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Sample records for blind randomised study

  1. 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

  2. Early laryngeal outcome of prolonged intubation using an anatomical tube: a double blind, randomised study.

    PubMed

    Nordang, Leif; Lindholm, Carl-Eric; Larsson, Jan; Linder, Arne

    2016-03-01

    The objective of this study was to study the short-term impact on larynx by a newly designed anatomical tube. A prospective randomised trial of a newly designed anatomical tube versus a standard endotracheal tube in patients operated under general anaesthesia for at least 12 h. Seventy adults were included and randomised to either type of tube. The patients were evaluated by means of fibre-optic laryngoscopy and VAS-rating of symptoms on two occasions in the first post-operative week. The evaluating investigators and the patients were blinded to the type of tube used. 27 cases and 23 controls had complete data for evaluation. Age, gender and intubation times were comparable. Symptoms such as hoarseness, coughing, and pain were rated above 30 % of maximum during at least one of the first post-operative days by 21 and 19 patients, respectively. At the first examination (within 24 h), 38 % of patients in the anatomical tube group stated no hoarseness; compared to 13 % of the controls (p = 0.057). Fibre-optic laryngoscopy showed some kind of pathology in all the patients examined within 24 h of extubation. After 3-6 days, seven patients with the anatomical tube and four patients in the control group showed complete resolution of the lesions, and the changes were limited to redness in the vocal process area in another seven and four, respectively. The differences between the groups did not attain statistical significance. The study shows considerable short-term laryngeal morbidity after prolonged intubation, and the anatomical tube only showed an advantage concerning hoarseness. Further improvement of the endotracheal tubes and intubation routines are still needed.

  3. 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

  4. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study.

    PubMed

    Rice, A S; Maton, S

    2001-11-01

    A multicentre double blind, randomised, placebo controlled 7-week study evaluated the efficacy and safety of gabapentin 1800 or 2400 mg/day in treating postherpetic neuralgia. Three hundred and thirty-four men and women aged at least 18 years (mean 73) received gabapentin 1800 or 2400 mg daily or placebo in three divided doses with a forced titration schedule. The primary outcome measure was change in average daily pain diary score (baseline week v final week). Secondary outcomes included mean weekly sleep interference score; Short Form-McGill Pain Questionnaire (SF-MPQ); Clinician and Patient Global Impression of Change (CGIC/PGIC); Short Form-36 Health Survey (SF-36). From week 1, pain scores showed a significantly greater improvement with gabapentin: the final difference v baseline was -34.5% for the 1800 mg dose, -34.4% for the 2400 mg dose compared with -15.7% for the placebo group. The difference vs. placebo was 18.8% for the 1800 mg dose (95% confidence interval 10.9-26.8%; P<0.01) and 18.7% for the 2400 mg dose (10.7-26.7%; P<0.01). Sleep interference diaries showed a similar pattern. There were significant differences in favour of gabapentin for number of patients reporting >50% reduction in their pain intensity, in the CGIC and PGIC, in the sensory and total scores of the SF-MPQ (both doses), in the visual analogue scale of pain of the SF-MPQ (2400 mg only) and in the vitality, bodily pain and mental health domains of the SF-36. Overall gabapentin was well tolerated. The most common adverse events were dizziness and somnolence, particularly during the titration phase. Thus, this study confirms the role of gabapentin as an efficacious and well-tolerated treatment for postherpetic neuralgia.

  5. 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

  6. Probiotics and respiratory and gastrointestinal tract infections in Finnish military conscripts - a randomised placebo-controlled double-blinded study.

    PubMed

    Kalima, K; Lehtoranta, L; He, L; Pitkäniemi, J; Lundell, R; Julkunen, I; Roivainen, M; Närkiö, M; Mäkelä, M J; Siitonen, S; Korpela, R; Pitkäranta, A

    2016-09-01

    Military conscripts are susceptible to respiratory and gastrointestinal tract infections. In previous studies probiotics have shown potency to reduce upper respiratory and gastrointestinal infections. The aim was to study whether probiotic intervention has an impact on seasonal occurrence of upper respiratory and gastrointestinal infections in two different conscript groups. In a randomised, double-blinded, placebo controlled study (https://clinicaltrials.gov NCT01651195), a total of 983 healthy adults were enrolled from two intakes of conscripts. Conscripts were randomised to receive either a probiotic combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis ssp. lactis BB12 (BB12) or a control chewing tablet twice daily for 150 days (recruits) or for 90 days (reserve officer candidates). Clinical examinations were carried out and daily symptom diaries were collected. Outcome measures were the number of days with respiratory and gastrointestinal symptoms and symptom incidence, number and duration of infection episodes, number of antibiotic treatments received and number of days out of service because of the infection. Statistically no significant differences were found between the intervention groups either in the risk of symptom incidence or duration. However, probiotic intervention was associated with reduction of specific respiratory infection symptoms in military recruits, but not in reserve officer candidates. Probiotics did not significantly reduce overall respiratory and gastrointestinal infection morbidity. PMID:27048835

  7. 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

  8. 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

  9. 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

  10. 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

  11. Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study

    PubMed Central

    Fox, Michael J; Ahuja, Kiran D K; Robertson, Iain K; Ball, Madeleine J; Eri, Rajaraman D

    2015-01-01

    Objective To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children. Design and setting This was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia. Participants and interventions Children (aged 1–12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment. Outcomes Stool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis. Results 72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥6, ≥3 stools/day for ≥2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p=0.025). There was also only one episode of minor diarrhoea (stool consistency ≥5, ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite and 1 had nausea). Conclusions A yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12609000281291

  12. 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

  13. 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

  14. Naturalistic conversation improves daytime motorway driving performance under a benzodiazepine: a randomised, crossover, double-blind, placebo-controlled study.

    PubMed

    Moták, Ladislav; Bayssac, Laëtitia; Taillard, Jacques; Sagaspe, Patricia; Huet, Nathalie; Terrier, Patrice; Philip, Pierre; Daurat, Agnès

    2014-06-01

    The adverse effects of benzodiazepines on driving are widely recognised. The aims of this study were both to determine the impact of naturalistic conversation on the driving ability of drivers under a benzodiazepine, and to measure the accuracy of drivers' assessments of the joint effects of the benzodiazepine and conversation. Sixteen healthy male participants (29.69 ± 3.30 years) underwent a randomised, crossover, double-blind, placebo-controlled study with the benzodiazepine lorazepam (2mg). They drove 200 km (125 miles) on a motorway in the morning. We measured two driving ability-related variables (i.e., lane-keeping performance), and collected a set of self-assessed variables (i.e., self-assessment of driving performance) during two 10-min sequences of interest (no conversation vs. conversation). An analysis of variance revealed an interaction whereby lane-keeping performance under lorazepam was worse in the no-conversation condition than in the conversation condition. No such difference was detected under placebo. Pearson's correlation coefficients revealed that self-assessments were (i) not at all predictive of lane-keeping when performed before the drive, but (ii) moderately predictive of lane-keeping performance when performed during or after the drive. We conclude that conversation with a passenger may contribute to safer lane-keeping when driving under a benzodiazepine. Moreover, a degree of awareness may be attained after some experience of driving under the influence of this type of medication. PMID:24631977

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. The Effect of Eplerenone on Adenosine Formation in Humans In Vivo: A Double-Blinded Randomised Controlled Study

    PubMed Central

    van den Berg, T. N. A.; Deinum, Jaap; Bilos, Albert; Donders, A. Rogier T.; Rongen, Gerard A.; Riksen, Niels P.

    2014-01-01

    Background It has been suggested that mineralocorticoid receptor antagonists have direct cardioprotective properties, because these drugs reduce mortality in patients with heart failure. In murine models of myocardial infarction, mineralocorticoid receptor antagonists reduce infarct size. Using gene deletion and pharmacological approaches, it has been shown that extracellular formation of the endogenous nucleoside adenosine is crucial for this protective effect. We now aim to translate this finding to humans, by investigating the effects of the selective mineralocorticoid receptor antagonist eplerenone on the vasodilator effect of the adenosine uptake inhibitor dipyridamole, which is a well-validated surrogate marker for extracellular adenosine formation. Methods and Results In a randomised, double-blinded, placebo-controlled, cross-over study we measured the forearm blood flow response to the intrabrachial administration of dipyridamole in 14 healthy male subjects before and after treatment with placebo or eplerenone (50 mg bid for 8 days). The forearm blood flow during administration of dipyridamole (10, 30 and 100 µg·min−1·dl−1) was 1.63 (0.60), 2.13 (1.51) and 2.71 (1.32) ml·dl−1·min−1 during placebo use, versus 2.00 (1.45), 2.68 (1.87) and 3.22 (1.94) ml·dl−1·min−1 during eplerenone treatment (median (interquartile range); P = 0.51). Concomitant administration of the adenosine receptor antagonist caffeine attenuated dipyridamole-induced vasodilation to a similar extent in both groups. The forearm blood flow response to forearm ischemia, as a stimulus for increased formation of adenosine, was similar during both conditions. Conclusion In a dosage of 50 mg bid, eplerenone does not augment extracellular adenosine formation in healthy human subjects. Therefore, it is unlikely that an increased extracellular adenosine formation contributes to the cardioprotective effect of mineralocorticoid receptor antagonists. Trial Registration Clinical

  2. 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

  3. 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

  4. Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study.

    PubMed

    Montalescot, Gilles; Sideris, Georgios; Cohen, Remy; Meuleman, Catherine; Bal dit Sollier, Claire; Barthélémy, Olivier; Henry, Patrick; Lim, Pascal; Beygui, Farzin; Collet, Jean-Philippe; Marshall, Debra; Luo, Junxiang; Petitjean, Helene; Drouet, Ludovic

    2010-01-01

    Compared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 microM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

  5. 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

  6. Study protocol: Brief intervention for medication overuse headache - A double-blinded cluster randomised parallel controlled trial in primary care

    PubMed Central

    2012-01-01

    Background Chronic headache (headache ≥ 15 days/month for at least 3 months) affects 2–5% of the general population. Medication overuse contributes to the problem. Medication-overuse headache (MOH) can be identified by using the Severity of Dependence Scale (SDS). A “brief intervention” scheme (BI) has previously been used for detoxification from drug and alcohol overuse in other settings. Short, unstructured, individualised simple information may also be enough to detoxify a large portion of those with MOH. We have adapted the structured (BI) scheme to be used for MOH in primary care. Methods/Design A double-blinded cluster randomised parallel controlled trial (RCT) of BI vs. business as usual. Intervention will be performed in primary care by GPs trained in BI. Patients with MOH will be identified through a simple screening questionnaire sent to patients on the GPs lists. The BI method involves an approach for identifying patients with high likelihood of MOH using simple questions about headache frequency and the SDS score. Feedback is given to the individual patient on his/her score and consequences this might have regarding the individual risk of medication overuse contributing to their headache. Finally, advice is given regarding measures to be taken, how the patient should proceed and the possible gains for the patient. The participating patients complete a headache diary and receive a clinical interview and neurological examination by a GP experienced in headache diagnostics three months after the intervention. Primary outcomes are number of headache days and number of medication days per month at 3 months. Secondary outcomes include proportions with 25 and 50% improvement at 3 months and maintenance of improvement and quality of life after 12 months. Discussion There is a need for evidence-based and cost-effective strategies for treatment of MOH but so far no consensus has been reached regarding an optimal medication withdrawal method. To our

  7. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

    PubMed Central

    Coffey, Frank; Wright, John; Hartshorn, Stuart; Hunt, Paul; Locker, Thomas; Mirza, Kazim; Dissmann, Patrick

    2014-01-01

    Objective To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. Methods STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12–17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. Results A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of −18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. Conclusion The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. Trial registration number: NCT01420159. PMID:24743584

  8. Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

    PubMed Central

    2011-01-01

    Background Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk. Methods/Design The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner. Discussion It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities. Trial registration Current Controlled Trials ISRCTN02839188 PMID:22136261

  9. 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

  10. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype: a randomised, double-blind, and placebo-controlled, phenotype panel study.

    PubMed

    Demant, Dyveke T; Lund, Karen; Finnerup, Nanna B; Vollert, Jan; Maier, Christoph; Segerdahl, Märtha S; Jensen, Troels S; Sindrup, Søren H

    2015-11-01

    In neuropathic pain with irritable nociceptor (IN) phenotype, upregulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype panel, crossover study with 4-week treatment periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale, and the primary objective was to compare the effect of lidocaine in patients with and without IN phenotype as defined by hypersensitivity and preserved small-fibre function determined by quantitative sensory testing. Forty-six patients with neuropathic pain due to nerve injury or postherpetic neuralgia were randomised. The modified intention-to-treat population comprised 15 patients with irritable nociceptor and 25 patients with nonirritable nociceptor. In the total sample, lidocaine reduced pain by 0.3 numeric rating scale points (95% confidence interval [CI]: 0.1-0.5) and pain-related sleep disturbance by 0.6 points (95% CI: 0.4-0.8) more than placebo (P = 0.007 and P < 0.001) and relieved pain by 0.4 verbal score (-1-5) points more (P = 0.036). For these measures, there was no significant interaction between treatment and phenotype, but there was a significant interaction for pain paroxysms (0.8, 95% CI: 0.4-1.2, P < 0.001) and deep aching pain (0.6, 95% CI: 0.1-1.0, P = 0.013). In conclusion, lidocaine 5% patch had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with IN phenotype. The lack of significant phenotype differences may be caused by too low statistical power.

  11. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study.

    PubMed

    Demant, Dyveke T; Lund, Karen; Vollert, Jan; Maier, Christoph; Segerdahl, Märtha; Finnerup, Nanna B; Jensen, Troels S; Sindrup, Søren H

    2014-11-01

    In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype.

  12. 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

  13. 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

  14. Effect of intravenous GLutamine supplementation IN Trauma patients receiving enteral nutrition study protocol (GLINT Study): a prospective, blinded, randomised, placebo-controlled clinical trial

    PubMed Central

    Paratz, Jennifer D; Cohen, Jeremy; Banks, Merrilyn; Dulhunty, Joel; Roberts, Jason A; Lipman, Jeffrey

    2011-01-01

    Background Trauma patients are characterised by alterations in the immune system, increased exposure to infectious complications, sepsis and potentially organ failure and death. Glutamine supplementation to parenteral nutrition has been proven to be associated with improved clinical outcomes. However, glutamine supplementation in patients receiving enteral nutrition and its best route are still controversial. Previous trials have been limited by a small sample size, use of surrogate outcomes or a limited period of supplementation. The aim of this trial is to investigate if intravenous glutamine supplementation to trauma patients receiving enteral nutrition is associated with improved clinical outcomes in terms of decreased organ dysfunction, infectious complications and other secondary outcomes. Methods/design Eighty-eight critically ill patients with multiple trauma receiving enteral nutrition will be recruited in this prospective, triple-blind, block-randomised, placebo-controlled clinical trial to receive either 0.5 g/kg/day intravenous undiluted alanyl-glutamine or intravenous placebo by continuous infusion (24 h/day). Both groups will be receiving the same standard enteral nutrition protocol and the same standard intensive care unit care. Supplementation will continue until discharge from the intensive care unit, death or a maximum duration of 3 weeks. The primary outcome will be organ-dysfunction evaluation assessed by the pattern of change in sequential organ failure assessment score over a 10-day period. The secondary outcomes are: the changes in total sequential organ failure assessment score on the last day of treatment, infectious complications during the ICU stay, 60-day mortality, length of stay in the intensive care unit and body-composition analysis. Discussion This study is the first trial to investigate the effect of intravenous alanyl-glutamine supplementation in multiple trauma patients receiving enteral nutrition on reducing severity of

  15. Effect of intravenous GLutamine supplementation IN Trauma patients receiving enteral nutrition study protocol (GLINT Study): a prospective, blinded, randomised, placebo-controlled clinical trial.

    PubMed

    Al Balushi, Ruqaiya M; Paratz, Jennifer D; Cohen, Jeremy; Banks, Merrilyn; Dulhunty, Joel; Roberts, Jason A; Lipman, Jeffrey

    2011-01-01

    Background Trauma patients are characterised by alterations in the immune system, increased exposure to infectious complications, sepsis and potentially organ failure and death. Glutamine supplementation to parenteral nutrition has been proven to be associated with improved clinical outcomes. However, glutamine supplementation in patients receiving enteral nutrition and its best route are still controversial. Previous trials have been limited by a small sample size, use of surrogate outcomes or a limited period of supplementation. The aim of this trial is to investigate if intravenous glutamine supplementation to trauma patients receiving enteral nutrition is associated with improved clinical outcomes in terms of decreased organ dysfunction, infectious complications and other secondary outcomes. Methods/design Eighty-eight critically ill patients with multiple trauma receiving enteral nutrition will be recruited in this prospective, triple-blind, block-randomised, placebo-controlled clinical trial to receive either 0.5 g/kg/day intravenous undiluted alanyl-glutamine or intravenous placebo by continuous infusion (24 h/day). Both groups will be receiving the same standard enteral nutrition protocol and the same standard intensive care unit care. Supplementation will continue until discharge from the intensive care unit, death or a maximum duration of 3 weeks. The primary outcome will be organ-dysfunction evaluation assessed by the pattern of change in sequential organ failure assessment score over a 10-day period. The secondary outcomes are: the changes in total sequential organ failure assessment score on the last day of treatment, infectious complications during the ICU stay, 60-day mortality, length of stay in the intensive care unit and body-composition analysis. Discussion This study is the first trial to investigate the effect of intravenous alanyl-glutamine supplementation in multiple trauma patients receiving enteral nutrition on reducing severity of organ

  16. Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double-blind 1-year extension study

    PubMed Central

    Haak, T; Meinicke, T; Jones, R; Weber, S; von Eynatten, M; Woerle, H-J

    2013-01-01

    Objective To determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes. Methods This 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233). Results All three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, –1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, –1.32 ± 1.06%; metformin 1000 bid, –1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events. Discussion Initial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone. Conclusion The initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets. PMID:24118640

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Central corneal thickness changes in bevel-up versus bevel-down phacoemulsification cataract surgery: study protocol for a randomised, triple-blind, parallel group trial

    PubMed Central

    Kaup, Soujanya; KS, Divyalakshmi; Arunachalam, Cynthia; Varghese, Rejitha Chinnu

    2016-01-01

    Introduction Corneal endothelial damage following phacoemulsification is still one of the major concerns of modern day cataract surgery. Although many techniques have been proposed, the risks of posterior capsular rupture and corneal endothelium damage persist. In theory, damage to the corneal endothelium is minimised by delivering the lowest phaco energy only in the direction necessary to emulsify the lens nucleus. Hence, it is believed that the bevel of the needle should be turned towards the nucleus or the nuclear fragment (ie, bevel-down. However, there is a difference of opinion among ophthalmologists with reference to the phaco tip's position (bevel-up vs bevel-down) during phacoemulsification. This subject has not been extensively studied earlier. Methods and analysis This is a prospective, triple-blinded (trial participant, outcome assessor and the data analyst), randomised controlled trial with 2 parallel groups and with an allocation ratio of 1:1. It will be conducted in a tertiary care hospital, Mangaluru, India. The objective is to compare the postoperative central corneal thickness changes between the bevel-up and bevel-down techniques of phacoemulsification. Patients aged >18 years with immature cataract undergoing phacoemulsification will be selected for the study. The important exclusion criteria are the history of previous significant ocular trauma or intraocular surgery, corneal pathology, pseudoexfoliation syndrome, intraocular inflammation, a preoperative fully dilated pupil <6 mm, anterior chamber depth <2.5 mm and nuclear sclerosis grade >4. After randomisation, patients will undergo phacoemulsification surgery either by a bevel-up or bevel-down procedure. With an estimated power of 80%, the calculated sample size is 55 patients in each group. The recruitment will start from April 2016. Ethics and dissemination Yenepoya University Ethics Committee, India has approved the study protocol (YUEC/148/2016 on 18 February 2016). It complies

  8. Balanced versus chloride-rich solutions for fluid resuscitation in brain-injured patients: a randomised double-blind pilot study

    PubMed Central

    2013-01-01

    Introduction We sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury. Methods We conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours. Results Forty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387). Conclusions This study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint

  9. Addition of sub-anaesthetic dose of ketamine reduces gag reflex during propofol based sedation for upper gastrointestinal endoscopy: A prospective randomised double-blind study

    PubMed Central

    Tandon, Manish; Pandey, Vijay Kant; Dubey, Gaurav Kumar; Pandey, Chandra Kant; Wadhwa, Nitya

    2014-01-01

    Background and Aims: Gag reflex is unwanted during upper gastrointestinal endoscopy (UGIE). Experimental studies have demonstrated that N-methyl-D-aspartate receptor antagonism prevents gag reflex. We conducted a study to determine if sub-anaesthetic doses of ketamine, added to propofol, reduce the incidence of gag reflex. Methods: This prospective, randomised, double-blind and placebo-controlled study was done in a tertiary care hospital. A total of 270 patients undergoing UGIE, were randomised to propofol (P) group (n = 135) or propofol plus ketamine (PK) group (n = 135). All patients received propofol boluses titrated to Ramsay sedation score of not <4. Patients in PK group in addition received ketamine, 0.15 mg/kg immediately before the first-propofol dose. Top-up doses of propofol were given as required. Stata 11 software (StataCorp.) was used to calculate the proportion of patients with gag reflex and the corresponding relative risk. Propofol consumed and time to recovery in the two groups was compared using Student's t-test and Cox proportional hazards regression respectively. Results: Significantly, fewer patients in the PK group had gag reflex compared to the P group (3 vs. 23, risk ratio = 0.214, 95% confidence interval [CI], 0.07-0.62; P = 0.005). The incidence of hypotension (6 vs. 16, risk ratio = 0.519, 95% CI = 0.25-1.038; P = 0.06), number of required airway manoeuvres (4 vs. 19, risk ratio = 0.32, 95% CI = 0.13-0.74; P = 0.014), median time to recovery (4 min vs. 5 min, hazard ratio = 1.311, 95% CI = 1.029-1.671; P = 0.028) and propofol dose administered (152 mg vs. 167 mg, 95% CI = 4.74-24.55; P = 0.004) was also less in the PK group compared to the P group. Conclusion: Ketamine in sub-anaesthetic dose decreases gag reflex during UGIE. PMID:25197112

  10. 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

  11. Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study

    PubMed Central

    Hawkey, C J; Laine, L; Simon, T; Quan, H; Shingo, S; Evans, J

    2003-01-01

    Background: Previous studies in patients with osteoarthritis have suggested that the selective cyclooxygenase (COX)-2 inhibitor rofecoxib results in less gastrointestinal damage than non-selective non-steroidal antiinflammatory drugs (NSAIDs). This study compared the incidence of endoscopically detected gastroduodenal ulcers in rheumatoid arthritis patients treated with rofecoxib or a non-selective NSAID. Methods: In this multicentre, randomised, double blind, 12 week study, patients with rheumatoid arthritis were allocated to rofecoxib 50 mg once daily (n=219), naproxen 500 mg twice daily (n=220), or placebo (n=221). Endoscopy was performed at baseline and at six and 12 weeks. Lifetable analysis and log rank tests were used to analyse the incidence of gastroduodenal ulcers ≥3 mm. Gastric or duodenal ulcers ≥5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events. Results: The cumulative incidence of ulcers ≥3 mm at 12 weeks was significantly higher in patients on naproxen (25.5%) than in patients receiving rofecoxib (6.8%; difference 18.7% (95% confidence interval (CI) 11.7%, 25.7%); p<0.001) or placebo (2.9%; difference 22.6% (95% CI 16.1%, 29.1%); p<0.001). The difference between rofecoxib (6.8%) and placebo (2.9%) did not reach statistical significance (p=0.066). Results were similar for ulcers ≥5 mm and for mean changes from baseline in the number of gastroduodenal erosions. The overall incidence of clinical adverse events was similar among treatment groups (61% of patients on placebo, 62% in patients on rofecoxib, and 66% in patients on naproxen). Conclusions: Rofecoxib 50 mg daily (twice the dose recommended for this patient population) resulted in a lower incidence of endoscopically detected gastroduodenal ulcers and erosions than treatment with naproxen 500 mg twice daily. PMID:12740337

  12. Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

    PubMed Central

    2010-01-01

    Background It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. Methods/Design The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. Discussion This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion

  13. Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea.

