Sathyapalan, Thozhukat; Thatcher, Natalie J.; Hammersley, Richard; Rigby, Alan S; Pechlivanis, Alexandros; Gooderham, Nigel J; Holmes, Elaine; le Roux, Carel W.; Stephen L. Atkin; Courts, Fraser
Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight indivi...
Full Text Available Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation.This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics.Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008 and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04, reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects.Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that
Full Text Available Background and Aims: Dexmedetomidine (α2 adrenergic agonist has been used for prevention of post anaesthesia shivering. Its use for the treatment of post-spinal anaesthesia shivering has not been evaluated. The aim of this study was to evaluate and compare the efficacy, haemodynamic and adverse effects of dexmedetomidine with those of tramadol, when used for control of post-spinal anaesthesia shivering. Methods: A prospective, randomised, and double-blind study was conducted in 50 American Society of Anaesthesiologists Grade I and II patients of either gender, aged between 18 and 65 years, scheduled for various surgical procedures under spinal anaesthesia. The patients were randomised in two groups of 25 patients each to receive either dexmedetomidine 0.5 μg/kg or tramadol 0.5 mg/kg as a slow intravenous bolus. Grade of shivering, onset of shivering, time for cessation of shivering, recurrence, response rate, and adverse effects were observed at scheduled intervals. Unpaired t-test was used for analysing the data. Results: Time taken for cessation of shivering was significantly less with dexmedetomidine when compared to tramadol. Nausea and vomiting was observed only in tramadol group (28% and; 20% respectively. There was not much difference in the sedation profile of both the drugs. Conclusion: We conclude that although both drugs are effective, the time taken for cessation of shivering is less with dexmedetomidine when compared to tramadol. Moreover, dexmedetomidine has negligible adverse effects, whereas tramadol is associated with significant nausea and vomiting.
Full Text Available This double-blind randomised parallel-group study comparing the efficacy and side effects of minocycline with that of cotrimoxazole in chancroid, had 56 analysable cases, 28 in each group. All admissible cases were assessed clinically on a scale of 0 to 3 for number and size of ulcers, pain, discharge, surrounding erythema and bubo. Each drug individually showed significant improvement in all clinical parameters. Minocycline showed significantly better improvement than cotrimoxazole in all parameters. Minocycline had 43% cure rate, and no failures, against 36% cure and 25% failure for cotrimoxazole. Both the drug were well tolerated. We conclude that minocycline is a superior alternative to cotrimoxazole in the therapy of chancroid.
Vugt, J.P.P. van; Siesling, S.; Vergeer, M; van der Velde, E A; R. Roos
OBJECTIVES—To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease. METHODS—Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored usin...
Katagiri, Mikiyuki; Satoh, Akira; Tsuji, Shinji; Shirasawa, Takuji
In this study we tried to confirm the effect of an astaxanthin-rich Haematococcus pluvialis extract on cognitive function in 96 subjects by a randomised double-blind placebo-controlled study. Healthy middle-aged and elderly subjects who complained of age-related forgetfulness were recruited. Ninety-six subjects were selected from the initial screen, and ingested a capsule containing astaxanthin-rich Haematococcus pluvialis extract, or a placebo capsule for 12 weeks. Somatometry, haematology, ...
Curtis, Katrina J.; O'Brien, Katie A; Tanner, Rebecca J; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I; Edwards, Lindsay M.; Hopkinson, Nicholas S
Background: Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD. Methods: We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nit...
Ramnani, Priya; Costabile, Adele; Bustillo, A. G. R.; Glenn R Gibson
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 ...
Full Text Available 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.
Dubertret, Louis; Zalupca, Lavinia; Cristodoulo, Tania; Benea, Vasile; Medina, Iris; Fantin, Sara; Lahfa, Morad; Pérez, Iñaki; Izquierdo, Iñaki; Arnaiz, Eva
This randomised, double-blind, placebo-controlled, parallel-group, international, dose-ranging study investigated the effect of treatment with rupatadine 5, 10 and 20 mg once daily for 4 weeks on symptoms and interference with daily activities and sleep in 12-65 years-old patients with moderate-to-severe chronic idiopathic urticaria (CIU). Rupatadine 10 and 20 mg significantly reduced pruritus severity by 62.05% and 71.87% respectively, from baseline, over a period of 4 weeks compared to reduction with placebo by 46.59% (p CIU. Rupatadine decreased pruritus severity, in a dose- and time-dependent manner. PMID:17478385
Full Text Available Abstract Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730 on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-workers that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo. Results In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p L. reuteri group (p L. reuteri group(p
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
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
Punga, Anna Rostedt; Eriksson, Annika; Alimohammadi, Mohammad
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 ...
Pinter, M.; Pogarell, O.; Oertel, W.
OBJECTIVES—Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. METHODS—Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pra...
Zuckerman, J N; Sabin, C.; Craig, F. M.; Williams, A.; Zuckerman, A J
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...
Combe, B.; Codreanu, C; Fiocco, U; Gaubitz, M; Geusens, P P; Kvien, T K; Pavelka, K.; P N Sambrook; Smolen, J S; Khandker, R; Singh, A.; Wajdula, J; Fatenejad, S; ,
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 therap...
Rainey-Smith, Stephanie R; Brown, Belinda M; Sohrabi, Hamid R; Shah, Tejal; Goozee, Kathryn G; Gupta, Veer B; Martins, Ralph N
Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n 96) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; time×treatment; F=3·85, Pdifferences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration. PMID:27102361
Stokland, E.; Jacobsson, B.; Ljung, B. [Dept. of Paediatric Radiology and Clinical Physiology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden); Andreasson, S. [Dept. of Paediatric Anaesthesiology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden); Jodal, U. [Dept. of Paediatrics, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)
Background: Sedation with midazolam facilitates the performance of diagnostic procedures in children, including voiding cystourethrography (VCUG). However, the influence of sedation on voiding and imaging results have not been adequately evaluated. Objective: Midazolam and placebo were compared to assess discomfort during VCUG and to evaluate if sedation influenced the outcome of the examination. Materials and methods: The study was prospective, randomized and double-blind, and included 95 children, 48 in the midazolam group (median age 2.2 years) and 47 in the placebo group (median age 3.2 years). The evaluation included the child's/parent's experience of the VCUG, as well as the examination results. Results: The children/parents in the midazolam group experienced the VCUG as less distressing compared to those in the placebo group (P < 0.001). Forty-six of 48 children sedated with midazolam could void during the imaging procedure compared to 38 of 47 children given placebo (NS). There was no difference in frequency or grade of vesicoureteric reflux or bladder emptying between the groups. Conclusions: When sedation is required to perform VCUG in children, midazolam can be used without negative effect on the outcome of the examination. (orig.)
Background: Sedation with midazolam facilitates the performance of diagnostic procedures in children, including voiding cystourethrography (VCUG). However, the influence of sedation on voiding and imaging results have not been adequately evaluated. Objective: Midazolam and placebo were compared to assess discomfort during VCUG and to evaluate if sedation influenced the outcome of the examination. Materials and methods: The study was prospective, randomized and double-blind, and included 95 children, 48 in the midazolam group (median age 2.2 years) and 47 in the placebo group (median age 3.2 years). The evaluation included the child's/parent's experience of the VCUG, as well as the examination results. Results: The children/parents in the midazolam group experienced the VCUG as less distressing compared to those in the placebo group (P < 0.001). Forty-six of 48 children sedated with midazolam could void during the imaging procedure compared to 38 of 47 children given placebo (NS). There was no difference in frequency or grade of vesicoureteric reflux or bladder emptying between the groups. Conclusions: When sedation is required to perform VCUG in children, midazolam can be used without negative effect on the outcome of the examination. (orig.)
Hauge, Anne Werner; Asghar, Mohammad Sohail; Schytz, Henrik W;
BACKGROUND: Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. METHODS: In this randomised, double-blind, placebo-controlled crossover...... significantly different between placebo and tonabersat groups (3.0 days in each group; p=0.09). Tonabersat was well tolerated but overall had more side-effects than placebo. INTERPRETATION: Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its...... trial, 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months. Randomisation was by computer-generated list. Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura, migraine...
Ramnani, P; Costabile, A; Bustillo, A G R; Gibson, G R
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
Prashant A Biradar
Full Text Available Background: Different additives have been used to prolong brachial plexus block. We performed a prospective, randomised, double-blind study to evaluate the effect of dexamethasone added to lidocaine on the onset and duration of supraclavicular brachial plexus block as this is the most common type of brachial block performed in our institute. Methods: Sixty American Society of Anaesthesiologist′s physical status I and II patients undergoing elective hand, forearm and elbow surgery under brachial plexus block were randomly allocated to receive either 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of normal saline (group C, n=30 or 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of dexamethasone (8 mg (group D, n=30. The block was performed using a nerve stimulator. Onset and duration of sensory and motor blockade were assessed. The sensory and motor blockade of radial, median, ulnar and musculocutaneous nerves were evaluated and recorded at 5, 10, 20, 120 min, and at every 30 min thereafter. Results: Two patients were excluded from the study because of block failure. The onset of sensory and motor blockade (13.4±2.8 vs. 16.0±2.3 min and 16.0±2.7 vs. 18.7±2.8 min, respectively were significantly more rapid in the dexamethasone group than in the control group ( P=0.001. The duration of sensory and motor blockade (326±58.6 vs. 159±20.1 and 290.6±52.7 vs. 135.5±20.3 min, respectively were significantly longer in the dexamethasone group than in the control group ( P=0.001. Conclusion: Addition of dexamethasone to 1.5% lidocaine with adrenaline in supraclavicular brachial plexus block speeds the onset and prolongs the duration of sensory and motor blockade.
Blanco Rojo, R.; Pérez Granados, Ana M.; Toxqui, Laura; González-Vizcayno, C.; Delgado, Manuel, 1956-; Vaquero, M. Pilar
Iron deficiency anaemia is a worldwide health problem. We studied the influence of consuming an iron fortified fruit juice on iron status in menstruating women. A randomised double-blind placebo-controlled study of 16-weeks of duration was performed. Two groups: P group (n=58) or F group (n=64) consumed, as a supplement to their usual diet, 500 mL/day of placebo fruit juice or iron-fortified fruit juice, respectively. The iron fortified-juice, containing microencapsulated iron pyrophospha...
Demant, Dyveke T; Lund, Karen; Vollert, Jan;
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...
Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam;
haemodynamic stability and this study describes short and long-term effects of ARB treatment vs. placebo on intradialytic haemodynamic parameters in a cohort of Danish HD patients. Methods Adult HD patients were randomised for double-blind treatment with the ARB irbesartan or placebo using a predialytic...... equally and significantly over time. The mean intradialytic haemodynamic response showed decreased CO, SV, MAP, and CBV, whereas HR increased from HDSTART to HDEND. TPR did not change significantly. Overall, this pattern remained stable over time in both groups and there was no significant impact of ARB...
S S Nethra
Full Text Available Background and Aim: The newer trend in regional anaesthesia for ambulatory anorectal surgeries advocate use of lower dose of local anaesthetic, providing segmental block with adjuvants such as opioids and α2 agonists to prolong analgesia. The current study investigated effects of addition of 5 μg of dexmedetomidine to 6 mg of hyperbaric bupivacaine on duration of analgesia, sensory and motor block characteristics for perianal ambulatory surgeries. Methods: This study is a prospective randomised controlled double blind study. Forty adult patients between 18 and 55 years of age were divided into 2 groups. Group D received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml with injection dexmedetomidine 5 μg in 0.5 ml of normal saline and Group N received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml with 0.5 ml of normal saline. The parameters assessed were time to regression of sensory blockade, motor blockade, ambulation, time to void, first administration of analgesic. Statistical analysis was done using appropriate tests. Results: Time for regression of sensory level and time for first administration of analgesic were prolonged in Group D (430.05 ± 89.13 min, 459.8 ± 100.9 min, respectively in comparison to Group N (301.10 ± 94.86 min, 321.85 ± 95.08 min, respectively. However, the duration of motor blockade, time to ambulation, and time to void were also significantly prolonged in Group D (323.05 ± 54.58 min, 329.55 ± 54.06 min, 422.30 ± 87.59 min than in Group N (220.10 ± 63.61 min, 221.60 ± 63.84 min, 328.45 ± 113.38 min. Conclusion: Intrathecal dexmedetomidine 5 μg added to intrathecal bupivacaine 6 mg as adjuvant may not be suitable for ambulatory perianal surgeries due to prolongation of motor blockade.
Curtis, Katrina J.; O’Brien, Katie A.; Tanner, Rebecca J.; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I.; Edwards, Lindsay M.; Hopkinson, Nicholas S.
Background Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD. Methods We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage. Results 21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve. Conclusions Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype. Trial Registration ISRCTN Registry ISRCTN66099139 PMID:26698120
Katrina J Curtis
Full Text Available Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9 mmoles nitrate or placebo (nitrate-depleted beetroot juice 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.21 subjects successfully completed the study (age 68 ± 7 years; BMI 25.2 ± 5.5 kg/m2; FEV1 percentage predicted 50.1 ± 21.6%; peak VO2 18.0 ± 5.9 ml/min/kg. Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7 ± 8 mmHg nitrate vs. -1 ± 8 mmHg placebo; p = 0.008. Median endurance time did not differ significantly; nitrate 5.65 (3.90-10.40 minutes vs. placebo 6.40 (4.01-9.67 minutes (p = 0.50. However, isotime oxygen consumption (VO2 was lower following nitrate supplementation (16.6 ± 6.0 ml/min/kg nitrate vs. 17.2 ± 6.0 ml/min/kg placebo; p = 0.043, and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve.Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.ISRCTN Registry ISRCTN66099139.
Högberg, L.; Laurin, P; Fälth-Magnusson, K.; Grant, C.; Grodzinsky, E.; Jansson, G; Ascher, H; Browaldh, L; Hammersjö, J-Å; Lindberg, E.; Myrdal, U; Stenhammar, L
Background: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed.
Thorens, J; Froehlich, F.; Schwizer, W; Saraga, E.; Bille, J; Gyr, K; Duroux, P; Nicolet, M; Pignatelli, B.; Blum, A L; Gonvers, J J; Fried, M
BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four ...
Objective: We investigated whether the inflammatory response and delayed onset of muscle soreness after a marathon are altered by resveratrol, a natural polyphenolic flavonoid antioxidant. Design: Double blind placebo-controlled randomised pilot study. Setting: London Marathon. Participants: Marathon race participants. Interventions: 7 healthy male athletes were randomised to receive Resveratrol (600 mg Resveratrol daily for 7 days immediately before the marathon) or a placebo. ...
A randomised, double-blind, placebo-controlled, multicentre study of the safety and efficacy of BIOBYPASS (AdGVVEGF121.10NH) gene therapy in patients with refractory advanced coronary artery disease: the NOVA trial
Kastrup, Jens; Jørgensen, Erik; Fuchs, Shmuel;
Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH])....
van Ameringen Michael
Full Text Available Abstract Background Although serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed. Methods We undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks. Results There was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p Conclusions In this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations.
Ahmed, Jamil; Reddy, Bala S.; Mølbak, Lars;
Background & aims: The aim of this study was to investigate the spectrum of colonic microflora in patients with colitis and if this could be altered with one month's treatment with synbiotics. MethodsThis was a pilot study in which patients were randomised to either receive a synbiotics preparation...... for a month and then “crossed over” to receive a placebo, or alternatively to receive the placebo first followed in the second month by synbiotic. Stool samples were collected on entry into the study and then at the end of first and second months respectively. Colonic microflora was measured by terminal...... identified in stool samples but did not alter overall spectrum of microflora. In this pilot study we were unable to identify any specific characteristics related to nature of colitis. ConclusionsThis study suggests that there is no difference in colonic microflora between patients with Crohn's or Ulcerative...
Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam;
(HD) patients in a double-blind randomised placebo-controlled one year intervention trial using a pre-defined systolic blood pressure (BP) target of 140 mmHg. Patients (41 in each group) did not differ in terms of age, BP, co-morbidity, antihypertensive treatment, dialysis parameters, and residual...... such as central aortic BP, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal prohormone of brain natriuretic peptide, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic BP during the study period...... correlated significantly with changes in left ventricular mass (P=0.02) and changes in arterial stiffness (P<0.001). In conclusion, significant effects of irbesartan on intermediate CV endpoints beyond BP reduction were absent in HD patients....
Punga, Anna Rostedt; Eriksson, Annika; Alimohammadi, Mohammad
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
Naser, Syed Mohammed; Sarkar, Niladri; Biswas, Arunava; Kamal, Firdaus; Prakash, Raghu; Rahaman, Q M; Das, Anup Kumar
The study was conducted to evaluate the efficacy and safety of flupirtine maleate 100 mg thrice daily compared to tramadol hydrochloride 50 mg thrice daily as postoperative pain management for 5 days. A total of 113 postoperative patients were recruited for the study. Those who met the inclusion criteria (n = 104) were randomised into two treatment groups. One of the groups received flupirtine maleate and the other tramadol hydrochloride both orally. The pain intensity was assessed by visual analogue scale. Patients were informed to report any adverse effect encountered during the study period. The overall effect of the drug (global assessment of the study medication) on pain and side-effects was assessed by the patients at the end of the trial on a categorical scale. There was significant reduction in pain score (p flupirtine group with almost equal efficacy to that of tramadol group but the incidence of adverse effects were much less (7.4%) and didn't need discontinuation of the study. All drugs were assessed as good. Therefore it can be concluded that oral flupirtine can deliver the same analgesic efficacy as oral tramadol for postoperative pain relief, which might be beneficial for avoiding the adverse effects ofopioids and non-steroidal anti-inflammatory drug therapy. PMID:23029946
van Weelden Huib
Full Text Available Abstract Background Home ultraviolet B (UVB treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis". Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI and the Self Administered PASI (SAPASI scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population
Patel Jeetesh V
Full Text Available Abstract 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
Saba M Lambert
Full Text Available Erythema Nodosum Leprosum (ENL is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL.Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin.This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale.
Sousa, Ana R; Riley, John H; Church, Alison; Zhu, Chang-Qing; Punekar, Yogesh S; Fahy, William A
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
Full Text Available Abstract 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
Cluver, Catherine A; Walker, Susan P; Mol, Ben W; Theron, Gerard B; Hall, David R; Hiscock, Richard; Hannan, N; Tong, S
Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB
Gueimonde, Laura; Vesterlund, Satu; García-Pola, María J; Gueimonde, Miguel; Söderling, Eva; Salminen, Seppo
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
Full Text Available Background/Aims: Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF. Normalization of ceramide concentrations in lungs of CF mice employing the functional acid sphingomyelinase inhibitor amitriptyline also normalized mucociliary clearance, chronic inflammation and infection susceptibility to pulmonary P. aeruginosa in these mice. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study. Twenty-one CF patients were treated with 25 mg/d amitriptyline twice daily for 28 days. The placebo consisted of 19 patients and was also treated twice per day. The primary endpoint was the change in lung function in the intention-to-treat (ITT population. Secondary endpoints were ceramide levels in epithelial cells and safety. Results: After treatment, forced expiratory volume in 1 sec predicted (FEV1 increased 6.3±11.5% (p=0.08 in the ITT population (36 of 40 CF patients and 8.5±10% (p=0.013 in the per protocol (PP population (29 of 40 patients. Ceramide levels decreased in nasal epithelial cells after amitriptyline treatment. Amitriptyline had no severe and only mild and mostly transient adverse effects, i.e. xerostomia and tiredness. Conclusion: Amitriptyline is safe in CF-patients, increases FEV1 and reduces ceramide in lung cells of CF patients.
Kurhekar, Pranjali; Kumar, S Madan; Sampath, D
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.
A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study)
Jorsal, Anders; Wiggers, Henrik; Holmager, Pernille; Nilsson, Brian; Nielsen, Roni; Boesgaard, Trine Welløv; Kumme, Anja; Møller, Jacob Eifer; Videbæk, Lars; Kistorp, Caroline; Gustafsson, Ida; Tarnow, Lise; Flyvbjerg, Allan
ANALYSIS: An investigator-initiated, multicentre, randomised, double-blind, parallel, placebo-controlled intervention trial. In total, 240 patients with CHF (with and without T2D) with LVEF≤45% will be randomised to either subcutaneous injection of liraglutide 1.8 mg or matching placebo once daily for 24...... weeks. The effect of liraglutide on left ventricular function will be evaluated by advanced echocardiography, including three-dimensional contrast echocardiography. ETHICS AND DISSEMINATION: The study will be performed and monitored according to the Good Clinical Practice-International Conference on...... Harmonisation (GCP-ICH) regulations and conducted according to the principles of the Helsinki Declaration. The Danish Medicines Agency, the local Research Ethics Committee and the Danish Data Protection Agency have approved the study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01472640....
Full Text Available Abstract Background Hip replacement surgery is increasingly common due to an ageing population, and rising levels of obesity. The provision of excellent pain relief with minimal side effects is important in order to facilitate patient mobilisation and rehabilitation. Spinal opioids provide excellent analgesia but are associated with adverse effects. The fascia-iliaca block is an alternative technique which provides analgesia to the nerves innervating the hip. The success of fascia iliaca blocks has been demonstrated to be superior when using ultrasound compared to landmark techniques. However, the clinical benefit of this improvement has yet to be investigated. The aim of this study is to compare the efficacy and safety of ultrasound guided fascia iliaca block with spinal morphine for hip replacement surgery. Methods/Design This study is a randomised, blinded, placebo-controlled, noninferiority trial. Patients scheduled to undergo unilateral primary hip arthroplasty will receive a study information sheet and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either; (i Ultrasound guided fascia iliaca block using levobupivacaine, plus spinal anaesthesia with hyperbaric bupivacaine containing no morphine, or (ii sham ultrasound guided fascia iliaca block performed with sterile saline, and spinal anaesthesia containing hyperbaric bupivacaine and 0.1 mg of spinal morphine. A total of 108 patients will be recruited. Primary outcome is post-operative morphine consumption in a 24 hour period. Secondary outcomes include; pain scores at 3, 6, 12, 24, 36 and 48 hours, episodes of respiratory depression, hypotension, nausea and vomiting, pruritus, sedation, time to first mobilisation and patient satisfaction. Conclusions There are no studies to date comparing ultrasound guided fascia iliaca block with spinal morphine for pain control after hip arthroplasty. If the ultrasound guided fascia iliaca
Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup;
central sensitisation is abnormal activation of the N-methyl-D-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. METHODS AND ANALYSIS: 40 patients with CP will be enrolled. Patients are...... randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points...
van Velde Romuald
Full Text Available Abstract Background With an ageing population, older persons become a larger part of the hospital population. The incidence of delirium is high in this group, and experiencing delirium has major short- and long-term sequelae, which makes prevention crucial. During delirium, a disruption of the sleep-wake cycle is frequently observed. Melatonin plays an important role in the regulation of the sleep-wake cycle, so this raised the hypothesis that alterations in the metabolism of melatonin might play an important role in the development of delirium. The aim of this article is to describe the design of a randomised, placebo controlled double-blind trial that is currently in progress and that investigates the effects of melatonin versus placebo on delirium in older, postoperative hip fracture patients. Methods/Design Acutely hospitalised patients aged 65 years or older admitted for surgical repair of hip fracture are randomised (n = 452 into a treatment or placebo group. Prophylactic treatment consists of orally administered melatonin (3 mg at 21:00 h on five consecutive days. The primary outcome is the occurrence of delirium, to be diagnosed according to the Confusion Assessment Method, within eight days after start of the study medication. Secondary outcomes are delirium severity, measured by the Delirium Rating Scale; duration of delirium; differences in subtypes of delirium; differences in total length of hospital stay; total dose of antipsychotics and/or benzodiazepine use during delirium; and in-hospital complications. In the twelve-month follow up visit, cognitive function is measured by a Mini-Mental state examination and the Informant Questionnaire on Cognitive Decline in the Elderly. Functional status is assessed with the Katz ADL index score (patient and family version and grip strength measurement. The outcomes of these assessments are compared to the outcomes that were obtained during admission. Discussion The proposed study will
Full Text Available Abstract 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
Full Text Available OBJECTIVE: Studies have demonstrated frequent contamination of stethoscope and usefulness of different disinfectants. Albeit, studies on the precise mode of cleaning and frequency of cleaning are lacking. This study was carried out to determine efficacy of 66% ethyl alcohol as disinfectant, rate of recontamination without cleaning and benefits of daily versus immediate cleaning. METHODOLOGY: Prospective, randomised, double blind study of 100 stethoscopes. Four cultures were obtained: before cleaning (Group A, immediately after cleaning with 66% ethyl alcohol (Group B, at the end of 4 days without cleaning (Group C and at the end of 4 days after cleaning once a day (Group D. Samples were analysed using standard microbiological methods and Colony-forming unit (CFU count and residual microorganism was computed for all the positive cultures. Medical staff was asked about the cleaning practices. Statistical analysis was carried out using 95% confidence interval and Chi-square test. RESULTS: 90% of the stethoscopes were contaminated with one or more microorganisms. Immediate cleaning and daily cleaning were associated with a significant reduction in the rate of contamination to 28% and 25% respectively. CFU count in groups B and D dropped to less than 10 in 75% and 84.7%, while the mean residual rates were 5.2% and 3.65% respectively. Groups B and D showed no statistically significant difference in terms of efficacy of disinfection. CONCLUSIONS: 66% ethyl alcohol is an effective disinfectant. The effects of immediate cleaning and cleaning once a day on residual flora on the diaphragm of stethoscope is comparable.
Lehmann, K A; Klaschik, M
NMDA receptors are assumed to play an important role for neuronal plasticity. In vitro and animal experiments confirmed that NMDA antagonistic drugs can prevent hyperexitability of dorsal root neurons after strong pain stimuli. Clinical data, however, are more or less controversial in this respect. It was the aim of the present prospective, randomised, double-blind study to verify if low-dose preoperative ketamine, an NMDA antagonist, provides relevant postoperative analgesia in surgical patients and to re-examine positive results published by other investigators. 80 ASA I-II patients undergoing elective laparoscopic or proctologic surgery received at induction of general anaesthesia a single i.v. bolus dose of either ketamine 0.15 mg/kg or placebo (0.9% NaCl). Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using the opioid piritramide. Cardiovascular parameters, respiration, sedation, cumulative piritramide consumption and pain scores (visual analogue scale 1-10, verbal rating scale 0-4) were monitored at 1, 2, 3, 4, 5, 6, 12 and 24 hours after surgery. Additionally, a retrospective pain score was documented after the 24 hours observation period. There was no statistically significant difference in any study parameter. Cumulative PCA piritramide consumption after 24 hours was 25.0+/-16.2 mg in the ketamine group and 29.5+/-20.4 mg in the placebo group. Ketamine-specific side effects such as hallucinations or bad dreams were not observed. It is concluded that under the study conditions used, low dose ketamine, contrary to previously reported results , does not provide a clinically relevant pre-emptive analgesic effect in postoperative patients. PMID:11810363
Full Text Available BACKGROUND AND AIMS There are number of drugs like Tramadol, Clonidine, Pethidine, etc., which are being used as an anti-shivering agent during perioperative period. Perioperative shivering can be very harmful for the patients, thus focus should be on prevention rather than treatment. The aim of this study was to compare Dexmedetomidine and Tramadol for prevention of shivering in more susceptible group of patients–elderly age group (55 and above being operated for Transurethral Resection of Prostate (TURP under spinal anaesthesia. METHOD A prospective, randomised and double blind study conducted on 300 American Society of Anaesthesiologists (ASA Grade I, II and III male patients posted for TURP surgery. The patients were randomized in two groups of 150 patients each to receive either intravenous Dexmedetomidine 1µg/kg/min over a period of 10 minutes followed by infusion of 0.4µg/kg/min during surgery or intravenous Tramadol 1mg/kg min over a period of 10 minutes followed by infusion of dextrose 0.4µg/kg/min during surgery. Appearance of shivering hemodynamics and any adverse effects were observed at scheduled intervals. Unpaired T-test was used for analyzing data. RESULT Both the drugs were equally effective in prevention of shivering (Dexmedetomidine and Tramadol. CONCLUSION Both the drugs are effective in prevention of shivering in the respective doses we used in the study with patients who were more predisposed to shivering. Tramadol is associated with significant more nausea and vomiting. Adequate sedation with no respiratory compromise seen in both group.
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
Full Text Available Abstract 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
Kojury, Javad; Zolghadrasli, Abdolali; Karimi, Mehran; Babaee Beighi, Mohammad Ali; Namazi, Soha
Background Heart failure is the most common cause of mortality in β-thalassaemia major. However, the management of this disease, apart from chelation therapy, is largely empirical. Therefore, we decided to evaluate the effect of metoprolol succinate on patients with thalassaemia cardiomyopathy (TCM). Materials and methods In this clinical trial, 45 patients with TCM were randomised to receive either metoprolol (n=26) or placebo (n=19). Echocardiography and a 6 min walk test were performed at baseline and repeated after 6 months and the values compared. Results In the metoprolol group, left ventricular ejection fraction (LVEF) rose from 38.65% to 42.84% (pmetoprolol group decreased from 154.31 to 144.26 g (p=0.02), while in the placebo group it increased from 174.32 to 200.15 g (p=0.68); the difference between the two groups was significant (pmetoprolol group from 42.19 to 36.73 cm3 (pMetoprolol succinate as a β-blocker may have the potential to significantly improve systolic function in patients with TCM and reverse LV remodelling to the same extent as in other types of cardiomyopathy. Trial registration number NCT01863173.
Full Text Available Abstract Background Indacaterol is a novel, once-daily (o.d. inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD. This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD. Methods Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose at Week 12 (primary endpoint and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms. Safety was assessed by adverse events (AEs, mean serum potassium and blood glucose, QTc (Fridericia, and vital signs. Results Patients were randomised (n = 416, mean age 63 years to receive either indacaterol 150 μg o.d. (n = 211 or placebo (n = 205 via a single-dose dry-powder inhaler; 87.5% completed the study. Trough FEV1 (LSM ± SEM at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p 1 after one dose was significantly higher with indacaterol than placebo (p 1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM of 190 ± 28 (p 1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose at Week 12 were all significantly greater with indacaterol than placebo (p 500 ms. Conclusions Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo. Trial registration NCT00624286
Gaussem, Pascale; Alhenc-Gelas, Martine; Thomas, Jean-Louis; Bachelot-Loza, Christilla; Remones, Veronique; Ali, Fouad Dali; Aiach, Martine; Scarabin, Pierre-Yves
Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this. PMID:21225090
Werdelin, L; Dalager, T; Fuglsang-Frederiksen, Anders;
OBJECTIVE: The significance of electromyography (EMG) guidance in botulinum toxin (BT) treatment has been much debated. The aim of this study was to evaluate if EMG guidance in the treatment of torticollis in BT-naive patients had a better outcome than treatment after clinical evaluation alone...
Scholey, Andrew; Ossoukhova, Anastasia; Owen, Lauren; Ibarra, Alvin; Pipingas, Andrew; HE, KAN; Roller, Marc; Stough, Con
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 ...
