·6 % (P=0·012) and diastolic BP (DBP) by 4·7 % (P=0·049) after 6 weeks of intervention period, which was significantly different (SBP; P=0·03) or tended to be different (DBP; P=0·08) from Placebo. BP returned to baseline after the 4-week discontinuation period of GSE beverage. Subjects with higher initial BP experienced greater BP reduction; nearly double the effect size. Fasting insulin and insulin sensitivity tended to improve after 6 weeks of GSE beverage supplementation (P=0·09 and 0·07, respectively); no significant changes were observed with fasting plasma lipids, glucose, oxidised LDL, flow-mediated dilation or vascular adhesion molecules. Total plasma phenolic acid concentrations were 1·6 times higher after 6 weeks of GSE v. Placebo. GSE was found to be safe and to improve BP in people with pre-hypertension, supporting the use of GSE as a functional ingredient in a low-energy beverage for BP control. PMID:26568249

  7. Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

    PubMed Central

    Savitz, Jonathan; Preskorn, Sheldon; Teague, T Kent; Drevets, Douglas; Yates, William

    2012-01-01

    Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1). Methods and analysis 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery–Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines. Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every

  8. Correcting non cephalic presentation with moxibustion: study protocol for a multi-centre randomised controlled trial in general practice

    PubMed Central

    Vas, Jorge; Aranda, José Manuel; Barón, Mercedes; Perea-Milla, Emilio; Méndez, Camila; Ramírez, Carmen; Aguilar, Inmaculada; Modesto, Manuela; Lara, Ana María; Martos, Francisco; García-Ruiz, Antonio J

    2008-01-01

    Background Non cephalic presentation in childbirth involves various risks to both the mother and the foetus. The incidence in Spain is 3.8% of all full-term pregnancies. The most common technique used to end the gestation in cases of non cephalic presentation is that of caesarian section, and although it provokes a lower rate of morbi-mortality than does vaginal delivery in such situations, there remains the possibility of traumatic injury to the foetal head and neck, while maternal morbidity is also increased. The application of heat (moxibustion) to an acupuncture point, in order to correct non cephalic presentation, has been practised in China since ancient times, but as yet there is insufficient evidence of its real effectiveness. Methods/Design The experimental design consists of a multi-centre randomised controlled trial with three parallel arms, used to compare real moxibustion, sham moxibustion and the natural course of events, among pregnant women with a non cephalic presentation and a gestational duration of 33–35 weeks (estimated by echography). The participants in the trial will be blinded to both interventions. The results obtained will be analyzed by professionals, blinded with respect to the allocation to the different types of intervention. In addition, we intend to carry out a economic analysis. Discussion This trial will contribute to the development of evidence concerning moxibustion in the correction of non cephalic presentations. The primary outcome variable is the proportion of cephalic presentations at term. As secondary outcomes, we will evaluate the proportion of cephalic presentations at week 38 of gestation, determined by echography, together with the safety of the technique, the specificity of moxibustion and the control of the blinding process. This study has been funded by the Health Ministry of the Andalusian Regional Government. Trial registration Current Controlled Trials ISRCTN10634508. PMID:18495031

  9. Effect of Baduanjin exercise on cognitive function in older adults with mild cognitive impairment: study protocol for a randomised controlled trial

    PubMed Central

    Zheng, Guohua; Huang, Maomao; Li, Shuzhen; Li, Moyi; Xia, Rui; Zhou, Wenji; Tao, Jing; Chen, Lidian

    2016-01-01

    Introduction Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and dementia characterised by a reduction in memory and/or other cognitive processes. An increasing number of studies have indicated that regular physical activity/exercise may have beneficial association with cognitive function of older adults with or without cognitive impairment. As a traditional Chinese Qigong exercise, Baduanjin may be even more beneficial in promoting cognitive ability in older adults with MCI, but the evidence is still insufficient. The main purpose of this study is to investigate the effect of Baduanjin exercise on neuropsychological outcomes of community-dwelling older adults with MCI, and to explore its mechanism of action from neuroimaging based on functional MRI (fMRI) and cerebrovascular function. Methods and analysis The design of this study is a randomised, controlled trial with three parallel groups in a 1:1:1 allocation ratio with allocation concealment and assessor blinding. A total of 135 participants will be enrolled and randomised to the 24-week Baduanjin exercise intervention, 24-week brisk walking intervention and 24-week usual physical activity control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 9, 17, 25 and 37 weeks after randomisation, while the structure and function of brain regions related to cognitive function and haemodynamic variables of the brain will be measured by fMRI and transcranial Doppler, respectively, at baseline and 25 and 37 weeks after randomisation. Ethics and dissemination Ethics approval was given by the Medical Ethics Committee of the Second People's Hospital of Fujian Province (approval number 2014-KL045-02). The findings will be disseminated through peer-reviewed publications and at scientific conferences. Trial registration number

  10. Acute effects of traditional Thai massage on cortisol levels, arterial blood pressure and stress perception in academic stress condition: A single blind randomised controlled trial.

    PubMed

    Bennett, Surussawadi; Bennett, Michael John; Chatchawan, Uraiwon; Jenjaiwit, Patcharaporn; Pantumethakul, Rungthip; Kunhasura, Soontorn; Eungpinichpong, Wichai

    2016-04-01

    Traditional Thai massage (TTM) has been applied widely to promote relaxation. However, there is little evidence to support its efficacy on academic stress. A randomised controlled trial was performed to examine the acute effects of TTM on cortisol level, blood pressure, heart rate and stress perception in academic stress. This prospective trial included 36 physiotherapy students with a self perceived stress score of between 3 and 5. They were randomly allocated into the TTM (18 people) group or the control group (18 people). Saliva cortisol level, blood pressure, heart rate and stress perception rating were measured before and after the intervention. Both groups showed a significant reduction in cortisol level and heart rate when compared with baseline (p < 0.001). There were no significant differences in cortisol level between the two groups. The results suggest the need for further study into other possible physiological effects on stress of TTM. PMID:27210845

  11. Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

    PubMed Central

    2012-01-01

    Background Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Methods/Design Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Discussion Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy

  12. Treating Parents to Reduce NICU Transmission of Staphylococcus aureus (TREAT PARENTS) trial: protocol of a multisite randomised, double-blind, placebo-controlled trial

    PubMed Central

    Milstone, Aaron M; Koontz, Danielle W; Voskertchian, Annie; Popoola, Victor O; Harrelson, Kathleen; Ross, Tracy; Aucott, Susan W; Gilmore, Maureen M; Carroll, Karen C; Colantuoni, Elizabeth

    2015-01-01

    Introduction More than 33 000 healthcare-associated infections occur in neonatal intensive care units (NICUs) each year in the USA. Parents, rather than healthcare workers, may be a reservoir from which neonates acquire Staphylococcus aureus (S. aureus) colonisation in the NICU. This study looks to measure the effect of treating parents with short course intranasal mupirocin and topical chlorhexidine antisepsis on acquisition of S. aureus colonisation and infection in neonates. Methods and analysis The TREAT PARENTS trial (Treating Parents to Reduce Neonatal Transmission of S. aureus) is a multicentre randomised, masked, placebo-controlled trial. Shortly after a neonate is admitted to the NICU, parents will be tested for S. aureus colonisation. If either parent screens positive for S. aureus, then both parents as a pair will be enrolled and randomised to one of the two possible masked treatment arms. Arm 1 will include assignment to intranasal 2% mupirocin plus topical antisepsis with chlorhexidine gluconate impregnated cloths for 5 days. Arm 2 will include assignment to placebo ointment and placebo cloths for skin antisepsis for 5 days. The primary outcome will be neonatal acquisition of an S. aureus strain that is concordant to the parental baseline S. aureus strain as determined by periodic surveillance cultures or a culture collected during routine clinical care that grows S. aureus. Secondary outcomes will include neonatal acquisition of S. aureus, neonatal S. aureus infection, eradication of S. aureus colonisation in parents, natural history of S. aureus colonisation in parents receiving placebo, adverse reactions to treatment, feasibility of intervention, and attitudes and behaviour in consented parents. Four hundred neonate-parent pairs will be enrolled. Ethics and dissemination The study was approved by Johns Hopkins University IRB in June 2014 (IRB number 00092982). Protocol V.7 was approved in November 2014. Findings will be published in peer

  13. Effectiveness of cognitive behavioural therapy augmentation in major depression treatment (ECAM study): study protocol for a randomised clinical trial

    PubMed Central

    Nakagawa, Atsuo; Sado, Mitsuhiro; Mitsuda, Dai; Fujisawa, Daisuke; Kikuchi, Toshiaki; Abe, Takayuki; Sato, Yuji; Iwashita, Satoru; Mimura, Masaru; Ono, Yutaka

    2014-01-01

    Introduction Major depression is a serious mental disorder that causes substantial distress and impairment in individuals and places an enormous burden on society. Although antidepressant treatment is the most common therapy provided in routine practice, there is little evidence to guide second-line therapy for patients who have failed to respond to antidepressants. The aim of this paper is to describe the study protocol for a randomised controlled trial that measures the clinical effectiveness of cognitive behavioural therapy (CBT) as an augmentation strategy to treat patients with non-psychotic major depression identified as suboptimal responders to usual depression care. Methods and analysis The current study is a 16-week assessor-blinded randomised, parallel-groups superiority trial with 12-month follow-up at an outpatient clinic as part of usual depression care. Patients aged 20–65 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Major Depressive Disorder who have experienced at least one failed trial of antidepressants as part of usual depression care, will be randomly assigned to receive CBT plus treatment as usual, or treatment as usual alone. The primary outcome is the change in clinician-rated 17-item GRID-Hamilton Depression Rating Scale (GRID-HAMD) score at 16 weeks, and secondary outcomes include severity and change in scores of subjective depression symptoms, proportion of responders and remitters, safety and quality of life. The primary population will be the intention-to-treat patients. Ethics and dissemination All protocols and the informed consent form comply with the Ethics Guideline for Clinical Research (Japanese Ministry of Health, Labour and Welfare). Ethics review committees at the Keio University School of Medicine and the Sakuragaoka Memorial Hospital approved the study protocol. The results of the study will be disseminated at several research conferences and as published articles in peer