    PubMed

    Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

    2011-01-01

    OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID:22095308

  14. A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

    PubMed Central

    Armstrong, D K; Maw, R D; Dinsmore, W W; Morrison, G D; Pattman, R S; Watson, P G; Nathan, P M; Moss, T; Nayagam, A; Wade, A

    1994-01-01

    OBJECTIVES--The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN--Randomised, double-blind parallel group study. SETTING--Multicentre study in six genitourinary clinics within the U.K. PATIENTS--One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES--Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS--At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS--At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events. PMID:7705855

  15. 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

  16. 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

  17. Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study

    PubMed Central

    Combe, B; Codreanu, C; Fiocco, U; Gaubitz, M; Geusens, P P; Kvien, T K; Pavelka, K; Sambrook, P N; Smolen, J S; Khandker, R; Singh, A; Wajdula, J; Fatenejad, S

    2009-01-01

    Objective: To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. Methods: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2–3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). Results: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n  =  103), etanercept plus sulfasalazine (n  =  101) and sulfasalazine (n  =  50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). Conclusion: Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine. PMID:18794178

  18. The analgesic effect of intrathecal dexmedetomidine or clonidine, with bupivacaine, in trauma patients undergoing lower limb surgery: a randomised, double-blind study.

    PubMed

    Solanki, S L; Bharti, N; Batra, Y K; Jain, A; Kumar, P; Nikhar, S A

    2013-01-01

    This randomised, double-blind study was designed to compare the duration of analgesia and adverse effects following intrathecal administration of dexmedetomidine or clonidine, both with bupivacaine, in trauma patients. Ninety adult trauma patients of American Society of Anesthesiologists physical status I-II, scheduled for lower limb surgery under subarachnoid block, were randomly allocated to one of three groups. All groups received hyperbaric bupivacaine 0.5% 3 ml, to which was added saline 0.5 ml (Group B): clonidine 50 µg (Group C) or dexmedetomidine 5 µg (Group D). The onset and duration of sensory and motor blockade, severity of postoperative pain, time to first rescue analgesia and total analgesic requirement for 24 hours were noted. There was no significant difference in the onset time of the block but the duration of sensory and motor blockade was prolonged in Groups C and D, compared with Group B. The time to analgesia was significantly prolonged in Group D (824±244 minutes) compared with Group C (678±178 minutes; P=0.01), the latter being longer than Group B (406±119 minutes; P=0.0001). Postoperative pain scores were lower in Groups C and D compared with group b. The requirement for rescue analgesia during the first 24 postoperative hours was significantly less in Groups C and D as compared to Group B (P=0.0001), but comparable between Groups C and D (P=0.203). In conclusion, dexmedetomidine 5 µg added to intrathecal bupivacaine 15 mg produces longer postoperative analgesia than clonidine 50 µg among trauma patients undergoing lower limb surgery.

  19. 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

  20. 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

  1. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study.

    PubMed

    Reichelt, A; Förster, K K; Fischer, M; Rovati, L C; Setnikar, I

    1994-01-01

    Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of osteoarthritis. When orally given, it is more effective than placebo and at least as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis symptoms. The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group study was to assess the efficacy and safety of glucosamine sulfate intramuscularly given on the same parameters. 155 out-patients with knee osteoarthritis (Lequesne's criteria), radiological stage between I and III, Lequesne's severity index of at least 4 points and symptoms for at least 6 months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week baseline, at weekly intervals during treatment and 2 weeks after drug discontinuation. Responders to treatment were considered those patients with a reduction of at least 3 points in the Lequesne index, together with a positive overall judgement by the investigator. The Lequesne index was slightly over 10 points in average in both groups at the beginning of treatment. A significant decrease in the index was observed for glucosamine compared to placebo (3.3 vs. 2.0 points in average, respectively; p < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n = 69) with placebo (p = 0.012, Fisher's Exact Test). According to the intention-to-treat approach, considering also drop-outs, these proportions were 51% vs. 30% (p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8135881

  2. A randomised, single-blind technical study comparing the ultrasonic visibility of smooth-surfaced and textured needles in a soft embalmed cadaver model.

    PubMed

    Munirama, S; Joy, J; Columb, M; Habershaw, R; Eisma, R; Corner, G; Cochran, S; McLeod, G

    2015-05-01

    Visibility of the needle tip and shaft is important during ultrasound-guided regional anaesthesia in order to prevent nerve trauma. Tip and shaft visibility is reduced when needles are inserted in-plane at wide angles and out-of-plane at narrow angles to the ultrasound probe. Although textured needles are more reflective than smooth needles, we hypothesised that poor visibility of the tip and shaft still remained using the above angle-probe combinations. In a single-blind study, we compared the visibility of a textured Tuohy needle, a textured single-shot needle and a conventional smooth-surfaced Tuohy needle when inserted into the biceps and deltoid muscles of a soft embalmed cadaver. One hundred and forty-four needles were block-randomised to in-plane and out-of-plane insertions at 30°, 45°, 60° and 75° to the ultrasound beam. Two blinded raters assessed needle tip visibility on video recordings of the insertions using a binary scale (0 = not visible, 1 = visible) and shaft visibility using a 5-point Likert scale. The median (IQR [range]) proportions of visible needle tips were 83% (67-83 [50-100]%) for the textured Tuohy, 75% (67-83 [33-83]%) for the textured single-shot needle and 33% (33-46 [0-50]%) for the smooth-surfaced Tuohy (p = 0.0007). Median (IQR [range]) needle shaft visibility was rated as 4.0 (3.5-4.7 [3.0-4.9]) for the textured Tuohy, 4.0 (3.8-4.5 [2.7-4.9]) for the textured single-shot needle and 3.0 (2.4-3.3 [2.3-3.5]) for the smooth-surfaced Tuohy (p = 0.015). Nevertheless, visibility was reduced at wide angles in-plane and narrow angles out-of-plane both for needle tips (p = 0.004) and shafts (p = 0.005).

  3. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study

    PubMed Central

    Brightling, Christopher E; Bleecker, Eugene R; Panettieri, Reynold A; Bafadhel, Mona; She, Dewei; Ward, Christine K; Xu, Xiao; Birrell, Claire; van der Merwe, René

    2016-01-01

    Summary Background Chronic obstructive pulmonary disease (COPD) is associated with eosinophilic airway inflammation in 10–20% of patients. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, depletes blood and sputum eosinophils. We aimed to establish whether benralizumab reduces acute exacerbations of COPD in patients with eosinophilia and COPD. Methods We did this randomised, double-blind, placebo-controlled, phase 2a study between Nov 18, 2010, and July 13, 2013, at 26 sites in the UK, Poland, Germany, Canada, the USA, Denmark, and Spain. Adults aged 40–85 years, with moderate-to-severe COPD, at least one acute exacerbation of COPD, and a sputum eosinophil count of 3·0% or more within the previous year, were randomly assigned (1:1) via computer-generated permuted block randomisation (block size of four), with an interactive voice or web-response system, to receive placebo or 100 mg benralizumab subcutaneously, every 4 weeks (three doses), then every 8 weeks (five doses) over 48 weeks. Study site personnel included in study assessments, participants, and data analysts, were masked to treatment allocation. The primary endpoint was the annualised rate of acute exacerbations of COPD at week 56, defined as the number of acute exacerbations divided by total duration of person-year follow-up. Secondary and exploratory endpoints included COPD-specific Saint George’s Respiratory Questionnaire (SGRQ-C), Chronic Respiratory Questionnaire self-administered standardised format (CRQ-SAS), pre-bronchodilator forced expiratory volume in 1 second (FEV1), and safety. We did a prespecified subgroup analysis by baseline blood eosinophil count. Analyses were by intention to treat and per-protocol. This trial is registered with ClinicalTrials.gov, number NCT01227278. Findings We randomly assigned 101 patients to receive placebo (n=50) or benralizumab (n=51), of whom 88 (87%) patients completed the study. Six patients who completed the study were excluded from

  4. 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

  5. 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

  6. 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

  7. The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block: a dose-finding randomised, controlled, double-blind study.

    PubMed

    Abdulatif, M; Fawzy, M; Nassar, H; Hasanin, A; Ollaek, M; Mohamed, H

    2016-10-01

    This randomised, controlled, double-blind study investigated the effects of different doses of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block in patients undergoing arthroscopic knee surgery. Ultrasound-guided femoral nerve block was performed before general anaesthesia using 25 ml of bupivacaine 0.5% combined with normal saline in the control group, and 25 μg, 50 μg or 75 μg of dexmedetomidine in three treatment groups (n = 15 for each group). All patients received a standard general anaesthetic and multimodal postoperative analgesic regimen. The use of the 50 μg and 75 μg dose levels of dexmedetomidine was associated with reduction of the onset time, extension of the duration of block, prolonged time to the first postoperative request for rescue analgesia, and reduced postoperative morphine requirements. The times to first request for postoperative analgesia were mean (SD) 10.8 (1.6) h in the control group and 11.0 (7.1), 21.8 (3.0) and 28.6 (10.0) in the 25 μg, 50 μg and 75 μg treatment groups, respectively. These times were significantly longer in the 50 μg and 75 μg treatment groups compared with the 25 μg (p < 0.0001) and control group (p < 0.0001). The total 24-h postoperative morphine consumption was 7.6 (5.1) mg in the control group, and 6.5 (3.5), 3.9 (3.4), 1.8 (2.6) in the 25 μg, 50 μg and 75 μg treatment groups, respectively. Postoperative morphine consumption was significantly higher in the control group compared with the 50 μg (p = 0.045) and the 75 μg (p = 0.001) treatment groups. The best analgesic profile was achieved at the 75 μg dose, but this was associated with increased risk of hypotension. PMID:27611039

  8. (In)Consistencies in Responses to Sodium Bicarbonate Supplementation: A Randomised, Repeated Measures, Counterbalanced and Double-Blind Study

    PubMed Central

    Froio de Araujo Dias, Gabriela; da Eira Silva, Vinicius; de Salles Painelli, Vitor; Sale, Craig; Giannini Artioli, Guilherme; Gualano, Bruno; Saunders, Bryan

    2015-01-01

    Objectives Intervention studies do not account for high within-individual variation potentially compromising the magnitude of an effect. Repeat administration of a treatment allows quantification of individual responses and determination of the consistency of responses. We determined the consistency of metabolic and exercise responses following repeated administration of sodium bicarbonate (SB). Design and Methods 15 physically active males (age 25±4 y; body mass 76.0±7.3 kg; height 1.77±0.05 m) completed six cycling capacity tests at 110% of maximum power output (CCT110%) following ingestion of either 0.3 g∙kg-1BM of SB (4 trials) or placebo (PL, 2 trials). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, post-exercise and 5-min post-exercise. Total work done (TWD) was recorded as the exercise outcome. Results SB supplementation increased blood pH, bicarbonate and base excess prior to every trial (all p ≤ 0.001); absolute changes in pH, bicarbonate and base excess from baseline to pre-exercise were similar in all SB trials (all p > 0.05). Blood lactate was elevated following exercise in all trials (p ≤ 0.001), and was higher in some, but not all, SB trials compared to PL. TWD was not significantly improved with SB vs. PL in any trial (SB1: +3.6%; SB2 +0.3%; SB3: +2.1%; SB4: +6.7%; all p > 0.05), although magnitude-based inferences suggested a 93% likely improvement in SB4. Individual analysis showed ten participants improved in at least one SB trial above the normal variation of the test although five improved in none. Conclusions The mechanism for improved exercise with SB was consistently in place prior to exercise, although this only resulted in a likely improvement in one trial. SB does not consistently improve high intensity cycling capacity, with results suggesting that caution should be taken when interpreting the results from single trials as to the efficacy of SB supplementation. Trial Registration

  9. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol

    PubMed Central

    Perez-Ruiz, Fernando; Sundy, John S; Miner, Jeffrey N; Cravets, Matthew; Storgard, Chris

    2016-01-01

    Objectives To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol. Methods Patients (N=227) with an inadequate response to allopurinol, defined as serum urate (sUA) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol, were randomised 2:1 to 4 weeks of double-blind treatment with lesinurad (200, 400 or 600 mg/day) or matching placebo in combination with their prestudy allopurinol dose (200–600 mg/day). Colchicine prophylaxis for gout flares was required. The primary end point was percent reduction from baseline sUA levels at 4 weeks. A pharmacokinetic substudy was also conducted. Safety was assessed throughout. Results Patients (n=208) received ≥1 dose of blinded medication. Lesinurad 200, 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with placebo (p<0.0001, all doses vs placebo). Similar results were observed in patients with mild or moderate renal insufficiency (estimated creatinine clearance 30 to <90 mL/min). The incidence of ≥1 treatment-emergent adverse event was 46%, 48% and 54% with lesinurad 200, 400 and 600 mg, respectively, and 46% with placebo (most frequent, gout flares, arthralgia, headache and nasopharyngitis), with no deaths or serious adverse events. Conclusions Lesinurad achieves clinically relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone. Trial registration number NCT01001338. PMID:26742777

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

    PubMed

    Bramhall, S R; Schulz, J; Nemunaitis, J; Brown, P D; Baillet, M; Buckels, J A C

    2002-07-15

    Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified. PMID

  16. 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.

  17. Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

    PubMed Central

    Gyr, K; Meier, R; Häussler, J; Boulétreau, P; Fleig, W E; Gatta, A; Holstege, A; Pomier-Layrargues, G; Schalm, S W; Groeneweg, M; Scollo-Lavizzari, G; Ventura, E; Zeneroli, M L; Williams, R; Yoo, Y; Amrein, R

    1996-01-01

    BACKGROUND: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE. AIMS: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease. PATIENTS: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study. METHODS: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement). RESULTS: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated. CONCLUSIONS: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil. PMID:8977350

  18. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study

    PubMed Central

    Kurdi, Madhuri S; Muthukalai, Sindhu Priya

    2016-01-01

    Background and Aims: Melatonin (MT), a naturally occurring pituitary hormone has a sleep promoting effect. There are very few studies on pre-operative oral MT (0.2–0.5 mg/kg) in children. We planned a study to assess the efficacy of oral MT in two doses and compare it with oral midazolam and placebo for pre-operative anxiolysis, sedation, maintenance of cognition and psychomotor skills, parental separation behaviour and venepuncture compliance. Methods: This prospective double-blind randomised study was conducted after ethical committee approval on 100 children aged 5–15 years, American Society of Anaesthesiologists physical status I and II undergoing elective surgery at our hospital from January 1, 2014, to December 31, 2014. Mentally disordered children were excluded from the study. They were randomised into four groups of 25 each (A, B, C, D) to receive either oral MT 0.5 mg/kg or 0.75 mg/kg or oral midazolam 0.5 mg/kg or placebo 45–60 min, respectively, before induction. The child's anxiety, cognition and psychomotor function before and after pre-medication, behaviour during the parental separation and venepuncture were appropriately scored. Kruskal–Wallis analysis of variance for intergroup and Wilcoxon matched pairs tests for intragroup comparisons of data were applied. Results: The four groups were comparable regarding mean age, weight and sex. The anxiety score reductions in the three groups when compared to placebo were statistically significant. Children receiving MT 0.75 mg/kg had maximum anxiolysis and venepuncture compliance (P < 0.05). Cognition was decreased with maximum sedation, successful parental separation and psychomotor impairment in the midazolam group (P < 0.05). Conclusion: Oral MT (0.5 mg/kg and 0.75 mg/kg) in children decreases pre-operative anxiety without impairing cognitive and psychomotor functions, the 0.75 mg/kg dose being most effective. PMID:27761038

  19. Early intervention with tiotropium in Chinese patients with GOLD stages I–II chronic obstructive pulmonary disease (Tie-COPD): study protocol for a multicentre, double-blinded, randomised, controlled trial

    PubMed Central

    Li, Xiaochen; Zhou, Yumin; Chen, Shuyun; Zheng, Jinping; Zhong, Nanshan; Ran, Pixin

    2014-01-01

    Introduction Owing to the high and increasing morbidity and mortality, chronic obstructive pulmonary disease (COPD) has become a major public health problem worldwide. Although the majority of patients with COPD are in the early stages, little attention has been paid to them, in particular regarding to early intervention. Tiotropium bromide can significantly relieve symptoms and reduce the incidence of acute exacerbations of COPD. Therefore, we hypothesise that therapy with tiotropium bromide will benefit patients with COPD with early-stage disease. Method/analysis A randomised, double-blinded, placebo-controlled, parallel-group, multicentre clinical trial (Tiotropium In Early COPD study, Tie-COPD study) is being conducted to evaluate the efficacy and safety of long-term intervention with tiotropium in patients with COPD with early-stage disease. A total of 839 patients with COPD who satisfied the eligibility criteria were randomly assigned (1:1) to receive a once daily inhaled capsule of either tiotropium bromide (18 μg) or matching placebo for 2 years. Measurements will include forced expiratory volume in 1 s, health-related quality of life, grade degree of breathlessness related to activities, COPD exacerbations and pharmacoeconomic analysis. Ethics/dissemination This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. Recruitment started in November 2011 and ended in October 2013, with 839 patients randomised. The treatment follow-up of participants with Tie-COPD is currently ongoing and is due to finish in November 2015. The authors will disseminate the findings in peer-reviewed publications, conferences and seminar presentations. Trial registration ClinicalTrials.gov (NCT01455129). PMID:24549160

  20. 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

  1. 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

  2. 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

  3. 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

  4. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping of blood pressure during night time: protocol for a randomised, placebo-controlled, double-blind, two-way crossover study

    PubMed Central

    Hjortkær, Henrik; Jensen, Tonny; Kofoed, Klaus; Mogensen, Ulrik; Køber, Lars; Hilsted, Karen Lisa; Corinth, Helle; Theilade, Simone; Hilsted, Jannik

    2014-01-01

    Introduction Cardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been demonstrated. The present protocol describes a trial to test the efficacy of bedtime dosing of the ACE inhibitor enalapril on night time blood pressure and left ventricular mass in patients with type 1 diabetes. Materials and methods In a randomised, double-blind, two-way cross-over study, 24 normoalbuminuric patients with type 1 diabetes with CAN will be treated for 12 weeks with either morning or bedtime dosing of 20 mg enalapril, followed by 12 weeks of switched treatment regimen. During each treatment period, two 24 h ambulatory blood pressure measurements will be performed and after each treatment period left ventricular mass will be determined by multisliced CT. Primary end points will be reduction in blood pressure and reduction in left ventricular mass. 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 Hospital) 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 number EudraCT (2012- 002136-90). PMID:25293387

  5. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    PubMed

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. PMID:23702393

  6. The study protocol of a blinded randomised-controlled cross-over trial of lavender oil as a treatment of behavioural symptoms in dementia

    PubMed Central

    2010-01-01

    Background The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Increasingly more attention is being paid to alternative interventions that are associated with fewer risks than pharmacology. Lavandula angustifolia (lavender) has been thought, for centuries, to have soothing properties, but the existing evidence is limited and shows mixed results. The aim of the current study is to test the effectiveness of topically applied pure lavender oil in reducing actual counts of challenging behaviours in nursing home residents. Methods/Design We will use a blinded repeated measures design with random cross-over between lavender oil and placebo oil. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to lavender or placebo blocks for one week then switched to the other condition for the following week. In each week the oils will be applied on three days with at least a two-day wash out period between conditions. Trained observers will note presence of target behaviours and predominant type of affect displayed during the 30 minutes before and the 60 minutes after application of the oil. Nursing staff will apply 1 ml of 30% high strength essential lavender oil to reduce the risk of missing a true effect through under-dosing. The placebo will comprise of jojoba oil only. The oils will be identical in appearance and texture, but can easily be identified by smell. For blinding purposes, all staff involved in applying the oil or observing the resident will apply a masking cream containing a mixture of lavender and other essential oils to their upper lip. In addition, nursing staff will wear a nose clip during the few minutes it takes to massage the oil to the resident's forearms. Discussion If our results show

  7. A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol.

    PubMed

    Young, Paul Jeffrey; Dalley, Paul; Garden, Alexander; Horrocks, Christopher; La Flamme, Anne; Mahon, Barry; Miller, John; Pilcher, Janine; Weatherall, Mark; Williams, Jenni; Young, William; Beasley, Richard

    2012-05-01

    The efficacy of remote ischemic preconditioning (RIPC) in high-risk cardiac surgery is uncertain. In this study, 96 adults undergoing high-risk cardiac surgery were randomised to RIPC (3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or control. Main endpoints were plasma high-sensitivity troponin T (hsTNT) levels at 6 and 12 h, worst post-operative acute kidney injury (AKI) based on RIFLE criteria, and noradrenaline duration. hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [810 ng/ml (IQR 527-1,724) vs. 634 ng/ml (429-1,012); ratio of means 1.41 (99.17% CI 0.92-2.17); P=0.04] and 12 h [742 ng/ml (IQR 427-1,700) vs. 514 ng/ml (IQR 356-833); ratio of means 1.56 (99.17% CI 0.97-2.53); P=0.01]. After adjustment for baseline confounders, the ratio of means of hsTNT at 6 h was 1.23 (99.17% CI 0.88-1.72; P=0.10) and at 12 h was 1.30 (99.17% CI 0.92-1.84; P=0.05). In the RIPC group, 35/48 (72.9%) had no AKI, 5/48 (10.4%) had AKI risk, and 8/48 (16.7%) had either renal injury or failure compared to the control group where 34/48 (70.8%) had no AKI, 7/48 (14.6%) had AKI risk, and 7/48 (14.6%) had renal injury or failure (Chi-squared 0.41; two degrees of freedom; P = 0.82). RIPC increased post-operative duration of noradrenaline support [21 h (IQR 7-45) vs. 9 h (IQR 3-19); ratio of means 1.70 (99.17% CI 0.86-3.34); P=0.04]. RIPC does not reduce hsTNT, AKI, or ICU-support requirements in high-risk cardiac surgery.