Dunn, Liam; Flenady, Vicki; Kumar, Sailesh
Background Labour is perhaps the most hazardous time in pregnancy. As many as 20 % of cerebral palsy cases in term infants result from intrapartum events and up to 63 % of babies who develop intrapartum compromise have no prior risk factors. Sildenafil citrate (SC), a phosphodiesterase 5 inhibitor, improves uterine blood supply through vasodilatation and potentially could improve placental perfusion and hence reduce the risk of intrapartum fetal hypoxia. The aim of this study is to evaluate t...
Fonseca Sofia; Smith Natalie; Sheran Jane; Thomas Michael; Lee Amanda J
Abstract 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 o...
Klek, Stanislaw; Chambrier, Cecile; Singer, Pierre;
The aim of this study was to evaluate the safety and tolerance of a soybean/MCT/olive/fish oil emulsion in intestinal failure patients on long-term parenteral nutrition. 73 patients took part in a randomized, double-blind, multi-centre study. The study demonstrates that the lipid emulsion contain...
Bødtger, U; Poulsen, Lars K.; Jacobi, H H;
There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America.......There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America....
Bello, Segun; Wei, Maoling; Hilden, Jørgen;
BACKGROUND: Blinding is a pivotal method to avoid bias in randomised clinical trials. In blinded drug trials, experimental and control interventions are often designed to be matched, i.e. to appear indistinguishable. It is unknown how often matching procedures are inadequate, so we decided to sys...
Full Text Available Abstract Background The Estonian Postmenopausal Hormone Therapy (EPHT Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT, with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001 received open-label HT or no treatment, participants in the blind trial (N = 777 remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes. Methods Effect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial. Results The women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71 and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91 than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied. Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93, cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92, and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94 was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42, bone fractures (0.93; 95% CI: 0
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)
Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas
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
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
Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise;
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......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...... 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/m(2)) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this...
Vickers, A J; Fisher, P.; Smith, C.; Wyllie, S E; Lewith, G T
OBJECTIVE: To pilot a model for determining whether a homoeopathic medicine is superior to placebo for delayed onset muscle soreness (DOMS). DESIGN: Randomised double blind placebo controlled trial. SETTING: Physiotherapy department of a homoeopathic hospital. SUBJECTS: Sixty eight healthy volunteers (average age 30; 41% men) undertook a 10 minute period of bench stepping carrying a small weight and were randomised to a homoeopathic medicine or placebo. OUTCOME MEASURES: Mean muscle soreness ...
Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE" study: a double-blind randomised controlled multicenter clinical trial
Full Text Available Abstract Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT: NCT01031667
Dejgård, A; Hilsted, J
this therapy we performed a double-blind placebo controlled cross-over study with Pindolol (15 mg/day). Eight Type 1 (insulin-dependent) diabetic patients with autonomic neuropathy and signs and symptoms of orthostatic hypotension (systolic blood pressure decrease greater than 30 mm Hg when standing......) participated in the study. Patients were treated for 10 weeks. Clinical examinations were performed every fortnight and patients registered postural symptoms twice daily on a visual analog scale. No significant changes were seen in blood pressure recordings, heart-rate or visual analog scale registration...
Nygaard, Birte; Bastholt, Lars; Bennedbæk, Finn Noe; Klausen, Tobias Wirenfeldt; Bentzen, Jens
BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. OBJECTIVE: To compare QOL in...... OUTCOME MEASURES: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake. RESULTS: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy. CONCLUSION: This...
Sikjær, Tanja Tvistholm; Rejnmark, Lars; Mosekilde, Leif
and 7 were not in need of active vitamin D. With the actual add on therapy there were no change in renal calcium excretion in response to treatment. Compared with placebo, bone mineral density (BMD) decreased significantly at the hip (-1.59 ± 0.57%), lumbar spine (-1.76 ± 1.03%) and whole body (-1...... interstitial bone packets. In conclusion, PTH substitution therapy is capable of maintaining normal p-calcium levels with a significantly reduced need for calcium supplements and active vitamin D. In contrast to the effect of PTH(1-84) treatment in patients with osteoporosis, causing an increase in BMD......Conventional treatment of hypoparathyroidism (hypoPT) with calcium supplements and active vitamin D analoges causes a high renal calcium excretion and over-mineralized bone. We studied 62 patients with known hypoPT randomised to 6 months of treatment with either PTH(1-84) 100 µg/d s.c. or similar...
Fallowfield, L; Gagnon, D.; Zagari, M; Cella, D.; Bresnahan, B; Littlewood, T J; McNulty, P.; Gorzegno, G; Freund, M.
Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life. Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia, the impact of this treatment on quality of life was evaluated in a multinational, randomised, double-blind, placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy. The cancer-specific measures of quality of life included the general scale (FACT-G Total) a...
A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study
Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf
Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260
A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study
Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen
Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259
Efficacy of orally disintegrating film of ondansetron versus intravenous ondansetron in prophylaxis of postoperative nausea and vomiting in patients undergoing elective gynaecological laparoscopic procedures: A prospective randomised, double-blind placebo-controlled study
Harihar V Hegde
Full Text Available Background and Aims: Ondansetron is one of the most widely used drugs for postoperative nausea and vomiting (PONV prophylaxis. Orally disintegrating film (ODF formulations are relatively recent innovations. We evaluated the efficacy of ODF of ondansetron for the prophylaxis of PONV. Methods: One hundred and eighty American Society of Anaesthesiologists-I or II women, in the age group 18-65 years, scheduled for elective gynaecological laparoscopic procedures were studied in a prospective randomised, double-blind, placebo-controlled trial. The patients were randomised into four groups: Placebo, intravenous (IV ondansetron 4 mg, ODF of ondansetron 4 mg (ODF4 and 8 mg (ODF8 groups. PONV was assessed in two epochs of 0-6 and 7-24 h. Primary outcome measure was the incidence of PONV and secondary outcome measures were severity of nausea, need for rescue anti-emetic, analgesic consumption, time to oral intake, overall patient satisfaction and side effects such as headache and dizziness. PONV was compared using analysis of variance or Mann-Whitney U-test as applicable. Results: Data of 173 patients were analysed. The incidence of postoperative nausea was significantly lower (P = 0.04 only during the 0-6 h in the ODF8 group when compared with the placebo group. During the 0-6 h interval postoperatively, the ODF8 group had a significantly lower incidence of vomiting when compared with the placebo (P = 0.002 and the IV group (P = 0.044. During the 0-24 h interval postoperatively, ODF4 (P = 0.01 and ODF8 (P = 0.002 groups had a significantly lower incidence of vomiting compared to the placebo group. Conclusions: Orally disintegrating film of ondansetron is an efficacious, novel, convenient and may be a cost-effective option for the prophylaxis of PONV.
Efficacy of orally disintegrating film of ondansetron versus intravenous ondansetron in prophylaxis of postoperative nausea and vomiting in patients undergoing elective gynaecological laparoscopic procedures: A prospective randomised, double-blind placebo-controlled study
Hegde, Harihar V; Yaliwal, Vijay G; Annigeri, Rashmi V; Sunilkumar, KS; Rameshkumar, R; Rao, P Raghavendra
Background and Aims: Ondansetron is one of the most widely used drugs for postoperative nausea and vomiting (PONV) prophylaxis. Orally disintegrating film (ODF) formulations are relatively recent innovations. We evaluated the efficacy of ODF of ondansetron for the prophylaxis of PONV. Methods: One hundred and eighty American Society of Anaesthesiologists-I or II women, in the age group 18-65 years, scheduled for elective gynaecological laparoscopic procedures were studied in a prospective randomised, double-blind, placebo-controlled trial. The patients were randomised into four groups: Placebo, intravenous (IV) ondansetron 4 mg, ODF of ondansetron 4 mg (ODF4) and 8 mg (ODF8) groups. PONV was assessed in two epochs of 0-6 and 7-24 h. Primary outcome measure was the incidence of PONV and secondary outcome measures were severity of nausea, need for rescue anti-emetic, analgesic consumption, time to oral intake, overall patient satisfaction and side effects such as headache and dizziness. PONV was compared using analysis of variance or Mann–Whitney U-test as applicable. Results: Data of 173 patients were analysed. The incidence of postoperative nausea was significantly lower (P = 0.04) only during the 0-6 h in the ODF8 group when compared with the placebo group. During the 0-6 h interval postoperatively, the ODF8 group had a significantly lower incidence of vomiting when compared with the placebo (P = 0.002) and the IV group (P = 0.044). During the 0-24 h interval postoperatively, ODF4 (P = 0.01) and ODF8 (P = 0.002) groups had a significantly lower incidence of vomiting compared to the placebo group. Conclusions: Orally disintegrating film of ondansetron is an efficacious, novel, convenient and may be a cost-effective option for the prophylaxis of PONV. PMID:25197110
Brock-Jacobsen, Iben; Vind, B F; Korsholm, L;
To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia. Methods: Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients’ satisfaction were...... examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed...... by hospitalization where episodes of spontaneous hypoglycaemia and counter-regulatory hormone responses were evaluated from frequently obtained blood samples. Results: No difference between soluble insulin and insulin Aspart was found regarding HbA1c (7.0 0.2 vs. 7.0 0.2%, ns), hypoglycaemic...
Objectives To compare the efficacy of intravenous ondansetron (4 mg, 2 mL) and granisetron (2 mg, 2 mL) for preventing postoperative nausea and vomiting (PONV) in patients during oral and maxillofacial surgical procedures under general anesthesia. Materials and Methods A prospective, randomized, and double blind clinical study was carried out with 60 patients undergoing oral and maxillofacial surgical procedures under general anesthesia. Patients were divided into two groups of 30 individuals each. Approximately two minutes before induction of general anesthesia, each patient received either 4 mg (2 mL) ondansetron or 2 mg (2 mL) granisetron intravenously in a double blind manner. Balanced anesthetic technique was used for all patients. Patients were assessed for episodes of nausea, retching, vomiting, and the need for rescue antiemetic at intervals of 0-2, 3, 6, 12, and 24 hours after surgery. Incidence of complete response and adverse effects were assessed at 24 hours postoperatively. Data was tabulated and subjected to statistical analysis using the chi-square test, unpaired t-test, or the Mann-Whitney U-test as appropriate. A P-value less than 0.05 was considered statistically significant. Results There was no statistically significant difference between the two groups for incidence of PONV or the need for rescue antiemetic. Both study drugs were well tolerated with minimum adverse effects; the most common adverse effect was headache. The overall incidence of complete response in the granisetron group (86.7%) was significantly higher than the ondansetron group (60.0%). Conclusion Granisetron at an intravenous dose of 2 mg was found to be safe, well tolerated, and more effective by increasing the incidence of complete response compared to 4 mg intravenous ondansetron when used for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia. Benefits of granisetron include high receptor specificity and high potency, which make it a
Full Text Available Abstract Background Inhaled glucocorticoids are efficient in protecting against asthma exacerbations, but methods to compare their efficacy vs systemic effects have only been attempted in larger multi-centre studies. The aim of the current study was therefore to directly compare the effects of two separate inhaled glucocorticoids, mometasone and budesonide, to compare the effects on the early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma, and sputum eosinophils, and to relate the clinical positive effects to any systemic effects observed. Methods Twelve patients with documented early and late asthmatic responses (EAR and LAR to inhaled allergen at a screening visit were randomized in a double-blind fashion to treatment with mometasone (200 μg × 2 or 400 μg × 2, budesonide (400 μg × 2 or placebo in a double-blind crossover fashion for a period of seven days. Challenge with the total allergen dose causing both an EAR and LAR was given on the last day of treatment taken in the morning. Lung function was assessed using FEV1, and systemic glucocorticoid activity was quantified using 24 h urinary cortisol. Results Mometasone and budesonide attenuate both EAR and LAR to allergen to a similar degree. No significant dose-related effects on the lung function parameters were observed. Both treatments reduced the relative amount of sputum eosinophils (% after allergen. At the dose of 800 μg daily, mometasone reduced 24 h urinary cortisol by approximately 35%. Both drugs were well tolerated. Conclusions Mometasone and budesonide are equieffective in reducing early and late asthmatic responses induced by inhaled allergen challenge. Mometasone 800 μg given for seven days partially affects the HPA axis.
Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter
Full Text Available Abstract Background Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia. Methods A randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day or placebo (n = 20 in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS, Cambridge Neuropsychological Test Automated Battery (CANTAB, and Positive and Negative Syndrome Scale (PANSS scores were measured. Results In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial. Conclusions This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.
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
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 Japa...
O'Connor Daniel W
Full Text Available Abstract 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
Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz
Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. PMID:26932256
Walton Gemma E
Full Text Available Abstract Background Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. Methods A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA levels in saliva were also measured. Results Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. Conclusions AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated.
Hill Karen M
Full Text Available Abstract Background Whey protein isolates (WPI supplementation is known to improve resistance training adaptations. However, limited information is available on the effects of WPI plus carbohydrate (CHO supplementation on endurance training adaptations. Method Six endurance trained male cyclists and triathletes (age 29 ± 4 years, weight 74 ± 2 kg, VO2 max 63 ± 3 ml oxygen. kg-1. Min-1, height 183 ± 5 cm; mean ± SEM were randomly assigned to one of two dietary interventions in a single blind cross over design; CHO or CHO + WPI. Each dietary intervention was followed for 16 days which included the last 2 days having increased CHO content, representing a CHO loading phase. The dietary interventions were iso-caloric and carbohydrate content matched. On completion of the dietary intervention, participants performed an exercise bout, consisting of cycling for 60 min at 70% VO2 max, followed by time trial to exhaustion at 90% VO2 max and recovered in the laboratory for 6 hours. Blood samples and muscle biopsies were taken at various time points at rest and through the exercise trial and recovery. Results Compared to CHO, CHO + WPI increased plasma insulin during recovery at 180 mins (P Conclusion This study showed co-ingestion of CHO + WPI may have beneficial effects on recovery and adaptations to endurance exercise via, increased insulin response and up regulation of PGC-1α mRNA expression.
Enander, Jesper; Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alstroem, Katarina; Andersson, Gerhard; Ljotsson, Brjann; Rueck, Christian
Objectives To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. Design A 12 week single blind parallel group randomised controlled trial. Setting Academic medical centre. Participants 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥20. Concurrent psychotrop...
Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Nielsen, Claus H.; Jensen, Jens Dam; Christensen, Kent Lodberg; Bibby, Bo Martin; Jespersen, Bente
as factors using Stata/IC 12.1. Results Eighty-two patients were randomised (placebo/irbesartan: 41/41) and 56 completed one year of treatment. The groups (placebo/irbesartan) were comparable at baseline (mean±SD): Males 26(63%)/30(73%); age 62±14/61±16 years; systolic blood pressure (BP) 145......-reactive protein (hsCRP), interleukin (IL) 1β, IL-6, IL-8, IL-18, and transforming growth factor β (TGF-β) were measured using Luminex immunoassay technology. Data were analysed based on a multivariate repeated measurements model (xtmixed) with time and drug (placebo or irbesartan) and the interaction between them...
Full Text Available 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.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.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.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, particularly with respect to the
Kluge, Michael; Hegerl, Ulrich; Sander, Christian; Dietzel, Jens; Mergl, Roland; Bitter, István; Demyttenaere, Koen; Gusmão, Ricardo M.; González-Pinto, Ana María; Pérez-Solà, Victoŕ; Vieta, Eduard; Juckel, Georg; Zimmermann, Ulrich S.; Bauer, Michael S.; Sienaert, Pascal A.
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...
Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study
van der Woude Hanneke J
Full Text Available Abstract Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1 after inhaling adenosine 5'-monophosphate (AMP, were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours. Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg, formoterol (4.5 μg, salbutamol (2 × 100 μg or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours
Full Text Available BACKGROUND : Dexmedetomidine , a potent α 2 - adrenoceptor agonist , is approximately eight - times more selective towards the α 2 - adrenoceptor than clonidine. AIM : Comparison of clonidine and dexmedetomidine as an adjuvant to local anaesthetic in supraclavicular brachial bl ock. MATERIALS AND METHODS : Sixty patients of age group 18 - 60 years , scheduled for various elective orthopaedic surgeries on forearm and around the elbow under supraclavicular brachial block were divided into two equal groups in a randomized , double - blinded fashion. In group C ( n = 30 , 30 ml of 0.25% bupivacaine+clonidine 1μg/kg ; and in group D ( n=30 , 30 ml of 0.25% bupivacaine+ dexmedetomidine 1μg/kg were given. Onset of motor and sensory block , duration of sensory and motor block , quality o f block , and duration of postoperative analgesia were recorded. RESULTS : Demographic data and surgical characteristics were similar in both groups. The sensory and motor block onset time was same in both groups ( P >0.05 . Sensory and motor blockade duratio ns were longer in group D than in group C ( P 0.05 . CONCLUSIONS : Dexmedetomidine added to bupivacaine for supracl avicular brachial plexus block prolongs the duration of the motor and sensory block and the duration of postoperative analgesia significantly as compared to clonidine.
Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D A; Shaw, P N; N. Rutter
AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and tw...
Uhari, M.; Kontiokari, T; Koskela, M.; Niemelä, M. (Mika)
OBJECTIVE: To examine whether xylitol, which reduces the growth of Streptococcus pneumoniae, might have clinical importance in the prevention of acute otitis media. DESIGN: A double blind randomised trial with xylitol administered in chewing gum. SETTING: Eleven day care nurseries in the city of Oulu. Most of the children had had problems with recurrent acute otitis media. SUBJECTS: 306 day care children: 149 children in the sucrose group (76 boys; mean (SD) age 4.9 (1.5) years) and 157 in th...
WCW, Wong; A, Lee; AT, Lam; KT, Li; CYM, Leung; PC, Leung; ELY, Wong; JL, Tang
Background Rigorous scientific and well-designed clinical trials to evaluate the effect of traditional Chinese medicine (TCM) is lacking. We, therefore, designed this study to evaluate the effectiveness of a commonly used TCM preparation in treating acute cough of uncomplicated URTI in adults and to search for a safe, effective and affordable alternative treatment for this common condition. Methods A randomised, double-blinded, placebo-control study comparing this TCM preparation with a place...
Schaik, I.N. van; Eftimov, F.; Doorn, P.A. van; Brusse, E.; Berg, L.H. van den; Pol, W.L. van der; Faber, C.G.; Oostrom, J.C. van; Vogels, O.J.M.; Hadden, R.D.; Kleine, B.U.; Norden, A.G.W. van; Verschuuren, J.J.; Dijkgraaf, M.G.; Vermeulen, M.
BACKGROUND: Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pa
van Schaik, Ivo N.; Eftimov, Filip; van Doorn, Pieter A.; Brusse, Esther; van den Berg, Leonard H.; van der Pol, W. Ludo; Faber, Catharina G.; van Oostrom, Joost C. H.; Vogels, Oscar J. M.; Hadden, Rob D. M.; Kleine, Bert U.; van Norden, Anouk G. W.; Verschuuren, Jan J. G. M.; Dijkgraaf, Marcel G. W.; Vermeulen, Marinus
Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pat
I.N. van Schaik; F. Eftimov; P.A. van Doorn; E. Brusse; L.H. van den Berg; W.L. van der Pol; C.G. Faber; J.C. van Oostrom; O.J. Vogels; R.D. Hadden; B.U. Kleine; A.G. van Norden; J.J. Verschuuren; M.G. Dijkgraaf; M. Vermeulen
Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pat
Koska, J; Ortega, E; Bunt, J C;
Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-...
Stan Vlaicu; Tubelius Py; Zachrisson Anders
Abstract Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730) on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-...
Becerra-Camargo, Jesus; Martinez-Martinez, Fernando; Garcia-Jimenez, Emilio
Background Admission to an emergency department (ED) is a key vulnerable moment when patients are at increased risk of medication discrepancies and medication histories are an effective way of ensuring that fewer errors are made. This study measured whether a pharmacist-acquired medication history in an ED focusing on a patient’s current home medication regimen, and available to be used by a doctor when consulting in the ED, would reduce the number of patients having at least 1 medication dis...
Lee, Dong-Hyo; Seo, Eun-Sung; Hong, Jin-Tae; Lee, Gang-Tai; You, Young-Kyoung; Lee, Kun-Kook; Jo, Ga-Won; Kim, Nam-kwen
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 moisturi...
Stokman, MA; Spijkervet, FKL; Burlage, FR; Dijkstra, PU; Manson, WL; de Vries, EGE; Roodenburg, JLN
Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial. Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative ra...
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. Patien...
González de Vega, C; Speed, C; Wolfarth, B.; González, J.
Background Acute ankle sprains are common and activity limiting injuries, and topical diclofenac gel has proven efficacy in alleviating pain and restoring function. This trial aimed to compare a topical natural agent, Traumeel with topical diclofenac gel (1%) in the management of acute ankle sprain. Methods This prospective, multicentre, randomised, blinded, active-control and non-inferiority study involved 449 physically active adults sustaining unilateral grade 1 or 2 ankle sprain within th...
Gildea, Sarah; Arkins, Sean; Walsh, Cathal; Cullinane, Ann
Many racing authorities, sales companies and equestrian bodies have mandatory vaccination policies for equine influenza (EI). The consequences of lack of vaccine efficacy include clinical disease, disruption to training programmes, the cancellation of equestrian events and the introduction of virus to susceptible populations. The correlation between antibody against the virus haemagglutinin and protection against influenza has been well established. The objective of this study was to compare the antibody responses of 66 unvaccinated Thoroughbred weanlings on four different stud farms, following primary vaccination (V1, V2 and V3) with the five EI vaccines commercially available in Ireland (Duvaxyn IET Plus, Equilis Resequin, Equip FT, Equilis Prequenza Te, ProteqFlu Te). Antibody responses were monitored for 6 months post V3 by single radial haemolysis. The pattern of antibody response was similar for all vaccines and for all antigens tested. A rapid decline of antibody level was observed by 3 months post V2 for all vaccines. The antibody response of the horses vaccinated with the whole virus vaccine Duvaxyn IET Plus was significantly higher than that of the horses vaccinated with the other four products. Five weanlings had maternally derived antibodies (MDA) at the time of V1. The canary pox recombinant vaccine, subunit vaccine and whole virus inactivated vaccines administered to these weanlings did not induce a detectable antibody response against the background of MDA but effectively primed the animals as revaccination resulted in a strong antibody response. In this study 43% of the weanlings failed to seroconvert after V1. This high incidence of poor responders has not been reported in previous experimental studies relating to these products. The poor responders were observed in all vaccine groups except those vaccinated with Duvaxyn IET Plus. Post V2 the incidence of poor responders was reduced to 7% and all horses responded to V3. The study demonstrates that
Andersen, Rikke; Mølgaard, Christian; Skovgaard, Lene T.;
Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in...... D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 mu g vitamin D-3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 mu g increased S-25OHD concentrations 2-fold and...... 20 mu g 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone...
Ainsworth, Hannah; Hewitt, Catherine E.; Higgins, Steve; Wiggins, Andy; Torgerson, David J.; Torgerson, Carole J.
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…
Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA
Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43 f
Lassen, Michael Rud; Raskob, Gary E; Gallus, Alexander;
, patients, statisticians, adjudicators, and steering committee were masked to allocation. Apixaban was started 12-24 h after wound closure and enoxaparin 12 h before surgery; both drugs were continued for 10-14 days, when bilateral ascending venography was scheduled. Primary outcome was the composite of...... receive oral apixaban 2.5 mg twice daily (n=1528) or subcutaneous enoxaparin 40 mg once daily (1529). The randomisation schedule was generated by the Bristol-Myers Squibb randomisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four. Investigators...
Margraf, Jurgen; And Others
Compared alprazolam, imipramine, and placebo in the treatment of panic disorder patients (n=59) to investigate concerns about the internal validity of the double-blind design. Found that the great majority of patients and physicians were able to rate accurately whether active drug or placebo had been given and physicians could distinguish between…
Nurmikko, Turo J; Serpell, Mick G; Hoggart, Barbara; Toomey, Peter J; Morlion, Bart J; Haines, Derek
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 (psativex 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
Savović, J; Jones, He; Altman, Dg;
The design of randomised controlled trials (RCTs) should incorporate characteristics (such as concealment of randomised allocation and blinding of participants and personnel) that avoid biases resulting from lack of comparability of the intervention and control groups. Empirical evidence suggests...
Koek, Mayke B. G.; Buskens, Erik; van Weelden, Huib; Steegmans, Paul H. A.; Bruijnzeel-Koomen, Carla A. F. M.; Sigurdsson, Vigfus
Objective To determine whether ultraviolet B phototherapy at home is equally safe and equally effective as ultraviolet B phototherapy in an outpatient setting for patients with psoriasis. Design Pragmatic multicentre single blind randomised clinical trial (PLUTO study). Setting Dermatology departmen
Full Text Available Abstract Background The Breathlessness Intervention Service is a novel service for patients with intractable breathlessness regardless of aetiology. It is being evaluated using the Medical Research Council's framework for the evaluation of complex interventions. This paper describes the feasibility results of Phase II: a single-blinded fast-track pragmatic randomised controlled trial. Methods A single-blinded fast-track pragmatic randomised controlled trial was conducted for patients with chronic obstructive pulmonary disease referred to the service. Patients were randomised to either receive the intervention immediately for an eight-week period, or receive the intervention after an eight-week period on a waiting list during which time they received standard care. Outcomes examined included: response rates to the trial; response rates to the individual questionnaires and items; comments relating to the trial functioning made during interviews with patients, carers, referrers and service providers; and, researcher fieldwork notes. Results 16 of the 20 eligible patients agreed to participate in a recruitment visit (16/20; 14 respondents went on to complete a recruitment visit/baseline interview. The majority of those who completed a recruitment visit/baseline interview completed the RCT protocol (13/14; 12 of their carers were recruited and completed the protocol. An unblinding rate of 6/25 respondents (patients and carers was identified. Missing data were minimal and only one patient was lost to follow up. The fast-track trial methodology proved feasible and acceptable. Two of the baseline/outcome measures proved unsuitable: the WHO performance scale and the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW. Conclusion This study adds to the evidence that fast-track randomised controlled trials are feasible and acceptable in evaluations of palliative care interventions for patients with non-malignant conditions
Feurle, G E; Theuer, D; Velasco, S; Barry, B A; Wördehoff, D; Sommer, A; Jantschek, G; Kruis, W.
The effect of olsalazine, an analogue of sulphasalazine, consisting of two molecules 5-aminosalicylic acid linked by an azobond has been investigated for the treatment of ulcerative colitis. In a randomised double blind trial we compared 2 g olsalazine with placebo for four weeks. Of the 105 patients, with mild to moderate ulcerative colitis, entered in the trial 52 received olsalazine, and 53 placebo. Treatment had to be terminated prematurely because of untoward effects of olsalazine (mainl...
Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial
Comi, G; Martinelli, V; Rodegher, M;
glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was...... time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224. FINDINGS: All...... randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease...
Background and purpose: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. Patients and methods: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n=44) or placebo (n=22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm2) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. Results: At 12 months post-randomisation, ≥50% reduction in surface area (cm2) of breast induration was recorded in13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. Conclusions: The study failed to show efficacy of orally-adminstered GSPE in patients with breast induration following radiotherapy for breast cancer
Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.
Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study
Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen;
with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...... to subcutaneous injection of exenatide once-weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. The primary endpoints are safety and weight loss after 3 months. Secondary endpoints include several metabolic measurements, various psychopathological and cognitive measures...
Treatment of antipsychotic-associated obesity with a GLP-1 receptor agnoist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study - the TAO study
Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen;
with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Materials and methods: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs...... will be randomised to subcutaneous injection of exenatide once-weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. The primary endpoints are safety and weight loss after 3 months. Secondary endpoints include several metabolic measurements, various psychopathological and cognitive...
Cosentino, R; De Stefano, R; SELVI, E.; Frati, E; S. Manca; Frediani, B; R. Marcolongo
Methods: 70 patients showing chronic, symptomatic, calcifying tendinitis of the shoulder were examined. A single blind randomised study was performed with 35 patients undergoing a regular treatment (group 1) and 35 a simulated one (group 2). Pain and functional assessment was carried out according to Constant and Murley. Variations in the dimension of the calcification were evaluated by anteroposterior x ray films.
Sofi, Francesco; Whittaker, Anne; Gori, Anna Maria; Cesari, Francesca; Surrenti, Elisabetta; Abbate, Rosanna; Gensini, Gian Franco; Benedettelli, Stefano; Casini, Alessandro
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 (Pwheat 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 (Pwheat 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 products. PMID:24521561
Full Text Available Abstract Background Enzyme treatment is the mainstay for management of exocrine pancreatic insufficiency (EPI in dogs. ‘Enteric-coated’ preparations have been developed to protect the enzyme from degradation in the stomach, but their efficacy has not been critically evaluated. The hypothesis of the current study was that enteric coating would have no effect on the efficacy of pancreatic enzyme treatment for dogs with EPI. Thirty-eight client-owned dogs with naturally occurring EPI were included in this multicentre, blinded, randomised controlled trial. Dogs received either an enteric-coated enzyme preparation (test treatment or an identical preparation without the enteric coating (control treatment over a period of 56 days. Results There were no significant differences in either signalment or cobalamin status (where cobalamin deficient or not between the dogs on the test and control treatments. Body weight and body condition score increased in both groups during the trial (PPPP=0.225. Clinical disease severity score decreased over time for both groups (P=0.011 and no difference was noted between groups (P=0.869. No significant adverse effects were reported, for either treatment, for the duration of the trial. Conclusions Enteric coating a pancreatic enzyme treatment improves response in canine EPI.
Borges, Cynthia M; Papadimitriou, Alexandros; Duarte, Diego A; Lopes de Faria, Jacqueline M; Lopes de Faria, José B
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
Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.
Callum B Pearce
Full Text Available Context :Current best evidence is in favour of early institution of enteral feeding in acute severe pancreatitis with promising results from trials in immunonutrition on other patient groups. Objective: To identify which groups of patients and products are associated with benefit, we investigated immunonutrition in patients with predicted acute severe pancreatitis. Design :A randomised trial of a study feed containing glutamine, arginine, tributyrin and antioxidants versus an isocaloric isonitrogenous control feed was undertaken. Patients: Thirty-one patients with a diagnosis of acute pancreatitis predicted to develop severe disease: 15 study feeds and 16 control feeds. Interventions: Enteral feeding via nasojejunal tube for 3 days. If patients required further feeding the study was continued up to 15 days. Main outcome measures :Reduction in Creactive protein (CRP by 40 mg/L after 3 days of enteral feeding was the primary endpoint. Carboxypeptidase B activation peptide (CAPAP levels were taken at regular intervals. Results :After 3 days of feeding, in the study group 2/15 (13% of patients had reduced their CRP by 40 mg/L or more. In the control group 6/16 (38% of patients had reduced their CRP by this amount. This difference was found to be near the statistical significant limit (P=0.220. Conclusions :The cause of the unexpectedly higher CRP values in the study group is unclear. The rise in CRP was without a commensurate rise in CAPAP or outcome measures so there was no evidence that this represented pancreatic necrosis. The contrast between the CRP and CAPAP results is of interest and we believe that specific pancreatic indices such as CAPAP should be considered in larger future studies.