  14. An epidemiological study of blindness in an Indian rural community.

    PubMed

    Srivastava, R N; Verma, B L

    1978-06-01

    A house-to-house survey of blindness in an Indian rural community covering a population of 20 134 in 12 villages revealed a prevalence rate of 35 blind and 144 partially blind persons per 10 000 population. Blindness was significantly associated with the age, sex, marital status, occupation, and socioeconomic status of the respondents. Caratact, glaucoma, smallpox and trachoma were the main causes of blindness. Preventive measures can reduce the toll of blindness in such a community. PMID:681587

  15. Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

    PubMed Central

    Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

    2016-01-01

    Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial

  16. Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

    PubMed Central

    2009-01-01

    Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH). Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A), and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%). Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50) and 1740 (S.E. 291) in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237) and 1126 (S.E. 182) in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes. Trial Registration Current controlled trials ISRCTN44215995. PMID:19228385

  17. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial

    PubMed Central

    Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W; S Lund, Søren; Wiinberg, Niels; Perrild, Hans; Krarup, Thure; Snorgaard, Ole; Gade-Rasmussen, Birthe; Thorsteinsson, Birger; Røder, Michael; Mathiesen, Elisabeth R; Jensen, Tonny; Vestergaard, Henrik; Hedetoft, Christoffer; Breum, Leif; Duun, Elsebeth; Sneppen, Simone B; Pedersen, Oluf; Hemmingsen, Bianca; Carstensen, Bendix; Madsbad, Sten; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Almdal, Thomas P

    2016-01-01

    Objective To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. Design and setting Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design conducted at eight hospitals in Denmark. Participants and interventions 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤7.0% (≤53 mmol/mol). Outcomes The primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes. Results Change in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI −0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference −0.42% (95% CI −0.62% to −0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference −2.6 kg (95% CI −3.3 to −1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001). Conclusions Metformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power

  18. A comparison of customised and prefabricated insoles to reduce risk factors for neuropathic diabetic foot ulceration: a participant-blinded randomised controlled trial

    PubMed Central

    2012-01-01

    Background Neuropathic diabetic foot ulceration may be prevented if the mechanical stress transmitted to the plantar tissues is reduced. Insole therapy is one practical method commonly used to reduce plantar loads and ulceration risk. The type of insole best suited to achieve this is unknown. This trial compared custom-made functional insoles with prefabricated insoles to reduce risk factors for ulceration of neuropathic diabetic feet. Method A participant-blinded randomised controlled trial recruited 119 neuropathic participants with diabetes who were randomly allocated to custom-made functional or prefabricated insoles. Data were collected at issue and six month follow-up using the F-scan in-shoe pressure measurement system. Primary outcomes were: peak pressure, forefoot pressure time integral, total contact area, forefoot rate of load, duration of load as a percentage of stance. Secondary outcomes were patient perceived foot health (Bristol Foot Score), quality of life (Audit of Diabetes Dependent Quality of Life). We also assessed cost of supply and fitting. Analysis was by intention-to-treat. Results There were no differences between insoles in peak pressure, or three of the other four kinetic measures. The custom-made functional insole was slightly more effective than the prefabricated insole in reducing forefoot pressure time integral at issue (27% vs. 22%), remained more effective at six month follow-up (30% vs. 24%, p=0.001), but was more expensive (UK £656 vs. £554, p<0.001). Full compliance (minimum wear 7 hours a day 7 days per week) was reported by 40% of participants and 76% of participants reported a minimum wear of 5 hours a day 5 days per week. There was no difference in patient perception between insoles. Conclusion The custom-made insoles are more expensive than prefabricated insoles evaluated in this trial and no better in reducing peak pressure. We recommend that where clinically appropriate, the more cost effective prefabricated insole

  19. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

    PubMed Central

    Hochberg, Marc C; Martel-Pelletier, Johanne; Monfort, Jordi; Möller, Ingrid; Castillo, Juan Ramón; Arden, Nigel; Berenbaum, Francis; Blanco, Francisco J; Conaghan, Philip G; Doménech, Gema; Henrotin, Yves; Pap, Thomas; Richette, Pascal; Sawitzke, Allen; du Souich, Patrick; Pelletier, Jean-Pierre

    2016-01-01

    Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Methods Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. Results The adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. Conclusions CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile. Trial

  20. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

    PubMed Central

    Reginster, Jean-Yves; Badurski, Janusz; Bellamy, Nicholas; Bensen, William; Chapurlat, Roland; Chevalier, Xavier; Christiansen, Claus; Genant, Harry; Navarro, Federico; Nasonov, Evgeny; Sambrook, Philip N; Spector, Timothy D; Cooper, Cyrus

    2013-01-01

    Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day. PMID:23117245

  1. Skills Training to Avoid Inadvertent Plagiarism: Results from a Randomised Control Study

    ERIC Educational Resources Information Center

    Newton, Fiona J.; Wright, Jill D.; Newton, Joshua D.

    2014-01-01

    Plagiarism continues to be a concern within academic institutions. The current study utilised a randomised control trial of 137 new entry tertiary students to assess the efficacy of a scalable short training session on paraphrasing, patch writing and plagiarism. The results indicate that the training significantly enhanced students' overall…

  2. Comparative effectiveness of long-acting antipsychotics: issues and challenges from a pragmatic randomised study.

    PubMed

    Ostuzzi, G; Barbui, C

    2016-02-01

    Although long-acting antipsychotics are widely used in individuals with psychotic disorders, it is unclear which long-acting preparation should be considered as first-line treatment in clinical practice. In this commentary, the main strengths and weaknesses of a recently published pragmatic randomised study comparing long-acting paliperidone palmitate v. long-acting haloperidol decanoate are briefly analysed. PMID:26515607

  3. A double-blind randomised controlled trial of a natural oil-based emulsion (Moogoo Udder Cream®) containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer

    PubMed Central

    2012-01-01

    Background Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration ACTRN 12612000568819 PMID:22849762

  4. Absence of adverse events in healthy individuals using probiotics - analysis of six randomised studies by one study group.

    PubMed

    Tapiovaara, L; Lehtoranta, L; Poussa, T; Mäkivuokko, H; Korpela, R; Pitkäranta, A

    2016-03-11

    Consumption of live bacteria as probiotic supplements is increasing. There is, however, a lack of information on the safety of ingested probiotics. The main objective of this study was to investigate the adverse events (AEs) of specific probiotics (Lactobacillus rhamnosus GG (LGG) alone or LGG in combination with L. rhamnosus Lc705, Propionibacterium freudenreichii JS, Bifidobacterium lactis BB12, or Bifidobacterium breve 99) studied in six of our study groups' clinical trials, by analysing individual participant data. A secondary objective was to study AEs associated with the consumed probiotic species and mixtures in three specific categories; 'gastrointestinal disorders', 'respiratory, thoracic and mediastinal disorders' and 'infections and infestations'. Six randomised, double-blind, placebo-controlled clinical studies by our study group were included in this AE analysis (study population n=1,909). All AE data were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0. From the 26 CTCAE System Organ Classes, we identified AEs in 20 classes among 1,909 subjects. Probiotic ingestion did not result in statistically significant differences in AEs in different groups, when compared to placebo. A subgroup analysis of gastrointestinal, respiratory, thoracic and mediastinal disorders, infections and infestations, found no differences between the intervention groups or for different probiotic combinations (risk ratio (RR) = 0.97, 95% confidence interval (CI): 0.93-1.02, P=0.30; RR=0.99, 95% CI: 0.97-1.01, P=0.35; RR=0.99, 95% CI: 0.93-1.06, P=0.62, respectively). As a conclusion, ingestion of probiotic supplementations containing LGG alone, or LGG in combination with L. rhamnosus Lc705, P. freudenreichii JS, B. breve 99, or B. lactis BB12 did not seem to cause AEs in young and elderly subjects in this analysis. PMID:26689224

  5. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial

    PubMed Central

    Smolen, J; Landewé, R B; Mease, P; Brzezicki, J; Mason, D; Luijtens, K; van Vollenhoven, R F; Kavanaugh, A; Schiff, M; Burmester, G R; Strand, V; Vencovský, J; van der Heijde, D

    2009-01-01

    Background: Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. Objective: To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). Methods: An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. Results: Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. Conclusion: Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. Trial registration number: NCT00175877 PMID:19015207

  6. Polyphenol- and fibre-rich dried fruits with green tea attenuate starch-derived postprandial blood glucose and insulin: a randomised, controlled, single-blind, cross-over intervention.