  8. Multivitamin and dietary supplements, body weight and appetite: results from a cross-sectional and a randomised double-blind placebo-controlled study.

    PubMed

    Major, Geneviève C; Doucet, Eric; Jacqmain, Mélanie; St-Onge, Myriam; Bouchard, Claude; Tremblay, Angelo

    2008-05-01

    Two studies were conducted to compare characteristics of consumers and non-consumers of vitamin and/or dietary supplements (study 1) and to assess the effect of a multivitamin and mineral supplementation during a weight-reducing programme (study 2). Body weight and composition, energy expenditure, and Three-Factor Eating Questionnaire scores were compared between consumers and non-consumers of micronutrients and/or dietary supplements in the Québec Family Study (study 1). In study 2, these variables and appetite ratings (visual analogue scales) were measured in forty-five obese non-consumers of supplements randomly assigned to a double-blind 15-week energy restriction ( - 2930 kJ/d) combined with a placebo or with a multivitamin and mineral supplement. Compared with non-consumers, male consumers of vitamin and/or dietary supplements had a lower body weight (P < 0.01), fat mass (P < 0.05), BMI (P < 0.05), and a tendency for greater resting energy expenditure (P = 0.06). In women, the same differences were observed but not to a statistically significant extent. In addition, female supplements consumers had lower disinhibition and hunger scores (P < 0.05). In study 2, body weight was significantly decreased after the weight-loss intervention (P < 0.001) with no difference between treatment groups. However, fasting and postprandial appetite ratings were significantly reduced in multivitamin and mineral-supplemented women (P < 0.05). Usual vitamin and/or dietary supplements consumption and multivitamin and mineral supplementation during a weight-reducing programme seems to have an appetite-related effect in women. However, lower body weight and fat were more detectable in male than in female vitamin and/or dietary supplements consumers.

  9. 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.

  10. Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

    PubMed

    Rao, Amanda; Steels, Elizabeth; Inder, Warrick J; Abraham, Suzanne; Vitetta, Luis

    2016-06-01

    This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men. PMID:26791805

  11. Albuminuria induced by exercise in hypertensive type I and type II diabetic patients: a randomised, double-blind study on the effects of acute administration of captopril and nifedipine.

    PubMed

    Romanelli, G; Giustina, A; Cravarezza, P; Caldonazzo, A; Agabiti-Rosei, E; Giustina, G

    1991-06-01

    Physical exercise can increase urinary albumin excretion rate (UAER) in diabetic patients without microalbuminuria at rest (stage II diabetic nephropathy) or with baseline microalbuminuria (stage III diabetic nephropathy). The aim of this study was to compare the acute effects of captopril, an ACE inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in hypertensive insulin-dependent (Type I) and non-insulin-dependent (Type II) diabetic patients with early stage nephropathy. Non-obese diabetic patients, 13 Type I (7 with stage II and 6 with stage III nephropathy) and 14 Type II (6 with stage II and 8 with stage III nephropathy), with hypertension, WHO stages I-II, underwent five submaximal cycloergometric tests: the first two in basal conditions, the other three after 24 hour administration of captopril (25 mg twice daily), placebo (1 tab twice daily) or nifedipine AR (20 mg twice daily) according to a randomised, double-blind design. Acute administration of both captopril and nifedipine was able to reduce exercise-induced microalbuminuria in hypertensive Type I and Type II diabetic patients regardless of the stage of their nephropathy. Captopril reduced systolic blood pressure less than nifedipine, in both Type I and Type II diabetics, but was more effective than nifedipine in blunting exercise-induced microalbuminuria, especially in Type I diabetics.

  12. 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

  13. 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.

  14. A pilot study to evaluate the effect of Taeumjowi-tang on obesity in Korean adults: study protocol for a randomised, double-blind, placebo-controlled, multicentre trial

    PubMed Central

    2012-01-01

    Background Obesity, which is described as excessive or abnormal body fat, increases the risk of diet-related diseases. In Korea and around the world, the prevalence of obesity has grown annually from 1998 to 2008. This growth has continued despite various therapeutic efforts. The discovery of new and alternative treatments for obesity should be considered an important priority. Taeumjowi-tang (TJ001), a traditional Korean medicinal extract consisting of eight herbs, is a widely used herbal remedy for obesity in Korea. However, the efficacy and safety of TJ001 have not been fully investigated in a clinical trial. The purpose of this pilot study is to estimate obesity-related parameters and to assess the efficacy and safety of TJ001. Methods Our study is a randomised, double-blind, placebo-controlled, multicentre clinical trial of Taeumjowi-tang (TJ001). For this study, we will recruit obese Korean patients of both sexes, ages 18 to 65 years, from four university hospitals. A total of 104 subjects will be recruited. The participants will receive either 7 g of TJ001 or a placebo three times daily for 12 weeks. The primary end point will be the rate of subjects who lose at least 5% of their baseline body weight. The secondary end points will be changes in body weight, body mass index, waist circumference, hip circumference, waist/hip circumference ratio, lipid profiles, body fat composition, blood pressure, fasting glucose concentration, C-reactive protein and questionnaires related to the quality of life. The outcomes will be measured every 4 weeks. The study period will be 12 weeks and will include a total of five visits with each subject (at screening and at 0, 4, 8 and 12 weeks). Conclusions The results of our study will inform various estimates of TJ001 and will serve as the basis for a larger-scale trial. This study will assess the efficacy and safety of TJ001 as an alternative herbal remedy for obesity. Trial registration Current Controlled Trials ISRCTN87153759

  15. Influence of habitual dietary fibre intake on the responsiveness of the gut microbiota to a prebiotic: protocol for a randomised, double-blind, placebo-controlled, cross-over, single-centre study

    PubMed Central

    Healey, Genelle; Brough, Louise; Butts, Chrissie; Murphy, Rinki; Whelan, Kevin; Coad, Jane

    2016-01-01

    Introduction The commensal gut microbiota have been shown to have an impact on human health as aberrant gut microbiota have been linked to disease. Dietary constituents are influential in shaping the gut microbiota. Diet-specific therapeutic strategies may therefore play a role in optimising human health via beneficial manipulation of the gut microbiota. Research has suggested that an individual's baseline gut microbiota composition may influence how the gut microbiota respond to a dietary intervention and individuals with differing habitual dietary intakes appear to have distinct baseline gut microbiota compositions. The responsiveness of the gut microbiota may therefore be influenced by habitual dietary intakes. This study aims to investigate what influence differing habitual dietary fibre intakes have on the responsiveness of the gut microbiota to a prebiotic intervention. Methods and analysis In this randomised, double-blind, placebo-controlled, cross-over, single-centre study, 20 low dietary fibre (dietary fibre intake <18 g/day for females and <22 g/day for males) and 20 high dietary fibre (dietary fibre intake ≥25 g/day for females and ≥30 g/day for males) consumers will be recruited. Participants will be randomised to a placebo (Glucidex 29 Premium) or a prebiotic (Synergy 1) intervention for 3 weeks with a 3-week washout followed by 3 weeks of the alternative intervention. Outcome measures of gut microbiota composition (using 16S rRNA gene sequencing) and functional capacity (faecal short chain fatty acid concentrations and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) as well as appetite (visual analogue scale appetite questionnaire) will be assessed at the beginning and end of each intervention phase. Ethics and dissemination The Massey University Human Ethics Committee approved this study (Massey University HEC: Southern A application—15/34). Results will be disseminated through peer

  16. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

    PubMed Central

    Smolen, Josef S; Kay, Jonathan; Landewé, Robert B M; Matteson, Eric L; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T; Zhou, Yiying; Hsia, Elizabeth C; Doyle, Mittie K

    2012-01-01

    Objective The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Methods Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported. Results 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70–73% and 75–81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. Conclusion In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57–67% of patients who continued treatment. Golimumab

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

    PubMed Central

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

    2016-01-01

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

  18. How Does Anodal Transcranial Direct Current Stimulation of the Pain Neuromatrix Affect Brain Excitability and Pain Perception? A Randomised, Double-Blind, Sham-Control Study

    PubMed Central

    Vaseghi, Bita; Zoghi, Maryam; Jaberzadeh, Shapour

    2015-01-01

    Background Integration of information between multiple cortical regions of the pain neuromatrix is thought to underpin pain modulation. Although altered processing in the primary motor (M1) and sensory (S1) cortices is implicated in separate studies, the simultaneous changes in and the relationship between these regions are unknown yet. The primary aim was to assess the effects of anodal transcranial direct current stimulation (a-tDCS) over superficial regions of the pain neuromatrix on M1 and S1 excitability. The secondary aim was to investigate how M1 and S1 excitability changes affect sensory (STh) and pain thresholds (PTh). Methods Twelve healthy participants received 20 min a-tDCS under five different conditions including a-tDCS of M1, a-tDCS of S1, a-tDCS of DLPFC, sham a-tDCS, and no-tDCS. Excitability of dominant M1 and S1 were measured before, immediately, and 30 minutes after intervention respectively. Moreover, STh and PTh to peripheral electrical and mechanical stimulation were evaluated. All outcome measures were assessed at three time-points of measurement by a blind rater. Results A-tDCS of M1 and dorsolateral prefrontal cortex (DLPFC) significantly increased brain excitability in M1 (p < 0.05) for at least 30 min. Following application of a-tDCS over the S1, the amplitude of the N20-P25 component of SEPs increased immediately after the stimulation (p < 0.05), whilst M1 stimulation decreased it. Compared to baseline values, significant STh and PTh increase was observed after a-tDCS of all three stimulated areas. Except in M1 stimulation, there was significant PTh difference between a-tDCS and sham tDCS. Conclusion a-tDCS of M1 is the best spots to enhance brain excitability than a-tDCS of S1 and DLPFC. Surprisingly, a-tDCS of M1 and S1 has diverse effects on S1 and M1 excitability. A-tDCS of M1, S1, and DLPFC increased STh and PTh levels. Given the placebo effects of a-tDCS of M1 in pain perception, our results should be interpreted with caution

  19. 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

  20. 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.

  1. Fermented milk containing Bifidobacterium lactis DN-173 010 improves gastrointestinal well-being and digestive symptoms in women reporting minor digestive symptoms: a randomised, double-blind, parallel, controlled study.

    PubMed

    Guyonnet, Denis; Schlumberger, Armelle; Mhamdi, Leila; Jakob, Stefan; Chassany, Olivier

    2009-12-01

    The ability of probiotics to improve bowel habits or transit time has been shown in healthy populations. Additional data are required to support the use of specific probiotics to improve gastrointestinal (GI) well-being. The present study was designed to investigate the effect of consuming fermented milk (FM) on GI well-being, digestive symptoms and health-related quality of life (HRQoL) amongst women without diagnosed GI disorders. In this double-blind, controlled, parallel-design study, subjects were randomised to ingest daily either 2 x 125 g FM containing Bifidobacterium lactis DN-173 010 and yoghurt strains or a control non-fermented dairy product for 4 weeks followed by a 4-week wash-out period. GI well-being and digestive symptoms were assessed weekly. HRQoL was measured every 4 weeks. Data were analysed using analysis of covariance and logistic regression, correcting for baseline values on the full analysis set population of 197 women (aged 18-60 years). The percentage of women reporting an improvement in their GI well-being was significantly (P < 0.01) higher in the FM group v. the control group (OR 1.69; 95 % CI 1.17, 2.45). A significantly (P < 0.05) more pronounced decrease in the composite score of digestive symptoms was observed in the FM group when comparing with the control group (least squares mean - 0.57; 95 % CI - 1.12, - 0.02). Among HRQoL dimensions, the digestive comfort score was significantly (P < 0.05) improved in the FM group compared with the control group. The present study showed that the daily consumption of a specific FM is able to improve GI well-being and digestive symptoms in adult women without GI disorders. PMID:19622191

  2. 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

  3. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

    PubMed Central

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-01-01

    Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876

  4. 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

    2016-05-28

    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.

  5. 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

    2016-05-28

    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

  6. 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

  7. 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

  8. Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis

    PubMed Central

    Smieja, M; MacPherson, D; Kean, W; Schmuck, M; Goldsmith, C; Buchanan, W; Hart, L; Mahony, J

    2001-01-01

    OBJECTIVE—To determine whether long term doxycycline improves symptoms in patients with chronic seronegative or reactive arthritis.
METHODS—A randomised, triple blind, controlled clinical trial of three months' treatment with doxycycline or placebo of patients with chronic reactive or seronegative arthritis was conducted. The primary study end points were three month pain and functional status measured by a self administered Arthritis Impact Measurement Scales version 2 (AIMS2) quality of life questionnaire. Secondary end points were pain and functional status at 6-12 months, three month rheumatologist assessed joint count, pain, and arthritis activity, and treatment efficacy in those with previous exposure to chlamydia.
RESULTS—Of 60 patients randomly allocated to receive doxycycline or placebo, results from 37 were evaluable at three months. Groups were well balanced for major prognostic variables. Doxycycline had no detectable effect at three months on pain change scores (mean difference 1.5, 95% CI −1.2 to 4.2, p=0.25) or composite functional change scores (mean difference 0.8, 95% CI −5.6 to 7.1, p=0.81). Furthermore, there were no differences in secondary study end points, and no apparent treatment effect in patients with previous chlamydia infection.
CONCLUSION—Three months' treatment with doxycycline did not improve pain or functional status in patients with chronic reactive or seronegative arthritis.

 PMID:11709448

  9. Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

    PubMed Central

    Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

    2007-01-01

    Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

  10. 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

  11. A single blinded randomised controlled pilot trial of prism adaptation for improving self-care in stroke patients with neglect.

    PubMed

    Turton, Ailie J; O'Leary, Kelly; Gabb, Judith; Woodward, Rebecca; Gilchrist, Iain D

    2010-04-01

    Prism adaptation has been shown to alleviate the symptoms of unilateral spatial neglect following stroke in single case and small group studies. The purposes of this single blinded pilot randomised controlled trial were to determine the feasibility of delivering prism adaptation treatment in a clinically valid sample and to assess its impact on self-care. Thirty seven right hemisphere stroke patients with unilateral spatial neglect were randomised into either prism adaptation (using 10 dioptre, 6 degree prisms) or sham treatment (using plain glasses) groups. Treatment was delivered each weekday for two weeks. Pointing accuracy, without vision of the finger, was recorded each day before treatment. Outcome was measured, by blinded assessors, four days and eight weeks after the end of treatment using the Catherine Bergego Scale (CBS) and the conventional neuropsychological tests from the Behavioural Inattention Test (BIT). Thirty four patients received treatment: 16 with prisms, 18 sham. Mean compliance was 99% and 97%, respectively. Over the treatment days only the prism treated group showed increased leftward bias in open loop pointing to targets on a touch screen. However, despite the group level changes in pointing behaviour no overall effect of the treatment on self-care or BIT were found.

  12. Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery.

    PubMed

    Jenkins, C D; McDonnell, P J; Spalton, D J

    1990-12-01

    Comparatively little attention has been paid to the conjunctival toxicity of antibiotics administered at the time of cataract surgery. We have observed the effect of subconjunctival gentamicin and cefuroxime injection, using colour photography in a randomised single blind trial of 121 patients undergoing routine cataract surgery. Our results suggest that a hyperaemic eye is likely to occur about twice as often in patients injected with gentamicin (p less than 0.001). Gentamicin is associated with more pain postoperatively (p less than 0.05). Significant manifestations of gentamicin toxicity are conjunctival oedema and capillary closure. Cefuroxime has some theoretical advantages over gentamicin in its antibacterial spectrum.

  13. 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

  14. A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat

    PubMed Central

    2011-01-01

    Background Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. Methods In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. Results Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in

  15. Effectiveness of intravenous haemocoagulase on haemorrhage control in bi-maxillary orthognathic surgery-A prospective, randomised, controlled, double-blind study.

    PubMed

    Shetty, Vikram; Sriram S, Ganapathy

    2015-12-01

    Haemocoagulase is a snake venom protein derivative that is known to possess haemostatic activity. It is reported to minimise blood loss in orthopaedic, otorhinolaryngologic, and abdominal surgeries. The use of intravenous haemocoagulase in orthognathic surgery is unknown and not yet reported. The purpose of this trial is to study the efficacy of haemocoagulase in haemorrhage control in orthognathic surgery. Forty-six consecutive patients scheduled to undergo bi-maxillary orthognathic surgery within the time period of the study were recruited and randomized. They received either the study drug or placebo. All patients underwent operation with hypotensive anaesthesia. Intraoperative blood loss, operating time, drop in haemoglobin and haematocrit were the variables analysed in the study. Haemocoagulase caused an 11% (52 ml) reduction in blood loss in the study group (p = 0.01). There was no adverse reaction in any of the patients.

  16. 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.

  17. 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

  18. Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres.

    PubMed

    Blagden, M; Christian, J; Miller, K; Charlesworth, A

    2002-03-01

    The flurbiprofen 8.75 mg lozenge is a novel formulation that combines a demulcent effect with the analgesic activity of a non-steroidal anti-inflammatory drug. Previous controlled clinical studies have demonstrated the single- and multi-dose efficacy of these lozenges over placebo. The current study reflected the treatment of sore throat in general practice, investigating multiple dose efficacy where patients also had access to concomitant antibiotics and rescue medication. The efficacy of flurbiprofen 8.75 mg lozenge over placebo was confirmed: there was a significant difference in pain relief obtained from flurbiprofen 8.75 mg versus placebo, along with a significant reduction of difficulty in swallowing from the time of first assessment and significantly greater reductions in throat soreness and difficulty in swallowing throughout the study period. Additionally, significant benefit over placebo was demonstrated where concomitant antibiotic use was introduced, indicating that flurbiprofen 8.75 mg lozenges can be co-administered when antibiotic therapy is appropriate. No significant safety issues were identified. PMID:11926713

  19. Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres.

    PubMed

    Blagden, M; Christian, J; Miller, K; Charlesworth, A

    2002-03-01

    The flurbiprofen 8.75 mg lozenge is a novel formulation that combines a demulcent effect with the analgesic activity of a non-steroidal anti-inflammatory drug. Previous controlled clinical studies have demonstrated the single- and multi-dose efficacy of these lozenges over placebo. The current study reflected the treatment of sore throat in general practice, investigating multiple dose efficacy where patients also had access to concomitant antibiotics and rescue medication. The efficacy of flurbiprofen 8.75 mg lozenge over placebo was confirmed: there was a significant difference in pain relief obtained from flurbiprofen 8.75 mg versus placebo, along with a significant reduction of difficulty in swallowing from the time of first assessment and significantly greater reductions in throat soreness and difficulty in swallowing throughout the study period. Additionally, significant benefit over placebo was demonstrated where concomitant antibiotic use was introduced, indicating that flurbiprofen 8.75 mg lozenges can be co-administered when antibiotic therapy is appropriate. No significant safety issues were identified.

  20. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder.

    PubMed

    Woelk, H; Schläfke, S

    2010-02-01

    Generalized and persistent anxiety, accompanied by nervousness and other symptoms (Generalised Anxiety Disorder, GAD) is frequent in the general population and leads to benzodiazepine usage. Unfortunately, these substances induce sedation and have a high potential for drug abuse, and there is thus a need for alternatives. As the anxiolytic properties of lavender have already been demonstrated in pharmacological studies and small-scale clinical trials, it was postulated that lavender has a positive effect in GAD. A controlled clinical study was then performed to evaluate the efficacy of silexan, a new oral lavender oil capsule preparation, versus a benzodiazepine. In this study, the efficacy of a 6-week-intake of silexan compared to lorazepam was investigated in adults with GAD. The primary target variable was the change in the Hamilton Anxiety Rating Scale (HAM-A-total score) as an objective measurement of the severity of anxiety between baseline and week 6. The results suggest that silexan effectively ameliorates generalized anxiety comparable to a common benzodiazepine (lorazepam). The mean of the HAM-A-total score decreased clearly and to a similar extent in both groups (by 11.3+/-6.7 points (45%) in the silexan group and by 11.6+/-6.6 points (46%) in the lorazepam group, from 25+/-4 points at baseline in both groups). During the active treatment period, the two HAM-A subscores "somatic anxiety" (HAM-A subscore I) and "psychic anxiety" (HAM-A subscore II) also decreased clearly and to a similar extent in both groups. The changes in other subscores measured during the study, such as the SAS (Self-rating Anxiety Scale), PSWQ-PW (Penn State Worry Questionnaire), SF 36 Health survey Questionnaire and Clinical Global Impressions of severity of disorder (CGI item 1, CGI item 2, CGI item 3), and the results of the sleep diary demonstrated comparable positive effects of the two compounds. In conclusion, our results demonstrate that silexan is as effective as lorazepam

  1. 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

  2. Flurbiprofen microgranules for relief of sore throat: a randomised, double-blind trial

    PubMed Central

    Russo, Marc; Bloch, Mark; de Looze, Fred; Morris, Christopher; Shephard, Adrian

    2013-01-01

    Background Many people with sore throat seek, and are often inappropriately prescribed, antibiotics. Aim The objective of this study was to determine the analgesic efficacy of flurbiprofen 8.75 mg microgranules versus placebo. These microgranules are a possible alternative treatment for patients with sore throat due to upper respiratory tract infection (URTI). Design and setting Randomised, double-blind, placebo-controlled, multiple-dose study conducted at eight primary care sites in Australia. Method Participants with sore throat of onset within the past 4 days received either flurbiprofen 8.75 mg microgranules or non-medicated placebo microgranules. Throat soreness, difficulty in swallowing, sore throat pain intensity, sore throat relief, oral temperature, and treatment benefits were all assessed at regular intervals. Result Of 373 patients from eight centres, 186 received flurbiprofen 8.75 mg microgranules and 187 received placebo microgranules (intent-to-treat population). Throat soreness was significantly reduced over the first 2 hours after the first dose. Reductions in difficulty in swallowing were observed at all time points from 5 to 360 minutes after the first dose, after taking flurbiprofen microgranules versus placebo. Sore throat relief was also evident at 1 minute and lasted for at least 6 hours. The multiple-dose efficacy results showed reduction of difficulty in swallowing at the end of days 1–3 and sore throat relief at the end of day 1. Conclusion Microgranules containing flurbiprofen 8.75 mg provided fast and effective relief from sore throat due to URTI and represent an alternative treatment option to antibiotic therapy. PMID:23561694

  3. Comparison of intrathecal ropivacaine-fentanyl and bupivacaine-fentanyl for major lower limb orthopaedic surgery: A randomised double-blind study