Schache Anthony G
Full Text Available Abstract Background The patellofemoral joint (PFJ is one compartment of the knee that is frequently affected by osteoarthritis (OA and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA. Methods 90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks. Physiotherapy treatment will consist of (i quadriceps muscle retraining; (ii quadriceps and hip muscle strengthening; (iii patellar taping; (iv manual PFJ and soft tissue mobilisation; and (v OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction. Conclusion This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the
Background and purpose: Treatment-induced arm lymphoedema is a common and distressing complication of curative surgery and radiotherapy for early breast cancer. A number of studies testing alpha-tocopherol (vitamin E) and pentoxifylline suggest evidence of clinical regression of superficial radiation-induced fibrosis but there is only very limited evidence from randomised trials. Arm lymphoedema after lymphatic radiotherapy and surgery has been used in the present study as a clinical system for testing these drugs in a double-blind placebo-controlled randomised phase II trial. Patients and methods: Sixty-eight eligible research volunteers with a minimum 20% increase in arm volume at a median 15.5 years (range 2-41) after axillary/supraclavicular radiotherapy (plus axillary surgery in 51/68 (75%) cases) were randomised to active drugs or placebo. All volunteers were given dl-alpha tocopheryl acetate 500 mg twice a day orally plus pentoxifylline 400 mg twice a day orally, or corresponding placebos, for 6 months. The primary endpoint was volume of the ipsilateral limb measured opto-electronically using a perometer and expressed as a percentage of the contralateral limb volume. Results: At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of arm volume. Absolute change in arm volume at 12 months was 2.5% (95% CI -0.40 to 5.3) in the treatment group compared to 1.2% (95% CI -2.8 to 5.1) in the placebo group. The difference in mean volume change between randomisation groups at 12 months was not statistically significant (P=0.6), -1.3% (95% CI -6.1 to 3.5), nor was there a significant difference in response at 6 months (P=0.7), where mean change in arm volume from baseline in the treatment and placebo groups was -2.3% (95% CI -7.9 to 3.4) and -1.1% (95% CI -3.9 to 1.7), respectively. There were no significant differences between randomised groups in terms of secondary endpoints, including tissue induration
Weiss, Eric Alan; Oldham, George; Lin, Michelle; Foster, Tammy; Quinn, James Victor
Objective To determine if there is a significant difference in the infection rates of wounds irrigated with sterile normal saline (SS) versus tap water (TW), before primary wound closure. Design Single centre, prospective, randomised, double-blind controlled trial. Wound irrigation solution type was computer randomised and allocation was done on a sequential basis. Setting Stanford University Medical Center Department of Emergency Medicine. Participants Patients older than 1 year of age, who ...
Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial
Pinnock, Hilary; Hanley, Janet; McCloughan, Lucy; Todd, Allison; Krishan, Ashma; Lewis, Stephanie; Stoddart, Andrew; van der Pol, Marjon; MacNee, William; Sheikh, Aziz; Pagliari, Claudia; McKinstry, Brian
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 unab...
Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial
Pinnock, Hilary; Hanley, Janet; McCloughan, Lucy; Todd, Allison; Krishan, Ashma; Lewis, Stephanie; Stoddart, Andrew; van der Pol, Marjon; MacNee, William; Sheikh, Aziz; Pagliari, Claudia; McKinstry, Brian
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 t...
Gault, E.J.; Perry, R J; Cole, T J; Casey, S.; Paterson, W.F.; Hindmarsh, P. C.; Betts, P; Dunger, D B; Donaldson, M D C
Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomised to oxandrolone (0...
Gault, E.J.; Perry, R J; Cole, T J; Casey, S.; Paterson, W.M.; Hindmarsh, P.J.; Betts, P; Dunger, D B; Donaldson, M D C
Objective: To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design: Randomised, double blind, placebo controlled trial. Setting:36 paediatric endocrinology departments in UK hospitals. Participants: Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomise...
Springborg, J B; Møller, C; Gideon, P;
BACKGROUND: Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. METHODS: A larger scale clinical trial was planned but...... preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i...... statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. CONCLUSIONS: Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted....
Romani Vestman, N; Hasslöf, P; Keller, M K; Granström, E; Roos, S; Twetman, S; Stecksén-Blicks, C
This study assessed whether the persistence of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 in saliva could delay the regrowth of mutans streptococci (MS) after a full-mouth disinfection with chlorhexidine (CHX). A randomised, double-blind, placebo-controlled study with a 6-week intervention period and 3- and 6-month follow-up was performed. 62 healthy subjects with moderate to high counts of MS were randomly assigned to a test group (n = 32) or a placebo group (n = 30). Before onset of the intervention, subjects received two sessions of professional cleaning, flossing, and application of CHX varnish and rinsed their mouth with a CHX solution between the sessions (2 days). Thereafter, the test group used probiotic lozenges (2/day) containing L. reuteri (DSM 17938 and ATCC PTA 5289; 1 × 10(8) CFU of each strain), and the placebo group used identical lozenges lacking the lactobacilli. Saliva samples were collected and cultured onto selective media, and isolates of L. reuteri as well as DNA directly extracted from saliva were tested by polymerase chain reaction (PCR) with specific primers. Presence of salivary MS was analysed with a chair-side test. L. reuteri was frequently detected by culture during the intervention period but in only 3 test group subjects at follow-ups. Regrowth of MS statistically significantly differed depending on the presence or absence of L. reuteri DSM 17938 detected by PCR. We conclude that cultivable L. reuteri strains may only sporadically be confirmed after termination of the intervention, but subjects with PCR-detected L. reuteri demonstrated slower regrowth of MS. PMID:23486236
Zelen, Charles M; Serena, Thomas E.; Robert J. Snyder
The aim of this study is to determine if weekly application of dehydrated human amnion/chorion membrane allograft reduce time to heal more effectively than biweekly application for treatment of diabetic foot ulcers. This was an institutional review board-approved, registered, prospective, randomised, comparative, non-blinded, single-centre clinical trial. Patients with non-infected ulcers of ≥ 4 weeks duration were included for the study. They were randomised to receive weekly or biweekly app...
Dunzhu, S; Wang, F S; Courtright, P; Liu, L; Tenzing, C; Noertjojo, K; WILKIE, A; Santangelo, M.; Bassett, K L
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.
... Got Homework? Here's Help White House Lunch Recipes Blindness KidsHealth > For Kids > Blindness Print A A A ... help, are sometimes called "legally blind." What Causes Blindness? Vision problems can develop before a baby is ...
To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. A randomised, investigator blinded, controlled trial was used in a large, public clinic associated with a referral hospital in Blantyre, M...
Evans, Malkanthi; Salewski, Ryan P; Christman, Mary C; Girard, Stephanie-Anne; Tompkins, Thomas A
Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics. PMID:27169634
Robinson, Sian; Zincuk, Aleksander; Strøm, Thomas; Larsen, Torben Bjerregaard; Rasmussen, Bjarne; Toft, Palle
an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02). CONCLUSIONS: Our study...... the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients. METHODS: The 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24...... hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. RESULTS: Median peak (4 hours after administration), aFXa levels increased significantly with...
Wallius, Barbro M; Tidholm, Anna E
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. PMID:18996037
Full Text Available Objective: The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro. Exploratory studies in the osteoporosis trialsreport that strontium ranelate reduces biomarkers of cartilage degradation, and attenuates the progression and clinical symptoms of spinal osteoarthritis, suggesting symptom- and structure-modifying activity in osteoarthritis. We describethe rationale and design of a randomised trial evaluating the efficacy and safety of strontium ranelate in knee osteoarthritis.Research design, methods, and results: This double-blind, placebo-controlled trial (98 centres, 18 countries includes ambulatory Caucasian men and women aged ≥50 years with primary knee osteoarthritis of the medial tibiofemoralcompartment (Kellgren and Lawrence grade 2 or 3, joint space width (JSW 2.5 to 5 mm, and knee pain on most days in the previous month (intensity ≥40 mm on a visual analogue scale. Patients are randomly allocated to three groups (strontium ranelate 1 or 2g/day, or placebo. Follow-up is expected to last 3 years. The primary endpoint is radiographic change in JSW from baseline in each group versus placebo. The main clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at every visit. It is estimated that 1600 patients are required to establish statistical significance with power >90% (0.2 mm ±10% between-group difference in change in JSW over 3 years. Recruitment started in April 2006. The results are expected in spring 2012.Clinical trial registration: The trial is registered on www.controlled-trials.com (number ISRCTN41323372.Conclusions: This randomised, double blind, placebo-controlled study will establish the potential of strontium ranelate in improving structure and symptoms in patients with knee osteoarthritis.
Klupp, Nerida L; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z; Chang, Dennis H
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
Hunter David J
Full Text Available Abstract Background Lower limb strengthening exercises are an important component of the treatment for knee osteoarthritis (OA. Strengthening the hip abductor and adductor muscles may influence joint loading and/or OA-related symptoms, but no study has evaluated these hypotheses directly. The aim of this randomised, single-blind controlled trial is to determine whether hip abductor and adductor muscle strengthening can reduce knee load and improve pain and physical function in people with medial compartment knee OA. Methods/Design 88 participants with painful, radiographically confirmed medial compartment knee OA and varus alignment will be recruited from the community and randomly allocated to a hip strengthening or control group using concealed allocation stratified by disease severity. The hip strengthening group will perform 6 exercises to strengthen the hip abductor and adductor muscles at home 5 times per week for 12 weeks. They will consult with a physiotherapist on 7 occasions to be taught the exercises and progress exercise resistance. The control group will be requested to continue with their usual care. Blinded follow up assessment will be conducted at 12 weeks after randomisation. The primary outcome measure is the change in the peak external knee adduction moment measured during walking. Questionnaires will assess changes in pain and physical function as well as overall perceived rating of change. An intention-to-treat analysis will be performed using linear regression modelling and adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effect of hip strengthening on knee loads and symptoms in people with medial compartment knee OA. If shown to reduce the knee adduction moment, hip strengthening has the potential to slow disease progression. Trial Registration Australia New Zealand Clinical Trials Registry ACTR12607000001493
The main difference between macrocyclic Gd-DOTA and linear Gd-DTPA complexes is the greater stability of the former which theoretically might reduce biological interactions in man. To evaluate the clinical relevance of this property, 300 unselected neurological patients were included in a randomised double-blind comparison involving five European centres, focused mainly on the tolerance of these two contrast media. Clinical tolerance was assessed immediately after the procedure and 24 h later. Adverse events were found with a similar frequency in the two groups (17.3% for Gd-DOTA and 19.3% for Gd-DTPA). Minor neurological symptoms were the most frequent (48.6%) headache being the most common (29.2% of adverse events). No difference in efficacy was found. (orig.)
Hopper Sandy M
Full Text Available Abstract Background Painful infectious mouth conditions are a common presentation to emergency departments. Although self limiting, painful ulcerative lesions and inflamed mucosa can decrease oral intake and can lead to dehydration. Oral analgesia is of limited efficacy and is often refused by the patient. Despite widespread use of oral 2% viscous lidocaine for many years, there is little evidence for its efficacy as an analgesic and in aiding oral intake in children with painful infectious mouth conditions. This study aims to establish the effectiveness of 2% viscous lidocaine in increasing oral intake in these children by comparing it with placebo. Methods/Design This study is a randomised double-blind placebo controlled trial of children between 6 months and 8 years of age with painful infectious mouth conditions defined as gingivostomatitis (herpetic or non herpetic, ulcerative pharyngitis, herpangina and hand foot and mouth disease as assessed by the treating clinician in association with a history of poor oral fluid intake. It will be conducted at a single tertiary paediatric emergency department in Melbourne Australia. 20 patients have already been randomised to receive 2% lidocaine or placebo in a pilot study to determine the sample size in a preplanned adaptive design. A further 80 patients will be randomised to receive either 2% lidocaine or placebo. The placebo agent is identical to lidocaine in terms of appearance, flavour and smell. All clinical and research staff involved, patients and their parents will be blinded to treatment allocation. The primary endpoint is the amount of fluid ingested by each child, expressed in ml/kg, within 60 minutes from the time of administration of the study mixture. Secondary endpoints are the proportion of patients ingesting 5 ml/kg and 10 ml/kg at 30 and 60 minutes after drug administration and the incidence of adverse events. Longer term outcomes will include the proportion of patients requiring
Full Text Available Abstract 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
Vischer, T L
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-...
Jensen, Morten Lind; Lippert, Freddy; Hesselfeldt, Rasmus;
retention of learning. Materials and methods: This was a prospective single blinded randomised controlled study of the learning outcome from a standard ALS course on a volunteer sample of the entire cohort of newly graduated doctors from Copenhagen University. The outcome measurement was ALS...... immediately following graduation. Results: Invitation to participate was accepted by 154/240 (64%) graduates and 117/154 (76%) completed the study. There was no difference between the intervention and control groups with regard to the imme- diate learning outcome. The intervention group had significantly...... small but statistically significant impact on the retention of learning, but not on the immediate learning outcome....
Full Text Available UNLABELLED: The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women with idiopathic chronic fatigue (ICF in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day(-1 or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS and a visual analogue scale (VAS as a primary endpoint. Serum levels of reactive oxygen species (ROS, malondialdehyde (MDA, total glutathione (GSH contents and glutathione reductase (GSH-Rd activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05. Mental NRS score was significantly improved by P. ginseng administrations as 20.4 ± 5.0 to 15.1 ± 6.5 [95% CI 2.3 ~ 8.2] for 1 g and 20.7 ± 6.3 to 13.8 ± 6.2 [95% CI -0.1 ~ 4.2] for 2 g compared with placebo 20.9 ± 4.5 to 18.8 ± 2.9 [95% CI 4.1 ~ 9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3 ± 1.3 to 4.4 ± 1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1 ± 1.0 to 5.8 ± 1.3 [95% CI 2.2 ~ 3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. TRIAL REGISTRATION: Clinical Research Information Service (CRIS KCT0000048.
Garaiova, I.; Muchová, J; Nagyová, Z; Wang, D; Li, J. V.; Országhová, Z; Michael, D R; Plummer, S F; Ďuračková, Z
Background: This pilot study investigates the efficacy of a probiotic consortium (Lab4) in combination with vitamin C on the prevention of respiratory tract infections in children attending preschool facilities. Subjects/methods: In a double-blind, randomised, placebo-controlled pilot study with children aged 3–6 years, 57 received 1.25 × 1010 colony-forming units of Lactobacillus acidophilus CUL21 (NCIMB 30156), Lactobacillus acidophilus CUL60 (NCIMB 30157), Bifidobacterium bifidum CUL20 (NC...
Sandal, Louise Fleng; Thorlund, Jonas Bloch; Ulrich, Roger S; Dieppe, Paul A; Roos, Ewa M
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...... 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....... 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...
Akkermans Louis MA
Full Text Available Abstract Background Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. Methods/design PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641 or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. Conclusion The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis.
Cognitive training plus a comprehensive psychosocial programme (OPUS versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial: A study protocol for a centrally randomised, observer-blinded multi-centre clinical trial
Full Text Available Abstract Background Up to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone. Methods The NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patient's cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem. Discussion Results from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia. Trial Registration Clinicaltrials.gov NCT00472862.
Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers;
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...
Bjermer, Leif; Bisgaard, H; Bousquet, J.; Fabbri, LM; Greening, AP; Haahtela, T.; Holgate, ST; Picado, C; Menten, J.; Dass, SB; Leff, JA; Polos, PG
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 ...
Schoenfeld, P.; Pimentel, M; Chang, L.; Lembo, A; Chey, W. D.; Yu, J.; Paterson, C; Bortey, E.; Forbes, W P
Summary Background The efficacy of rifaximin, a nonsystemic, gut‐targeted antibiotic for reducing non–constipation‐predominant irritable bowel syndrome (non‐C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double‐blind, placebo‐controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow‐up periods are lacking. Aim To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phas...