    PubMed

    Nyambe-Silavwe, H; Williamson, G

    2016-08-01

    Polyphenol- and fibre-rich foods (PFRF) have the potential to affect postprandial glycaemic responses by reducing glucose absorption, and thus decreasing the glycaemic response of foods when consumed together. A randomised, single-blind, cross-over study was conducted on sixteen healthy volunteers to test whether PFRF could attenuate postprandial blood glucose in healthy volunteers when added to a source of carbohydrate (starch in bread). This is the first study to examine the effects of a meal comprised of components to inhibit each stage of the biochemical pathway, leading up to the appearance of glucose in the blood. The volunteers were fasted and attended four visits: two control visits (bread, water, balancing sugars) and two test visits (single and double dose of PFRF) where they consumed bread, water and PFRF. Blood samples were collected at 0 (fasted), 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption. The PFRF components were tested for α-amylase and α-glucosidase inhibitory potential in vitro. Plasma glucose was lower after consumption of both doses compared with controls: lower dose, change in mean incremental areas under the glucose curves (IAUC)=-27·4 (sd 7·5) %, P<0·001; higher dose, IAUC=-49·0 (sd 15·3) %, P<0·001; insulin IAUC was also attenuated by-46·9 (sd 13·4) %, P<0·01. Consistent with this, the polyphenol components of the PFRF inhibited α-amylase (green tea, strawberry, blackberry and blackcurrant) and α-glucosidase (green tea) activities in vitro. The PFRF have a pronounced and significant lowering effect on postprandial blood glucose and insulin response in humans, due in part to inhibition of α-amylase and α-glucosidase, as well as glucose transport. PMID:27278405

  7. Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon

    PubMed Central

    Lenglet, A; Arnéz, A M; Carneiro, I

    2007-01-01

    Objective To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening. Design A double blind, placebo controlled cluster-randomised clinical study. Setting Rural villages and peri-urban districts in the Bolivian Amazon. Participants 4008 individuals in 860 households. Interventions All individuals slept under treated nets; one group also used a plant based insect repellent each evening, a second group used placebo. Main outcome measure Episodes of Plasmodium falciparum or P vivax malaria confirmed by rapid diagnostic test or blood slide, respectively. Results We analysed 15 174 person months at risk and found a highly significant 80% reduction in episodes of P vivax in the group that used treated nets and repellent (incidence rate ratio 0.20, 95% confidence interval 0.11 to 0.38, P<0.001). Numbers of P falciparum cases during the study were small and, after adjustment for age, an 82% protective effect was observed, although this was not significant (0.18, 0.02 to 1.40, P=0.10). Reported episodes of fever with any cause were reduced by 58% in the group that used repellent (0.42, 0.31 to 0.56, P<0.001). Conclusions Insect repellents can provide protection against malaria. In areas where vectors feed in the early evening, effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime. This has important implications in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents, as advocated for most tourists travelling to high risk areas, is fully justified. Registration NCT 00144716. PMID:17940319

  8. 100 positive double-blind studies: enough or too little?

    NASA Astrophysics Data System (ADS)

    Tuner, Jan; Hode, Lars

    2000-06-01

    A major argument among the opponents of laser therapy has been the absence of scientific documentation. This was a valid position in the 80s and partly in the 90s. But today, is this still a sound argument. There are more than 2,000 published studies in the field, including meeting abstracts and anecdotal reports. The vast majority of these papers reports positive effects of LLLT in vitro and in vivo. It is fair to argue that negative results are less prone to be published, but certainly more than 80 percent of the published studies are positive. In the field of dentistry, for instance, the positive percentage is well above 90 percent. The present literature study will look at the heart of the positive documentation: the positive double blind studies. It may come as a surprise to many critics that there are more than 100 positive double blind studies in the field laser therapy. This is a god base for a further understanding of the effects of low level laser in the clinical setting. We must, however, be as critical as the sceptics themselves in order to obtain a constructive dialogue between 'attorneys' and sceptics. In this paper, a critical review of 100 positive double blind studies will be presented.

  9. [Value of hydroxyzine in generalized anxiety disorder: controlled double-blind study versus placebo].

    PubMed

    Ferreri, M; Hantouche, E G; Billardon, M

    1994-01-01

    A multi-centre study was designed to evaluate the efficacy of hydroxyzine in the treatment of patients presenting a generalized anxiety disorder (GAD). One hundred and thirty three patients, suffering from a GAD (according to DSM III-R criteria with 6 months duration criteria), were enrolled in a randomised, double-blind, hydroxyzine (50 mg/day) versus placebo, over a 4-week trial period. By the end of the first week, the decrease of anxiety scores was significant for the hydroxyzine group, as compared to placebo (in respect of all rating criteria of anxiety). The statistical superiority for hydroxyzine continued to the end of the 4-weeks study period, and persisted at a further evaluation a week after abrupt discontinuation of active treatment. The tolerance evaluation showed that side effects were reported in 52% of hydroxyzine group versus 35% of placebo group. The most commun side effects were sleepiness (28% vs 14% with placebo), weight gain (12% vs 10%), dry mouth (14% vs 5%), loss of concentration (9% vs 8%) and insomnia (9% vs 6%). Sleepiness in the hydroxyzine group appeared during the first week and progressively disappeared later during treatment. We concluded that hydroxyzine at 50 mg/day produces a statistically and clinically significant anxiolytic effect, commencing during the first week of treatment and maintained throughout the 4-week period and after abrupt discontinuation without rebound of anxiety or withdrawal symptoms. The most commun side effect with hydroxyzine is transient sleepiness. PMID:7875114

  10. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

    PubMed Central

    2011-01-01

    Background Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. Methods A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. Trial Registration ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836 PMID:21645332

  11. Topical capsaicin—a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study

    PubMed Central

    Lysy, J; Sistiery-Ittah, M; Israelit, Y; Shmueli, A; Strauss-Liviatan, N; Mindrul, V; Keret, D; Goldin, E

    2003-01-01

    Purpose: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. Methods: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. Results: Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 “responders” needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5–7 days) to remain symptom free (or nearly symptom free). Conclusion: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani. PMID:12912865

  12. A randomised controlled trial of acceptance and commitment therapy (ACT) for psychosis: study protocol

    PubMed Central

    2014-01-01

    Background Cognitive behavior therapy for psychosis has been a prominent intervention in the psychological treatment of psychosis. It is, however, a challenging therapy to deliver and, in the context of increasingly rigorous trials, recent reviews have tempered initial enthusiasm about its effectiveness in improving clinical outcomes. Acceptance and commitment therapy shows promise as a briefer, more easily implemented therapy but has not yet been rigorously evaluated in the context of psychosis. The purpose of this trial is to evaluate whether Acceptance and Commitment Therapy could reduce the distress and disability associated with psychotic symptoms in a sample of community-residing patients with chronic medication-resistant symptoms. Methods/Design This is a single (rater)-blind multi-centre randomised controlled trial comparing Acceptance and Commitment Therapy with an active comparison condition, Befriending. Eligible participants have current residual hallucinations or delusions with associated distress or disability which have been present continuously over the past six months despite therapeutic doses of antipsychotic medication. Following baseline assessment, participants are randomly allocated to treatment condition with blinded, post-treatment assessments conducted at the end of treatment and at 6 months follow-up. The primary outcome is overall mental state as measured using the Positive and Negative Syndrome Scale. Secondary outcomes include preoccupation, conviction, distress and disruption to life associated with symptoms as measured by the Psychotic Symptom Rating Scales, as well as social functioning and service utilisation. The main analyses will be by intention-to-treat using mixed-model repeated measures with non-parametric methods employed if required. The model of change underpinning ACT will be tested using mediation analyses. Discussion This protocol describes the first randomised controlled trial of Acceptance and commitment therapy in

  13. A double-blind randomised controlled trial testing the effect of a barley product containing varying amounts and types of fibre on the postprandial glucose response of healthy volunteers.

    PubMed

    Ames, Nancy; Blewett, Heather; Storsley, Joanne; Thandapilly, Sijo J; Zahradka, Peter; Taylor, Carla

    2015-05-14

    The aim of the present study was to determine if the consumption of barley tortillas varying in fibre and/or starch composition affected postprandial glucose, insulin, glucagon-like peptide-1 (GLP-1) or peptide YY concentrations. A double-blind, randomised, controlled trial was performed with twelve healthy adults. They each consumed one of five barley tortillas or a glucose drink on six individual visits separated by at least 1 week. Tortillas were made from 100% barley flour blends using five different milling fractions to achieve the desired compositions. All treatments provided 50 g of available carbohydrate and were designed to make the following comparisons: (1) low-starch amylose (0%) v. high-starch amylose (42%) with similar β-glucan and insoluble fibre content; (2) low β-glucan (4.5 g) v. medium β-glucan (7.8 g) v. high β-glucan (11.6 g) with similar starch amylose and insoluble fibre content; and (3) low insoluble fibre (7.4 g) v. high insoluble fibre (19.6 g) with similar starch amylose and β-glucan content. Blood was collected at fasting and at multiple intervals until 180 min after the first bite/sip of the test product. Amylose and insoluble fibre content did not alter postprandial glucose and insulin, but high-β-glucan tortillas elicited a lower glucose and insulin response as compared to the low-β-glucan tortillas. The tortillas with high insoluble fibre had a higher AUC for GLP-1 as compared to the tortillas with low insoluble fibre, whereas amylose and β-glucan content had no effect. Results show that processing methods can be used to optimise barley foods to reduce postprandial blood glucose responses and factors that may influence satiety. PMID:25850814

  14. Double-blind cluster randomised controlled trial of wheat flour chapatti fortified with micronutrients on the status of vitamin A and iron in school-aged children in rural Bangladesh.