    PubMed Central

    Jagtap, Sheetal; Chhabra, Anita; Dawoodi, Sunny; Jain, Ankit

    2014-01-01

    Background and Aims: Intrathecal bupivacaine results in complete anaesthetic block of longer duration than ropivacaine. Fentanyl as an adjuvant may improve the quality of spinal block of ropivacaine while maintaining its advantage of early motor recovery. In this study, we proposed to compare the efficacy and safety of intrathecal ropivacaine-fentanyl (RF) with bupivacaine-fentanyl (BF) for major lower limb orthopaedic surgeries. Methods: Sixty patients were randomly allocated to receive either intrathecal 15 mg 0.5% ropivacaine with 25 mcg fentanyl (Group RF) or 15 mg 0.5% bupivacaine with 25 mcg fentanyl (Group BF). The onset, duration, spread of sensory and motor block, haemodynamic parameters and side effects were recorded. Statistical Package for Social Sciences 20 software was used for statistical analysis. Results: Time to reach highest sensory level and complete motor block were comparable. Sensory regression to L1 dermatome was 226 ± 46.98 min in Group RF and 229.33 ± 50.51 min in Group BF, P = 0.36. The motor recovery to Bromage scale 1 was faster in Group RF (242.8 ± 47.06 min) than Group BF (268 ± 49.9 min) P = 0.023. Time for rescue analgesia was prolonged in Group BF (263.33 ± 63 min) when compared to Group RF (234.44 ± 58.76 min), P = 0.021. The haemodynamic stability was better in Group RF than Group BF. Conclusion: Intrathecal RF provided satisfactory anaesthesia with haemodynamic stability for major lower limb orthopaedic surgery. It provided similar sensory but shorter duration of motor block compared to BF which is a desirable feature for early ambulation, voiding and physiotherapy. PMID:25197113

  4. 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

  5. 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…

  6. 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

  7. 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

  8. 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

  9. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis

    PubMed Central

    Schumacher, H Ralph; Boice, Judith A; Daikh, David I; Mukhopadhyay, Saurabh; Malmstrom, Kerstin; Ng, Jennifer; Tate, Guillermo A; Molina, Javier

    2002-01-01

    Objective To assess the safety and efficacy of etoricoxib, a selective cyclo-oxygenase-2 inhibitor, in comparison with indometacin in the treatment of acute gouty arthritis. Design Randomised, double blind, active comparator controlled trial. Setting 43 outpatient study centres in 11 countries. Participants 142 men and eight women (75 patients per treatment group) aged 18 years or over presenting with clinically diagnosed acute gout within 48 hours of onset. Interventions Etoricoxib 120 mg administered orally once daily versus indometacin 50 mg administered orally three times daily, both for 8 days Main outcome measures Patients' assessment of pain in the study joint over days 2 to 5 (primary end point); investigators' and patients' global assessments of response to treatment and tenderness of the study joint (key secondary end points). Results Etoricoxib showed efficacy comparable to indometacin. Patients' assessment of pain in the study joint (0-4 point Likert scale, “no pain” to “extreme pain”) over days 2 to 5 showed a least squares mean change from baseline of −1.72 (95% confidence interval −1.90 to −1.55) for etoricoxib and −1.83 (−2.01 to −1.65) for indometacin. The difference between treatment groups met prespecified comparability criteria. All other efficacy end points, including those reflecting reduction in inflammation and analgesia, provided corroborative evidence of comparable efficacy. Significant pain relief was evident at the first measurement, 4 hours after the first dose of treatment. Prespecified safety analyses revealed that drug related adverse experiences occurred significantly less frequently with etoricoxib (22.7%) than with indometacin (46.7%) (P=0.003), although overall adverse experience rates were similar between the two treatment groups. Conclusion Etoricoxib 120 mg once daily provides rapid and effective treatment for acute gouty arthritis comparable to indometacin 50 mg three times daily. Etoricoxib was generally

  10. Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study.

    PubMed

    Kramer, A; Roth, B; Müller, G; Rudolph, P; Klöcker, N

    2004-01-01

    The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells.

  11. 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

  12. Blindness and eye diseases in Tibet: findings from a randomised, population based survey

    PubMed Central

    Dunzhu, S; Wang, F S; Courtright, P; Liu, L; Tenzing, C; Noertjojo, K; Wilkie, A; Santangelo, M; Bassett, K L

    2003-01-01

    Background: Public health officials of the Tibet Autonomous Region (TAR) of China requested a survey of blindness, eye diseases, and eye care service utilisation to assist the development of a 10 year blindness prevention and treatment plan. The objective of the survey was to determine the prevalence of blindness and visual impairment, as well as cataract surgical coverage and surgical outcome in the TAR. Methods: The Tibet Eye Care Assessment was a cross sectional prevalence study of three of the seven prefectures (provinces) of the TAR (Lhoka, Nakchu, and Lingzhr) selected to represent its three main environmental regions. The survey sample was selected using a random multistage cluster method. Two teams conducted the survey in a standardised fashion in each prefecture, Lhoka during May and Nakchu during June 1999, and Lingzhr during May 2000. Visual acuity, cause of vision loss, trachoma, and vitamin A deficiency were included in the clinical examination. Results: Among the 15 900 people enumerated, 12 644 were examined for an overall response rate of 79.6%. The crude prevalence of blindness (presenting better eye visual acuity of less than 6/60) was 2.3%; age and sex adjusted blindness prevalence was 1.4% (95% CI 1.3 to 1.5). Visual impairment (better eye presenting visual acuity of 6/24 to 6/60) was found in 10.9% (95% CI 10.5 to 11.2) of the population (age and sex adjusted). Cataract was the primary cause of blindness (50.7%), followed by macular degeneration (12.7%) and corneal opacity (9.7%). Conclusion: Blindness is a serious public health problem in Tibet, with prevalence higher than in similar studies in eastern China. As elsewhere in the world, women have an excess burden of blindness compared to men. About 75% of blindness in Tibet can be either prevented or treated. Eye care planning for Tibet must focus on cataract, particularly among women. PMID:14660448

  13. 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

  14. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study

    PubMed Central

    Thomas, R; Williams, M; Sharma, H; Chaudry, A; Bellamy, P

    2014-01-01

    Background: Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been evaluated within an adequately powered randomised controlled trial. Methods: In total, 199 men, average age 74 years, with localised prostate cancer, 60% managed with primary active surveillance (AS) or 40% with watchful waiting (WW) following previous interventions, were randomised (2:1) to receive an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric, or an identical placebo for 6 months. Results: The median rise in PSA in the food supplement group (FSG) was 14.7% (95% confidence intervals (CIs) 3.4–36.7%), as opposed to 78.5% in the placebo group (PG) (95% CI 48.1–115.5%), difference 63.8% (P=0.0008). In all, 8.2% of men in the FSG and 27.7% in the PG opted to leave surveillance at the end of the intervention (χ2 P=0.014). There were no significant differences within the predetermined subgroups of age, Gleason grade, treatment category or body mass index. There were no differences in cholesterol, blood pressure, blood sugar, C-reactive protein or adverse events. Conclusions: This study found a significant short-term, favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated, specific blend of concentrated foods. Its influence on decision-making suggests that this intervention is clinically meaningful, but further trials will evaluate longer term clinical effects, and other makers of disease progression. PMID:24614693

  15. 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

  16. 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

  17. 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

  18. Flutrimazole shampoo 1% versus ketoconazole shampoo 2% in the treatment of pityriasis versicolor. A randomised double-blind comparative trial.

    PubMed

    Rigopoulos, D; Gregoriou, S; Kontochristopoulos, G; Ifantides, A; Katsambas, A

    2007-05-01

    Flutrimazole is an imidazole derivative that has been proven to be efficient in superficial skin fungal infections. The aim of this randomised double-blind study was to compare for the first time, the efficiency and safety of flutrimazole 1% shampoo versus ketoconazole 2% shampoo in the treatment of tinea versicolor. Study population consisted of 60 patients with pityriasis versicolor diagnosed clinically and through direct microscopy and culture. Patients were randomly assigned to two groups: one instructed to apply flutrimazole shampoo 1% and one instructed to apply ketoconazole shampoo 2% both on head and body for 14 days. Patients were re-evaluated 14 days after the end of treatment clinically and through direct microscopy and culture. Twenty-one of 26 patients (80.8%) in the ketoconazole and 22 of 29 patients (75.9%) in the flutrimazole group had both visual healing and negative mycological evaluation. Comparison of the response between the two groups with the Yates' corrected chi-square was found statistically not significant (chi(2) = 0.19, d.f. = 1, P = 0.91). None of the patients in the two groups reported any adverse effects. Fourteen (53%) patients in the ketoconazole group and 23 (79%) in the flutrimazole group assessed the shampoos as cosmetically acceptable regarding texture, smell and foam properties. Flutrimazole shampoo 1% appears to present efficacy comparable with ketoconazole 2% in the treatment of tinea versicolor.

  19. Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design

    PubMed Central

    2010-01-01

    Background Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Methods Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Results Mean Ca absorption (± SEE) from the three different Ca sources were 21.9 ± 1.7%, 22.5 ± 1.7% and 27.4 ± 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. Conclusion We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements. PMID:20646299

  20. 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

  1. 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

  2. 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.

  3. Postoperative pharyngolaryngeal adverse events with laryngeal mask airway (LMA Supreme) in laparoscopic surgical procedures with cuff pressure limiting 25 cmH₂O: prospective, blind, and randomised study.

    PubMed

    Kang, Joo-Eun; Oh, Chung-Sik; Choi, Jae Won; Son, Il Soon; Kim, Seong-Hyop

    2014-01-01

    To reduce the incidence of postoperative pharyngolaryngeal adverse events, laryngeal mask airway (LMA) manufacturers recommend maximum cuff pressures not exceeding 60 cmH₂O. We performed a prospective randomised study, comparing efficacy and adverse events among patients undergoing laparoscopic surgical procedures who were allocated randomly into low (limiting 25 cmH₂O, L group) and high (at 60 cmH₂O, H group) LMA cuff pressure groups with LMA Supreme. Postoperative pharyngolaryngeal adverse events were evaluated at discharge from postanaesthetic care unit (PACU) (postoperative day 1, POD 1) and 24 hours after discharge from PACU (postoperative day 2, POD 2). All patients were well tolerated with LMA without ventilation failure. Before pneumoperitoneum, cuff volume and pressure and oropharyngeal leak pressure (OLP) showed significant differences. Postoperative sore throat at POD 2 (3 versus 12 patients) and postoperative dysphagia at POD 1 and POD 2 (0 versus 4 patients at POD 1; 0 versus 4 patients at POD 2) were significantly lower in L group, compared with H group. In conclusion, LMA with cuff pressure limiting 25 cmH₂O allowed both efficacy of airway management and lower incidence of postoperative adverse events in laparoscopic surgical procedures. This clinical trial is registered with KCT0000334.

  4. A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes Based on Multiples of 25,000 IU Doses.

    PubMed

    Cavalier, Etienne; Faché, Werner; Souberbielle, Jean-Claude

    2013-01-01

    Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug (n = 140) or placebo (n = 35). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects.

  5. A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes Based on Multiples of 25,000 IU Doses

    PubMed Central

    Cavalier, Etienne; Faché, Werner; Souberbielle, Jean-Claude

    2013-01-01

    Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug (n = 140) or placebo (n = 35). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects. PMID:23431293

  6. GuidAge study: a 5-year double blind, randomised trial of EGb 761 for the prevention of Alzheimer's disease in elderly subjects with memory complaints. i. rationale, design and baseline data.

    PubMed

    Andrieu, Sandrine; Ousset, Pierre-Jean; Coley, Nicola; Ouzid, Mehemed; Mathiex-Fortunet, Hélène; Vellas, Bruno

    2008-08-01

    Primary and secondary prevention strategies for Alzheimer's disease (AD) are urgently needed. We have initiated a five-year prospective prevention study involving patients spontaneously reporting memory complaints. The primary objective is to determine the effect of treatment with EGb 76 on the rate of conversion from memory complaints to AD using survival analysis. Ambulatory patients aged at least 70 years who spontaneously reported a memory complaint during a GP or memory centre consultation were eligible for inclusion. Patients with major objective memory impairment or clinically relevant symptoms of anxiety and depression were excluded. Subjects were randomised to receive either EGb 761 120mg bid or matching placebo. Participants undergo an annual visit at a memory centre, where a series of neuropsychological tests are administered to assess cognitive function (Grober and Buschke, Trail-Making and controlled oral word association tests) and cognitive status (MMS and CDR). Functional status is evaluated with the Instrumental Activities of Daily Living questionnaire. The primary outcome is the transition to a diagnosis of AD (DSM-IV and NINCDS-ADRDA criteria), determined at the annual memory centre visit. A total of 4066 patients were screened for participation, of whom 2854 fulfilled the eligibility criteria and were entered into the study. Their mean age was 76.8+/-4.4 years and 66.7% were female. The mean MMSE score was 27.8+/-1.7 and 55.5% presented a CDR score of 0.5. This study will enable us to evaluate the efficacy of EGb761 in the prevention of AD, and to assess the usefulness of various baseline characteristics as predictors of conversion to AD in this population.

  7. Acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) versus acupuncture or NSAIDs alone for the treatment of chronic neck pain: an assessor-blinded randomised controlled pilot study

    PubMed Central

    Cho, Jae-Heung; Nam, Dong-Hyun; Kim, Ki-Tack; Lee, Jun-Hwan

    2014-01-01

    Objective To investigate the feasibility and sample size required for a full-scale randomised controlled trial of the effectiveness of acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) for chronic neck pain compared with acupuncture or NSAID treatment alone. Methods A total of 45 patients with chronic neck pain participated in the study. For 3 weeks the acupuncture with NSAIDs treatment group took NSAIDs (zaltoprofen, 80 mg) daily while receiving acupuncture treatment three times a week. The acupuncture treatment group received treatment three times a week and the NSAID treatment group took NSAIDs daily. The primary outcomes were to determine the feasibility and to calculate the sample size. As secondary outcomes, pain intensity and pain-related symptoms for chronic neck pain were measured. Results With regard to enrolment and dropout rates, 88.2% of patients consented to be recruited to the trial and 15.6% of participants were lost to follow-up. The sample size for a full-scale trial was estimated to be 120 patients. Although preliminary, there was a significant change in the visual analogue scale (VAS) for neck pain intensity between the baseline measurement and each point of assessment in all groups. However, there was no difference in VAS scores between the three groups. Conclusions This pilot study has provided the feasibility and sample size for a full-scale trial of acupuncture with NSAIDs for chronic neck pain compared with acupuncture or NSAID treatment alone. Further research is needed to validate the effects of acupuncture with NSAIDs. Clinical Trial Registration NIH ClinicalTrials.gov NCT01205958. PMID:24171895

  8. 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

  9. 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

  10. 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

  11. Aesthetic comparison between synthetic glue and subcuticular sutures in thyroid and parathyroid surgery: a single-blinded randomised clinical trial.

    PubMed

    Alicandri-Ciufelli, M; Piccinini, A; Grammatica, A; Molteni, G; Spaggiari, A; DI Matteo, S; Tassi, S; Ghidini, A; Izzo, L; Gioacchini, F M; Marchioni, D; DI Saverio, S; Presutti, L

    2014-12-01

    The aim of our study was to compare, in terms of aesthetic results, the use of synthetic glue to intradermal absorbable sutures in postthyroidectomy and parathyroidectomy wound closure in a single blinded, randomised, per protocol equivalence study. From September 2008 to May 2010, patients undergoing thyroid or parathyroid surgery (with an external approach) at the Otolaryngology Department of the University Hospital of Modena were assessed for eligibility. In total, 42 patients who had had synthetic glue application on surgical incisions (A) and 47 patients who had subcuticular sutures on their surgical incisions (B) were enrolled. The mean of the endpoint (based on the Wound Registry Scale) of group A at 10 days was 1.4, while that in group B (based on the Stony Brook Scar Evaluation Scale) was 2.9. Statistically significant (p = 0.002) and clinically significant (difference of the means = 1.5) differences in the aesthetic results were found between groups A and B at 10 days, with better results in group B. On the other hand, at 3 months, the mean of the endpoint in group A was 3.1 while that in group B was 2.8; no statistically significant (p = 0.62) or clinically significant (difference in means = 0.3) differences were found between groups A and B. In conclusion, synthetic glue differs from subcuticular suture in post-thyroidectomy or post-parathyroidectomy incision for early aesthetic results, with better outcomes for subcuticular sutures. At 3 months, there were no differences in aesthetic outcomes between groups. Moreover, sex, incision length, age, cold/hot blade and correspondence of the incision with a wrinkle in the skin did not seem to influence aesthetic outcomes with this type of incision.

  12. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial

    PubMed Central

    Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

    2012-01-01

    Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle. Results VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash. Conclusion It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy. PMID:22930695

  13. 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

  14. Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety.

    PubMed

    Watson, N; Nimmo, W S; Christian, J; Charlesworth, A; Speight, J; Miller, K

    2000-10-01

    In this double-blind study, 301 patients with subjective and objective signs of sore throat were randomly assigned to flurbiprofen 8.75 mg (n = 129), flurbiprofen 12.5 mg (n = 43) or placebo (demulcent lozenge without active drug [n = 129]). Efficacy was assessed by changes in subjective rating scales primarily after a single dose and also over a 4-day period. Flurbiprofen 8.75 mg was superior to placebo in a number of efficacy parameters, notably throat soreness. Throat soreness was significantly reduced after 15 minutes (p < 0.05), with effects sustained for at least 2 hours (p < 0.05). Multiple dosing with flurbiprofen 8.75 mg lozenges continued to provide effective symptomatic relief over the 4-day treatment period. The small sample size was considered contributory to the variable results obtained with flurbiprofen 12.5 mg lozenges, but overall these were not inconsistent with previous trials. Both treatments were tolerated well. Flurbiprofen 8.75 mg lozenges provide an effective and well tolerated treatment for sore throat.

  15. Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety.

    PubMed

    Watson, N; Nimmo, W S; Christian, J; Charlesworth, A; Speight, J; Miller, K

    2000-10-01

    In this double-blind study, 301 patients with subjective and objective signs of sore throat were randomly assigned to flurbiprofen 8.75 mg (n = 129), flurbiprofen 12.5 mg (n = 43) or placebo (demulcent lozenge without active drug [n = 129]). Efficacy was assessed by changes in subjective rating scales primarily after a single dose and also over a 4-day period. Flurbiprofen 8.75 mg was superior to placebo in a number of efficacy parameters, notably throat soreness. Throat soreness was significantly reduced after 15 minutes (p < 0.05), with effects sustained for at least 2 hours (p < 0.05). Multiple dosing with flurbiprofen 8.75 mg lozenges continued to provide effective symptomatic relief over the 4-day treatment period. The small sample size was considered contributory to the variable results obtained with flurbiprofen 12.5 mg lozenges, but overall these were not inconsistent with previous trials. Both treatments were tolerated well. Flurbiprofen 8.75 mg lozenges provide an effective and well tolerated treatment for sore throat. PMID:11198725

  16. 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

    2014-06-14

    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 wheat

  17. Use of captopril as an isolated agent for the management of stable angina pectoris--a double blind randomised trial.

    PubMed

    Dhawan, S; Soni, D; Chandra, N; Dviwedi, S; Agarwal, A; Puri, V K

    1992-01-01

    In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation.

  18. 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.

  19. Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study

    PubMed Central

    Gurwith, Marc; Lock, Michael; Taylor, Eve M; Ishioka, Glenn; Alexander, Jeff; Mayall, Tim; Ervin, John E; Greenberg, Richard N; Strout, Cynthia; Treanor, John J; Webby, Richard; Wright, Peter F

    2013-01-01

    Summary Background Replication-competent virus vector vaccines might have advantages compared with non-replicating vector vaccines. We tested the safety and immunogenicity of an oral adenovirus serotype 4 vector vaccine candidate (Ad4-H5-Vtn) expressing the haemagglutinin from an avian influenza A H5N1 virus. Methods We did this phase 1 study at four sites in the USA. We used a computer-generated randomisation list (block size eight, stratified by site) to assign healthy volunteers aged 18–40 years to receive one of five doses of Ad4-H5-Vtn (107 viral particles [VP], 108 VP, 109 VP, 1010 VP, 1011 VP) or placebo (3:1). Vaccine or placebo was given on three occasions, about 56 days apart. Participants, investigators, and study-site personnel were masked to assignment throughout the study. Subsequently, volunteers received a boost dose with 90 μg of an inactivated parenteral H5N1 vaccine. Primary immunogenicity endpoints were seroconversion by haemagglutination-inhibition (HAI), defined as a four-times rise compared with baseline titre, and HAI geometric mean titre (GMT). We solicited symptoms of reactogenicity daily for 7 days after each vaccination and recorded symptoms that persisted beyond 7 days as adverse events. Primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01006798. Findings We enrolled 166 participants (125 vaccine; 41 placebo) between Oct 19, 2009, and Sept 9, 2010. HAI responses were low: 13 of 123 vaccinees (11%, 95% CI 6–17) and three of 41 placebo recipients (7%, 2–20) seroconverted. HAI GMT was 6 (95% CI 5–7) for vaccinees, and 5 (5–6) for placebo recipients. However, when inactivated H5N1 vaccine became available, one H5N1 boost was offered to all participants. In this substudy, HAI seroconversion occurred in 19 of 19 participants in the 1011 VP cohort (100%; 95% CI 82–100) and eight of 22 placebo recipients (36%; 17–59); 17 of 19 participants in the 1011 VP cohort (89%; 67–99) achieved

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Use of pentosan polysulphate in cats with idiopathic, non-obstructive lower urinary tract disease: a double-blind, randomised, placebo-controlled trial.

    PubMed

    Wallius, Barbro M; Tidholm, Anna E

    2009-06-01

    Idiopathic feline lower urinary tract disease (FLUTD) is a common clinical entity where different treatments, for example glycosaminoglycans (GAGs) such as pentosan polysulphate (PPS), are advocated. However, few treatments have been investigated by well-controlled clinical trials. This paper compares the use of PPS in FLUTD compared to placebo. Of the 18 cats in the experiment, nine were treated with PPS and nine were treated with placebo with subcutaneous injections of 3mg/kg PPS or placebo day 1, 2, 5 and 10. The study was double-blind, randomised and placebo-controlled. Revaluation was performed after 5 and 10 days, 2 weeks, 2, 6 and 12 months. There were no statistically significant differences concerning clinical signs between groups during treatment or at re-evaluation, except for pretreatment stressful events where PPS-treated cats had experienced significantly more stressful events compared to cats treated with placebo before entering the study. Six cats (33%) showed recurrence of clinical signs during the entire study period, and only one of these cats had more than one recurrent episode. One cat (placebo) was euthanased 7 days after initial treatment because of recurrence of clinical signs. Another cat (placebo) was euthanased due to other reasons after 6 months. At 2 weeks two cats (placebo and PPS) showed clinical signs. At 2 months re-evaluation one cat showed mild clinical signs. At 6 and 12 months all remaining 16 cats were healthy. Idiopathic, non-obstructive FLUTD is a self-limiting disease with good short-term and excellent long-term prognosis without treatment. Whether or not PPS may be beneficial in a subpopulation of cats with continuous or frequently recurring clinical signs may be elucidated in forthcoming double-blind, randomised and placebo-controlled trials including only this subpopulation of cats.