Heal, Clare F; Petra G Buettner; Cruickshank, Robert; Graham, David; Browning, Sheldon; Pendergast, Jayne; Drobetz, Herwig; Gluer, Robert; Lisec, Carl
Objective To determine the effectiveness of a single application of topical chloramphenicol ointment in preventing wound infection after minor dermatological surgery. Design Prospective randomised placebo controlled double blind multicentre trial. Setting Primary care in a regional centre in Queensland, Australia. Participants 972 minor surgery patients. Interventions A single topical dose of chloramphenicol (n=488) or paraffin ointment (n=484; placebo). Main outcome measure Incidence of infe...
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/p...
Full Text Available Abstract Background Evidence supports the use of exercise for chronic low back pain (CLBP; however, adherence is often poor due to ongoing pain. Auricular acupuncture is a form of pain relief involving the stimulation of points on the outer ear corresponding with specific body parts. It may be a useful adjunct to exercise in managing CLBP; however, there is only limited evidence to support its use with this patient group. Methods/Design This study was designed to test the feasibility of an assessor-blind randomised controlled trial which assess the effects on clinical outcomes and exercise adherence of adding manual auricular acupuncture to a personalised and supervised exercise programme (PEP for CLBP. No sample size calculation has been carried out as this study aims to identify CLBP referral rates within the catchment area of the study site. The researchers aim to recruit four cohorts of n = 20 participants to facilitate a power analysis for a future randomised controlled trial. A computer generated random allocation sequence will be prepared centrally and used to allocate participants by cohort to one of the following interventions: 1 six weeks of PEP plus manual auricular acupuncture; 2 six weeks of PEP alone. Both groups will also complete a further six weeks of self-paced exercise with telephone follow-up support. In addition to a baseline and exit questionnaire at the beginning and end of the study, the following outcomes will be collected at baseline, and after 7, 13 and 25 weeks: pain frequency and bothersomeness, back-specific function, objective assessment and recall of physical activity, use of analgesia, perceived self-efficacy, fear avoidance beliefs, and beliefs about the consequences of back pain. Since this is a feasibility study, significance tests will not be presented, and treatment effects will be represented by point estimates and confidence intervals. For each outcome variable, analysis of covariance will be performed on
Dijkgraaf Marcel G
Full Text Available Abstract Background Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. Methods/Design The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. Discussion To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease. Trial registration The Netherlands National Trial Register (NTR1303
Maes, Michael; Ashton, Melanie; Berk, Lesley; Kanchanatawan, Buranee; Sughondhabirom, Atapol; Tangwongchai, Sookjareon; Ng, Chee; Dowling, Nathan; Malhi, Gin S.; Berk, MIchael
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
... Prevalent Cases of Blindness (in thousands) by Age, Gender, and Race/Ethnicity Table for 2010 U.S. Prevalent ... Prevalent Cases of Blindness (in thousands) by Age, Gender, and Race/Ethnicity Table for 2000 U.S. Prevalent ...
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
Full Text Available Abstract 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
Tfelt-Hansen, Peer Carsten
Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs are...... published in full. Naratriptan 2.5 mg is superior to placebo for acute migraine treatment in 6 RCTs, but inferior to sumatriptan 100 mg and rizatriptan 10 mg in one RCT each. This dose of naratriptan has no more adverse events than placebo. Naratriptan 1 mg b.i.d. has some effect in the short......-term prophylactic treatment of menstruation-associated migraine in 3 RCTs. In 2 RCTs, naratriptan 2.5 mg was equivalent to naproxen sodium 375 mg for migraine-related quality of life. Naratriptan 2.5 mg (34% preference) was superior to naproxen sodium 500 mg (25% preference). Naratriptan 2.5 mg is better than...
Gerritsen Pieter G
Full Text Available Abstract Background Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain. Methods The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work and recurrence. Both groups will be evaluated. Success rate of hernia repair and complications will be measured as safeguard for quality. To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP technique reduces postoperative pain to Discussion The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP technique, compared to Lichtenstein. In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein. Trial registration ISRCTN 93798494
Smith Alison J
Full Text Available Abstract Background For the majority of patients with osteoarthritis (OA, joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR and total hip replacement (THR for OA. Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain
Full Text Available Abstract Background Chronic rotator cuff pathology (CRCP is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI, average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36, Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health
Filippi, M.; Wolinsky, J.S.; Comi, G.
BACKGROUND: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation a
Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia
MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S.; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G
INTRODUCTION: Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat vers...
Full Text Available Abstract Background Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. Methods We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years, displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12% as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. Results The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038, reduction of viral load (p = 0.026, and lower incidence of secondary infections with other respiratory viruses (p = 0.046 indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. Conclusion In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. Trial registration ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/
Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial
Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus;
BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We...... interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability...... status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets...
Full Text Available We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD (mm3, EDSS (Expanded Disability Status Scale, annual relapse Rate (ARR, timed 25-foot walk (T25FW, and timed 10-foot tandem walk (TT10W at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.
Aksoy, Huseyin; Aksoy, Ulku; Ozyurt, Sezin; Ozoglu, Nil; Acmaz, Gokhan; Aydın, Turgut; İdem Karadağ, Özge; Tayyar, Ahter Tanay
Surgical abortion is one of the most frequently performed gynaecological procedures and its associated pain has always been a problem in gynaecology. Here we studied the analgesic efficacy of lidocaine spray and paracervical block (PCB) in patients undergoing first-trimester surgical abortion. A randomised double-blind placebo-controlled study was conducted on 108 women requesting pregnancy termination. The subjects were randomly assigned into four groups: Group 1 (PCB plus lidocaine spray) (n=27), Group 2 (PCB) (n=27), Group 3 (lidocaine spray) (n=27) and Group 4 (placebo) (n=27). Intra-procedural and post-procedural pain scores were measured with a standard visual analogue scale (VAS). The median VAS scores during procedure in placebo, lidocaine spray, PCB plus lidocaine spray and PCB groups were 8 (7-9), 5 (4-8), 4 (3-4) and 5 (3-5), respectively. The most effective method of pain relief during first-trimester abortion can be achieved through a combined use of PCB plus lidocaine spray. Therefore, lidocaine spray is a non-invasive complementary anaesthetic method versus traditional PCB for first-trimester surgical abortion. PMID:26926158
Full Text Available Abstract Background High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics. However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke. Methods Trial Design: Double blind parallel group external pilot randomised controlled trial. Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals. Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset and hypertension (systolic BP>160 mmHg. Intervention: Lisinopril 5-10 mg (intervention group, matched placebo (control group, daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics. Outcomes: Study feasibility (recruitment rate, compliance with data collection and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function. Discussion This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke
Narelle M. Berry
Full Text Available Background and aim: Preliminary evaluation of a wild green oat extract (WGOE (Neuravena® ELFA®955, Frutarom, Switzerland revealed an acute cognitive benefit of supplementation. This study investigated whether regular daily WGOE supplementation would result in sustained cognitive improvements. Method: A 12-week randomised, double-blind, placebo-controlled cross-over trial of WGOE supplementation (1500 mg/day versus placebo was undertaken in 37 healthy adults aged 67 ± 0.8 years (mean ± SEM. Cognitive assessments included the Stroop colour-word test, letter cancellation, the rule-shift task, a computerised multi-tasking test battery and the trail-making task. All assessments were conducted in Week 12 and repeated in Week 24 whilst subjects were fasted and at least 18 h after taking the last dose of supplement. Result: Chronic WGOE supplementation did not affect any measures of cognition. Conclusion: It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment.
Rizal, A M; Aljunid, S M; Normalina, M; Hanom, A Faridah; Chuah, K L; Suzainah, Y; Zainal, M; Azman, A B
A randomised single blinded clinical trial to compare the cost of cataract surgery between extracapsular cataract extraction (ECCE) and phacoemulsification (PEA) was conducted at Hospital Universiti Kebangsaan Malaysia (HUKM) between March and December 2000. A total of 60 patients were included in this study. The cost of a cataract surgery incurred by hospital, patients and households up to two months after discharge were included. The costs of training, loss of patients' income after discharge and intangible costs were excluded. Results showed that the average cost for one ECCE operation is RM1,664.46 (RM1,233.04-RM2,377.64) and for PEA is RM1,978.00 (RM1,557.87-RM3,334.50). During this short period of follow up, it can be concluded that ECCE is significantly cheaper than PEA by an average difference of RM 313.54 per patient (p < 0.001). Cost of equipment and low frequency of PEA technique done in HUKM were the two main reasons for the high unit cost of PEA as compared to ECCE. PMID:14750378
Whitmont, Kaley; McKelvey, Kelly J; Fulcher, Gregory; Reid, Ian; March, Lyn; Xue, Meilang; Cooper, Alan; Jackson, Christopher J
Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo-controlled, double-blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC-treated wounds (p = 0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one saline-treated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial. PMID:23848141
WHEDA study: Effectiveness of occupational therapy at home for older people with dementia and their caregivers - the design of a pragmatic randomised controlled trial evaluating a Dutch programme in seven German centres
Vernooij-Dassen Myrra; Schornstein Katrin; Leonhart Rainer; Graff Maud; Voigt-Radloff Sebastian; Olde-Rikkert Marcel; Huell Michael
Abstract Background A recent Dutch mono-centre randomised controlled trial has shown that occupational therapy improves daily functioning in dementia. The aim of this present study is to compare the effects of the Dutch community occupational therapy programme with a community occupational therapy consultation on daily functioning in older people with mild or moderate dementia and their primary caregivers in a German multi-centre context. Methods/Design A multi-centre single blind randomised ...
Sandset, Else Charlotte; Bath, Philip M W; Boysen, Gudrun;
BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised...... blood pressure. METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included...... within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked...
Hutchings, H. A.; Wareham, K; Baxter, J. N.; Atherton, P.; J. G. C. Kingham; Duane, P; Thomas, L.; Thomas, M.; C. L. Ch'ng; Williams, J G
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. Pat...
Dodel, Richard; Rominger, Axel; Bartenstein, Peter; Barkhof, Frederik; Blennow, Kai; Förster, Stefan; Winter, Yaroslav; Bach, Jan-Philipp; Popp, Julius; Alferink, Judith; Wiltfang, Jens; Buerger, Katharina; Otto, Markus; Antuono, Piero; Jacoby, Michael; Richter, Ralph; Stevens, James; Melamed, Isaac; Goldstein, Jerome; Haag, Stefan; Wietek, Stefan; Farlow, Martin; Jessen, Frank
Background Three small trials have suggested effects of intravenous immunoglobulins (IVIG) on biomarkers and symptoms of mild-to-moderate Alzheimer’s disease (AD). We explored the safety, the effective dose, and the infusion interval for Octagam®10% in this patients’ group. Methods The study was a 24-week multicentre, double-blind, placebo-controlled phase II trial with 8 treatment arms at 7 sites in the USA and 5 sites in Germany. Participants aged 50–85 years were randomised (using a computer-generated randomisation sequence) to either 4 weekly infusions (n=22) (0.2 g/0.5 g/0.8 g/kg body weight), 2 weekly infusions (0.1g/0.25 g/0.4 g/kg) (n=21) or to placebo (n=7, 4-weekly, n=8, 2 weekly). The primary endpoint was the mean area under the curve (AUC) of plasma Aβ1–40 after the last infusion for one infusion interval. We considered the AUC of plasma Aβ1–40 being more representative of the potential effect of IVIG than a single time point measurement. Secondary outcomes included changes in (a) the concentrations of Aβ1–40, Aβ1–42, anti-Aβ autoantibodies in CSF/plasma and tau/ptau181 in CSF, (b) cognitive and functional scales, and (c) brain imaging (MRI/FDG-PET). Patients’ safety was assessed by recording of adverse events, clinical examinations, MRI investigations, electrocardiography and laboratory tests. The infusions were performed by site personnel who were otherwise not involved in any other assessments; therefore, the patients, caregivers, and investigators were blinded to the treatment allocations. The study medication was blinded by using intransparent overpouches and infusion lines. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). Findings Fifty-six patients were randomized. AUC of plasma Aβ1–40, was not significantly different from the placebo for five of the six IVIG arms (median with range: −18.00 [−1347.0; 1068.5] for 0.2 g/kg; 364.25 [−5834.5; 1953.5] for 0.5 g
Full Text Available Abstract Background Depression, cardiovascular disease (CVD risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. Methods/Design This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Discussion Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on
Dutta, P; Mitra, U.; Manna, B.; Niyogi, S; K Roy; Mondal, C.; Bhattacharya, S.
AIMS—To compare the clinical efficacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea. METHODS—In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32). RESULTS—Stool output (52.3 v 96.6 g/kg/day)...
Wahlbeck Kristian; Paile-Hyvärinen Maria; Eriksson Johan G
Abstract Background Depression is prevalent in people with type 2 diabetes and affects both glycemic control and overall quality of life. The aim of this trial was to evaluate the effect of the antidepressant paroxetine on metabolic control, quality of life and mental well-being in mildly depressed women with type 2 diabetes. Methods We randomised 15 mildly depressed women with non-optimally controlled type 2 diabetes to a 10-week single-blind treatment with either paroxetine 20 mg per day or...
Full Text Available Abstract 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 ( 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 wipes and to health professionals who support their use. Trial registration Current Controlled
Full Text Available 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
Full Text Available Abstract Background Intramuscular pethidine is routinely used throughout the UK for labour analgesia. Studies have suggested that pethidine provides little pain relief in labour and has a number of side effects affecting mother and neonate. It can cause nausea, vomiting and dysphoria in mothers and can cause reduced fetal heart rate variability and accelerations. Neonatal effects include respiratory depression and impaired feeding. There are few large studies comparing the relative side effects and efficacy of different opioids in labour. A small trial comparing intramuscular pethidine with diamorphine, showed diamorphine to have some benefits over pethidine when used for labour analgesia but the study did not investigate the adverse effects of either opioid. Methods The Intramuscular Diamorphine versus Intramuscular Pethidine (IDvIP trial is a randomised double-blind two centre controlled trial comparing intramuscular diamorphine and pethidine regarding their analgesic efficacy in labour and their side effects in mother, fetus and neonate. Information about the trial will be provided to women in the antenatal period or in early labour. Consent and recruitment to the trial will be obtained when the mother requests opioid analgesia. The sample size requirement is 406 women with data on primary outcomes. The maternal primary outcomes are pain relief during the first 3 hours after trial analgesia and specifically pain relief after 60 minutes. The neonatal primary outcomes are need for resuscitation and Apgar Score Discussion If the trial demonstrates that diamorphine provides better analgesia with fewer side effects in mother and neonate this could lead to a change in national practice and result in diamorphine becoming the preferred intramuscular opioid for analgesia in labour. Trial Registration ISRCTN14898678 Eudra No: 2006-003250-18, REC Reference No: 06/Q1702/95, MHRA Authorisation No: 1443/0001/001-0001, NIHR UKCRN reference 6895, RfPB grant
Effect of a mixture of inulin and fructo-oligosaccharide on lactobacillus and bifidobacterium intestinal microbiota of patients receiving radiotherapy: a randomised, double-blind, placebo-controlled trial Efecto de una mezcla de inulina y fructo-oligosacárido sobre la microflora intestinal de lactobacillus y bifidobacterium de pacientes que reciben radioterapia: un ensayo aleatorio, a doble ciego y controlado con placebo
P. García-Peris; Velasco, C; M. A. Lozano; Moreno, Y.; L. Paron; C. de la Cuerda; I. Bretón; M. Camblor; J. García-Hernández; Guarner, F; M Hernández
Background & aims: The pathogenesis of enteritis after abdominal radiotherapy is unknown, although changes in faecal microbiota may be involved. In several studies, Lactobacillus and Bifidobacterium have proven beneficial for the host. Prebiotics stimulate the proliferation of Lactobacillus and Bifidobacterium, and this may have positive effects on the intestinal mucosa during abdominal radiotherapy. Methods: We performed a randomised double-blind, placebo-controlled trial including 31 patien...