    PubMed

    Rahman, Ahmed S; Ahmed, Tahmeed; Ahmed, Faiz; Alam, Mohammad S; Wahed, Mohammad A; Sack, David A

    2015-12-01

    Food fortification is a cost-effective and sustainable strategy to prevent or correct micronutrient deficiencies. A double-blind cluster (bari) randomised controlled trial was conducted in a rural community in Bangladesh to evaluate the impact of consumption of chapatti made of micronutrient-fortified wheat flour for 6 months by school-aged children on their vitamin A, haemoglobin and iron status. A total of 43 baris (group of households) were randomly selected. The baris were randomly assigned to either intervention or control group. The intervention group received wheat flour fortified with added micronutrients (including 66 mg hydrogen-reduced elemental iron and 3030 μg retinol equivalent as retinyl palmitate per kilogram of flour), while the control group received wheat flour without added micronutrients. A total of 352 children were enrolled in the trial, 203 in the intervention group and 149 in the control group. Analyses were carried out on children who completed the study (191 in the intervention group and 143 in the control group). Micronutrient-fortified wheat flour chapatti significantly increased serum retinol concentration at 6 months by 0.12 μmol L(-1) [95% confidence interval (CI): 0.06, 0.19; P < 0.01]. The odds of vitamin A deficiency was significantly lower for children in the intervention group at 3 months [odds ratio (OR) = 0.26; 95% confidence interval (CI): 0.07, 0.89; P < 0.05] and 6 months (OR = 0.21; 95% CI: 0.06, 0.68; P < 0.01). No demonstrable effect of fortified chapatti consumption on iron status, haemoglobin levels or anaemia was observed. Consumption of fortified chapattis demonstrated a significant improvement in the vitamin A status, but not in iron, haemoglobin or anaemia status. PMID:23800099

  15. Efficacy of wheat-based biscuits fortified with microcapsules containing ferrous sulfate and potassium iodate or a new hydrogen-reduced elemental iron: a randomised, double-blind, controlled trial in Kuwaiti women.

    PubMed

    Biebinger, Ralf; Zimmermann, Michael B; Al-Hooti, Suad N; Al-Hamed, Nawal; Al-Salem, Ebtehal; Zafar, Tasleem; Kabir, Yearul; Al-Obaid, I'nam; Petry, Nicolai; Hurrell, Richard F

    2009-11-01

    Adverse sensory changes prevent the addition of highly bioavailable ferrous sulfate (FeSO4) to most wheat flours. Poorly absorbable reduced Fe powders are commonly used. Encapsulation of FeSO4 can overcome these sensory changes, but the particle size of commercial compounds is too large to be used by flour mills. The first objective of the study was to measure the efficacy in wheat flour of two newly developed Fe compounds, an H-reduced Fe powder (NutraFine RS; North America Höganäs High Alloys LLC, Johnstown, PA, USA) and small particle-sized (40 microm) encapsulated FeSO4. As a second objective, the microcapsules were evaluated as a vehicle for iodine fortification. A randomised, double-blind controlled intervention trial was conducted in Kuwaiti women (n 279; aged 18-35 years) with low body Fe stores (serum ferritin (SF) < 25 microg/l) randomly assigned to one of three groups (20 mg Fe as NutraFine RS, 10 mg Fe as encapsulated FeSO4 and 150 microg iodine, or no fortification Fe) who consumed wheat-based biscuits 5 d per week. At baseline and 22 weeks, Hb, SF, transferrin receptor, urinary iodine and body Fe stores were measured. Relative to control, mean SF in the encapsulated FeSO4 group increased by 88 % (P < 0.001) and body Fe stores increased from - 0.96 to 2.24 mg/kg body weight (P < 0.001), while NutraFine RS did not significantly increase SF or body Fe stores. The median urinary iodine concentration increased from 140 to 213 microg/l (P < 0.01). NutraFine RS added at double the amount of Fe as FeSO4 was not efficacious in improving Fe status. The newly developed microcapsules were highly efficacious in improving both Fe stores and iodine status. PMID:19653920

  16. The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial

    PubMed Central

    Avidan, Michael S; Fritz, Bradley A; Maybrier, Hannah R; Muench, Maxwell R; Escallier, Krisztina E; Chen, Yulong; Ben Abdallah, Arbi; Veselis, Robert A; Hudetz, Judith A; Pagel, Paul S; Noh, Gyujeong; Pryor, Kane; Kaiser, Heiko; Arya, Virendra Kumar; Pong, Ryan; Jacobsohn, Eric; Grocott, Hilary P; Choi, Stephen; Downey, Robert J; Inouye, Sharon K; Mashour, George A

    2014-01-01

    Introduction Postoperative delirium is one of the most common complications of major surgery, affecting 10–70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. Methods The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1–3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. Ethics and dissemination The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. Registration details The study is

  17. Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study.

    PubMed Central

    Husby, S; Agertoft, L; Mortensen, S; Pedersen, S

    1993-01-01

    The aim of this prospective, randomised, double blind study was to evaluate whether nebulised local steroid treatment is effective in the treatment of croup. Thirty six infants and children (0.4-4.9 years of age) admitted to hospital with moderate to severe croup were allocated to receive either 2 mg nebulised budesonide (20 children) or saline (16 children). Disease severity was assessed by a clinical total croup score based on stridor, cough, retractions, dyspnoea, and cyanosis. In addition the overall clinical impression was evaluated (0-100). Two hours after treatment there was a significant improvement in the total croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical impression assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The total croup score and overall clinical severity were significantly better in the group treated with budesonide than in the placebo group. No side effects were observed. The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children and infants with moderate to severe croup. PMID:8466237

  18. Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study

    PubMed Central

    Mayer, Lloyd; Sandborn, William J; Stepanov, Yuriy; Geboes, Karel; Hardi, Robert; Yellin, Michael; Tao, Xiaolu; Xu, Li An; Salter-Cid, Luisa; Gujrathi, Sheila; Aranda, Richard; Luo, Allison Y

    2014-01-01

    Objective Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. Design In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure–response relationship and histological improvement. Results 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108–235 μg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. Conclusions Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose–response studies are warranted. Clinical Trial Registration Number: ClinicalTrials.gov NCT00656890. PMID:23461895

  19. Effect of plant sterols on the lipid profile of patients with hypercholesterolaemia. Randomised, experimental study

    PubMed Central

    2011-01-01

    Background Studies have been conducted on supplementing the daily diet with plant sterol ester-enriched milk derivatives in order to reduce LDL-cholesterol levels and, consequently, cardiovascular risk. However, clinical practice guidelines on hypercholesterolaemia state that there is not sufficient evidence to recommend their use in subjects with hypercholesterolaemia. The main objective of this study is to determine the efficacy of the intake of 2 g of plant sterol esters a day in lowering LDL-cholesterol levels in patients diagnosed with hypercholesterolaemia. The specific objectives are: 1) to quantify the efficacy of the daily intake of plant sterol esters in lowering LDL-cholesterol, total cholesterol and cardiovascular risk in patients with hypercholesterolaemia; 2) to evaluate the occurrence of adverse effects of the daily intake of plant sterol esters; 3) to identify the factors that determine a greater reduction in lipid levels in subjects receiving plant sterol ester supplements. Methods/Design Randomised, double-blind, placebo controlled experimental trial carried out at family doctors' surgeries at three health centres in the Health Area of Albacete (Spain). The study subjects will be adults diagnosed with "limit" or "defined" hypercholesterolaemia and who have LDL cholesterol levels of 130 mg/dl or over. A dairy product in the form of liquid yoghurt containing 2 g of plant sterol ester per container will be administered daily after the main meal, for a period of 24 months. The control group will receive a daily unit of yogurt not supplemented with plant sterol esters that has a similar appearance to the enriched yoghurt. The primary variable is the change in lipid profile at 1, 3, 6, 12, 18 and 24 months. The secondary variables are: change in cardiovascular risk, adherence to the dairy product, adverse effects, adherence to dietary recommendations, frequency of food consumption, basic physical examination data, health problems, lipid

  20. Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial

    PubMed Central

    Devakumar, Delan; Chaube, Shiva Shankar; Wells, Jonathan C K; Saville, Naomi M; Ayres, Jon G; Manandhar, Dharma S; Costello, Anthony; Osrin, David

    2014-01-01

    Summary Background In 2002–04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained. Methods For this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5–19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934. Findings Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI −0·09 to 0·19), 0·02 in height-for-age (−0·10 to 0·15), and 0·04 in BMI-for-age (−0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes. Interpretation We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or

  1. Transcranial direct current stimulation and exercises for treatment of chronic temporomandibular disorders: a blind randomised-controlled trial.

    PubMed

    Oliveira, L B; Lopes, T S; Soares, C; Maluf, R; Goes, B T; Sá, K N; Baptista, A F

    2015-10-01

    To evaluate the effect of adding transcranial direct current stimulation (tDCS) to exercises for chronic pain, dysfunction and quality of life in subjects with temporomandibular disorders (TMD). Participants were selected based on the RDC/TMD criteria and assessed for pain intensity, pressure pain threshold over temporomandibular joint and cervical muscles and quality of life. After initial assessment, all individuals underwent a 4-week protocol of exercises and manual therapy, together with active or sham primary motor cortex tDCS. Stimulation was delivered through sponge electrodes, with 2 mA amplitude, for 20 min daily, over the first 5 days of the trial. A total of 32 subjects (mean age 24.7 ± 6.8 years) participated in the evaluations and treatment protocol. Mean pain intensity pre-treatment was 5.5 ± 1.4 for active tDCS group, and 6.3 ± 1.2 for sham tDCS. Both groups showed a decrease in pain intensity scores during the trial period (time factor--F(4.5,137.5) = 28.7, P < 0.001; group factor--F(1.0,30.0 = 7.7), P < 0.05). However, there were no differences between the groups regarding change in pain intensity (time*group interaction--F(4.5,137.5) = 1.5, P = 0.137). This result remained the same after 5 months (t-test t = 0.29, P > 0.05). Pressure pain thresholds decrease and improvement in quality of life were also noticeable in both groups, but again without significant differences between them. Absolute benefit increase was 37.5% (CI 95%: -15.9% to 90.9%), and number needed to treat was 2.66. This study suggests that there is no additional benefit in adding tDCS to exercises for the treatment of chronic TMD in young adults. PMID:25891021

  2. Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

    PubMed Central

    Grube, Barbara; Chong, Pee-Win; Alt, Felix; Uebelhack, Ralf

    2015-01-01

    Background. Litramine (IQP-G-002AS) was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day) or a matching placebo. Primary endpoints were difference of mean body weight (kg) between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (−0.62 ± 1.55 kg versus 1.62 ± 1.48 kg, p < 0.001). More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387. PMID:26435849

  3. Update on the Preventive Antibiotics in Stroke Study (PASS): a randomised controlled phase 3 clinical trial

    PubMed Central

    2014-01-01

    Background Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections. Results To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute stroke trials, as it increases statistical power. For PASS, funding is insufficient for inclusion of 3,200 patients with the overall inclusion rate of 15 patients per week. Therefore we change the analysis of our primary outcome from dichotomisation to ordinal regression analysis on the mRS. Power analysis showed that with similar assumptions 2,550 patients are needed using ordinal regression analysis. We expect to complete follow-up in June 2014. A full statistical analysis plan will be

  4. Effect of dietary supplementation with omega-3 fatty acid and gamma-linolenic acid on acne vulgaris: a randomised, double-blind, controlled trial.