  7. 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

  8. 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

  9. The effect of triclosan coated sutures on rate of Surgical Site Infection after hip and knee replacement: a protocol for a double-blind randomised controlled trial

    PubMed Central

    2014-01-01

    Background 187,000 hip and knee joint replacements are performed every year in the National Health Service (NHS). One of the commonest complications is surgical site infection (SSI), and this represents a significant burden in terms of patient morbidity, mortality and cost to health services around the world. The aim of this randomised controlled trial (RCT) is to determine if the addition of triclosan coated sutures to a standard regimen can reduce the rate of SSI after total knee replacement (TKR) and total hip replacement (THR). Methods 2400 patients due to undergo a total hip or knee replacement are being recruited into this two-centre RCT. Participants are recruited before surgery and randomised to either standard care or intervention group. Participants, outcome assessors and statistician are blind to treatment allocation throughout the study. The intervention consists of triclosan coated sutures vs. standard non-coated sutures. The primary outcome is the Health protection Agency (HPA) defined superficial surgical site infection at 30 days. Secondary outcomes include HPA defined deep surgical site infection at 12 months, length of hospital stay, critical care stay, and payer costs. Discussion To date there are no orthopaedic randomised controlled trials on this scale assessing the effectiveness of a surgical intervention, particularly those that can be translated across the surgical specialities. The results from this trial will inform evidence-based recommendations for suture selection in the management of patients undergoing total hip or knee replacement. If triclosan coated sutures are found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip and knee replacement. Trial registration Current Controlled Trials ISRCTN 17807356. PMID:25027459

  10. 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

    2016-08-11

    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.

  11. 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

  12. Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients

    PubMed Central

    W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

    2012-01-01

    Background: Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. Objectives: The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. Methods: The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. Results: There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). Conclusions: The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds. PMID:23071904

  13. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial

    PubMed Central

    ten Hoedt, Amber E.; de Sonneville, Leo M. J.; Francois, Baudouin; ter Horst, Nienke M.; Janssen, Mirian C. H.; Rubio-Gozalbo, M. Estela; Wijburg, Frits A.; Hollak, Carla E. M.

    2010-01-01

    The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients’ mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted “diet for life” might be an advisable option for many. PMID:21153445

  14. 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

  15. 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

  16. 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

  17. Impact of autologous blood injections in treatment of mid-portion Achilles tendinopathy: double blind randomised controlled trial

    PubMed Central

    Fulcher, Mark L; Rowlands, David S; Kerse, Ngaire

    2013-01-01

    Objective To assess the effectiveness of two peritendinous autologous blood injections in addition to a standardised eccentric calf strengthening programme in improving pain and function in patients with mid-portion Achilles tendinopathy. Design Single centre, participant and single assessor blinded, parallel group, randomised, controlled trial. Setting Single sports medicine clinic in New Zealand. Participants 53 adults (mean age 49, 53% men) with symptoms of unilateral mid-portion Achilles tendinopathy for at least three months. Participants were excluded if they had a history of previous Achilles tendon rupture or surgery or had undergone previous adjuvant treatments such as injectable therapies, glyceryl trinitrate patches, or extracorporeal shockwave therapy. Interventions All participants underwent two unguided peritendinous injections one month apart with a standardised protocol. The treatment group had 3 mL of their own whole blood injected while the control group had no substance injected (needling only). Participants in both groups carried out a standardised and monitored 12 week eccentric calf training programme. Follow-up was at one, two, three and six months. Main outcome measures The primary outcome measure was the change in symptoms and function from baseline to six months with the Victorian Institute of Sport Assessment-Achilles (VISA-A) score. Secondary outcomes were the participant’s perceived rehabilitation and their ability to return to sport. Results 26 participants were randomly assigned to the treatment group and 27 to the control group. In total, 50 (94%) completed the six month study, with 25 in each group. Clear and clinically worthwhile improvements in the VISA-A score were evident at six months in both the treatment (change in score 18.7, 95% confidence interval 12.3 to 25.1) and control (19.9, 13.6 to 26.2) groups. The overall effect of treatment was not significant (P=0.689) and the 95% confidence intervals at all points precluded

  18. 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

  19. 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

  20. 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

  1. 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

  2. Adjunctive aripiprazole in risperidone-induced hyperprolactinaemia: double-blind, randomised, placebo-controlled trial

    PubMed Central

    Raghuthaman, G.; Venkateswaran, R.

    2015-01-01

    Background Hyperprolactinaemia is a troublesome side-effect of treatment with antipsychotics. Aims This double-blind, placebo-controlled study aimed at examining the effect of adjunctive treatment with 10 mg aripiprazole on prolactin levels and sexual side-effects in patients with schizophrenia symptomatically maintained on risperidone. Method Thirty patients taking risperidone were enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a fixed daily dose of 10 mg/day for 8 weeks. Serum prolactin was measured at baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology and side-effects were evaluated every 2 weeks. Results Prolactin levels decreased by 58% in the aripiprazole group compared with an increase by 22% in the placebo group. Prolactin levels normalised in 46% of patients in the aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved erectile dysfunction in five out of six patients. There were no significant differences in change in psychopathology or side-effects between groups. Conclusions Adjunctive aripiprazole reduced prolactin levels in those treated with risperidone, with no effect on psychopathology and extrapyramidal symptoms. This is a potential treatment for hyperprolactinaemia observed during treatment with second-generation antipsychotics. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703744

  3. Ayurvedic treatment of obesity: a randomised double-blind, placebo-controlled clinical trial.

    PubMed

    Paranjpe, P; Patki, P; Patwardhan, B

    1990-04-01

    Seventy obese subjects were randomised into four groups. Ayurvedic drug treatments were given for three months while one group received a placebo. Physical, clinical and pathological investigations were carried out at regular intervals. A significant weight loss was observed in drug therapy groups when compared with the placebo. Body measurements such as skin fold thickness and hip and waist circumferences were significantly decreased. Decreases in serum cholesterol and triglyceride levels were observed. No side effects of any kind were observed during the treatment period. PMID:2278549

  4. 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

  5. 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

  6. Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

    PubMed Central

    Daneshmend, T. K.; Hawkey, C. J.; Langman, M. J.; Logan, R. F.; Long, R. G.; Walt, R. P.

    1992-01-01

    OBJECTIVE--To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN--Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING--The medical wards of University and City Hospitals, Nottingham. SUBJECTS--1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES--Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS--Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS--Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena. PMID:1737157

  7. The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive–behavioural therapy

    PubMed Central

    Murphy, Glynis H.; Shepstone, Lee; Wilson, Edward C.F.; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

    2016-01-01

    Background There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. Aims To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Method Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. Results The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Conclusions Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703772

  8. 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

  9. Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

    PubMed

    Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

    2015-02-01

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.

  10. 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

  11. Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Roll, Stephanie; Nocon, Marc; Willich, Stefan N

    2011-01-01

    Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18-65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact.

  12. 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

  13. 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

  14. A randomised controlled trial linking mental health inpatients to community smoking cessation supports: A study protocol

    PubMed Central

    2011-01-01

    Background Mental health inpatients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence. Despite the advent of smoke free policies within mental health hospitals, limited systems are in place to support a cessation attempt post hospitalisation, and international evidence suggests that most smokers return to pre-admission smoking levels following discharge. This protocol describes a randomised controlled trial that will test the feasibility, acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness. Methods/Design This study will be conducted as a randomised controlled trial. 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility. Participants will complete a baseline survey and will be randomised to either a multimodal smoking cessation intervention or provided with hospital smoking care only. Randomisation will be stratified by diagnosis (psychotic, non-psychotic). Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge: nicotine replacement therapy (NRT); referral to Quitline; smoking cessation groups; and fortnightly telephone support. Outcome data, including cigarettes smoked per day, quit attempts, and self-reported 7-day point prevalence abstinence (validated by exhaled carbon monoxide), will be collected via blind interview at one week, two months, four months and six months post discharge. Process information will also be collected, including the use of cessation supports and cost of the intervention. Discussion This study will provide comprehensive data on the potential of an integrated, multimodal smoking cessation intervention for persons with an acute mental illness, linking inpatient with community cessation support. Trial Registration Australian and New Zealand

  15. 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

  16. A randomised, double-blind, vehicle-controlled study to evaluate the efficacy and safety of MAS063D (Atopiclair) in the treatment of mild to moderate atopic dermatitis.

    PubMed

    Belloni, G; Pinelli, S; Veraldi, S

    2005-01-01

    MAS063D (Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis (AD). The putative active ingredients of MAS063D are hyaluronic acid, telmesteine, Vitis vinifera, glycyrrhetinic acid. A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control. MAS063D improved the total body area affected (17.2% --> 13.2%, p < 0.001), itch score (2.7 --> 1.3 on a 10-point scale, p = 0.001) and EASI score (28.3 --> 24.3, p = 0.024) after 22 days treatment compared to baseline. The patients' opinion of MAS063D (patient's view of itch control, and view of study substance) was rated by participating patients as significantly better than control (p = 0.008, p = 0.042 respectively). Based on these preliminary results in a small scale study, it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD. PMID:15701590

  17. 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

    2014-06-14

    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 Bi-07 on the gut

  18. 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

  19. 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.

  20. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators' Group.

    PubMed

    Gallus, A; Cade, J; Ockelford, P; Hepburn, S; Maas, M; Magnani, H; Bucknall, T; Stevens, J; Porteous, F

    1993-10-18

    This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.

  1. 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

  2. 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

  3. 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 ...

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up.

    PubMed

    Olivan-Blázquez, Bárbara; Herrera-Mercadal, Paola; Puebla-Guedea, Marta; Pérez-Yus, Mari-Cruz; Andrés, Eva; Fayed, Nicolas; López-Del-Hoyo, Yolanda; Magallon, Rosa; Roca, Miquel; Garcia-Campayo, Javier

    2014-12-01

    Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.

  13. 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

  14. Low-dose laser acupuncture for non-specific chronic low back pain: a double-blind randomised controlled trial

    PubMed Central

    Glazov, Gregory; Yelland, Michael; Emery, Jon

    2014-01-01

    Objective To determine if infrared laser acupuncture (LA) may have a specific effect in reducing pain and disability in treatment of chronic low back pain (LBP). Methods This was a double-blind sham laser controlled trial performed in general practices in Perth, Western Australia. The participants were 144 adults with chronic non-specific LBP. They were randomised to receive eight once-weekly treatments. Laser machines (20 mW, 840 nm diode, power density 0.1 W/cm2) stimulated points in three treatment groups: sham (0 joules/point), low dose (0.2 J/point) and high dose (0.8 joules/point). Participants were followed-up at 1 and 6 weeks, and 6 and 12 months post treatment. Primary outcomes were pain (Numerical Pain Rating Scale (NPRS)) and disability (Oswestry Disability Inventory (ODI)) at 6 weeks post treatment. Secondary outcomes included numerical rating scale for limitation of activity, global assessment of improvement, analgesic usage and adverse effects after treatment. Results The analysis showed no difference between sham and the laser groups at 6 weeks for pain or disability. There was a significant reduction in mean pain and disability in all groups at 6 weeks (p<0.005); NPRS: sham (−1.5 (95% CI −2.1 to −0.8)), low dose (−1.3 (−2.0 to −0.8)), high dose (−1.1 (−1.7 to −0.5)). ODI: sham (−4.0 (−7.1 to −1.0)), low dose (−4.1, (−6.7 to −1.5)), high dose (−2.6 (−5.7 to 0.5)). All secondary outcomes also showed clinical improvement over time but with no differences between groups. Conclusions LA using energy density range (0–4 J/cm2) for the treatment of chronic non-specific LBP resulted in clinical improvement unrelated to laser stimulation. Trial registration http://www.anzctr.org.au ACTRN12610000043033. PMID:24280948

  15. Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial

    PubMed Central

    Mosquera, Ricardo A; Gomez-Rubio, Ana M; Harris, Tomika; Yadav, Aravind; McBeth, Katrina; Gonzales, Traci; Jon, Cindy; Stark, James; Avritscher, Elenir; Pedroza, Claudia; Smith, Keely; Colasurdo, Giuseppe; Wootton, Susan; Piedra, Pedro; Tyson, Jon E; Samuels, Cheryl

    2016-01-01

    Introduction Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade. Methods and analysis A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3–6 months during two respiratory syncytial virus (RSV) seasons (2015–2016 and 2016–2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach. Discussion We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters. Ethics and dissemination This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published. Trial registration number NCT02544984. PMID:27638496

  16. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Serisier, David J; Bilton, Diana; De Soyza, Anthony; Thompson, Philip J; Kolbe, John; Greville, Hugh W; Cipolla, David; Bruinenberg, Paul; Gonda, Igor

    2013-01-01

    Background The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery. Methods Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation—after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study. Results DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs −0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events. Conclusions Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population. PMID:23681906

  17. Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.

    PubMed

    Lopresti, Adrian L; Maes, Michael; Meddens, Marc J M; Maker, Garth L; Arnoldussen, Eddy; Drummond, Peter D

    2015-01-01

    A recent randomised, double-blind, placebo controlled study conducted by our research group, provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure. Compared to placebo, 8 weeks of curcumin supplementation was associated with elevations in urinary thromboxane B2 (p<0.05), and substance P (p<0.001); while placebo supplementation was associated with reductions in aldosterone (p<0.05) and cortisol (p<0.05). Higher baseline plasma endothelin-1 (rs=-0.587; p<0.01) and leptin (rs=-0.470; p<0.05) in curcumin-treated individuals was associated with greater reductions in IDS-SR30 score after 8 weeks of treatment. Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action. Plasma concentrations of leptin and endothelin-1 seem to have particular relevance to treatment outcome. Further investigations using larger samples sizes are required to elucidate these findings, as the multiple statistical comparisons completed in this study increased the risk of type I errors.

  18. 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

  19. 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

  20. 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.

  1. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Wang, I-K; Wu, Y-Y; Yang, Y-F; Ting, I-W; Lin, C-C; Yen, T-H; Chen, J-H; Wang, C-H; Huang, C-C; Lin, H-C

    2015-01-01

    Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

  2. 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

  3. 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

  4. 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

  5. Recovery of probiotic Lactobacillus rhamnosus GG in tonsil tissue after oral administration: randomised, placebo-controlled, double-blind clinical trial.

    PubMed

    Kumpu, Minna; Swanljung, Elisa; Tynkkynen, Soile; Hatakka, Katja; Kekkonen, Riina A; Järvenpää, Salme; Korpela, Riitta; Pitkäranta, Anne

    2013-06-28

    The present randomised, double-blind, placebo-controlled study was conducted to determine whether consumption of probiotic Lactobacillus rhamnosus GG (GG) would lead to the recovery of GG in tonsil tissue. After 3 weeks’ daily consumption of GG as a single strain (n 20), GG as a part of a multispecies combination (n 17) or placebo (n 20), tonsil tissue samples were collected from fifty-seven young adults during tonsillectomy due to chronic or recurrent tonsillitis. Strain-specific real-time PCR was used to detect GG in the tonsil tissue. GG was recovered in the tonsil sample of 40% of the subjects in the GG group, 41% in the multispecies group and 30% in the placebo group (P value between groups 0.79). In all subjects with positive recovery of GG in the tonsil tissue, GG was also recovered in the faecal sample taken at the start of the intervention and at the time of the tissue sample collection, which indicates more persistent adherence of the probiotic. To conclude, GG can be recovered from tonsil tissue after oral administration as a singlestrain probiotic or as a part of a multispecies probiotic combination. The present results suggest that individual variation exists in the ability of GG to adhere to tonsil tissue. Persistence of GG appears to be high in tonsil tissue as well, in addition to persistence in faecal samples, which has been demonstrated previously. Further clinical trials are warranted to evaluate whether probiotic adherence in the tonsil tissue could have a role in respiratory symptom prevalence.

  6. 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

  7. 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.

  8. 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.

  9. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

    PubMed Central

    Naumann, M; Lowe, N J

    2001-01-01

    Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type

  10. Presentation of continuous outcomes in randomised trials: an observational study

    PubMed Central

    Savage, Dan F; Altman, Douglas G

    2012-01-01

    Objective To characterise the percentage of available outcome data being presented in reports of randomised clinical trials with continuous outcome measures, thereby determining the potential for incomplete reporting bias. Design Descriptive cross sectional study. Data sources A random sample of 200 randomised trials from issues of 20 medical journals in a variety of specialties during 2007–09. Main outcome measures For each paper’s best reported primary outcome, we calculated the fraction of data reported using explicit scoring rules. For example, a two arm trial with 100 patients per limb that reported 2 sample sizes, 2 means, and 2 standard deviations reported 6/200 data elements (1.5%), but if that paper included a scatterplot with 200 points it would score 200/200 (100%). We also assessed compliance with 2001 CONSORT items about the reporting of results. Results The median percentage of data reported for the best reported continuous outcome was 9% (interquartile range 3–26%) but only 3.5% (3–7%) when we adjusted studies to 100 patients per arm to control for varying study size; 17% of articles showed 100% of the data. Tables were the predominant means of presenting the most data (59% of articles), but papers that used figures reported a higher proportion of data. There was substantial heterogeneity among journals with respect to our primary outcome and CONSORT compliance. Limitations We studied continuous outcomes of randomised trials in higher impact journals. Results may not apply to categorical outcomes, other study designs, or other journals. Conclusions Trialists present only a small fraction of available data. This paucity of data may increase the potential for incomplete reporting bias, a failure to present all relevant information about a study’s findings. PMID:23249670

  11. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials

    PubMed Central

    Moran, Antoinette; Bundy, Brian; Becker, Dorothy J; DiMeglio, Linda A; Gitelman, Stephen E; Goland, Robin; Greenbaum, Carla J; Herold, Kevan C; Marks, Jennifer B; Raskin, Philip; Sanda, Srinath; Schatz, Desmond; Wherrett, Diane K; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S; Pickersgill, Linda; de Koning, Eelco; Ziegler, Anette-G; Böehm, Bernhard; Badenhoop, Klaus; Schloot, Nanette; Bak, Jens Friis; Pozzilli, Paolo; Mauricio, Didac; Donath, Marc Y; Castaño, Luis; Wägner, Ana; Lervang, Hans Henrik; Perrild, Hans; Poulsen, Thomas Mandrup

    2013-01-01

    Summary Background Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved β-cell function in recent-onset type 1 diabetes. Methods We did two randomised, placebo-controlled trials in two groups of patients with recent-onset type 1 diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0·2 nM. Patients in the canakinumab trial were aged 6–45 years and those in the anakinra trial were aged 18–35 years. Patients in the canakinumab trial were enrolled at 12 sites in the USA and Canada and those in the anakinra trial were enrolled at 14 sites across Europe. Participants were randomly assigned by computer-generated blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300 mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo daily for 9 months. Participants and carers were masked to treatment assignment. The primary endpoint was baseline-adjusted 2-h area under curve C-peptide response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9 months (anakinra trial). Analyses were by intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and EudraCT number 2007-007146-34. Findings Patients were enrolled in the canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No interim analyses were done. 45 canakinumab-treated and 21 placebo-treated patients in the canakinumab trial

  12. Effects of supplemental oxygen on cardiac rhythm during upper gastrointestinal endoscopy: a randomised controlled double blind trial.

    PubMed Central

    Bowling, T E; Hadjiminas, C L; Polson, R J; Baron, J H; Foale, R A

    1993-01-01

    To investigate the effects of supplemental oxygen on cardiac rhythm during gastroscopy, 103 patients aged over 60 were randomised to receive either supplemental oxygen or air at 2 litres/minute during the procedure. Pulse rate, blood pressure, oxygen saturation, and a Holter cardiac trace were monitored before, during, and for one hour after the gastroscopy. A wide range of electrocardiographic abnormalities were recorded in both oxygen and air groups, of which ventricular and supraventricular ectopic beats were the most common. There were no significant differences in the rate of occurrence of any clinically important cardiac abnormality either between the oxygen and air groups or between the three monitored periods before, during, and after gastroscopy. There were significantly fewer patients, however, with supraventricular extra systoles when oxygen was given during gastroscopy (p < 0.05). Although supplemental oxygen during gastroscopy significantly improved oxygen saturation (p < 0.001; 95% confidence intervals for the difference between the means: 2.9 to 4.7), there was no correlation between oxygen saturation and any electrocardiographic changes. It is concluded that electrocardiographic abnormalities are common in patients over 60, but this study found no evidence that they are induced by gastroscopy. Supplemental oxygen increases oxygen saturation but does not reduce the incidence of clinically important cardiac arrhythmias. PMID:8244130

  13. 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

  14. 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

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

    2015-10-30

    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.

  15. 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

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

    2015-11-01

    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

  16. 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

  17. 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

  18. 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.

  19. 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…

  20. 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

  1. PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial

    PubMed Central

    McCormack, Sheena; Ramjee, Gita; Kamali, Anatoli; Rees, Helen; Crook, Angela M; Gafos, Mitzy; Jentsch, Ute; Pool, Robert; Chisembele, Maureen; Kapiga, Saidi; Mutemwa, Richard; Vallely, Andrew; Palanee, Thesla; Sookrajh, Yuki; Lacey, Charles J; Darbyshire, Janet; Grosskurth, Heiner; Profy, Albert; Nunn, Andrew; Hayes, Richard; Weber, Jonathan

    2010-01-01

    Summary Background Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0·5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa. Methods Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (≥16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0·5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org, number ISRCTN 64716212. Findings We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0·5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86–91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4·5 [95% CI 3·8–5·4] for 0·5% PRO2000

  2. 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

  3. 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

  4. Milk supplementation facilitates appetite control in obese women during weight loss: a randomised, single-blind, placebo-controlled trial.

    PubMed

    Gilbert, Jo-Anne; Joanisse, Denis R; Chaput, Jean-Philippe; Miegueu, Pierre; Cianflone, Katherine; Alméras, Natalie; Tremblay, Angelo

    2011-01-01

    Dairy products provide Ca and protein which may facilitate appetite control. Conversely, weight loss is known to increase the motivation to eat. This randomised controlled trial verified the influence of milk supplementation on appetite markers during weight loss. Low Ca consumer women participated in a 6-month energy-restricted programme (-2508 kJ/d or -600 kcal/d) and received either a milk supplementation (1000 mg Ca/d) or an isoenergetic placebo (n 13 and 12, respectively). Fasting appetite sensations were assessed by visual analogue scales. Anthropometric parameters and fasting plasma concentrations of glucose, insulin, leptin, ghrelin and cortisol were measured as well. Both groups showed a significant weight loss (P < 0·0001). In the milk-supplemented group, a time x treatment interaction effect showed that weight loss with milk supplementation induced a smaller increase in desire to eat and hunger (P < 0·05). Unlike the placebo group, the milk-supplemented group showed a lower than predicted decrease in fullness (-17·1 v. -8·8; -2·7 v. 3·3 mm, P < 0·05, measured v. predicted values, respectively). Even after adjustment for fat mass loss, changes in ghrelin concentration predicted those in desire to eat (r 0·56, P < 0·01), hunger (r 0·45, P < 0·05) and fullness (r -0·40, P < 0·05). However, the study did not show a between-group difference in the change in ghrelin concentration in response to the intervention. These results show that milk supplementation attenuates the orexigenic effect of body weight loss. PMID:21205360

  5. 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

  6. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

    PubMed Central

    Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

    2015-01-01

    Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

  7. Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial

    PubMed Central

    Pollock, M Anne; Sturrock, Alison; Marshall, Karen; Davidson, Kate M; Kelly, Christopher J G; McMahon, Alex D; McLaren, E Hamish

    2001-01-01

    Objectives To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants. Design Randomised double blind placebo controlled crossover trial. Setting Outpatient clinic in a general hospital. Participants 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls. Methods Participants were given thyroxine 100 μg or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase. Main outcome measures Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. Results 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the

  8. Dietary fructo-oligosaccharides in healthy adults do not negatively affect faecal cytotoxicity: a randomised, double-blind, placebo-controlled crossover trial.