Full Text Available Abstract Background The serious mental illness Health Improvement Profile [HIP] is a brief pragmatic tool, which enables mental health nurses to work together with patients to screen physical health and take evidence-based action when variables are identified to be at risk. Piloting has demonstrated clinical utility and acceptability. Methods/Design A single blind parallel group cluster randomised controlled trial with secondary economic analysis and process observation. Unit of randomisation: mental health nurses [MHNs] working in adult community mental health teams across two NHS Trusts. Subjects: Patients over 18 years with a diagnosis of schizophrenia, schizoaffective or bipolar disorder on the caseload of participating MHNs. Primary objective: To determine the effects of the HIP programme on patients' physical wellbeing assessed by the physical component score of the Medical Outcome Study (MOS 36 Item Short Form Health Survey version 2 [SF-36v2]. Secondary objectives: To determine the effects of the HIP programme on: cost effectiveness, mental wellbeing, cardiovascular risk, physical health care attitudes and knowledge of MHNs and to determine the acceptability of the HIP Programme in the NHS. Consented nurses (and patients will be randomised to receive the HIP Programme or treatment as usual. Outcomes will be measured at baseline and 12 months with a process observation after 12 months to include evaluation of patients' and professionals' experience and observation of any effect on care plans and primary-secondary care interface communication. Outcomes will be analysed on an intention-to-treat (ITT basis. Discussion The results of the trial and process observation will provide information about the effectiveness of the HIP Programme in supporting MHNs to address physical comorbidity in serious mental illness. Given the current unacceptable prevalence of physical comorbidity and mortality in the serious mental illness population, it is
Full Text Available Background: Postoperative nausea and vomiting (PONV are common and distressing symptoms after surgery performed under general anaesthesia. 5-hydroxytryptamine 3 antagonists are routinely used for prevention and treatment of PONV. The aim of our study was to compare the incidence of QTc prolongation and quantify the amount of QTc prolongation with ondansetron and granisetron. Methods: This prospective, randomised, single-blind study was carried out in the OT and Recovery Room (RR of a tertiary referral cancer centre. After obtaining Institutional Review Board approval and written informed consent from the patients, 70 patients undergoing elective surgery for carcinoma breast were included. In the RR, patients randomly received 8 mg of ondansetron or 1 mg of granisetron intravenously. Serial ECGs were recorded at various intervals, Non-invasive blood pressure and SpO 2 were also recorded. Chi-square test and Mann-Whiteny test were used for statistical analysis. Results: The demographics were similar in both groups. The incidence of significant QTc prolongation was significantly higher in the ondansetron group (22 of 37 (59.4% vs. 11 of 33 patients (33.33% ( P<0.05. There was an increase in the QTc interval in both the groups as compared to the baseline. The median prolongation in QTc interval from baseline was much more in the ondansetron group; this was statistically significant only at 5 and 15 min. Conclusion: Granisetron may be a safer option than ondanasetron for prevention and treatment of PONV due to lesser prolongation QTc interval. (ClinicalTrials.gov ID: NCT01352130
Yam Philippa S
Full Text Available Abstract Background Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds. Methods/design The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry; body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families. Discussion The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical
Koek, Mayke B. G.; Buskens, Erik; van Weelden, Huib; Steegmans, Paul H A; Bruijnzeel-Koomen, Carla A. F. M.; Sigurdsson, Vigfus
Objective To determine whether ultraviolet B phototherapy at home is equally safe and equally effective as ultraviolet B phototherapy in an outpatient setting for patients with psoriasis. Design Pragmatic multicentre single blind randomised clinical trial (PLUTO study). Setting Dermatology departments of 14 hospitals in the Netherlands. Participants 196 patients with psoriasis who were clinically eligible for narrowband (TL-01) ultraviolet B phototherapy. The first 105 consecutive patients we...
Luyten, F P; Geusens, P.; Malaise, Michel; Clerck, L. de; Westhovens, R; Raeman, F.; Vander Mijnsbrugge, D.; Mathy, Luc; Hauzeur, J. P.; De Keyser, F; Van den Bosch, F
Objective: To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare. Methods: In this 24-week, prospective, randomised, double-blind, placebo-controlled study, patients were randomly assigned to receive continuous (n = 62) or intermittent (n = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoa...
Moppett, Iain K; Greenhaff, Paul L; Ollivere, Ben J; Joachim, Theophillus; Lobo, Dileep N; Rowlands, Martin
Background Trauma such as hip fracture initiates a neurohumoral stress response that changes the balance between anabolism and catabolism resulting in muscle breakdown and reduced mobilisation. Various studies have demonstrated a reduction in catabolism with pre-operative carbohydrate loading but only in an elective setting. Methods/Design This is a two-centre, randomised double-blinded trial in the United Kingdom. Sample size will be 30 patients (approximately 15 from each centre). Randomisa...
Full Text Available Abstract Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA, there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259.
Payne-James, J J; Rogers, J; Bray, M J; Rana, S K; McSwiggan, D; Silk, D B
A series of 54 normal subjects were randomised to have either a Vialon or a PTFE-Teflon peripheral vein cannula inserted in a vein in each forearm to observe the development of thrombophlebitis. Cannulas were inspected twice daily for up to 5 days to observe the development of three signs, erythema, oedema or hardness and one symptom, pain. Each sign and symptom was recorded twice daily at three points, the cannula insertion site, the mid-point of the cannula and the cannula tip. The degree of change was recorded as less than 1, 1-2 and greater than 2 cm. Any cannula causing any sign greater than 2 cm was removed. By the end of the study over 40% of both types of cannula had been removed. There were no significant differences between the numbers of each type of cannula removed at any time point throughout the duration of the study. There were no significant differences in the amounts of erythema or hardness, but minimally increased swelling was observed at the mid-point of the PTFE-Teflon cannulas (P = 0.022). Despite the theoretical superiority of Vialon as a cannula material, under controlled conditions there appears to be little difference in its inherent capacity to cause the thrombophlebitis. PMID:1929137
Vermeulen, M.; van Doorn, P. A.; Brand, A; Strengers, P F; Jennekens, F G; Busch, H F
Patients with a clinical diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were randomised in a double-blind, placebo-controlled multicentre trial to investigate whether high-dose intravenous immunoglobulin treatment (IVIg) for 5 consecutive days has a beneficial effect. Fifteen patients were randomised to IVIg and 13 to placebo. In the IVIg treatment group 4 patients improved and 3 patients in the placebo group. The degree of improvement of the patients in the IVIg treatm...
David J. White
Full Text Available 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.
Randomised, double-blind and placebo-controlled study of the effect of a synbiotic dairy product on orocecal transit time in healthy adult women Estudio aleatorizado, doble-ciego y controlado por placebo del efecto de un simbiótico sobre el tránsito intestinal en mujeres adultas sanas
Full Text Available Objective: To evaluate oro-cecal intestinal transit time (ITT before and after administration of a dairy product containing Bifidobacterium BB12, Lactobacillus casei CRL 431 and fiber in healthy women. Methods: A prospective, randomised, double-blind and cross-over study with a 4-phase design (run-in: time 0 [T0], two intervention periods: time 1 [T1] and time 3 [T3] and a wash-out: time 2, [T2] was performed. Participants were asked about bowel movement and fiber consumption. ITT was assessed by the carmine red dye method. Results: Mean age was 40.7 years (n = 102 healthy women; 83 completed the study. In women with initial ITT (IITT > 48 h consuming the synbiotic product, mean IITT and final ITT (FITT was 86.9 ± 38.5 h and 51.2 ± 29.8 h (-40.9%, as compared to women consuming the control yoghurt (IITT, 80.8 ± 31.7 h; FITT, 69.5 ± 31.5 h; -13.8% (p = 0.001. IITT in women with functional constipation consuming the control yoghurt was 57.0 ± 30.0 h; such figure increased 2.8 h after yoghurt consumption (FITT, 59.8 ± 3 0.2 h; +4.9%. Conversely, IITT in women who received the synbiotic yoghurt was 69.0 ± 49.6 h, with a -27.5% decrease 19 h later (FITT, 50.0 ± 27.5 h; p = 0.023. Enteric lactic flora stabilization was significantly higher in women who initially consumed the synbiotic product (p Objetivo: Evaluar el tiempo de tránsito intestinal (TTI antes y después de consumir yogur con Bifidobacterium BB12, Lactobacillus casei CRL 431 y fibra (simbiótico. Métodos: Estudio prospectivo, cruzado, aleatorizado y doble-ciego con 4 fases: preparación (tiempo 0; intervención (yogur o simbiótico; tiempo 1 y tiempo 3; sin intervención (tiempo 2. Evaluamos la frecuencia de defecación y el consumo de fibra. El TTI se estimo con rojo carmín. Resultados: La edad promedio fue 40,7 años (n = 102 mujeres sanas; 83 completaron el estudio. En mujeres con TTI inicial (TTII > 48 h que consumieron el simbiótico, el TTII y el TTI final (TTIF fue 86
Full Text Available 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.
Full Text Available Abstract Background Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50–70 years. Methods We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A1c(GHbA1c. Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale. Results Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA1c (mean difference = 0.59%-units, p = 0.018 and in SF-36 score (mean difference = 11.0 points, p = 0.039. However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred. Conclusion This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub
Beck Anne Marie
Full Text Available Abstract Background Geriatric patients are at high risk of re-admission after discharge. Pre-existing nutritional risk amongst these patients is of primary concern, with former nutritional intervention studies being largely ineffective. None of these studies has included individual dietary counselling by a registered dietician or has considered competing medical conditions in the participants. A former randomised study has shown that comprehensive discharge follow-up in geriatric patients homes by general practitioners and district nurses was effective in reducing the re-admission risk in the intervention group compared to the control group. That study did not include a nutritional intervention. The purpose of this study is to assess the combined benefits of an intervention consisting of discharge follow-up in geriatric patients' home by a general practitioner and a registered dietician. Methods/design This single-blind randomised controlled study, will recruit 160 hospitalised geriatric medical patients (65+ y at nutritional risk. Participants will be randomly allocated to receive in their homes, either 12 weeks individualised nutritional counselling by a registered dietician complemented with follow-up by general practitioners or a 12 weeks follow-up by general practitioners alone. Discussion This trial is the first of its kind to provide individual nutritional intervention combined with follow-up by general practitioner as an intervention to reduce risk of re-admission after discharge among geriatric medical patients. The results will hopefully help to guide the development of more effective rehabilitation programs following hospital admissions, which may ultimately lead to reduced health care costs, and improvement in mobility, independence and quality of life for geriatric patients at nutritional risk. Trial Registration ClinicalTrials.gov 2010 NCT01249716
Cho, Yoonsu; Shin, So-Youn; Won, Sungho; Relton, Caroline L; Davey Smith, George; Shin, Min-Jeong
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
Astrup, Arne; Madsbad, Sten; Breum, Leif; Jensen, Thomas J; Kroustrup, Jens Peter; Larsen, Thomas Meinert
BACKGROUND: Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline, do......, dopamine, and serotonin-in patients with obesity. METHODS: We undertook a phase II, randomised, double-blind, placebo-controlled trial in five Danish obesity management centres. After a 2 week run-in phase, 203 obese patients (body-mass index 30-......BACKGROUND: Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline...
Juul, Anne Benedicte; Wetterslev, Jørn; Gluud, Christian;
Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University...... anaesthesia and surgical centres and one coordinating centre. Participants 921 patients aged > 39 scheduled for major non-cardiac surgery. Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. Main outcome...... was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of...
Torgerson, Carole J.
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…
Full Text Available Abstract Background Current evidence on electrotherapies for the management of chronic neck pain is either lacking or conflicting. New therapeutic devices being introduced to the market should be investigated for their effectiveness and efficacy. The ENAR® (Electro Neuro Adaptive Regulator therapy device combines Western biofeedback with Eastern energy medicine. Methods A small, preliminary randomised and controlled single-blinded trial was conducted on 24 participants (ten males, 14 females between the ages of 18 to 50 years (median age of 40.5 Consent was obtained and participants were randomly allocated to one of three groups – ENAR, Transcutaneous Electrical Nerve Stimulation (TENS, or control therapy – to test the hypothesis that ENAR therapy would result in superior pain reduction/disability and improvements in neck function compared with TENS or control intervention. The treatment regimen included twelve 15-minute treatment sessions over a six week period, followed by two assessment periods. Visual Analogue Scale (VAS pain scores, Neck Disability Index (NDI scores, Patient Specific Functional Scale (PSFS scores and Short Form 36v1 (SF-36 quality of life scores reported by participants were collected at each of the assessments points throughout the trial (0, 6, 12, 18 and 24 weeks. Results Eligible participants (n = 30 were recruited and attended clinic visits for 6 months from the time of randomisation. Final trial sample (n = 24 comprised 9 within the ENAR group, 7 within the TENS group and 8 within the control group. With an overall study power of 0.92, the ENAR group showed a decrease in mean pain score from measurement at time zero (5.0 ± 0.79 95%CI to the first follow-up measurement at six weeks (1.4 ± 0.83 95%CI. Improvement was maintained until week 24 (1.75 ± 0.9 95%CI. The TENS and control groups showed consistent pain levels throughout the trial (3.4 ± 0.96 95%CI and 4.1 ± 0.9 95%CI respectively. Wald analysis for pain
O'Gorman, Neil; Wright, David; Rolnik, Daniel L; Nicolaides, Kypros H; Poon, Liona C
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
Smith, C.; Vannak, U; Sokhey, L; Ngo, TD; Gold, J; Khut, K; Edwards, P.; Rathavy, T; Free, C
BACKGROUND Providing women with contraceptive methods following abortion is important to reduce repeat abortion rates, yet evidence for effective post-abortion family planning interventions are limited. This protocol outlines the evaluation of a mobile phone-based intervention using voice messages to support post-abortion family planning in Cambodia. METHODS/DESIGN A single blind randomised controlled trial of 500 participants. Clients aged 18 or over, attending for abortion at four Mari...
Forster Anne; Young John; Barber Sally; Clegg Andrew; Iliffe Steve
Abstract Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE) trial is a two arm, assessor blind pilot randomised controlled trial (RCT) to a...