    PubMed

    Jung, Jae Yoon; Kwon, Hyuck Hoon; Hong, Jong Soo; Yoon, Ji Young; Park, Mi Sun; Jang, Mi Young; Suh, Dae Hun

    2014-09-01

    This study was undertaken to evaluate the clinical efficacy, safety, and histological changes induced by dietary omega-3 fatty acid and γ-linoleic acid in acne vulgaris. A 10-week, randomised, controlled parallel dietary intervention study was performed in 45 participants with mild to moderate acne, which were allocated to either an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a γ-linoleic acid group (borage oil containing 400 mg γ-linoleic acid), or a control group. After 10 weeks of omega-3 fatty acid or γ-linoleic acid supplementation, inflammatory and non-inflammatory acne lesions decreased significantly. Patient subjective assessment of improvement showed a similar result. Heamatoxylin & eosin staining of acne lesions demonstrated reductions in inflammation and immunohistochemical staining intensity for interleukin-8. No severe adverse effect was reported. This study shows for the first time that omega-3 fatty acid and γ-linoleic acid could be used as adjuvant treatments for acne patients. PMID:24553997

  5. Effects of tanshinone on hyperandrogenism and the quality of life in women with polycystic ovary syndrome: protocol of a double-blind, placebo-controlled, randomised trial

    PubMed Central

    Shen, Wenjuan; Zhang, Yuehui; Li, Wei; Cong, Jing; Zhou, Ying; Ng, Ernest H Y; Wu, Xiaoke

    2013-01-01

    Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Chinese herbal medicine has been used for the treatment of PCOS, but the evidence for its efficacy and safety is minimal. Tanshinones are a class of bioactive molecules isolated from Salvia miltiorrhiza, a commonly used herb in Traditional Chinese Medicine. This study aims to evaluate the efficacy of tanshinones on hyperandrogenism and quality of life in women with PCOS who do not attempt to conceive. Methods and analysis A total of 100 patients will be recruited and randomised into the tanshinone or placebo group. Tanshinone or placebo capsules will be taken orally for 12 weeks. The primary outcome parameter will be a change in plasma testosterone. Secondary end points will be changes in human chorionic gonadotropin-induced androgen response, insulin resistance, reproductive hormones, fasting lipid profiles, oral glucose tolerance test, quality of life and side effects. Ethics and dissemination Written informed consent will be obtained from each participant at the time of enrolling in the study. The trial has been approved by the Ethics Committee of First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Results will be disseminated through a publicly accessible website. Registration details The study has been registered at the Chinese Clinical Trials Registry (ChiCTR-TRC-12002973) and at clinicaltrials.gov (NCT 01452477). PMID:24163207

  6. Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial.

    PubMed

    Reid, Marie; Hammersley, Richard; Duffy, Maresa; Ballantyne, Carrie

    2014-02-01

    To investigate whether obese women can compensate for sucrose added to the diet when it is given blind, rather than gaining weight or exhibiting dysfunctional regulation of intake, in the present study, forty-one healthy obese (BMI 30-35 kg/m²) women (age 20-50 years), not currently dieting, were randomly assigned to consume sucrose (n 20) or aspartame (n 21) drinks over 4 weeks in a parallel single-blind design. Over the 4 weeks, one group consumed 4 × 250 ml sucrose drinks (total 1800 kJ/d) and the other group consumed 4 × 250 ml aspartame drinks. During the baseline week and experimental weeks, body weight and other biometric data were measured and steps per day, food intake using 7 d unweighed food diaries, and mood using ten- or seven-point Likert scales four times a day were recorded. At the end of the experiment, the participants weighed 1·72 (SE 0·47) kg less than the value predicted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) model; the predicted body weight accounted for 94·3% of the variance in the observed body weight and experimental group accounted for a further 1·1% of the variance in the observed body weight, showing that women consuming sucrose drinks gained significantly less weight than predicted. The reported daily energy intake did not increase significantly, and sucrose supplements significantly reduced the reported voluntary sugar, starch and fat intake compared with aspartame. There were no effects on appetite or mood. Over 4 weeks, as part of everyday eating, sucrose given blind in soft drinks was partially compensated for by obese women, as in previous experiments with healthy and overweight participants. PMID:24164779

  7. N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design

    PubMed Central

    Fante, Claudia Del; Perotti, Cesare; Pavesi, Claudio Francesco; Coscia, Davide; Scotti, Valeria; Tinelli, Carmine

    2011-01-01

    Objective To investigate the use of a novel study design in analysis of bilateral elbow pain. Design N of 1, two contemporary arm, open label, randomised controlled clinical trial. Setting A clinical epidemiologist at a university hospital in Pavia, Italy. Participants Two elbows with epicondylitis. Interventions Autologous platelet lysate versus “wait and see” strategy. Main outcome measures Visual analogue scale for pain on elbow extension and resisted wrist extension. Results Over six months’ follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points). Conclusions Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs. PMID:22187187

  8. Short Term Recovery of Function following Total Knee Arthroplasty: A Randomised Study of the Medial Parapatellar and Midvastus Approaches

    PubMed Central

    Nutton, Richard W.; Wade, Frazer A.; Coutts, Fiona J.; van der Linden, Marietta L.

    2014-01-01

    This pilot double blind randomised controlled study aimed to investigate whether the midvastus (MV) approach without patellar eversion in total knee arthroplasty (TKA) resulted in improved recovery of function compared to the medial parapatellar (MP) approach. Patients were randomly allocated to either the MV approach or the MP approach. Achievements of inpatient mobility milestones were recorded. Knee kinematics, muscle strength, Timed Up and Go, WOMAC, and daily step count were assessed before and up to six months after surgery. Cohen's effect size d was calculated to inform the sample size in future trials. Twenty-eight participants (16 males, 12 females) participated. Patient mobility milestones such as straight leg raise were achieved on average 1.3 days (95% CI −3.4 to 0.7, d = 0.63) earlier in the MV group. Knee extensor strength at 6 weeks after surgery was higher (95% CI −0.38 to 0.61, d = 0.73) in the MV group. No trends for differences between the groups were observed in knee kinematics, TUG, WOMAC, or step count. Our results suggest a short term advantage in the first 6 weeks after surgery of the MV approach over the MP approach, but a larger study is required to confirm these findings. This trial is registered with NCT056445. PMID:25349736

  9. Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

    PubMed

    Schilling, J; Mueller, R S

    2012-07-28

    Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs. PMID:22678620

  10. A randomised controlled single-blind trial of the effects of Reiki and positive imagery on well-being and salivary cortisol.

    PubMed

    Bowden, Deborah; Goddard, Lorna; Gruzelier, John

    2010-01-15

    The study investigated whether participants who received Reiki would show greater health and well-being benefits than a group who received no Reiki. A method of blinding participants to Reiki was also tested, where non-contact Reiki or No-Reiki with random assignment was given to 35 healthy psychology undergraduates whose attention was absorbed in one of three tasks involving self-hypnosis/relaxation. Participants experienced ten 20-min intervention sessions over a period of two and a half to 12 weeks. Reiki was directed by the experimenter who sat behind the participants as they were absorbed in the tasks. Self-report measures of illness symptoms, mood and sleep were assessed pre-post-intervention as was salivary cortisol. While the Reiki group had a tendency towards a reduction in illness symptoms, a substantive increase was seen in the No-Reiki. The Reiki group also had a near-significant comparative reduction in stress, although they also had significantly higher baseline illness symptoms and stress scores. The Reiki blinding was successful - the groups did not differ statistically in their beliefs regarding group membership. The results are suggestive that the Reiki buffered the substantive decline in health in the course of the academic year seen in the No-Reiki group. PMID:19819311

  11. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial

    PubMed Central

    Brown, Morris J; Williams, Bryan; Morant, Steve V; Webb, David J; Caulfield, Mark J; Cruickshank, J Kennedy; Ford, Ian; McInnes, Gordon; Sever, Peter; Salsbury, Jackie; Mackenzie, Isla S; Padmanabhan, Sandosh; MacDonald, Thomas M

    2016-01-01

    Summary Background Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control. Methods We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18–80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete. Findings Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to

  12. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial

    PubMed Central

    Williams, Bryan; MacDonald, Thomas M; Morant, Steve; Webb, David J; Sever, Peter; McInnes, Gordon; Ford, Ian; Cruickshank, J Kennedy; Caulfield, Mark J; Salsbury, Jackie; Mackenzie, Isla; Padmanabhan, Sandosh; Brown, Morris J