    PubMed

    Scholtens, Petra A M J; Alles, Martine S; Willemsen, Linette E M; van den Braak, Claudia; Bindels, Jacques G; Boehm, Günther; Govers, Mirjam J A P

    2006-06-01

    Fructo-oligosaccharides (FOS) are widely used in commercial food products. Most studies on FOS concern the health benefits, but some negative effects were recently reported concerning the faecal cytotoxicity and excretion of mucin-type oligosaccharides in combination with a Ca-restricted diet. The present study was performed to investigate whether these effects of FOS are observed in adults consuming a regular diet unrestricted in Ca. The study was a randomised, double-blind, placebo-controlled crossover trial, involving eleven healthy adults, who consumed 25-30 g FOS or maltodextrin (control) in a random order for 2 weeks in addition to their regular diet. Stools were collected for analysis of pH and SCFA (as markers of fermentation), for the assessment of faecal water cytotoxicity, and for the analysis of alkaline phosphatase activity (as a marker of epithelial cell turnover) and O-linked oligosaccharides (to estimate the excretion of mucin-type oligosaccharides). FOS consumption significantly altered bacterial fermentation (increased percentage of acetate, decreased percentage of butyrate) and tended to decrease stool pH. Furthermore, FOS consumption resulted in a significantly higher stool frequency and in significantly more complaints of flatulence. No significant differences between the control and FOS period were observed in the mean cytotoxicity of faecal water (37.5 (SEM 6.9)% v. 18.5 (SEM 6.9)%; P=0.084), in mean alkaline phosphatase activity (27.7 (SEM 2.9) v. 24.6 (SEM 3.2) U/g dry faeces; P=0.496) or in the mean excretion of mucin-type oligosaccharides (49.9 (sem 4.0) v. 53.5 (SEM 4.3) mg/g dry faeces; P=0.553). We conclude that dietary FOS in a dose up to 25-30 g/d altered the bacterial fermentation pattern but did not affect faecal cytotoxicity or the faecal concentration of mucin-type oligosaccharides in human adults consuming a regular diet. PMID:16768837

  9. The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Viasus, Diego; Garcia-Vidal, Carolina; Simonetti, Antonella F; Dorca, Jordi; Llopis, Ferran; Mestre, Mariona; Morandeira-Rego, Francisco; Carratalà, Jordi

    2015-01-01

    Objectives It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines. Setting A tertiary teaching hospital in Barcelona, Spain. Participants Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group). Intervention Patients were randomly assigned to receive 20 mg of simvastatin or placebo administered in the first 24 h of hospital admission and once daily thereafter for 4 days. Outcome Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment administration. Results The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3 days, IQR 2–5 vs 3 days, IQR 2–5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-α (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08 and 0.53, respectively). Conclusions Our results suggest that the use of simvastatin, 20 mg once daily

  10. 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

  11. 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

  12. Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial

    PubMed Central

    Green, Jonathan; Charman, Tony; Pickles, Andrew; Wan, Ming W; Elsabbagh, Mayada; Slonims, Vicky; Taylor, Carol; McNally, Janet; Booth, Rhonda; Gliga, Teodora; Jones, Emily J H; Harrop, Clare; Bedford, Rachael; Johnson, Mark H

    2015-01-01

    Summary Background Risk markers for later autism identified in the first year of life present plausible intervention targets during early development. We aimed to assess the effect of a parent-mediated intervention for infants at high risk of autism on these markers. Methods We did a two-site, two-arm assessor-blinded randomised controlled trial of families with an infant at familial high risk of autism aged 7–10 months, testing the adapted Video Interaction to Promote Positive Parenting (iBASIS-VIPP) versus no intervention. Families were randomly assigned to intervention or no intervention groups using a permuted block approach stratified by centre. Assessors, but not families or therapists, were masked to group assignment. The primary outcome was infant attentiveness to parent. Regression analysis was done on an intention-to-treat basis. This trial is registered with ISCRTN Registry, number ISRCTN87373263. Findings We randomly assigned 54 families between April 11, 2011, and Dec 4, 2012 (28 to intervention, 26 to no intervention). Although CIs sometimes include the null, point estimates suggest that the intervention increased the primary outcome of infant attentiveness to parent (effect size 0·29, 95% CI −0·26 to 0·86, thus including possibilities ranging from a small negative treatment effect to a strongly positive treatment effect). For secondary outcomes, the intervention reduced autism-risk behaviours (0·50, CI −0·15 to 1·08), increased parental non-directiveness (0·81, 0·28 to 1·52), improved attention disengagement (0·48, −0·01 to 1·02), and improved parent-rated infant adaptive function (χ2[2] 15·39, p=0·0005). There was a possibility of nil or negative effect in language and responsivity to vowel change (P1: ES–0·62, CI −2·42 to 0·31; P2: −0·29, −1·55 to 0·71). Interpretation With the exception of the response to vowel change, our study showed positive estimates across a wide range of behavioural and brain function

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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);…

  19. 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…

  20. 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

  1. 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

  2. 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

    2016-07-12

    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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial

    PubMed Central

    Dobs, Adrian S; Boccia, Ralph V; Croot, Christopher C; Gabrail, Nashat Y; Dalton, James T; Hancock, Michael L; Johnston, Mary A; Steiner, Mitchell S

    2016-01-01

    Summary Background Cancer-induced muscle wasting begins early in the course of a patient's malignant disease, resulting in declining physical function and other detrimental clinical consequences. This randomised, double-blind, placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm, a selective androgen receptor modulator, in patients with cancer. Methods We enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days at US and Argentinian oncology clinics. The sponsor, study personnel, and participants were masked to assignment. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry. Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol-specified window of within 10 days before baseline or first study drug, and within 10 days of day 113 or end of study (evaluable efficacy population). Adverse events and other safety measurements were assessed in the intention-to-treat (safety) population. This trial is registered with ClinicalTrials.gov, number NCT00467844. Findings Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1·5 kg, range −2·1 to 12·6, p=0·0012; enodosarm 3 mg 1·0 kg, −4·8 to 11·5, p=0·046). Change in

  10. 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.

  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. 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

  13. 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

  14. 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

  15. 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

  16. Electroacupuncture as a complement to usual care for patients with non-acute pain after back surgery: a study protocol for a pilot randomised controlled trial

    PubMed Central

    Hwang, Man-Suk; Heo, Kwang-Ho; Cho, Hyun-Woo; Shin, Byung-Cheul; Lee, Hyeon-Yeop; Heo, In; Kim, Nam-Kwen; Choi, Byung-Kwan; Son, Dong-Wuk; Hwang, Eui-Hyoung

    2015-01-01

    Introduction Recurrent or persistent low back pain is common after back surgery but is typically not well controlled. Previous randomised controlled trials on non-acute pain after back surgery were flawed. In this article, the design and protocol of a randomised controlled trial to treat pain and improve function after back surgery are described. Methods and analysis This study is a pilot randomised, active-controlled, assessor-blinded trial. Patients with recurring or persistent low back pain after back surgery, defined as a visual analogue scale value of ≥50 mm, with or without leg pain, will be randomly assigned to an electroacupuncture-plus-usual-care group or to a usual-care-only group. Patients assigned to both groups will have usual care management, including physical therapy and patient education, twice a week during a 4-week treatment period that would begin at randomisation. Patients assigned to the electroacupuncture-plus-usual-care group will also have electroacupuncture twice a week during the 4-week treatment period. The primary outcome will be measured with the 100 mm pain visual analogue scale of low back pain by a blinded evaluator. Secondary outcomes will be measured with the EuroQol 5-Dimension and the Oswestry Disability Index. The primary and secondary outcomes will be measured at 4 and 8 weeks after treatment. Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Institutional Review Board (IRB) of Pusan National University Korean Hospital in September 2013 (IRB approval number 2013012). The study findings will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number This trial was registered with the US National Institutes of Health Clinical Trials Registry: NCT01966250. PMID:25652804

  17. 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

  18. Duration of cortisol suppression following a single dose of dexamethasone in healthy volunteers: a randomised double-blind placebo-controlled trial.

    PubMed

    Elston, M S; Conaglen, H M; Hughes, C; Tamatea, J A U; Meyer-Rochow, G Y; Conaglen, J V

    2013-09-01

    The synthetic glucocorticoid dexamethasone is administered to many patients receiving a general anaesthetic to reduce the risk of postoperative nausea and vomiting. Dexamethasone is known to suppress the hypothalamic-pituitary-adrenal axis; however, the duration of this suppression following the standard anti-emetic intravenous dose of 4 to 8 mg used with anaesthesia is unknown. A randomised controlled double-blind crossover trial assessing the effects of 8 mg intravenous dexamethasone versus saline control was performed in ten healthy male volunteers. The adrenal, thyroid and gonadal axes and glucose levels were assessed over a four-day period after dexamethasone administration. All participants had normal baseline hypothalamic-pituitary-adrenal axis function. No difference in cortisol levels was demonstrated at four or eight hours after dexamethasone administration compared with placebo. At 24 hours post dexamethasone, the cortisol had dropped to less than 5% of baseline and returned to normal during the subsequent day. Increased plasma glucose levels were also observed in the dexamethasone group as compared with placebo. A dose of 8 mg of dexamethasone results in significant suppression of the hypothalamic-pituitary-adrenal axis and elevated plasma glucose levels. The cortisol suppression is maximal at approximately 24 hours post dose.

  19. A randomised, double-blind field trial of ivermectin alone and in combination with albendazole for the treatment of Mansonella perstans infections in Uganda.

    PubMed

    Asio, Santa Maria; Simonsen, Paul E; Onapa, Ambrose W

    2009-03-01

    The effect of a single dose of ivermectin alone (150-200microg/kg body weight) or in combination with albendazole (total of 400mg) in Mansonella perstans infection was assessed in a randomised, double-blind field trial in two endemic communities in Mukono and Luwero districts of Uganda. No side effects were observed or reported during the first 7 days after treatment. The effect on microfilaraemia was analysed among individuals with >or=20 microfilariae (mf) per 100mul of blood at baseline, who took the treatment and who attended follow-up examinations at 6 months and 12 months after treatment (48 and 46 in Mukono and 48 and 40 in Luwero for the ivermectin and combination treatment, respectively). In both communities, the combination treatment appeared slightly more effective than ivermectin alone, but the difference was not statistically significant. Both drug regimens were more effective in Luwero than in Mukono, probably owing to different diets in the two areas. However, in general both treatment regimens in both communities had limited effect on microfilarial intensities, and only one individual (given combination treatment in Luwero) was mf-negative at 6 months and 12 months after treatment. [ClinicalTrials.gov identifier: NCT00215280]. PMID:19081121

  20. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

    PubMed Central

    Downs, S. H.; Black, N.

    1998-01-01

    OBJECTIVE: To test the feasibility of creating a valid and reliable checklist with the following features: appropriate for assessing both randomised and non-randomised studies; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting, internal validity (bias and confounding) and power, but also for external validity. DESIGN: A pilot version was first developed, based on epidemiological principles, reviews, and existing checklists for randomised studies. Face and content validity were assessed by three experienced reviewers and reliability was determined using two raters assessing 10 randomised and 10 non- randomised studies. Using different raters, the checklist was revised and tested for internal consistency (Kuder-Richardson 20), test-retest and inter-rater reliability (Spearman correlation coefficient and sign rank test; kappa statistics), criterion validity, and respondent burden. MAIN RESULTS: The performance of the checklist improved considerably after revision of a pilot version. The Quality Index had high internal consistency (KR-20: 0.89) as did the subscales apart from external validity (KR-20: 0.54). Test-retest (r 0.88) and inter-rater (r 0.75) reliability of the Quality Index were good. Reliability of the subscales varied from good (bias) to poor (external validity). The Quality Index correlated highly with an existing, established instrument for assessing randomised studies (r 0.90). There was little difference between its performance with non-randomised and with randomised studies. Raters took about 20 minutes to assess each paper (range 10 to 45 minutes). CONCLUSIONS: This study has shown that it is feasible to develop a checklist that can be used to assess the methodological quality not only of randomised controlled trials but also non-randomised studies. It has also shown that it is possible to produce a checklist that provides a profile of the paper, alerting reviewers to its particular

  1. 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

  2. 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

  3. 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

  4. 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

  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. A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life.

    PubMed

    Hutchings, H A; Wareham, K; Baxter, J N; Atherton, P; Kingham, J G C; Duane, P; Thomas, L; Thomas, M; Ch'ng, C L; Williams, J G

    2011-01-01

    Background. Irritable bowel syndrome (IBS) is a chronic, difficult to treat condition. The efficacy of Aloe vera in treating IBS symptoms is not yet proven. The purpose of this study was to determine if Aloe vera is effective in improving quality of life. Methods. A multicentre, randomised, double-blind, cross-over placebo controlled study design. Patients were randomised to Aloe vera, wash-out, placebo or placebo, washout, Aloe vera. Each preparation (60 mL) was taken orally twice a day. Patient quality of life was measured using the Gastrointestinal Symptoms Rating Score, Irritable Bowel Syndrome Quality of Life, EuroQol and the Short-Form-12 at baseline and treatment periods 1 and 2. Results. A total of 110 patients were randomised, but only 47 completed all questionnaires and both study arms. Statistical analysis showed no difference between the placebo and Aloe vera treatment in quality of life. Discussion. This study was unable to show that Aloe vera was superior to placebo in improving quality of life. Drop outs and other confounding factors may have impacted on the power of the study to detect a clinically important difference. Conclusion. This study failed to find Aloe vera superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients.

  8. Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study.

    PubMed Central

    Blum, A L; Bethge, H; Bode, J C; Domschke, W; Feurle, G; Hackenberg, K; Hammer, B; Hüttemann, W; Jung, M; Kachel, G

    1990-01-01

    A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer. PMID:2196208

  9. 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

  10. 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.

  11. 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

  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. Assessment of CAOS as a training model in spinal surgery: a randomised study

    PubMed Central

    Kurta, I. C.; Jasani, V.; Jones, C. H. Wynn; Rahmatalla, A.; MacKenzie, G.; Dove, J.

    2006-01-01

    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

  15. Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the "Rapid Intervention with GTN in Hypertensive Stroke Trial" (RIGHT, ISRCTN66434824).

    PubMed

    Ankolekar, Sandeep; Sare, Gillian; Geeganage, Chamila; Fuller, Michael; Stokes, Lynn; Sprigg, Nikola; Parry, Ruth; Siriwardena, A Niroshan; Bath, Philip M W

    2012-01-01

    Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included. Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited. Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40.

  16. Treatment of dentin hypersensitivity with a low-level laser-emitting toothbrush: double-blind randomised clinical trial of efficacy and safety.

    PubMed

    Ko, Y; Park, J; Kim, C; Park, J; Baek, S H; Kook, Y A

    2014-07-01

    Dentin hypersensitivity (DH) is defined as pain derived from exposed dentin in response to chemical, thermal, tactile, or osmotic stimuli that cannot be explained as having arisen from any other dental defect or disease. The aim of this trial was to test the efficacy and the safety of a low-level laser-emitting toothbrush on management of DH. A prospective, double blind, randomised clinical trial was designed; 96 individuals with hypersensitive teeth without caries or fracture were selected as subjects. The subjects were randomly allocated to either the test group with the 635 nm per 6 mW laser-emitting toothbrush, or the control group with the 635 nm per 12.9 μW light-emitting diode (LED) toothbrush. An air blast was applied with a dental air syringe held 3 mm away from the selected tooth and a visual analogue scale (VAS: 0-10) was used to quantify subjective pain. Assessments were completed at a screening visit and after 2-week and 4-week of using a test/control toothbrush. Results demonstrated that the use of both control and test toothbrushes resulted in decreased discomfort after 4 weeks. In the test group, pain intensity scores decreased from 5.8 ± 1.2 to 2.3 ± 1.6, and in the control group, the scores decreased from 6.4 ± 1.3 to 5.5 ± 2.0 (P < 0.05). This decrease was significantly greater in the test group. There were no significant adverse events or side effects. It was concluded that the use of the low-level laser emitting toothbrush is a safe and effective treatment option for the management of DH.

  17. 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

  18. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial

    PubMed Central

    Bjermer, Leif; Bisgaard, Hans; Bousquet, Jean; Fabbri, Leonardo M; Greening, Andrew P; Haahtela, Tari; Holgate, Stephen T; Picado, Cesar; Menten, Joris; Dass, S Balachandra; Leff, Jonathan A; Polos, Peter G

    2003-01-01

    Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol. Participants Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for ≥ 1 year, a baseline forced expiratory volume in one second (FEV1) value 50-90% predicted, and a β agonist improvement of ≥ 12% in FEV1. Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation. Results 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19.1% in the group receiving salmeterol and fluticasone; the difference was 1% (95% confidence interval -3.1% to 5.0%). With a risk ratio (montelukast-fluticasone/salmeterol-fluticasone) of 1.05 (0.86 to 1.29), treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone. Salmeterol and fluticasone significantly increased FEV1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone (P ≤ 0.001), whereas FEV1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups. Montelukast and fluticasone significantly (P = 0.011) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone. Both treatments were generally well tolerated. Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol. PMID:14563743

  19. Copper Bracelets and Magnetic Wrist Straps for Rheumatoid Arthritis – Analgesic and Anti-Inflammatory Effects: A Randomised Double-Blind Placebo Controlled Crossover Trial

    PubMed Central

    Richmond, Stewart J.; Gunadasa, Shalmini; Bland, Martin; MacPherson, Hugh

    2013-01-01

    Background Folklore remedies for pain and inflammation in rheumatoid arthritis include the application of magnets and copper to the skin. Despite the popular use of devices containing magnets or copper for this purpose, little research has been conducted to evaluate the efficacy of such treatments. Objective To investigate whether the practice of wearing magnetic wrists straps, or copper bracelets, offers any specific therapeutic benefit for patients with rheumatoid arthritis. Design Randomised double-blind placebo-controlled crossover trial. Methods 70 patients, aged 33 to 79 years and predominantly female (n = 52), with painful rheumatoid arthritis were recruited from general practices within Yorkshire. Participants were randomly allocated to wear four devices in a different order. Devices tested were: a standard (1502 to 2365 gauss) magnetic wrist strap, a demagnetised (<20 gauss) wrist strap, an attenuated (250 to 350 gauss) magnetic wrist strap, and a copper bracelet. Devices were each worn for five weeks, with treatment phases being separated by one week wash-out periods. The primary outcome measured was pain using a 100 mm visual analogue scale. Secondary pain measures were the McGill Pain Questionnaire and tender joint count. Inflammation was assessed using C-reactive protein and plasma viscosity blood tests and by swollen joint count. Physical function was assessed using the Health Assessment Questionnaire (Disability Index). Disease activity and medication use was also measured. Results 65 participants provided complete self-report outcome data for all devices, four participants provided partial data. Analysis of treatment outcomes did not reveal any statistically significant differences (P>0.05) between the four devices in terms of their effects on pain, inflammation, physical function, disease activity, or medication use. Conclusions Wearing a magnetic wrist strap or a copper bracelet did not appear to have any meaningful therapeutic effect, beyond

  20. Treatment of dentin hypersensitivity with a low-level laser-emitting toothbrush: double-blind randomised clinical trial of efficacy and safety.

    PubMed

    Ko, Y; Park, J; Kim, C; Park, J; Baek, S H; Kook, Y A

    2014-07-01

    Dentin hypersensitivity (DH) is defined as pain derived from exposed dentin in response to chemical, thermal, tactile, or osmotic stimuli that cannot be explained as having arisen from any other dental defect or disease. The aim of this trial was to test the efficacy and the safety of a low-level laser-emitting toothbrush on management of DH. A prospective, double blind, randomised clinical trial was designed; 96 individuals with hypersensitive teeth without caries or fracture were selected as subjects. The subjects were randomly allocated to either the test group with the 635 nm per 6 mW laser-emitting toothbrush, or the control group with the 635 nm per 12.9 μW light-emitting diode (LED) toothbrush. An air blast was applied with a dental air syringe held 3 mm away from the selected tooth and a visual analogue scale (VAS: 0-10) was used to quantify subjective pain. Assessments were completed at a screening visit and after 2-week and 4-week of using a test/control toothbrush. Results demonstrated that the use of both control and test toothbrushes resulted in decreased discomfort after 4 weeks. In the test group, pain intensity scores decreased from 5.8 ± 1.2 to 2.3 ± 1.6, and in the control group, the scores decreased from 6.4 ± 1.3 to 5.5 ± 2.0 (P < 0.05). This decrease was significantly greater in the test group. There were no significant adverse events or side effects. It was concluded that the use of the low-level laser emitting toothbrush is a safe and effective treatment option for the management of DH. PMID:24717149

  1. Palonosetron and aprepitant for the prevention of postoperative nausea and vomiting in patients indicated for laparoscopic gynaecologic surgery: a double-blind randomised trial

    PubMed Central

    2014-01-01

    Background Postoperative nausea and vomiting (PONV) is one of the most common postsurgical complications. Palonosetron, a 5-hydroxytryptamine receptor antagonist, is effective for PONV prevention. Herein, we compared palonosetron and aprepitant (a neurokinin-1 receptor antagonist) for PONV prevention in patients indicated for laparoscopic gynaecologic surgery. Methods Ninety-three patients who were scheduled to undergo laparoscopic gynaecologic surgery under general anaesthesia were assigned to receive either a single intravenous injection of 0.075-mg palonosetron or 40-mg oral aprepitant in a double-blind randomised trial. The primary efficacy end points included complete response (visual analogue scale [VAS] nausea score <4 and no use of rescue therapy) 0–48 h after surgery. Nausea severity (0–10) and use of rescue therapy were monitored for 0–48 h. The secondary efficacy end points were the effect of aprepitant quantified using a 10-point VAS for pain, consumption of intravenous patient-controlled analgesia, and use of rescue analgesics. Results Aprepitant was non-inferior to palonosetron in terms of complete response 0–48 hours after surgery (74% vs. 77%). At 0 and 2 h after administration, the nausea severity with 40-mg aprepitant was significantly lesser than that with 0.075-mg palonosetron (P < 0.05). At 6 and 24 h after administration, fentanyl consumption with 40-mg aprepitant was significantly lower than that with 0.075-mg palonosetron. Greater amounts of rescue analgesics were required in the aprepitant group. Conclusions Palonosetron and aprepitant were both effective for PONV prevention in the patients indicated for laparoscopic gynaecologic surgery. The drugs can be used in combination for multimodal therapy because they bind to different receptors. More research is needed to evaluate the effects of aprepitant on pain management in humans. PMID:25165427

  2. 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.