Full Text Available Abstract Background Consistently swelling proportion of the frail elderly within a modern society challenges the overstrained public health sector to provide both adequate medical care and comprehensive assistance in their multiple functional deficits of daily living. Easy-to-apply and task-specific ways of addressing this issue are being sought out, with a view to proposing systemic solutions for nationwide application. Methods The present randomised, double-blind, placebo-controlled, 7-week clinical trial aimed to determine whether specifically structured, intensive exercise regimens, combined with nutritional supplementation, might improve and help sustain individual muscle strength and mobility, and possibly enhance individual functional capabilities in an on-going quest for active prevention of care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years were recruited from both nursing home residents and community dwellers and randomly split into four groups: Group I – progressive resistance exercises (PRE + functionally-oriented exercises (FOE + nutritional supplementation (NS, Group II – PRE + FOE + placebo, Group III – standard exercises (SE + FOE + NS, Group IV – SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times weekly. The subjects' strength with regard to four muscle groups, i.e. hip and knee extensors and flexons, was assessed at 80% (1 RM weekly, whereas their balance and mobility at baseline and at the end of the study. Results The study was completed by 80 subjects. Despite its relatively short duration significant differences in muscle strength were noted both in Group I and Group II (p = 0.01; p = 0.04; respectively, although this did not translate directly into perceptible improvement in individual mobility. Notable improvements in individual mobility were reported in Group III and Group IV (p = 0.002, although without positive impact on individual muscle strength. Conclusion
Helland, Arne; Jenssen, Gunnar D; Lervåg, Lone-Eirin; Westin, Andreas Austgulen; Moen, Terje; Sakshaug, Kristian; Lydersen, Stian; Mørland, Jørg; Slørdal, Lars
The purpose of this study was to establish and validate a driving simulator method for assessing drug effects on driving. To achieve this, we used ethanol as a positive control, and examined whether ethanol affects driving performance in the simulator, and whether these effects are consistent with performance during real driving on a test track, also under the influence of ethanol. Twenty healthy male volunteers underwent a total of six driving trials of 1h duration; three in an instrumented vehicle on a closed-circuit test track that closely resembled rural Norwegian road conditions, and three in the simulator with a driving scenario modelled after the test track. Test subjects were either sober or titrated to blood alcohol concentration (BAC) levels of 0.5g/L and 0.9g/L. The study was conducted in a randomised, cross-over, single-blind fashion, using placebo drinks and placebo pills as confounders. The primary outcome measure was standard deviation of lateral position (SDLP; "weaving"). Eighteen test subjects completed all six driving trials, and complete data were acquired from 18 subjects in the simulator and 10 subjects on the test track, respectively. There was a positive dose-response relationship between higher ethanol concentrations and increases in SDLP in both the simulator and on the test track (psimulator, this dose-response was evident already after 15min of driving. SDLP values were higher and showed a larger inter-individual variability in the simulator than on the test track. Most subjects displayed a similar relationship between BAC and SDLP in the simulator and on the test track; however, a few subjects showed striking dissimilarities, with very high SDLP values in the simulator. This may reflect the lack of perceived danger in the simulator, causing reckless driving in a few test subjects. Overall, the results suggest that SDLP in the driving simulator is a sensitive measure of ethanol impaired driving. The comparison with real driving implies
Lanini, Simone; Zumla, Alimuddin; Ioannidis, John P A; Di Caro, Antonino; Krishna, Sanjeev; Gostin, Lawrence; Girardi, Enrico; Pletschette, Michel; Strada, Gino; Baritussio, Aldo; Portella, Gina; Apolone, Giovanni; Cavuto, Silvio; Satolli, Roberto; Kremsner, Peter; Vairo, Francesco; Ippolito, Giuseppe
The Ebola outbreak that has devastated parts of west Africa represents an unprecedented challenge for research and ethics. Estimates from the past three decades emphasise that the present effort to contain the epidemic in the three most affected countries (Guinea, Liberia, and Sierra Leone) has been insufficient, with more than 24,900 cases and about 10,300 deaths, as of March 25, 2015. Faced with such an exceptional event and the urgent response it demands, the use of randomised controlled trials (RCT) for Ebola-related research might be both unethical and infeasible and that potential interventions should be assessed in non-randomised studies on the basis of compassionate use. However, non-randomised studies might not yield valid conclusions, leading to large residual uncertainty about how to interpret the results, and can also waste scarce intervention-related resources, making them profoundly unethical. Scientifically sound and rigorous study designs, such as adaptive RCTs, could provide the best way to reduce the time needed to develop new interventions and to obtain valid results on their efficacy and safety while preserving the application of ethical precepts. We present an overview of clinical studies registered at present at the four main international trial registries and provide a simulation on how adaptive RCTs can behave in this context, when mortality varies simultaneously in either the control or the experimental group. PMID:25881871
Singh, Anil P.; Jena, Sritam S; Rajesh Kr Meena; Mallika Tewari; V Rastogi
Background and Aim: Intravenous (IV) route for fentanyl administration is the gold standard for post-operative pain relief, but complications such as respiratory depression, bradycardia and hypotension have limited this route. The aim of this randomised controlled trial was to compare the efficacy of nebulised fentanyl with IV fentanyl for post-operative pain relief after lower abdominal surgery. Methods: In the post-operative care unit, at the time of first onset of pain (visual analogue sca...
Zhang, Zhe-Qing; Chen, Yu-Ming; Wang, Ruo-Qin; Huang, Zhen-Wu; Yang, Xiao-Guang; Su, Yi-Xiang
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
Isa S Abubakar
Full Text Available BACKGROUND: In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358. METHODS: In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials. Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions. FINDINGS: Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0% of ET-Plus and 156/206 (75.7% of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05. ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8% and 39/206 (18.9% respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06. These reactions were classified as severe in 21 (10.8% and 11 (5.3% of patients, respectively. CONCLUSION: At these doses, ET-Plus was
Blum, A L; Bethge, H; Bode, J. C.; Domschke, W; Feurle, G; Hackenberg, K.; Hammer, B; Hüttemann, W; Jung, M; Kachel, G
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...
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);…
Bowden, Deborah; Goddard, Lorna; Gruzelier, John
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
Full Text Available 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.
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
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 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-results. PMID:27059469
Lenon, George B; Li, C. G.; C. da Costa; Thien, F. C. K.; Shen, Y.; Xue, C. C. L.
Background A herbal preparation, known as RMIT Chinese Medicine 102 (RCM-102) consisting of eight herbs which demonstrates inhibition of the release of key inflammatory mediators associated with seasonal allergic rhinitis (SAR) was used. This study evaluated the efficacy and safety of RCM-102 for SAR. Objective This study evaluated the efficacy and safety of RCM-102 for SAR. Methods This randomised placebo-controlled trial involved subjects aged between 18 and 65 who were randomly assigned to...
Full Text Available Abstract 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
Akbar, M S; Baker, K M; Aziz, M A; Khan, W A; Salim, A F
We compared the efficacy of a maltodextrin containing oral rehydration salts (ORS) solution with that of the WHO recommended glucose-ORS solution in a double blind randomized study of treating 69 children (33 in experimental group; 36 in control group) aged 4-36 months with acute diarrhoea causing mild to moderate dehydration. Both the groups of children were similar in initial clinical characteristics and received only ORS solutions. No significant differences in stool output (median 88.0, range 34-320 g/kg body wt. in experiment vs 75.0, 25-410 g/kg in control), intake of ORS solution (125.0, 58-360 ml/kg body wt. vs 154, 130-250 ml/kg), and duration of recovery from diarrhoea (2.0 d, range 1-6 vs 2.0 d, 1-9) were found between the groups. The haematocrit and serum electrolyte values in the two groups 24 hours after starting treatment were also similar. The results suggest that the ORS containing maltodextrin (50 g/l) in place of glucose has no advantage over WHO-ORS in correcting mild to moderate dehydration of children with acute diarrhoea. PMID:1869801
Cold, Frederik; Winther, Kristian H; Pastor-Barriuso, Roberto;
PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or...
Christensen Helen; Naismith Sharon L; Glozier Nick; Cockayne Nicole L; Neal Bruce; Hickie Ian B
Abstract Background Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised contro...
Payne-James, J J; Rogers, J.; Bray, M J; Rana, S.K.; McSwiggan, D; Silk, D B
A series of 54 normal subjects were randomised to have either a Vialon or a PTFE-Teflon peripheral vein cannula inserted in a vein in each forearm to observe the development of thrombophlebitis. Cannulas were inspected twice daily for up to 5 days to observe the development of three signs, erythema, oedema or hardness and one symptom, pain. Each sign and symptom was recorded twice daily at three points, the cannula insertion site, the mid-point of the cannula and the cannula tip. The degree o...
A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease
W. Reinisch; D.W. Hommes; G. van Assche; J.F. Colombel; J.P. Gendre; B. Oldenburg; A. Teml; K. Geboes; H. Ding; L. Zhang; M. Tang; M. Cheng; S.J.H. van Deventer; P. Rutgeerts; T. Pearce
Introduction: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD). Patients and methods: Forty five patients with a CD activity index (CDAI) of 250 - 450 were randomised in a double blind
Wright Stephen; Duncombe Paul; Altman Douglas G
Abstract Background Maintenance of the blind-to-treatment allocation is one of the most important means of avoiding bias in randomised controlled clinical trials. Commonly used methodologies to determine whether patients have become unblinded to treatment allocation are imperfect. This may be of particular concern in studies where outcomes are patient-reported, and with products which have a characteristic adverse event profile. We report the results of an evidence-based statistical approach ...
Maran, A; Lomas, J.; Archibald, H; Macdonald, I A; Gale, E A; Amiel, S. A.
OBJECTIVES--To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin. DESIGN--Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin. SETTING--Clinical investigation unit of teaching hospital recruiting from diabetes clinics of fiv...
De Wit, R.; Beijnen, J H; Tellingen, O Van; Schellens, J. H.; de Boer-Dennert, M.; Verweij, J.
We investigated the pharmacokinetic profile and the efficacy of ondansetron (day 1) given as 16 mg suppository once a day, as compared with ondansetron 8 mg tablets twice daily, in patients receiving moderately emetogenic chemotherapy. The study was primarily aimed at investigating the pharmacokinetics and was part of a large multinational, randomised, double-blind, double-dummy efficacy trial. Pharmacokinetic data were obtained in a total of 20 patients, 11 of whom had received a suppository...
Zheng, Ju-Sheng; Lin, Mei; Imamura, Fumiaki; Cai, Wenwen; Wang, Ling; Feng, Jue-Ping; Ruan, Yue; Tang, Jun; Wang, Fenglei; Yang, Hong; Li, Duo
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
Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial
Brüll, Verena; Burak, Constanze; Stoffel-Wagner, Birgit; Wolffram, Siegfried; Nickenig, Georg; Müller, Cornelius; Langguth, Peter; Alteheld, Birgit; Fimmers, Rolf; Naaf, Stefanie; Zimmermann, Benno F.; Stehle, Peter; Egert, Sarah
The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinde...
Effects of an exercise and manual therapy program on physical impairments, function and quality-of-life in people with osteoporotic vertebral fracture: a randomised, single-blind controlled pilot trial
Sherburn Margaret; Kelly Anne; Briggs Andrew; Greig Alison; Matthews Bernadette; Bennell Kim L; Larsen Judy; Wark John
Abstract Background This randomised, single-blind controlled pilot trial aimed to determine the effectiveness of a physiotherapy program, including exercise and manual therapy, in reducing impairments and improving physical function and health-related quality of life in people with a history of painful osteoporotic vertebral fracture. Methods 20 participants were randomly allocated to an intervention (n = 11) or control (n = 9) group. The intervention group attended individual sessions with a...
A James Daveson
Full Text Available BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. TRIAL REGISTRATION: ClinicalTrials.gov NCT00671138.
Downs, S. H.; Black, N.
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...
Hughes Thomas C
Full Text Available Abstract Background Advanced resuscitation skills training is an important and enjoyable part of medical training, but requires small group instruction to ensure active participation of all students. Increases in student numbers have made this increasingly difficult to achieve. Methods A single-blind randomised controlled trial of peer-led vs. expert-led resuscitation training was performed using a group of sixth-year medical students as peer instructors. The expert instructors were a senior and a middle grade doctor, and a nurse who is an Advanced Life Support (ALS Instructor. A power calculation showed that the trial would have a greater than 90% chance of rejecting the null hypothesis (that expert-led groups performed 20% better than peer-led groups if that were the true situation. Secondary outcome measures were the proportion of High Pass grades in each groups and safety incidents. The peer instructors designed and delivered their own course material. To ensure safety, the peer-led groups used modified defibrillators that could deliver only low-energy shocks. Blinded assessment was conducted using an Objective Structured Clinical Examination (OSCE. The checklist items were based on International Liaison Committee on Resuscitation (ILCOR guidelines using Ebel standard-setting methods that emphasised patient and staff safety and clinical effectiveness. The results were analysed using Exact methods, chi-squared and t-test. Results A total of 132 students were randomised: 58 into the expert-led group, 74 into the peer-led group. 57/58 (98% of students from the expert-led group achieved a Pass compared to 72/74 (97% from the peer-led group: Exact statistics confirmed that it was very unlikely (p = 0.0001 that the expert-led group was 20% better than the peer-led group. There were no safety incidents, and High Pass grades were achieved by 64 (49% of students: 33/58 (57% from the expert-led group, 31/74 (42% from the peer-led group. Exact
O’Cathain, A.; Hoddinott, P.; Lewin, S; Thomas, K J; Young, B; Adamson, J.; Jansen, J.F.M.; Mills, N; Moore, G.; Donovan, J.L.
Feasibility studies are increasingly undertaken in preparation for randomised controlled trials in order to explore uncertainties and enable trialists to optimise the intervention or the conduct of the trial. Qualitative research can be used to examine and address key uncertainties prior to a full trial. We present guidance that researchers, research funders and reviewers may wish to consider when assessing or undertaking qualitative research within feasibility studies for randomised controll...
Full Text Available Abstract 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
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.
Eskesen, Dorte; Jespersen, Lillian; Michelsen, Birgit; Whorwell, Peter J; Müller-Lissner, Stefan; Morberg, Cathrine M
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
Archiel Launch Tancawan
Full Text Available 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.
H Asita de Silva
Full Text Available BACKGROUND: Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. METHODS AND FINDINGS: In total, 1,007 patients were randomized, using a 2 × 2 × 2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously, promethazine (25 mg intravenously, and hydrocortisone (200 mg intravenously, each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75% patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25-67 at 1 h and by 38% (95% CI 26-49 up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. CONCLUSIONS: Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be
To prove that 1.0 M gadobutrol provides superior contrast enhancement and MRI image characteristics of primary and secondary brain tumours compared with 0.5 M gadoteridol, thereby providing superior diagnostic information. Brain MRI was performed in two separate examinations in patients scheduled for neurosurgery. Independent injections of 1.0 M gadobutrol and 0.5 M gadoteridol at doses of 0.1 mmol Gd/kg body weight were administered per patient in randomised order. Evaluation was performed in an off-site blinded read. Fifty-one patients in the full analysis set (FAS) were eligible for efficacy analysis and 44 for the per-protocol analysis. For the primary efficacy variable ''preference in contrast enhancement for one contrast agent or the other'', the rate of ''gadobutrol preferred'' was estimated at 0.73 (95 % confidence interval 0.61; 0.83), showing significant superiority of gadobutrol over gadoteridol. Calculated lesion-to-brain contrast and the results of all qualitative secondary efficacy variables were also in favour of gadobutrol. Keeping a sufficient time delay after contrast application proved to be essential to get optimal image quality. Compared with 0.5 M gadoteridol, 1.0 M gadobutrol was proven to have significantly superior contrast enhancement characteristics in a routine MRI protocol of primary and secondary brain tumours. (orig.)
Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W;
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...
Full Text Available Abstract Background In New Zealand, around 45,000 people live with stroke and many studies have reported that benefits gained during initial rehabilitation are not sustained. Evidence indicates that participation in physical interventions can prevent the functional decline that frequently occurs after discharge from acute care facilities. However, on-going stroke services provision following discharge from acute care is often related to non-medical factors such as availability of resources and geographical location. Currently most people receive no treatment beyond three months post stroke. The study aims to determine if the Augmented Community Telerehabilitation Intervention (ACTIV results in better physical function for people with stroke than usual care, as measured by the Stroke Impact Scale, physical subcomponent. Methods/design This study will use a multi-site, two-arm, assessor blinded, parallel randomised controlled trial design. People will be eligible if they have had their first ever stroke, are over 20 and have some physical impairment in either arm or leg, or both. Following discharge from formal physiotherapy services (inpatient, outpatient or community, participants will be randomised into ACTIV or usual care. ACTIV uses readily available technology, telephone and mobile phones, combined with face-to-face visits from a physiotherapist over a six-month period, to help people with stroke resume activities they enjoyed before the stroke. The impact of stroke on physical function and quality of life will be assessed, measures of cost will be collected and a discrete choice survey will be used to measure preferences for rehabilitation options. These outcomes will be collected at baseline, six months and 12 months. In-depth interviews will be used to explore the experiences of people participating in the intervention arm of the study. Discussion The lack of on-going rehabilitation for people with stroke diminishes the chance of their