    2015-01-01

    Summary Background Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure. Methods In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18–79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or ≥135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25–50 mg), bisoprolol (5–10 mg), doxazosin modified release (4–8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number, NCT02369081. Findings Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients

  13. Effectiveness of a multifactorial intervention on preventing development of frailty in pre-frail older people: study protocol for a randomised controlled trial

    PubMed Central

    Fairhall, Nicola; Kurrle, Susan E; Sherrington, Catherine; Lord, Stephen R; Lockwood, Keri; John, Beatrice; Monaghan, Noeline; Howard, Kirsten; Cameron, Ian D

    2015-01-01

    Introduction Frailty is a major concern due to its costly and widespread consequences, yet evidence of effective interventions to delay or reduce frailty is lacking. Our previous study found that a multifactorial intervention was feasible and effective in reducing frailty in older people who were already frail. Identifying and treating people in the pre-frail state may be an effective means to prevent or delay frailty. This study describes a randomised controlled trial that aims to evaluate the effectiveness of a multifactorial intervention on development of frailty in older people who are pre-frail. Methods and analysis A single centre randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. Two hundred and thirty people aged above 70 who meet the Cardiovascular Health Study frailty criteria for pre-frailty, reside in the community and are without severe cognitive impairment will be recruited. Participants will be randomised to receive a multifactorial intervention or usual care. The intervention group will receive a 12-month interdisciplinary intervention targeting identified characteristics of frailty and problems identified during geriatric assessment. Participants will be followed for a 12-month period. Primary outcome measures will be degree of frailty measured by the number of Cardiovascular Health Study frailty criteria present, and mobility measured with the Short Physical Performance Battery. Secondary outcomes will include measures of mobility, mood and use of health and community services. Ethics and dissemination The study was approved by the Northern Sydney Local Health District Health Research Ethics Committee (1207-213M). The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12613000043730. PMID:25667151

  14. Meige syndrome: double-blind crossover study of sodium valproate.

    PubMed Central

    Snoek, J W; van Weerden, T W; Teelken, A W; van den Burg, W; Lakke, J P

    1987-01-01

    A double-blind crossover study of sodium valproate and placebo was conducted in five patients with Meige syndrome. CSF neurotransmitter studies were performed at the end of each treatment period. GABA levels were not influenced by the administration of sodium valproate. An increase in HVA levels was observed in every patient, which may reflect an increase in central dopaminergic activity. This finding may explain the trend towards clinical deterioration which was observed during treatment with sodium valproate. Sodium valproate appears to be ineffective in Meige syndrome. PMID:3121795

  15. Effect of chocolate in migraine: a double-blind study

    PubMed Central

    Moffett, A. M.; Swash, M.; Scott, D. F.

    1974-01-01

    The effect of chocolate on a group of volunteer migrainous subjects, who had observed that headache regularly occurred after the ingestion of small amounts of cocoa products, was investigated. Two separate studies were carried out in a double-blind placebo controlled manner. Only 13 headaches occurred to chocolate alone in 80 subject sessions, and only two subjects responded consistently to chocolate in the two studies. This suggests that chocolate on its own is rarely a precipitant of migraine. Other possible implications of the results are also discussed. PMID:4838915

  16. How big should the pilot study for my cluster randomised trial be?

    PubMed

    Eldridge, Sandra M; Costelloe, Ceire E; Kahan, Brennan C; Lancaster, Gillian A; Kerry, Sally M

    2016-06-01

    There is currently a lot of interest in pilot studies conducted in preparation for randomised controlled trials. This paper focuses on sample size requirements for external pilot studies for cluster randomised trials. We consider how large an external pilot study needs to be to assess key parameters for input to the main trial sample size calculation when the primary outcome is continuous, and to estimate rates, for example recruitment rates, with reasonable precision. We used simulation to provide the distribution of the expected number of clusters for the main trial under different assumptions about the natural cluster size, intra-cluster correlation, eventual cluster size in the main trial, and various decisions made at the piloting stage. We chose intra-cluster correlation values and pilot study size to reflect those commonly reported in the literature. Our results show that estimates of sample size required for the main trial are likely to be biased downwards and very imprecise unless the pilot study includes large numbers of clusters and individual participants. We conclude that pilot studies will usually be too small to estimate parameters required for estimating a sample size for a main cluster randomised trial (e.g. the intra-cluster correlation coefficient) with sufficient precision and too small to provide reliable estimates of rates for process measures such as recruitment or follow-up rates. PMID:26071431

  17. Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol

    PubMed Central

    Coutsoudis, Anna; Daniels, Brodie; Moodley-Govender, Eshia; Ngomane, Noluthando; Zako, Linda; Spooner, Elizabeth; Kiepiela, Photini; Reddy, Shabashini; Kuhn, Louise; Ramjee, Gita

    2016-01-01

    Introduction No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study. Methods A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity. Ethics and dissemination The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13). Trial registration numbers PACTR201311000621110 and DOH-27-0614-4728; Pre-results. PMID:27406638

  18. Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)

    PubMed Central

    Adrion, Christine; Fischer, Carolin Simone; Wagner, Judith; Gürkov, Robert; Mansmann, Ulrich

    2016-01-01

    Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of

  19. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study

    PubMed Central

    Tyring, S.; Engst, R.; Corriveau, C.; Robillard, N.; Trottier, S.; Van Slycken, S.; Crann, R.; Locke, L.; Saltzman, R.; Palestine, A.

    2001-01-01

    AIMS—To compare the efficacy and safety of famciclovir with aciclovir for the treatment of ophthalmic zoster.
METHODS—Randomised, double masked, aciclovir controlled, parallel group in 87 centres worldwide including 454 patients with ophthalmic zoster of trigeminal nerve (V1) comprised the intent to treat population. Oral famciclovir 500 mg three times daily or oral aciclovir 800 mg five times daily for 7 days. Assessments included day 0 (screening), days 3 and 7 (during treatment), days 10, 14, 21, 28 and monthly thereafter, up to 6 months (follow up). Proportion of patients who experienced ocular manifestations, severe manifestations and non-severe manifestations; loss of visual acuity was the main outcome measure.
RESULTS—The percentage of patients who experienced one or more ocular manifestations was similar for famciclovir (142/245, 58.0%) and aciclovir (114/196, 58.2%) recipients, with no significant difference between groups (OR 0.99; 95% CI 0.68, 1.45). The percentage of patients who experienced severe and non-severe manifestations was similar between groups, with no significant difference. The prevalence of individual ocular manifestations was comparable between groups. There was no significant difference between groups for visual acuity loss.
CONCLUSION—Famciclovir 500 mg three times daily was well tolerated and demonstrated efficacy similar to aciclovir 800 mg five times daily.

 PMID:11316720

  20. Thermoregulatory effects of swaddling in Mongolia: a randomised controlled study

    PubMed Central

    Tsogt, Bazarragchaa; Manaseki-Holland, Semira; Pollock, Jon; Blair, Peter S; Fleming, Peter

    2016-01-01

    Objective To investigate thermal balance of infants in a Mongolian winter, and compare the effects of traditional swaddling with an infant sleeping-bag in apartments or traditional tents (Gers). Design A substudy within a randomised controlled trial. Setting Community in Ulaanbaatar, Mongolia. Subjects A stratified randomly selected sample of 40 swaddled and 40 non-swaddled infants recruited within 48 h of birth. Intervention Sleeping-bags and baby outfits of total thermal resistance equivalent to that of swaddled babies. Outcome measure Digital recordings of infants’ core, peripheral, environmental and microenvironmental temperatures at 30-s intervals over 24 h at ages 1 month and 3 months. Results In Gers, indoor temperatures varied greatly (<0–>25°C), but remained between 20°C and 22°C, in apartments. Despite this, heavy wrapping, bed sharing and partial head covering, infant core and peripheral temperatures were similar and no infants showed evidence of significant heat or cold stress whether they were swaddled or in sleeping-bags. At 3 months, infants in sleeping-bags showed the ‘mature’ diurnal pattern of a fall in core temperature after sleep onset, accompanied by a rise in peripheral temperature, with a reverse pattern later in the night, just before awakening. This pattern was not related to room temperature, and was absent in the swaddled infants, suggesting that the mature diurnal pattern may develop later in them. Conclusions No evidence of cold stress was found. Swaddling had no identifiable thermal advantages over sleeping-bags during the coldest times, and in centrally heated apartments could contribute to the risk of overheating during the daytime. Trial registration number ISRTN01992617. PMID:26515228

  1. Weight gain during a double-blind multidosage clozapine study.

    PubMed

    de Leon, Jose; Diaz, Francisco J; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2007-02-01

    Possible variables associated with weight gain during clozapine treatment include dosing, treatment duration, baseline body mass index (BMI), sex, and plasma norclozapine concentrations. Weight gains during a double-blind, randomized clozapine study using 100-, 300-, and 600-mg/d doses were analyzed. It was hypothesized that weight gain was associated with baseline BMI, clozapine dosing, and demographic factors. The possible contribution of plasma clozapine and norclozapine concentrations was explored. Fifty treatment-refractory schizophrenia patients were randomized to 100-, 300-, or 600-mg/d doses of clozapine for a 16-week, double-blind treatment in a research ward. Nonresponsive patients went onto a second and/or a third 16-week, double-blind treatment at the other doses. Weights of patients were measured every week. During the first clozapine treatment, weight gain varied across 3 baseline BMI categories (normal-weight patients [4.1 kg, P < 0.001], overweight patients [2.6 kg, P = 0.05], and obese patients [0.36 kg, not significant]) and according to dosing (600 mg/d [4.4 kg], 300 mg/d [2.6 kg], and 100 mg/d [1.3 kg]). Sex had no effect after controlling for baseline BMI and dose, but the African-American race had a strong significant effect despite the small number of African Americans (n = 6). At the end of the first clozapine treatment, plasma norclozapine concentration was not significantly correlated with weight gain in the total sample (r = 0.16, P = 0.32, n = 43), but seems to be strongly correlated in nonsmokers. Despite its limitations, this study indicates that baseline BMI, dosing, and, possibly, the African-American race may be major determinants of clozapine-induced weight gain. PMID:17224708