  3. Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial.

    PubMed

    Eichenseer, M; Johansen, C; Mueller, R S

    2013-11-01

    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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: a double-blind randomised clinical trial.

    PubMed

    Nadjarzadeh, A; Shidfar, F; Amirjannati, N; Vafa, M R; Motevalian, S A; Gohari, M R; Nazeri Kakhki, S A; Akhondi, M M; Sadeghi, M R

    2014-03-01

    Low seminal plasma concentrations of coenzyme Q10 (CoQ10) have been correlated with impaired sperm parameters, but the exact mechanism remains of dominating interest. This randomised, placebo-controlled study examined the effect of CoQ10 on catalase, superoxide dismutase (SOD) and F2 -isoprostanes in seminal plasma in infertile men and their relation with CoQ10 concentration. Sixty infertile men with idiopathic oligoasthenoteratozoospermia (OAT) were randomised to receive 200 mg d(-1) of CoQ10 or placebo for 3 months. 47 persons of them completed the study. Semen analysis, anthropometric measurements, diet and physical activity assessment were performed for subjects before and after treatment. Independent and paired t-test, chi-square test and ancova were compared outcomes of supplementation between two groups. CoQ10 levels increased from 44.74 ± 36.47 to 68.17 ± 42.41 ng ml(-1) following supplementation in CoQ10 (P < 0.001). CoQ10 group had higher catalase and SOD activity than the placebo group. There was a significant positive correlation between CoQ10 concentration and normal sperm morphology (P = 0.037), catalase (P = 0.041) and SOD (P < 0.001). Significant difference was shown between the mean of changes in seminal plasma 8-isoprostane in two groups (P = 0.003) after supplementation. Three-month supplementation with CoQ10 in OAT infertile men can attenuate oxidative stress in seminal plasma and improve semen parameters and antioxidant enzymes activity.

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

    PubMed Central

    2013-01-01

    Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). Trial registration ClinicalTrials.gov (http://NCT01558765). PMID:23782510

  19. 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

  20. Relation between sampling device and detection of abnormality in cervical smears: a meta-analysis of randomised and quasi-randomised studies.

    PubMed Central

    Buntinx, F.; Brouwers, M.

    1996-01-01

    OBJECTIVE: To assess the diagnostic yield of different sampling devices used in cervical screening. DESIGN: Meta-analysis of randomised and quasi-randomised studies. SETTING: All randomised and quasi-randomised studies comparing the yield of cytological or histological abnormalities when two or more different sampling devices were used. SUBJECTS: 85,000 patients included in 29 studies reported in 28 papers. MAIN OUTCOME MEASURES: Pooled relative risk and 95% confidence interval of the yield of mild dysplasia or worse in smears recovered by each sampling method versus each other method with which it was compared; sensitivity or positive predictive value, or both, of cytological versus histological results in six studies from which sufficient data were available. RESULTS: There were no substantial differences in the yield of cytological abnormalities between the Ayre spatula, the Cytobrush, and the cotton swab used alone. There were also no substantial differences in the yield of cytological abnormalities between the extended tip spatula, the Ayre spatula combined with the Cytobrush or cotton swab, or the Cervex brush. The Ayre spatula, Cytobruah, or cotton swab used alone generally performed significantly worse than the combinations, the extended tip spatula, or the Cervex brush. There were no substantial differences in sensitivity or positive predictive value between the sampling methods. CONCLUSIONS: These results support the use of either the extended tip spatula, a combination of any spatula plus the Cytobrush or cotton swab, or the Cervex brush for cervical screening. PMID:8942687

  1. Mendelian Randomisation Study of Childhood BMI and Early Menarche.

    PubMed

    Mumby, Hannah S; Elks, Cathy E; Li, Shengxu; Sharp, Stephen J; Khaw, Kay-Tee; Luben, Robert N; Wareham, Nicholas J; Loos, Ruth J F; Ong, Ken K

    2011-01-01

    To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established "BMI-increasing" genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39-77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2 and SH2B1), and for each individual a "BMI-increasing-allele-score" was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/m(2) increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6-8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche.

  2. 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…

  3. 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

  4. 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

  5. Evaluation of Bacillus subtilis R0179 on gastrointestinal viability and general wellness: a randomised, double-blind, placebo-controlled trial in healthy adults.

    PubMed

    Hanifi, A; Culpepper, T; Mai, V; Anand, A; Ford, A L; Ukhanova, M; Christman, M; Tompkins, T A; Dahl, W J

    2015-03-01

    A probiotic formulation of Enterococcus faecium R0026 and Bacillus subtilis R0179 has been evaluated in previous clinical trials. However, B. subtilis R0179 has not been evaluated as a single probiotic strain or in combination with other strains at doses higher than 0.1×109 cfu. To establish oral dose-response tolerance and gastrointestinal (GI) viability of B. subtilis R0179, a randomised, double-blind, placebo-controlled trial in healthy adults (n=81; 18-50 years old) was conducted. Participants received B. subtilis R0179 at 0.1, 1.0 or 10×109 cfu/capsule/day or placebo for four weeks. General wellness was assessed using a daily questionnaire evaluating GI, cephalic, ear-nose-throat, behavioural, emetic, and epidermal symptoms. GI symptoms were further evaluated using a weekly gastrointestinal symptom rating scale (GSRS). GI transit viability of B. subtilis R0179 was assessed by plating and microbiota analysis by 16S rRNA at baseline, week 4 of the intervention and washout. General wellness and GI function were not affected by oral consumption of B. subtilis R0179 at any dose. Daily questionnaire syndrome scores were not different from baseline and did not exceed a clinically significant score of 1. GSRS syndrome scores were not different from baseline and ranged from 1.1±0.1 to 1.9±0.2. Faecal viable counts of B. subtilis R0179 demonstrated a dose response: the placebo group (1.1±0.1 log10 cfu/g) differed from 0.1×109 (4.6±0.1 log10 cfu/g), 1×109 (5.6±0.1 log10 cfu/g) and 10×109 (6.4±0.1 log10 cfu/g) (P<0.0001). No significant changes in phyla were observed, but sequence reads binned to multiple operational taxonomic units matching closest to Ruminococci increased during probiotic supplementation. B. subtilis R0179 survives passage through the human GI tract and is well tolerated by healthy adults at intakes from 0.1 to 10×109 cfu/day. The trial has been registered at www.clinicaltrials.gov under NCT01802151. PMID:25062611

  6. Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation.

    PubMed

    Wightman, Emma L; Reay, Jonathon L; Haskell, Crystal F; Williamson, Gary; Dew, Tristan P; Kennedy, David O

    2014-07-28

    Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.

  7. 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

    2016-01-01

    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

  8. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies

    PubMed Central

    Hanania, Nicola A; Noonan, Michael; Corren, Jonathan; Korenblat, Phillip; Zheng, Yanan; Fischer, Saloumeh K; Cheu, Melissa; Putnam, Wendy S; Murray, Elaine; Scheerens, Heleen; Holweg, Cecile TJ; Maciuca, Romeo; Gray, Sarah; Doyle, Ramona; McClintock, Dana; Olsson, Julie; Matthews, John G; Yen, Karl

    2015-01-01

    Introduction In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity. Methods LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies. Results The median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose–response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed. Conclusions These data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and

  9. 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

  10. 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

  11. [Analgesia using oral administration of tilidine naloxone for extracorporeal shockwave lithotripsy. A double blind study].

    PubMed

    Hankemeier, U; Herberhold, D; Graff, J

    1991-05-01

    Reduction in pain perception during ESWL due to a technical modification of the lithotriptor was expected and prompted a reassessment of anaesthesia techniques for ESWL. In this study the need for analgesic treatment had to be investigated. After satisfactory preliminary results in a previous pilot study, the value of the oral combination of the anti-anxiety drug dipotassium clorazepate on the evening before ESWL together with the analgesic tilidine-naloxone before treatment was tested in a randomised double-blind study in 120 patients. In case of intolerable pain during the treatment all patients were free to ask for additional intravenous analgesic medication (fentanyl). During ESWL, 28.3% of the tilidine-N group patients and 6.7% of the placebo group were pain-free, whereas intolerable pain was reported by 30% of the tilidine-N group and 56.7% of the placebo group. Therefore, 70% of the tilidine-N group patients were treated without any additional analgesic or sedative medication. The good experience with this oral anaesthesia approach, the lack of significant side effects and a good acceptance by the patients warrant further recommendation of this technique.

  12. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial

    PubMed Central

    Pantzaris, Marios C; Loukaides, George N; Ntzani, Evangelia E; Patrikios, Ioannis S

    2013-01-01

    Objective To assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing–remitting multiple sclerosis (MS) who were either treated or not with disease-modifying treatment. Design A 30-month randomised, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study. Settings Cyprus Institute of Neurology and Genetics. Participants 80 participants were randomised into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18–65; a diagnosis of relapsing–remitting MS according to the McDonald criteria; a score of 0.0–5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent (<30 days) relapse, prior immunosuppressant or monoclonal antibody therapy, pregnancy or nursing, other severe disease compromising organ function, progressive MS, history of recent drug or alcohol abuse, use of any additional food supplements, vitamins or any form of polyunsaturated fatty acids, and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity. Interventions The first intervention (A) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt. Specifically, the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt, and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt. This intervention also included minor quantities of other specific polyunsaturated, monounsaturated and saturated fatty acids as well as vitamin A and vitamin E (α-tocopherol). The second intervention (B, PLP10) was a combination of A and γ-tocopherol. The third intervention (C) was

  13. Association between randomised trial evidence and global burden of disease: cross sectional study (Epidemiological Study of Randomized Trials—ESORT)

    PubMed Central

    Odutayo, Ayodele; Hsiao, Allan J; Shakir, Mubeen; Hopewell, Sally; Rahimi, Kazem; Altman, Douglas G

    2015-01-01

    Objectives To determine whether an association exists between the number of published randomised controlled trials and the global burden of disease, whether certain diseases are under-investigated relative to their burden, and whether the relation between the output of randomised trials and global burden of disease can be explained by the relative disease burden in high and low income regions. Design Cross sectional investigation. Study sample All primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013. Main outcome measures Number of trials conducted and number of participants randomised for each of 239 different diseases or injuries; variation in each outcome explainable by total disability adjusted life years (a measure of the overall burden of each disease) and the ratio of disability adjusted life years in low income to high income regions (a measure of whether a disease is more likely to affect people living in high income regions) quantified using multivariable regression. Results 4190 abstracts were reviewed and 1351 primary randomised trials identified, of which 1097 could be classified using the global burden of disease taxonomy. Total disability adjusted life years was poorly associated with number of randomised trials and number of participants randomised in univariable analysis (Spearman’s r=0.35 and 0.33, respectively), although it was a significant predictor in the univariable and multivariable models (P<0.001). Diseases for which the burden was predominantly located in low income regions had sevenfold fewer trials per million disability adjusted life years than diseases predominantly located in high income regions. However, only 26% of the variation in number of trials among diseases could be explained by total disability adjusted life years and the ratio of disability adjusted life years in low income regions to high income regions. Many high income type diseases (for example, neck pain

  14. 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

  15. 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.

  16. 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

  17. Sub-lingual administration of a polyvalent mechanical bacterial lysate (PMBL) in patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD) according to the GOLD spirometric classification: A multicentre, double-blind, randomised, controlled, phase IV study (AIACE study: Advanced Immunological Approach in COPD Exacerbation).

    PubMed

    Braido, Fulvio; Melioli, Giovanni; Cazzola, Mario; Fabbri, Leonardo; Blasi, Francesco; Moretta, Lorenzo; Canonica, Giorgio Walter

    2015-08-01

    Polyvalent mechanical bacterial lysates (PMBLs) have been shown to reduce the number of infectious episodes in patients with recurrent infections of the respiratory tract. Some previous investigations have also shown the effectiveness of PMBLs in reducing exacerbations of chronic obstructive pulmonary disease (COPD). The AIACE study, which was developed according to criteria of evidence-based medicine, evaluated whether the administration of PMBLs to COPD patients, in addition to the recommended treatment, was able to reduce the number of exacerbations by 25%. Two hundred eighty-eight patients with moderate to very severe COPD were recruited and randomly assigned to either placebo or PMBLs. The placebo or PMBLs were administered according to the standard scheme. The primary outcome of the study was not achieved. However, the number of days with fever (21 days per year versus 40.15; p < 0.001), the days of hospitalisation (65 days vs 162 days; p < 0.001), the interval between the first and second exacerbations (123.89 days vs 70.36; p = 0.03) and the number of days in poor health (109 days/year vs 171 days/year; p < 0.001) were significantly better in the PMBL group than in the placebo group. In conclusion, the results of this trials showed that Ismigen, in addition to guideline-suggested treatment, could not significantly reduce the number of exacerbations in the considered population; nevertheless, the secondary outcome results demonstrated potential benefits of this compound for relevant clinical outcomes. PMID:25951945

  18. 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

  19. Effect of eplerenone on insulin action in essential hypertension: a randomised, controlled, crossover study.

    PubMed

    McMurray, E M; Wallace, I R; Ennis, C; Hunter, S J; Atkinson, A B; Bell, P M

    2014-10-01

    An association exists between hyperaldosteronism, hypertension and impaired insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action. The aim of this study was to determine the effect of eplerenone on insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either eplerenone 25 mg twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting glucose, or fasting insulin between treatment with eplerenone or doxazosin. The measure of overall insulin sensitivity, exogenous glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg(-1) min(-1) after eplerenone and 23.3 (3.6) μmol kg(-1) min(-1) after doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production rates were similar after both treatments (eplerenone 9.4 (0.6) μmol kg(-1) min(-1) vs doxazosin 10.6 (0.7) μmol kg(-1) min(-1)). There was a trend for lower endogenous glucose production rates during hyperinsulinaemia following eplerenone compared with doxazosin (2.0 (0.8) μmol kg(-1) min(-1) vs 4.1 (0.9) μmol kg(-1) min(-1)). There was no difference in insulin stimulated peripheral glucose utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) μmol kg(-1) min(-1) vs 27.0 (3.9) μmol kg(-1) min(-1)). This study gives reassuring evidence of the neutral effect of eplerenone on insulin action in hypertensive, non-diabetic patients.

  20. 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

  1. Ascorbic acid in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial

    PubMed Central

    Pareyson, Davide; Reilly, Mary M; Schenone, Angelo; Fabrizi, Gian Maria; Cavallaro, Tiziana; Santoro, Lucio; Vita, Giuseppe; Quattrone, Aldo; Padua, Luca; Gemignani, Franco; Visioli, Francesco; Laurà, Matilde; Radice, Davide; Calabrese, Daniela; Hughes, Richard AC; Solari, Alessandra

    2011-01-01

    Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the

  2. 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

  3. Practicalities of Using a Modified Version of the Cochrane Collaboration Risk of Bias Tool for Randomised and Non-Randomised Study Designs Applied in a Health Technology Assessment Setting

    ERIC Educational Resources Information Center

    Robertson, Clare; Ramsay, Craig; Gurung, Tara; Mowatt, Graham; Pickard, Robert; Sharma, Pawana

    2014-01-01

    We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. Objectives: (1) To assess time to complete RoB assessment; (2) To assess inter-rater agreement; and (3) To explore the association between RoB and treatment effect size. Methods: Cochrane risk of…

  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. 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.

  6. The efficacy and safety of Grafix(®) for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial.

    PubMed

    Lavery, Lawrence A; Fulmer, James; Shebetka, Karry Ann; Regulski, Matthew; Vayser, Dean; Fried, David; Kashefsky, Howard; Owings, Tammy M; Nadarajah, Janaki

    2014-10-01

    In a randomised, controlled study, we compared the efficacy of Grafix(®) , a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase. The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix (62%) compared with controls (21%, P = 0·0001). The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls (P = 0·019). There were fewer Grafix patients with adverse events (44% versus 66%, P = 0·031) and fewer Grafix patients with wound-related infections (18% versus 36·2%, P = 0·044). Among the study subjects that healed, ulcers remained closed in 82·1% of patients (23 of 28 patients) in the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0·419). Treatment with Grafix significantly improved DFU healing compared with standard wound therapy. Importantly, Grafix also reduced DFU-related complications. The results of this well-controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than standard wound therapy.

  7. Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee – A Comparison of Randomised and Non-Randomised Studies

    PubMed Central

    Oeller, Patrick; Kasenda, Benjamin; Briel, Matthias; von Elm, Erik

    2016-01-01

    Background Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. Objectives To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. Methods We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Results Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Conclusions Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs. PMID:27792749

  8. 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.

  9. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants

    PubMed Central

    Ng, P; So, K; Fung, K; Lee, C; Fok, T; Wong, E; Wong, W; Cheung, K; Cheng, A

    2001-01-01

    AIM—To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.
METHODS—A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.
RESULTS—Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.
CONCLUSIONS—Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on

  10. 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

  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. 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

  14. The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

    PubMed Central

    de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

    2014-01-01

    Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

    PubMed Central

    Brown, Simon G A; Ball, Emma L; Perrin, Kyle; Read, Catherine A; Asha, Stephen E; Beasley, Richard; Egerton-Warburton, Diana; Jones, Peter G; Keijzers, Gerben; Kinnear, Frances B; Kwan, Ben C H; Lee, Y C Gary; Smith, Julian A; Summers, Quentin A; Simpson, Graham

    2016-01-01

    Introduction Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. Methods and analysis This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Ethics and dissemination Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high

  20. Coblation tonsillectomy: a double blind randomized controlled study.

    PubMed

    Timms, M S; Temple, R H

    2002-06-01

    Tonsillectomy has been performed by a number of techniques. This double blind randomized controlled study compares the technique of tissue coblation with bipolar dissection for the removal of tonsils in 10 adult patients with a history of chronic tonsillitis. A significant reduction in post-operative pain and more rapid healing of the tonsillar fossae were found in the side removed by tissue coblation. There were no episodes of primary or secondary haemorrhage on either side. This new technique for tonsil removal warrants further study.

  1. 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

  2. Study of the therapeutic effects of an advanced hippotherapy simulator in children with cerebral palsy: a randomised controlled trial

    PubMed Central

    2010-01-01

    Background Although hippotherapy treatment has been demonstrated to have therapeutic effects on children with cerebral palsy, the samples used in research studies have been very small. In the case of hippotherapy simulators, there are no studies that either recommend or advise against their use in the treatment of children with cerebral palsy. The aim of this randomised clinical study is to analyse the therapeutic effects or the contraindications of the use of a commercial hippotherapy simulator on several important factors relating to children with cerebral palsy such as their motor development, balance control in the sitting posture, hip abduction range of motion and electromyographic activity of adductor musculature. Methods/Design The study is a randomised controlled trial. It will be carried out with a sample of 37 children with cerebral palsy divided into two treatment groups. Eligible participants will be randomly allocated to receive either (a) Treatment Group with hippotherapy simulator, maintaining sitting posture, with legs in abduction and rhythmic movement of the simulator or (b) Treatment Group maintaining sitting posture, with legs in abduction and without rhythmic movement of the simulator. Data collection and analysis: all measurements will be carried out by a specially trained blind assessor. To ensure standardization quality of the assessors, an inter-examiner agreement will be worked out at the start of the study. The trial is funded by the Department of Research, Innovation and Development of the Regional Government of Aragon (Official Bulletin of Aragon 23 July 2007), project number PM059/2007. Discussion Interest in this project is due to the following factors: Clinical originality (there are no previous studies analysing the effect of simulators on the population group of children with CP, nor any studies using as many variables as this project); Clinical impact (infantile cerebral palsy is a chronic multisystemic condition that affects not

  3. 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

  4. 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.

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

    PubMed Central

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

    2016-01-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments. PMID:27730198

  6. Influence of a Specialized Trigonella foenum-graecum Seed Extract (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy Menstruating Women, a Randomised Placebo Controlled Study.

    PubMed

    Rao, Amanda; Steels, Elizabeth; Beccaria, Gavin; Inder, Warrick J; Vitetta, Luis

    2015-08-01

    The aim of the study was to evaluate the effect of Trigonella foenum-graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo-controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum-graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self-administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI-20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum-graecum may be a useful treatment for increasing sexual arousal and desire in women. PMID:25914334

  7. 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

  8. Dose reduction of edoxaban preserves efficacy and safety for the treatment of venous thromboembolism. An analysis of the randomised, double-blind HOKUSAI VTE trial.

    PubMed

    Verhamme, Peter; Wells, Philip S; Segers, Annelise; Ageno, Walter; Brekelmans, Marjolein P A; Cohen, Alexander T; Meyer, Guy; Grosso, Michael A; Raskob, Gary; Weitz, Jeffrey I; Zhang, George; Buller, Harry

    2016-09-27

    Direct oral anticoagulants simplify venous thromboembolism (VTE) treatment by obviating the need for coagulation monitoring. Nonetheless, renal function, body weight and P-glycoprotein inhibitors influence drug levels. The objective of this analysis was to determine whether reduction in edoxaban dose based on clinical criteria avoids excess drug exposure and preserves efficacy and safety in the Hokusai-VTE study. After initial heparin, patients received edoxaban or warfarin for 3-12 months. Edoxaban was given once daily at a dose of 60 mg, which was reduced to 30 mg in patients with a creatinine clearance of 30-50 ml/minute, body weight ≤60 kg or receiving certain P-glycoprotein inhibitors. The primary efficacy outcome was recurrent VTE and the principal safety outcome was major or clinically relevant non-major bleeding. A total of 8292 patients with acute VTE were randomised, 733 and 719 patients in the edoxaban and warfarin groups met the criteria for dose reduction. These patients were older, more often female or Asian and had more extensive VTE. Edoxaban levels were lower in the 30 mg edoxaban group. Rates of recurrent VTE and bleeding with the 30 mg and 60 mg edoxaban dose were comparable: VTE rates were 3.0 % and 3.2 % and clinically relevant bleeding rates were 7.9 % and 8.6 %, respectively. Rates of recurrent VTE and bleeding in the warfarin-treated patients meeting the criteria for dose reduction were 4.2 % and 12.8 %, respectively. The reduced dose edoxaban regimen maintained efficacy and safety compared with the 60 mg dose but was safer than warfarin in patients meeting the criteria for dose reduction.

  9. Effect of live and inactivated Lactobacillus rhamnosus GG on experimentally induced rhinovirus colds: randomised, double blind, placebo-controlled pilot trial.