  2. Treatment of irritable bowel syndrome: a review of randomised controlled trials

    PubMed Central

    AKEHURST, R; KALTENTHALER, E

    2001-01-01

    Irritable bowel syndrome (IBS) is a common chronic disorder that is associated with significant disability and health care costs. The purpose of this paper is to review and assess published randomised controlled trials examining the clinical effectiveness of interventions for IBS for 1987-1998. A literature search was conducted to identify randomised controlled trials of IBS treatments: 45 studies were identified that described randomised controlled trials and of these, six fulfilled all three criteria used to assess the quality of randomised controlled trials, as described by Jadad and colleagues.1 These criteria are: adequate description of randomisation, double blinding, and description of withdrawals and dropouts. It is concluded that there are few studies which offer convincing evidence of effectiveness in treating the IBS symptom complex. This review strongly suggests that future work should include well designed trials that: describe the randomisation method; use internationally approved diagnostic criteria; and are double blinded and placebo controlled. Clear well defined outcome measures are necessary. Inclusion of quality of life measures allows comparison between trials in different therapeutic areas. Conducting such studies will help to overcome some of the difficulties identified in this review.

 PMID:11156653

  3. Consumption of a calcium and vitamin D-fortified food product does not affect iron status during initial military training: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Hennigar, Stephen R; Gaffney-Stomberg, Erin; Lutz, Laura J; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

    2016-02-28

    Ca/vitamin D supplementation maintains bone health and decreases stress fracture risk during initial military training (IMT); however, there is evidence that Ca may negatively affect the absorption of other critical micronutrients, particularly Fe. The objective of this randomised, double-blind, placebo-controlled trial was to determine whether providing 2000 mg/d Ca and 25 µg/d vitamin D in a fortified food product during 9 weeks of military training affects Fe status in young adults. Male (n 98) and female (n 54) volunteers enrolled in US Army basic combat training (BCT) were randomised to receive a snack bar with Ca/vitamin D (n 75) or placebo (snack bar without Ca/vitamin D; n 77) and were instructed to consume 2 snack bars/d between meals throughout the training course. Circulating ionised Ca was higher (P0·05) in markers of Fe status between placebo and Ca/vitamin D groups. Collectively, these data indicate that Ca/vitamin D supplementation through the use of a fortified food product consumed between meals does not affect Fe status during IMT. PMID:26625709

  4. A randomised controlled pilot study of standardised counselling and cost-free pharmacotherapy for smoking cessation among stroke and TIA patients.

    PubMed

    Papadakis, Sophia; Aitken, Debbie; Gocan, Sophia; Riley, Dana; Laplante, Mary Ann; Bhatnagar-Bost, Abha; Cousineau, Donna; Simpson, Danielle; Edjoc, Rojiemiahd; Pipe, Andrew L; Sharma, Mukul; Reid, Robert D

    2011-01-01

    Background Tobacco use is a major risk factor for recurrent stroke. The provision of cost-free quit smoking medications has been shown to be efficacious in increasing smoking abstinence in the general population. Objective The objective of this pilot study was to assess the feasibility and obtain preliminary data on the effectiveness of providing cost-free quit smoking pharmacotherapy and counselling to smokers identified in a stroke prevention clinic. Trial design Cluster randomised controlled trial. Methods All patients seen at the Ottawa Hospital Stroke Prevention Clinic who smoked more five or more cigarettes per day, were ready to quit smoking in the next 30 days, and were willing to use pharmacotherapy were invited to participate in the study. All participants were advised to quit smoking and treated using a standardised protocol including counselling and pharmacotherapy. Participants were randomly assigned to either a prescription only usual care group or an experimental group who received a 4-week supply of cost-free quit smoking medications and a prescription for medication renewal. All patients received follow-up counselling. The primary outcome was biochemically validated quit rates at 26 weeks. The research coordinator conducting outcome assessment was blind to group allocation. Results Of 219 smokers screened, 73 were eligible, 28 consented and were randomised, and 25 completed the 26-week follow-up assessment. All 28 patients randomised were included in the analysis. The biochemically validated 7-day point prevalence abstinence rate in the experimental group compared to the usual care group was 26.6% vs 15.4% (adjusted OR 2.00, 95% CI 0.33 to 13.26; p=0.20). Conclusions It would be feasible to definitively evaluate this intervention in a large multi-site trial. Trial registration number http://ClinicalTrials.gov # UOHI2010-1. PMID:22123923

  5. Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention

    PubMed Central

    Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John

    2016-01-01

    Introduction Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. Methods and analysis 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethics and dissemination Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. Trial registration number ChiCTR-IOR-15006971. PMID:27334883

  6. The effect of MELatOnin on Depression, anxietY, cognitive function and sleep disturbances in patients with breast cancer. The MELODY trial: protocol for a randomised, placebo-controlled, double-blinded trial

    PubMed Central

    Madsen, Michael Tvilling; Hageman, Ida; Rasmussen, Lars Simon; Bokmand, Susanne; Rosenberg, Jacob; Gögenur, Ismail

    2012-01-01

    Introduction Breast cancer represents about one-third of all cancer diagnoses and accounts for about 15% of cancer deaths in women. Many of these patients experience depression, anxiety, sleep disturbances and cognitive dysfunction. This may adversely affect quality of life and also contribute to morbidity and mortality. Melatonin is a regulatory circadian hormone having, among others, a hypnotic and an antidepressive effect. It has very low toxicity and very few adverse effects compared with the more commonly used antidepressants and hypnotics. Methods and analysis The objective of this double-blind, randomised, placebo-controlled trial is to investigate whether treatment with oral melatonin has a prophylactic or ameliorating effect on depressive symptoms, anxiety, sleep disturbances and cognitive dysfunction in women with breast cancer. Furthermore, the authors will examine whether a specific clock-gene, PER3, is correlated with an increased risk of depressive symptoms, sleep disturbances or cognitive dysfunction. The MELODY trial is a prospective double-blinded, randomised, placebo-controlled trial in which the authors intend to include 260 patients. The primary outcome is depressive symptoms measured by the Major Depression Inventory. The secondary outcomes are anxiety measured by a Visual Analogue Scale, total sleep time, sleep efficiency, sleep latency and periods awake measured by actigraphy and changes in cognitive function measured by a neuropsychological test battery. Tertiary outcomes are fatigue, pain, well-being and sleep quality/quantity measured by Visual Analogue Scale and sleep diary and sleepiness measured by the Karolinska Sleepiness Scale. The PER3 genotype is also to be determined in blood samples. PMID:22240653

  7. Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial

    PubMed Central

    Tuñón, José; González-Hernández, Ignacio; Llanos-Jiménez, Lucía; Alonso-Martín, Joaquín; Escudier-Villa, Juan M; Tarín, Nieves; Cristóbal, Carmen; Sanz, Petra; Pello, Ana M; Aceña, Álvaro; Carda, Rocío; Orejas, Miguel; Tomás, Marta; Beltrán, Paula; Calero Rueda, Marta; Marcos, Esther; Serrano-Antolín, José María; Gutiérrez-Landaluce, Carlos; Jiménez, Rosa; Cabezudo, Jorge; Curcio, Alejandro; Peces-Barba, Germán; González-Parra, Emilio; Muñoz-Siscart, Raquel; González-Casaus, María Luisa; Lorenzo, Antonio; Huelmos, Ana; Goicolea, Javier; Ibáñez, Borja; Hernández, Gonzalo; Alonso-Pulpón, Luis M; Farré, Jerónimo; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Egido, Jesús

    2016-01-01

    Introduction Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. Methods and analysis The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. Primary objective: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). Secondary objectives: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. Ethics and dissemination This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of

  8. Topical Olive Oil Is Not Inferior to Hyperoxygenated Fatty Aids to Prevent Pressure Ulcers in High-Risk Immobilised Patients in Home Care. Results of a Multicentre Randomised Triple-Blind Controlled Non-Inferiority Trial

    PubMed Central

    2015-01-01

    Pressure ulcers represent a major current health problem and produce an important economic impact on the healthcare system. Most of studies to prevent pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids and to date, no studies have specifically examined the use of olive oil-based substances. Methods and Design Main objective: To assess the effectiveness of the use of olive oil, comparing it with hyperoxygenated fatty acids, for immobilised home-care patients at risk of suffering pressure ulcers. Design: Non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Scope: Population attending Primary Healthcare Centres in Andalusia (Spain). Sample: 831 immobilised patients at risk of suffering pressure ulcers. Results The follow-up period was 16 weeks. Groups were similar after randomization. In the per protocol analysis, none of the body areas evaluated presented risk differences for pressure ulcers incidence that exceeded the 10% delta value established. Sacrum: Olive Oil 8 (2.55%) vs HOFA 8 (3.08%), ARR 0.53 (-2.2 to 3.26) Right heel: Olive Oil 4 (1.27%) vs HOFA 5 (1.92)%, ARR0.65 (-1.43 to 2.73). Left heel: Olive Oil 3 (0.96%) vs HOFA 3 (1.15%), ARR0.2 (-1.49 to 1.88). Right trochanter: Olive Oil 0 (0%) vs HOFA 4 (1.54%), ARR1.54 (0.04 to 3.03). Left trochanter: Olive Oil 1 (0.32%) vs HOFA 1 (0.38%), ARR0.07 (-0.91 to 1.04). In the intention to treat analysis the lower limit of the established confidence interval was never exceeded. Discussion The results obtained confirmed that the use of topical extra-virgin olive oil to prevent PU in the home environment, for immobilised patients at high risk, is not inferior to the use of HOFA. Further studies are needed to investigate the mechanism by which olive oil achieves this outcome. Trial Registration Clinicaltrials.gov NCT01595347 PMID:25886152