    PubMed

    Kumpu, M; Kekkonen, R A; Korpela, R; Tynkkynen, S; Järvenpää, S; Kautiainen, H; Allen, E K; Hendley, J O; Pitkäranta, A; Winther, B

    2015-01-01

    The aim of this work was to investigate the usability of an experimental rhinovirus model in probiotic trials aiming to assess effectiveness in viral infections, and to provide preliminary data of live and inactivated probiotic Lactobacillus rhamnosus GG for larger-scale trials utilising the model. 59 subjects were randomised to receive 100 ml of fruit juice supplemented with 10(9) cfu of live or heat-inactivated (by spray-drying) L. rhamnosus GG or control juice daily for six weeks. After three weeks subjects were intranasally inoculated with experimental rhinovirus. Infection rate (at least one positive culture for challenge virus on five days following inoculation or at least four-fold rise in antibody response to challenge virus) was 14/19 in the group receiving live probiotic strain and 18/20 both in the group receiving heat-inactivated probiotic strain and in the control group (P=0.36). The occurrence and severity of cold symptoms on the five days following the inoculation was lowest in the group receiving live probiotic strain (P=0.45). This trial was the first one dedicated to the investigation of the effect of probiotics using the experimental rhinovirus model. The model showed potential for demonstration of efficacy of probiotics in controlled respiratory viral infections. Occurrence and severity of cold symptoms and number of subjects with rhinovirus infection was lowest in the group receiving live L. rhamnosus GG, but differences were not statistically significant. Further large-scale studies are needed to demonstrate the efficacy of L. rhamnosus GG in respiratory infections.

  10. Dose reduction of edoxaban preserves efficacy and safety for the treatment of venous thromboembolism. An analysis of the randomised, double-blind HOKUSAI VTE trial.

    PubMed

    Verhamme, Peter; Wells, Philip S; Segers, Annelise; Ageno, Walter; Brekelmans, Marjolein P A; Cohen, Alexander T; Meyer, Guy; Grosso, Michael A; Raskob, Gary; Weitz, Jeffrey I; Zhang, George; Buller, Harry

    2016-09-27

    Direct oral anticoagulants simplify venous thromboembolism (VTE) treatment by obviating the need for coagulation monitoring. Nonetheless, renal function, body weight and P-glycoprotein inhibitors influence drug levels. The objective of this analysis was to determine whether reduction in edoxaban dose based on clinical criteria avoids excess drug exposure and preserves efficacy and safety in the Hokusai-VTE study. After initial heparin, patients received edoxaban or warfarin for 3-12 months. Edoxaban was given once daily at a dose of 60 mg, which was reduced to 30 mg in patients with a creatinine clearance of 30-50 ml/minute, body weight ≤60 kg or receiving certain P-glycoprotein inhibitors. The primary efficacy outcome was recurrent VTE and the principal safety outcome was major or clinically relevant non-major bleeding. A total of 8292 patients with acute VTE were randomised, 733 and 719 patients in the edoxaban and warfarin groups met the criteria for dose reduction. These patients were older, more often female or Asian and had more extensive VTE. Edoxaban levels were lower in the 30 mg edoxaban group. Rates of recurrent VTE and bleeding with the 30 mg and 60 mg edoxaban dose were comparable: VTE rates were 3.0 % and 3.2 % and clinically relevant bleeding rates were 7.9 % and 8.6 %, respectively. Rates of recurrent VTE and bleeding in the warfarin-treated patients meeting the criteria for dose reduction were 4.2 % and 12.8 %, respectively. The reduced dose edoxaban regimen maintained efficacy and safety compared with the 60 mg dose but was safer than warfarin in patients meeting the criteria for dose reduction. PMID:27440518

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups. Discussion This trial will inform international debate and policy on the regulation and

  16. 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

  17. Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial

    PubMed Central

    2014-01-01

    Background Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control. The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus. Methods/design In a randomised double-blind placebo-controlled trial conducted in five general practices in the Netherlands three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are randomised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and six months. Secondary outcome measures include blood pressure, anthropometric parameters, lipid profile, insulin resistance, quality of life, advanced glycation end products and safety profiles. Quality of life will be measured by The Short Form (SF-36) Health Survey questionnaire. Advanced glycation end products are measured by an AGE-reader. Discussion This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus. Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus. Trial registration The Netherlands trial register: NTR3154 PMID:25033925

  18. 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

  19. The favourable effects of long-term selenium supplementation on regression of cervical tissues and metabolic profiles of patients with cervical intraepithelial neoplasia: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Karamali, Maryam; Nourgostar, Sepideh; Zamani, Ashraf; Vahedpoor, Zahra; Asemi, Zatollah

    2015-12-28

    This study was conducted to assess the effects of long-term Se administration on the regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This randomised, double-blind, placebo-controlled trial was carried out among fifty-eight women diagnosed with CIN1. To diagnose CIN1, we used specific diagnostic procedures of biopsy, pathological diagnosis and colposcopy. Patients were randomly assigned to two groups to receive 200 μg Se supplements as Se yeast (n 28) or placebo (n 28) daily for 6 months. After 6 months of taking Se supplements, a greater percentage of women in the Se group had regressed CIN1 (88·0 v. 56·0 %; P=0·01) compared with those in the placebo group. Long-term Se supplementation, compared with the placebo, resulted in significant decreases in fasting plasma glucose levels (-0·37 (sd 0·32) v. +0·07 (sd 0·63) mmol/l; P=0·002), serum insulin levels (-28·8 (sd 31·2) v. +13·2 (sd 40·2) pmol/l; P<0·001), homeostatic model assessment of insulin resistance values (-1·3 (se 1·3) v. +0·5 (se 1·4); P<0·001) and a significant elevation in quantitative insulin sensitivity check index (+0·03 (sd 0·03) v. -0·01 (sd 0·01); P<0·001). In addition, patients who received Se supplements had significantly decreased serum TAG (-0·14 (sd 0·55) v. +0·15 (sd 0·38) mmol/l; P=0·02) and increased HDL-cholesterol levels (+0·13 (sd 0·21) v. -0·01 (sd 0·15) mmol/l; P=0·003). In addition, compared with the placebo group, there were significant rises in plasma total antioxidant capacity (+186·1 (sd 274·6) v. +42·8 (sd 180·4) mmol/l; P=0·02) and GSH levels (+65·0 (sd 359·8) v. -294·2 (sd 581·8) μmol/l; P=0·007) and a significant decrease in malondialdehyde levels (-1·5 (sd 2·1) v. +0·1 (sd 1·4) μmol/l; P=0·001) among those who took Se supplements. Overall, taking Se supplements among patients with CIN1 led to its regression and had beneficial effects on their metabolic profiles. PMID

  20. Rationalisation of regimens of treatment of kala-azar with sodium stibogluconate in India: a randomised study

    PubMed Central

    Thakur, C P; Kumar, M; Kumar, P; Mishra, B N; Pandey, A K

    1988-01-01

    The efficacy and safety of six regimens of treatment for kala-azar (visceral leishmaniasis) with sodium stibogluconate were evaluated in a prospective randomised study to ascertain the optimal treatment for Indian patients. Altogether 371 patients with kala-azar were randomised to receive sodium stibogluconate intramuscularly at a dose of 10 mg/kg body weight/day for 20 or 40 days (groups A and A1, respectively), 15 mg/kg body weight/day for 20 or 40 days (groups B and B1, respectively), or 20 mg/kg body weight/day for 20 or 40 days (groups C and C1, respectively). Patients were examined blind before and at the end of treatment and every month for six months. The number of patients who were apparently cured—that is, those whose temperature had returned to normal at the end of their regimen of treatment—was 45 (78%) in group A, 53 (87%) in group A1, 50 (81%) in group B, 60 (95%) in group B1, 58 (92%) in group C, and 62 (97%) in group C1. At six months 62 patients (97%) in group C1, 51 (81%) in group C, 54 (86%) in group B1, 42 (68%) in group B, 45 (74%) in group A1, and 33 (57%) in group A had not relapsed and were cured as confirmed by a bone marrow aspirate free of parasites. The differences between groups C1 and C, B1 and B, and A1 and A were significant. Logistic regression of the proportion cured with the dose and length of treatment showed that both factors were significant in improving the rate of cure; the highest dose for the longer time (group C1) had the best rate of cure. One patient in group C1, 12 in group C, nine in group B1, 18 in group B, 15 in group A1, and 23 in group A were cured with extended courses of 20 mg sodium stibogluconate. One patient in each of groups C1, B, A1, and A became unresponsive to antimony and were cured with pentamidine. One patient in each of groups C1, B, and A became unresponsive to both antimony and pentamidine. The patients tolerated the longer duration of treatment safely, and side effects were minor. Sodium

  1. Comparative effectiveness of quetiapine and haloperidol in delirium: A single blind randomized controlled study

    PubMed Central

    Grover, Sandeep; Mahajan, Sudhir; Chakrabarti, Subho; Avasthi, Ajit

    2016-01-01

    AIM To evaluate the effectiveness of quetiapine and haloperidol in patients of delirium referred to psychiatry consultation liaison services. METHODS The study followed a single blind randomised controlled trial design. Thirty-two patients in the haloperidol group and 31 patients in the quetiapine group were assessed at the baseline and 6 consecutive days. Flexible dosing regimen (haloperidol: 0.25-1.25 mg; quetiapine 12.5-75 mg/d) was used. Delirium Rating Scale-Revised-98 (DRS-R-98) and mini mental status examination (MMSE) were the primary and secondary efficacy measures respectively. RESULTS Baseline DRS-R-98 severity score and MMSE scores did not differ between the 2 study groups. From baseline to day 6, there was significant reduction in the total DRS-R-98 scores, DRS-R-98 cognitive domain scores, DRS-R-98 non-cognitive domain scores and significant increase in the MMSE scores in both the groups. Both the groups did not differ on any of the assessments in terms of DRS-R98 and MMSE scores. The effectiveness of both the medications was similar in adult and elderly (≥ 60 years) patients. At the end of the trial, 68.75% and 67.74% of subjects in the haloperidol and quetiapine group respectively had mean DRS-R-98 scores below 10. By 6th day, 12 (37.5%) patients in haloperidol group and 9 (29.03%) patients in the quetiapine group had DRS-R98 score of “0” with no significant difference between the two groups (P = 0.47). CONCLUSION Quetiapine is as effective as haloperidol in the management of delirium. PMID:27679777

  2. Comparative effectiveness of quetiapine and haloperidol in delirium: A single blind randomized controlled study

    PubMed Central

    Grover, Sandeep; Mahajan, Sudhir; Chakrabarti, Subho; Avasthi, Ajit

    2016-01-01

    AIM To evaluate the effectiveness of quetiapine and haloperidol in patients of delirium referred to psychiatry consultation liaison services. METHODS The study followed a single blind randomised controlled trial design. Thirty-two patients in the haloperidol group and 31 patients in the quetiapine group were assessed at the baseline and 6 consecutive days. Flexible dosing regimen (haloperidol: 0.25-1.25 mg; quetiapine 12.5-75 mg/d) was used. Delirium Rating Scale-Revised-98 (DRS-R-98) and mini mental status examination (MMSE) were the primary and secondary efficacy measures respectively. RESULTS Baseline DRS-R-98 severity score and MMSE scores did not differ between the 2 study groups. From baseline to day 6, there was significant reduction in the total DRS-R-98 scores, DRS-R-98 cognitive domain scores, DRS-R-98 non-cognitive domain scores and significant increase in the MMSE scores in both the groups. Both the groups did not differ on any of the assessments in terms of DRS-R98 and MMSE scores. The effectiveness of both the medications was similar in adult and elderly (≥ 60 years) patients. At the end of the trial, 68.75% and 67.74% of subjects in the haloperidol and quetiapine group respectively had mean DRS-R-98 scores below 10. By 6th day, 12 (37.5%) patients in haloperidol group and 9 (29.03%) patients in the quetiapine group had DRS-R98 score of “0” with no significant difference between the two groups (P = 0.47). CONCLUSION Quetiapine is as effective as haloperidol in the management of delirium.

  3. 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?.

  4. 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.

  5. β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol

    PubMed Central

    Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

    2016-01-01

    Introduction A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. Methods and analyses This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. Ethics and dissemination The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national

  6. Maintaining endotracheal tube cuff pressure at 20 mm Hg to prevent dysphagia after anterior cervical spine surgery; protocol of a double-blind randomised controlled trial

    PubMed Central

    2013-01-01

    Background In anterior cervical spine surgery a retractor is obligatory to approach the spine. Previous studies showed an increase of endotracheal tube cuff pressure after placement of a retractor. It is known that high endotracheal tube cuff pressure increases the incidence of postoperative dysphagia, hoarseness, and sore throat. However, until now no evidence supports the fact whether adjusting the endotracheal tube cuff pressure during anterior cervical spine surgery will prevent this comorbidity. We present the design of a randomized controlled trial to determine whether adjusting endotracheal tube cuff pressure after placement of a retractor during anterior cervical spine surgery will prevent postoperative dysphagia. Methods/design 177 patients (aged 18–90 years) scheduled for anterior cervical spine surgery on 1 or more levels will be included. After intubation, endotracheal tube cuff pressure is manually inflated to 20 mm Hg in all patients. Patients will be randomized into two groups. In the control group endotracheal tube cuff pressure is not adjusted after retractor placement. In the intervention group endotracheal tube cuff pressure after retractor placement is maintained at 20 mm Hg and air is withdrawn when cuff pressure exceeds 20 mm Hg. Endotracheal tube cuff pressure is measured after intubation, before and after placement and removal of the retractor. Again air is inflated if cuff pressure sets below 20 mmHg after removal of the retractor. The primary outcome measure is postoperative dysphagia. Other outcome measures are postoperative hoarseness, postoperative sore throat, degree of dysphagia, length of hospital stay, and pneumonia. The study is a single centre double blind randomized trial in which patients and research nurses will be kept blinded for the allocated treatment during the follow-up period of 2 months. Discussion Postoperative dysphagia occurs frequently after anterior cervical spine surgery. This may be related to high

  7. Efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule on primary insomnia: study protocol for a randomised controlled trial

    PubMed Central

    Liu, Qing-Quan; Zhang, Jie; Guo, Rong-Juan; Xie, Ying-Zhen; Fu, Qing-Nan; He, Tian; Zhu, Xue-Qi; Du, Jie; Yang, Jing; Wang, Jia-Lin; Wei, Min-Min; Li, Qian-Qian; Shi, Guang-Xia; Liu, Cun-Zhi

    2016-01-01

    Introduction Insomnia is a highly prevalent, often debilitating and economically burdensome sleep disorder with limited effective therapies. Few data are available to understand which of the therapeutic alternatives is the most effective for patients with insomnia, especially for Traditional Chinese Medicine (TCM). Chinese herbal medicine, as a typical TCM, is one of the most popular complementary and alternative therapies for insomnia. We aim to evaluate the efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule (CSG), a Chinese herbal medicine treatment, in patients with primary insomnia. Methods and analysis This is a multicentre, placebo-controlled, double-blinded, randomised controlled clinical trial. A total of 258 participants are randomly allocated to two groups: the intervention group or the placebo group. The intervention group receives CSG and the placebo group receives a placebo granule. The patients receive either CSG or placebo two times daily for 8 weeks. The primary outcome is the Pittsburgh sleep quality index (PSQI). Secondary outcomes include the Insomnia Severity Index (ISI), Total Sleep Time (TST) and the Short-Form Health Survey (SF-36). The assessment is performed at baseline (before randomisation), 4, 8 and 12 weeks after randomisation. Ethics and dissemination The protocol has been approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (reference: 2014BL-003-01). The trial will be helpful in identifying the efficacy and safety of CSG in patients with primary insomnia. Trial registration number ISRCTN22001145; Pre-results. PMID:26839010

  8. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.

    PubMed

    White, David J; de Klerk, Suzanne; Woods, William; Gondalia, Shakuntla; Noonan, Chris; Scholey, Andrew B

    2016-01-19

    L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine.

  9. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.

    PubMed

    White, David J; de Klerk, Suzanne; Woods, William; Gondalia, Shakuntla; Noonan, Chris; Scholey, Andrew B

    2016-01-01

    L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine. PMID:26797633

  10. Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    PubMed Central

    White, David J.; de Klerk, Suzanne; Woods, William; Gondalia, Shakuntla; Noonan, Chris; Scholey, Andrew B.

    2016-01-01

    l-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an l-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18–40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the l-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of l-theanine. PMID:26797633

  11. Emollient efficacy and acceptability in the treatment of eczematous dry skin: A double-blind, randomised comparison of two UK-marketed products

    PubMed Central

    Djokic-Gallagher, Jasmina; Rosher, Philip; Walker, Jennine; Sykes, Krystyna; Hart, Valerie

    2016-01-01

    Abstract Objective: The aim of this study was to compare the moisturising efficacy and acceptability of physical characteristics of two commonly prescribed emollients licenced in the UK, Doublebase Dayleve gel (DELP) and Diprobase cream (DIPC). Methods: The study was a double-blind, concurrent bi-lateral comparison in female eczema subjects with dry skin. Results: In Part 1, comparing the area under the curve (AUC) change from baseline corneometer readings over 24 h following single applications of the emollients to the volar forearms of 34 subjects, the AUC for DELP was more than three times that seen for DIPC (p < 0.0001). In Part 2, comparing the same outcome measured over 5 days of twice daily applications to the lower legs in 36 subjects, the AUC for DELP was approximately five times that for DIPC (p < 0.0001). 69% of subjects “Like Slightly” or “Like Strongly” DELP compared to 33% for DIPC (p = 0.025). 72% indicated they would use DELP again compared to 33% for DIPC (p = 0.033). 75% of subjects preferred DELP, 17% preferred DIPC and 8% expressed no preference (p = 0.0004). PMID:26864095

  12. A randomized double blind study of two oral contraceptives.

    PubMed

    Sanhueza, H; Sivin, I; Kumar, S; Kessler, M; Carrasco, A; Yee, J

    1979-07-01

    To study the question of whether one brand of oral contraceptives may be as acceptable as another for use of publicly-assisted family planning programs, a double blind study of two well-known brands, Ovral and Norinyl, was undertaken in Costa Rica and Trinidad. The pills were randomly assigned to 1,200 women. Common side effects - nausea, dizziness, vomiting, headaches - were associated with both Norinyl and Ovral. Differences in event rates for these conditions were much more marked by country than by the pill used. Ovral was associated with increases in skin problems, notably chloasma, in Cost Rica. A higher percentage of women using Norinyl reported intermenstrual bleeding and spotting in both countries. In Costa Rica continuation rates for Norinyl were adversely affected by this. With these exceptions there appear to be no important differences between the brands that would affect their use in family planning programs. PMID:477315

  13. Prevention of surgical site infection in lower limb skin lesion excisions with single dose oral antibiotic prophylaxis: a prospective randomised placebo-controlled double-blind trial

    PubMed Central

    Smith, Samuel C; Heal, Clare F; Buttner, Petra G

    2014-01-01

    Objectives To determine the effectiveness of a single perioperative prophylactic 2 g dose of cephalexin in preventing surgical site infection (SSI) following excision of skin lesions from the lower limb. Design Prospective double-blinded placebo-controlled trial testing for difference in infection rates. Setting Primary care in regional North Queensland, Australia. Participants 52 patients undergoing lower limb skin lesion excision. Interventions 2 g dose of cephalexin 30–60 min before excision. Main outcome measures Incidence of SSI. Results Incidence of SSI was 12.5% (95% CI 2.7% to 32.4%) in the cephalexin group compared with 35.7% (95% CI 18.6% to 55.9%) in the placebo group (p=0.064). This represented an absolute reduction of 23.21% (95% CI −0.39% to 46.82%), relative reduction of 65.00% (95% CI −12.70% to 89.13%) and number-needed-to-treat of 4.3. Conclusions Administration of a single 2 g dose of cephalexin 30–60 min before skin lesion excision from the lower limb may produce a reduction in the incidence of infection; however, this study was underpowered to statistically determine this. Trial registration number ACTRN12611000595910. PMID:25079934

  14. Morinda citrifolia (Noni) as an Anti-Inflammatory Treatment in Women with Primary Dysmenorrhoea: A Randomised Double-Blind Placebo-Controlled Trial.

    PubMed

    Fletcher, H M; Dawkins, J; Rattray, C; Wharfe, G; Reid, M; Gordon-Strachan, G

    2013-01-01

    Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea. Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume. Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls. Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo.

  15. Sclerosing injections to treat midportion Achilles tendinosis: a randomised controlled study evaluating two different concentrations of Polidocanol.

    PubMed

    Willberg, Lotta; Sunding, Kerstin; Ohberg, Lars; Forssblad, Magnus; Fahlström, Martin; Alfredson, Håkan

    2008-09-01

    Two to three ultrasound (US) and colour Doppler (CD)-guided injections of the sclerosing substance Polidocanol (5 mg/ml) have been demonstrated to give good clinical results in patients with chronic midportion Achilles tendinopathy. This study aimed to investigate if a higher concentration of Polidocanol (10 mg/ml) would lead to a less number of treatments, and lower volumes, needed for good clinical results. Fifty-two consecutive Achilles tendons (48 patients, mean age 49.6 years) with chronic painful midportion Achilles tendinopathy, were randomised to treatment with Polidocanol 5 mg/ml (group A) or 10 mg/ml (group B). The patients and treating physician were blinded to the concentration of Polidocanol injected. All patients had structural tendon changes and neovascularisation in the Achilles midportion. Treatment was US + CD-guided injections targeting the region with neovascularisation (outside ventral tendon). A maximum of three treatments (6-8 weeks in between) were given before evaluation. Patients not satisfied after three treatments were given additional treatment with Polidocanol 10 mg/ml, up to five treatments. For evaluation, the patients recorded the severity of Achilles tendon pain during activity on a visual analogue scale (VAS), before and after treatment. Patient satisfaction with treatment was also assessed. At follow-up (mean 14 months) after three treatments, 18/26 patients in group A and 19/26 patients in group B were satisfied with the treatment and had a significantly reduced level of tendon pain (P < 0.05). After completion of the study, additional treatments with Polidocanol 10 mg/ml in the not satisfied patients resulted in 26/26 satisfied patients in both groups A and B. In summary, we found no significant differences in the number of satisfied patients, number of injections or volumes given, between patients treated with 5 or 10 mg/ml Polidocanol.

  16. Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol

    PubMed Central

    Liu, Zhao-min; Ho, Suzanne; Hao, Yuan-tao; Chen, Yu-ming; Woo, Jean; Wong, Samuel Yeung-shan; He, Qiqiang; Tse, Lap Ah; Chen, Bailing; Su, Xue-fen; Lao, Xiang-qian; Wong, Carmen; Chan, Ruth; Ling, Wen-hua

    2016-01-01

    Introduction Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women. Methods and analysis This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso-calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment. Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository. Trial registration number NCT02610322. PMID:27678545