  9. RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

    PubMed Central

    Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

    2015-01-01

    Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants

  10. Complementary therapies for labour and birth study: a randomised controlled trial of antenatal integrative medicine for pain management in labour

    PubMed Central

    Levett, Kate M; Smith, C A; Bensoussan, A; Dahlen, H G

    2016-01-01

    Objective To evaluate the effect of an antenatal integrative medicine education programme in addition to usual care for nulliparous women on intrapartum epidural use. Design Open-label, assessor blind, randomised controlled trial. Setting 2 public hospitals in Sydney, Australia. Population 176 nulliparous women with low-risk pregnancies, attending hospital-based antenatal clinics. Methods and intervention The Complementary Therapies for Labour and Birth protocol, based on the She Births and acupressure for labour and birth courses, incorporated 6 evidence-based complementary medicine techniques: acupressure, visualisation and relaxation, breathing, massage, yoga techniques, and facilitated partner support. Randomisation occurred at 24–36 weeks’ gestation, and participants attended a 2-day antenatal education programme plus standard care, or standard care alone. Main outcome measures Rate of analgesic epidural use. Secondary: onset of labour, augmentation, mode of birth, newborn outcomes. Results There was a significant difference in epidural use between the 2 groups: study group (23.9%) standard care (68.7%; risk ratio (RR) 0.37 (95% CI 0.25 to 0.55), p≤0.001). The study group participants reported a reduced rate of augmentation (RR=0.54 (95% CI 0.38 to 0.77), p<0.0001); caesarean section (RR=0.52 (95% CI 0.31 to 0.87), p=0.017); length of second stage (mean difference=−0.32 (95% CI −0.64 to 0.002), p=0.05); any perineal trauma (0.88 (95% CI 0.78 to 0.98), p=0.02) and resuscitation of the newborn (RR=0.47 (95% CI 0.25 to 0.87), p≤0.015). There were no statistically significant differences found in spontaneous onset of labour, pethidine use, rate of postpartum haemorrhage, major perineal trauma (third and fourth degree tears/episiotomy), or admission to special care nursery/neonatal intensive care unit (p=0.25). Conclusions The Complementary Therapies for Labour and Birth study protocol significantly reduced epidural use and caesarean section. This

  11. Change Blindness in Information Visualization: a Case Study

    SciTech Connect

    Nowell, Lucy T.; Hetzler, Elizabeth G.; Tanasse, Ted E.

    2001-08-20

    Change blindness occurs when people do not notice changes in visible elements of a scene. In using an information visualization system to compare document collection subsets partitioned by their time-stamps, change blindness makes it impossible for users to recognize even very major changes, let alone minor ones. We describe theories from cognitive science that account for the change blindness phenomenon, as well as solutions developed for two visual analysis tools, the SPIRE Galaxies visualization and the SPIRE ThemeView?.

  12. Protocol for a double-blind randomised controlled trial of low dose intradermal grass pollen immunotherapy versus a histamine control on symptoms and medication use in adults with seasonal allergic rhinitis (PollenLITE)

    PubMed Central

    2013-01-01

    Background Subcutaneous immunotherapy with high dose grass pollen (typically microgram quantities) was first described over 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. We previously reported that repeated 2-weekly intradermal injections of grass pollen - containing approximately 7 ng of major allergen Phl p 5 – led to a progressive suppression of the allergen-induced cutaneous response, and that by the sixth injection, this was inhibited by over 90%. The purpose of this trial is to investigate the clinical efficacy of intradermal desensitisation with low doses (i.e. nanogram quantities) of grass pollen allergen for seasonal allergic rhinitis. Methods/design The Pollen Low dose Intradermal therapy Evaluation (PollenLITE) is a single centre double-blind randomised parallel group controlled trial of the efficacy and safety of intradermal grass pollen injections plus standard treatment, versus histamine injections plus standard treatment, in adults with moderate-severe grass pollen-induced allergic rhinitis (‘summer hay fever’). A minimum of ninety adults with a history of moderate-severe persistent allergic rhinitis during the UK grass pollen season will be randomised into two equal groups to receive 7 or 8 intradermal injections of grass pollen extract (containing approximately 7 ng of major allergen Phl p 5) or histamine, before the grass pollen season. In the summer, participants will score their symptoms, medication requirements, visual analogue scores, and complete EuroQOL (EQ-5D-5 L) and mini Rhinoconjunctivitis Quality of Life Questionnaires. Global assessments will also be recorded at the end of the pollen season. Blood samples will be collected from all participants for mechanistic immune assays. Skin punch biopsies will also be collected in 40 participants selected at random from intradermal injection sites after the grass pollen season for mechanistic assays. Finally

  13. A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial

    PubMed Central

    Ypma, Paula F; van der Meer, Pieter F; Heddle, Nancy M; van Hilten, Joost A; Stijnen, Theo; Middelburg, Rutger A; Hervig, Tor; van der Bom, Johanna G; Brand, Anneke; Kerkhoffs, Jean-Louis H

    2016-01-01

    Introduction Patients with chemotherapy-induced thrombocytopaenia frequently experience minor and sometimes severe bleeding complications. Unrestrictive availability of safe and effective blood products is presumed by treating physicians as well as patients. Pathogen reduction technology potentially offers the opportunity to enhance safety by reducing bacterial and viral contamination of platelet products along with a potential reduction of alloimmunisation in patients receiving multiple platelet transfusions. Methods and analysis To test efficacy, a randomised, single-blinded, multicentre controlled trial was designed to evaluate clinical non-inferiority of pathogen-reduced platelet concentrates treated by the Mirasol system, compared with standard plasma-stored platelet concentrates using the percentage of patients with WHO grade ≥2 bleeding complications as the primary endpoint. The upper limit of the 95% CI of the non-inferiority margin was chosen to be a ≤12.5% increase in this percentage. Bleeding symptoms are actively monitored on a daily basis. The adjudication of the bleeding grade is performed by 3 adjudicators, blinded to the platelet product randomisation as well as by an automated computer algorithm. Interim analyses evaluating bleeding complications as well as serious adverse events are performed after each batch of 60 patients. The study started in 2010 and patients will be enrolled up to a maximum of 618 patients, depending on the results of consecutive interim analyses. A flexible stopping rule was designed allowing stopping for non-inferiority or futility. Besides analysing effects of pathogen reduction on clinical efficacy, the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) is designed to answer several other pending questions and translational issues related to bleeding and alloimmunisation, formulated as secondary and tertiary endpoints. Ethics and dissemination Ethics approval was obtained in all 3

  14. Change Blindness in Information Visualization: A Case Study

    SciTech Connect

    Nowell, Lucille T.; Hetzler, Elizabeth G.; Tanasse, Theodore E.

    2001-08-20

    AbstractChange blindness occurs when people do not notice changes in visible elements of a scene. If people use an infor-mation visualization system to compare document collec-tion subsets partitioned by their time-stamps, change blind-ness makes it impossible for them to recognize even very major changes, let alone minor ones. We describe theories from cognitive science that account for the change blindness phenomenon, as well as solutions de-veloped for two visual analysis tools, a dot plot (SPIRE Galaxies) and landscape (ThemeView?) visualizations.

  15. Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study.

    PubMed Central

    Gulliford, T.; Opomu, M.; Wilson, E.; Hanham, I.; Epstein, R.

    1997-01-01

    OBJECTIVE: To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography. DESIGN: Randomisation to conventional schedule of clinic visits or to visits only after mammography. Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms. SETTING: Combined breast clinic, Chelsea and Westminster Hospital. SUBJECTS: 211 eligible outpatients with a history of breast cancer. MAIN OUTCOME MEASURES: Acceptability of randomisation, interim use of telephone and general practitioner, satisfaction with allocation to follow up. RESULTS: Of 211 eligible patients, 196 (93%) opted for randomisation in the study. Of these, 55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not participate were more likely to be under 50 years, to be two to five years after diagnosis, and to have had aggressive primary disease. Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up. No increased use of local practitioner services or telephone triage was apparent in the cohort randomised to less frequent follow up by specialists. CONCLUSIONS: Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at standard risk in this cohort. A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes. PMID:9022429

  16. One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial

    PubMed Central

    Mol, G C; van de Ree, M A; Klok, F A; Tegelberg, M J A M; Sanders, F B M; Koppen, S; de Weerdt, O; Koster, T; Hovens, M M C; Kaasjager, H A H; Brouwer, R E; Kragten, E; Schaar, C G; Spiering, W; Arnold, W P; Biesma, D H

    2016-01-01

    Objective To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. Design Multicentre single blind non-inferiority randomised controlled trial. Setting Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. Participants Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. Interventions Continuation or cessation of ECS 12 months after deep venous thrombosis. Main outcome measures The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). Results 518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. Conclusion Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non

  17. Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation

    PubMed Central

    2013-01-01

    Background Electronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study. Methods/design Design: Parallel group, 3-arm, randomised controlled trial. Participants: People aged ≥18 years resident in Auckland, New Zealand (NZ) who want to quit smoking. Intervention: Stratified blocked randomisation to allocate participants to either Elusion™ e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. Participants randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline. Primary outcome: Biochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day. Sample size: 657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarett