Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

PubMed

Sagheb, Mohammad Mahdi; Dormanesh, Banafshe; Fallahzadeh, Mohammad Kazem; Akbari, Hamideh; Sohrabi Nazari, Sahar; Heydari, Seyed Taghi; Behzadi, Saeed

2012-05-01

Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial. Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (P<0.001); however, no differences were observed between these treatment groups. Vitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. Copyright © 2012 Elsevier B.V. All rights reserved.

Double-Blind Comparison of Phlebitis Produced by Cefazolin Versus Cephalothin

PubMed Central

Shemonsky, Natalie K.; Carrizosa, Jaime; Kaye, Donald; Levison, Matthew E.

1975-01-01

In a double-blind study with each patient as his own control, 1 g of cefazolin and 2 g of cephalothin were administered intravenously every 6 h to 20 patients in opposite arms for a period of 48 h each. The degree of phlebitis was significantly more severe with cephalothin than with cefazolin (P < 0.05); however, neither the incidence of phlebitis nor the time of onset of phlebitis was significantly different between the two drugs. PMID:1147583

Electrical stimulation for chronic non-specific low back pain in a working-age population: a 12-week double blinded randomized controlled trial.

PubMed

Thiese, Matthew S; Hughes, Matthew; Biggs, Jeremy

2013-03-28

Non-invasive electrotherapy is commonly used for treatment of chronic low back pain. Evidence for efficacy of most electrotherapy modalities is weak or lacking. This study aims to execute a high-quality, double-blinded randomized controlled clinical trial comparing 1) H-Wave(®) Device stimulation plus usual care with 2) transcutaneous electrical nerve stimulation (TENS) plus usual care, and 3) Sham electrotherapy plus usual care to determine comparative efficacy for treatment of chronic non-specific low back pain patients. Chronic non-specific low back pain patients between ages of 18-65 years, with pain of at least 3 months duration and minimal current 5/10 VAS pain. Patients will have no significant signs or symptoms of lumbosacral nerve impingement, malignancy, spinal stenosis, or mood disorders. Double blind RCT with 3 arms and 38 subjects per arm. Randomization by permuted blocks of random length, stratified by Workers Compensation claim (yes vs. no), and use of opioids. The null hypothesis of this study is that there are no statistically significant differences in functional improvement between treatment types during and at the end of a 12-week week treatment period. Subjective data will be collected using Filemaker Pro™ database management collection tools. Objective data will be obtained through functional assessments. Data will be collected at enrollment and at 1, 4, 8, and 12 weeks for each participant by a blinded assessor. H-Wave(®) device stimulation (Intervention A) plus usual care, transcutaneous electrical nerve stimulation (TENS) (Intervention B) plus usual care, and sham electrotherapy plus usual care (control). Each treatment arm will have identical numbers of visits (4) and researcher contact time (approximately 15 hours). Oswestry Disability Index. Secondary measures include: Rowland Morris Instrument, VAS pain score, functional evaluation including strength when pushing and pulling, pain free range of motion in flexion and extension. Outcome measures assessed at baseline, 1, 4, 8, and 12 weeks. Treatment failure will be defined if patient terminates assigned treatment arm for non-efficacy or undergoes invasive procedure or other excluded cointerventions. Data will be analyzed using intention-to-treat analysis and adjusted for covariates related to LBP (e.g. age) as needed. Study strengths include complex randomization, treatment group allocation concealment, double blinding, controlling for co-interventions, rigorous inclusion criteria, assessment of compliance, plans for limiting dropout, identical assessment methods and timing for each treatment arm, and planned intention-to-treat analyses.

Effects of Mangifera indica (Careless) on Microcirculation and Glucose Metabolism in Healthy Volunteers.

PubMed

Buchwald-Werner, Sybille; Schön, Christiane; Frank, Sonja; Reule, Claudia

2017-07-01

A commercial Mangifera indica fruit powder (Careless) showed beneficial acute effects on microcirculation in a randomized, double-blind, crossover pilot study. Here, long-term effects on microcirculation and glucose metabolism were investigated in a double-blind, randomized, placebo-controlled, 3-arm parallel-design study in healthy individuals. A daily dose of 100 mg or 300 mg of the fruit powder was compared to placebo after supplementation for 4 weeks. Microcirculation and endothelial function were assessed by the Oxygen-to-see System and pulse amplitude tonometry, respectively. Glucose metabolism was assessed under fasting and postprandial conditions by capillary glucose and HbA1c values.Microcirculatory reactive hyperemia flow increased, especially in the 100 mg group (p = 0.025). The 300 mg of the M. indica fruit preparation reduced postprandial glucose levels by trend if compared to placebo (p = 0.0535) accompanied by significantly lower HbA1c values compared to baseline. Furthermore, 300 mg intake significantly improved postprandial endothelial function in individuals with decreased endothelial function after high-dose glucose intake (p = 0.0408; n = 11).In conclusion, the study suggests moderate beneficial effects of M. indica fruit preparation on microcirculation, endothelial function, and glucose metabolism. Georg Thieme Verlag KG Stuttgart · New York.

A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE).

PubMed

Allen, S J; Wareham, K; Wang, D; Bradley, C; Sewell, B; Hutchings, H; Harris, W; Dhar, A; Brown, H; Foden, A; Gravenor, M B; Mack, D; Phillips, C J

2013-12-01

Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms. We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates. This trial is registered as ISRCTN70017204. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further project information.

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial.

PubMed

Jafarinia, Morteza; Afarideh, Mohsen; Tafakhori, Abbas; Arbabi, Mohammad; Ghajar, Alireza; Noorbala, Ahmad Ali; Saravi, Maryam Alamdar; Agah, Elmira; Akhondzadeh, Shahin

2016-11-01

Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain. This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150mg vs. diclofenac, fixed daily dosage of 150mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention. Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003). The limitations of the present study were its small sample size and the short-term follow-up period. Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Flux-dependent anti-crossing of resonances in parallel non-coupled double quantum dots

NASA Astrophysics Data System (ADS)

Joe, Yong S.; Hedin, Eric R.; Kim, Jiseok

2008-08-01

We present novel resonant phenomena through parallel non-coupled double quantum dots (QDs) embedded in each arm of an Aharonov-Bohm (AB) ring with magnetic flux passing through its center. The electron transmission through this AB ring with each QD formed by two short-range potential barriers is calculated using a scattering matrix at each junction and a transfer matrix in each arm. We show that as the magnetic flux modulates, a distortion of the grid-like square transmission occurs and an anti-crossing of the resonances appears. Hence, the modulation of magnetic flux in this system can have an equivalent effect to the control of inter-dot coupling between the two QDs.

The Influence of Two Different Doses of Magnesium Sulfate on Intraocular Pressure Variations after Injection of Succinylcholine and Endotracheal Intubation: A Prospective, Randomized, Parallel Three-Arm, Double-blind, Placebo-controlled Clinical Trial.

PubMed

Yassin, Hany Mahmoud; Abdel Moneim, Ahmed Tohamy; Mostafa Bayoumy, Ahmed Sherin; Bayoumy, Hasan Metwally; Taher, Sameh Galal

2017-01-01

The use of succinylcholine for rapid sequence induction in patients with open globe injuries may be detrimental to the eye. The aim of this study is to determine if the premedication with magnesium sulfate (MgSO 4 ) could attenuate the increase in intraocular pressure (IOP) associated with succinylcholine injection and intubation. Operation theaters in a tertiary care University Hospital between December 2014 and July 215. This was a prospective, randomized, parallel three-arm, double-blind, placebo-controlled clinical trial. One hundred and thirteen patients' physical status ASA Classes I and II underwent elective cataract surgery under general anesthesia. These patients allocated into three groups: Group C (control group) received 100 ml normal saline, Group M1 received 30 mg/kg MgSO 4 in 100 ml normal saline, and Group M2 received 50 mg/kg MgSO 4 in 100 ml normal saline. IOP, mean arterial pressure (MAP), and heart rate (HR) reported at 5-time points related to study drug administration. In addition, any adverse effects related to MgSO 4 were recorded. Intragroup and between-groups differences were examined by analysis of variance test. We noticed a significant decrease in IOP in M1 ( n = 38) and M2 ( n = 37) groups as compared with C group ( n = 38) after study drugs infusion, 2 and 5 min after intubation, P < 0.001. While the difference between M1 and M2 groups was insignificant, P = 0.296 and P = 0.647, respectively. There was a significant decrease in MAP and HR in M1 and M2 groups as compared with C group 2 and 5 min after intubation, P = 0.01. While the difference between M1 and M2 groups was insignificant, P = 1. MgSO 4 30 mg/kg as well as 50 mg/kg effectively prevented the rise in IOP, MAP, and HR associated with rapid sequence induction by succinylcholine and endotracheal intubation.

Lactic-fermented egg white reduced serum cholesterol concentrations in mildly hypercholesterolemic Japanese men: a double-blind, parallel-arm design.

PubMed

Matsuoka, Ryosuke; Usuda, Mika; Masuda, Yasunobu; Kunou, Masaaki; Utsunomiya, Kazunori

2017-05-30

Lactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels. The study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204-259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels. After 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p < 0.05) and a significantly greater decrease than for the 4 g group (3.1 ± 3.4 mg/dL; p < 0.05). Serum LDL-C levels in the 8 g group decreased by 13.7 ± 3.1 mg/dL, again a significant decrease compared with baseline (p < 0.05) and a significantly greater decrease than that for the 4 g group (2.1 ± 2.9 mg/dL; p < 0.05). Consumption of LE for 8 weeks at a daily dose of 8 g of proteins reduced serum TC and LDL-C levels in men with mild hypercholesterolemia, suggesting this may be effective in helping to prevent arteriosclerotic diseases. This clinical trial was retrospectively registered with the Japan Medical Association Center for Clinical Trials, (JMA-IIA00279; registered on 13/03/2017; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=6530 ).

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

PubMed Central

Ilowite, Norman T.; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

2015-01-01

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA. PMID:24839206

Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.

PubMed

Tejani, Furqan H; Thompson, Randall C; Iskandrian, Ami E; McNutt, Bruce E; Franks, Billy

2011-02-01

Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Bakhshi, Sameer; Batra, Atul; Biswas, Bivas; Dhawan, Deepa; Paul, Reeja; Sreenivas, Vishnubhatla

2015-11-01

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A 6-Month, Double-Blind, Maintenance Trial of Lithium Monotherapy Versus the Combination of Lithium and Divalproex for Rapid-Cycling Bipolar Disorder and Co-Occurring Substance Abuse or Dependence

PubMed Central

Kemp, David E.; Gao, Keming; Ganocy, Stephen J.; Rapport, Daniel J.; Elhaj, Omar; Bilali, Sarah; Conroy, Carla; Findling, Robert L.; Calabrese, Joseph R.

2011-01-01

Objective To assess whether combination treatment with lithium and divalproex is more effective than lithium monotherapy in prolonging the time to mood episode recurrence in patients with rapid-cycling bipolar disorder (RCBD) and comorbid substance abuse and/or dependence. Method A 6-month, double-blind, parallel group comparison was carried out in recently manic/hypomanic/mixed patients who had demonstrated a persistent bimodal response to combined treatment with lithium and divalproex. Subjects were randomly assigned to remain on combination treatment or to discontinue divalproex and remain on lithium monotherapy. Results Of 149 patients enrolled into the open-label acute stabilization phase, 79% discontinued prematurely (poor adherence: 42%; nonresponse: 25%; intolerable side effects: 10%). Of 31 patients (21%) randomly assigned to double-blind maintenance treatment, 55% relapsed (24% into depression and 76% into a manic/hypomanic/mixed episode), 26% completed the study, and 19% were poorly adherent or exited prematurely. The median time to recurrence of a new mood episode was 15.9 weeks for patients receiving lithium monotherapy and 17.8 weeks for patients receiving the combination of lithium and divalproex (p=NS). The rate of relapse into a mood episode for those receiving lithium monotherapy or the combination of lithium and divalproex was 56% and 53%, respectively. The rate of depressive relapse in both arms was 13%, while the rate of relapse into a manic, hypomanic, or mixed episode was 44% for lithium monotherapy and 40% for the combination of lithium and divalproex. Conclusion A small subgroup of patients in this study stabilized after six months of treatment with lithium plus divalproex. Of those who did, the addition of divalproex to lithium conferred no additional prophylactic benefit over lithium alone. Although depression is regarded as the hallmark of RCBD in general, these data suggest that recurrent episodes of mania tend to be more common in presentations accompanied by comorbid substance use. PMID:19192457

Comparison of lorazepam and zopiclone for insomnia in patients with stroke and brain injury: a randomized, crossover, double-blinded trial.

PubMed

Li Pi Shan, Rodney S; Ashworth, Nigel L

2004-06-01

To determine if lorazepam or zopiclone is more effective in providing a restful night of sleep and to assess the effects of these medications on cognition. A randomized, double-blinded, crossover trial was performed at a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of 18 brain-injured and stroke patients, aged 20-78 yrs, were administered lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75-7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and characteristics of sleep were measured. Effects on cognition were also measured using the Folstein Mini Mental Status Exam. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm. Zopiclone is equally effective as lorazepam in the treatment of insomnia in stroke and brain-injured patients.

Slow infusion of low{\\hyphen}dose ketamine reduces bothersome side effects compared to IV push: a double{\\hyphen}blind, double dummy, randomized controlled trial.

PubMed

Clattenburg, Eben J; Hailozian, Christian; Haro, Daniel; Yoo, Tina; Flores, Stefan; Louie, Derex; Herring, Andrew A

2018-04-12

We compared the analgesic efficacy and incidence of side effects when low{\\hyphen}dose (0.3 mg{\\sol}kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over one minute. This was a prospective, randomized, double blind, double dummy, placebo{\\hyphen}controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating score ≥ 5). Patients received ketamine 0.3mg{\\sol}kg administered either as a SI or IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference ({\\percnt}SPID). Fifty{\\hyphen}nine participants completed the study. 86.2{\\percnt} of the IVP arm and 70.0{\\percnt} of the SI arm experienced any side effect (difference 16.2{\\percnt}, 95{\\percnt}CI {\\hyphen}5.4 - 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9{\\percnt} reported moderate or greater side effects versus 43.4{\\percnt} in the SI arm (difference 32.5{\\percnt}, 95{\\percnt}CI 7.9 - 57.1). Additionally, the IVP arm experienced more hallucinations (n{\\equal}8, 27.6{\\percnt}) than the SI arm (SI n{\\equal}2, 6.7{\\percnt}; difference 20.9{\\percnt}, 95{\\percnt}CI 1.8 - 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean {\\percnt}SPID in the IVP and SI arms was 39.9{\\percnt} and 33.5{\\percnt}, respectively, with a difference of 6.5{\\percnt} (95{\\percnt}CI {\\hyphen}5.8 - 18.7). Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome.

PubMed

Lemmon, Monica E; Grados, Marco; Kline, Tina; Thompson, Carol B; Ali, Syed F; Singer, Harvey S

2015-06-01

It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome. In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with Tourette syndrome. We performed a parallel three-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with Tourette syndrome. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score; specifically, the total tic score and the combined score (total tic score + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group. Twenty-four patients (males = 21, ages 9-18) enrolled in the study; one patient dropped out before completion. Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups. The 6-week mean percent improvement of the riluzole (n = 10), D-serine (n = 9), and placebo (n = 5) groups in the combined Yale Global Tic Severity Scale score were 43.7, 39.5, and 30.2 and for total tic scores were 38.0, 25.0, and 34.0, respectively. There were no significant differences in Yale Global Tic Severity Scale score or total tic score, respectively, between the riluzole and placebo (P = 0.35, 0.85) or D-serine and placebo (P = 0.50, 0.69) groups. Tics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial.

PubMed

Bo, S; Ponzo, V; Evangelista, A; Ciccone, G; Goitre, I; Saba, F; Procopio, M; Cassader, M; Gambino, R

2017-05-01

The anti-inflammatory effects of the polyphenol resveratrol in patients with type 2 diabetes mellitus (T2DM) are controversial. Its role on pentraxin 3 (PTX3) concentrations, a human acute phase protein, has never been evaluated. Our aim was to determine whether a two-dosage resveratrol supplementation (500 and 40 mg/day) has an impact on PTX3 values in T2DM patients from a double-blind randomized placebo-controlled trial. Variations in total antioxidant status (TAS) were evaluated too. A total of 192 T2DM patients were randomized to receive resveratrol 500 mg/day (Resv 500 arm), resveratrol 40 mg/day (Resv 40 arm) or placebo for 6 months. At baseline and at the trial end, PTX3 and TAS values were determined. A dose-dependent increase in PTX3 concentrations of 4.7% (Resv 40 arm) and 26.3% (Resv 500 arm), and 8.0% reduction after placebo were found. Adjusted mean differences of change versus placebo were 0.16 (95% CI 0.01-0.32) and 0.25 (0.09-0.42) in the Resv 40 and Resv 500 arms, respectively. At subgroup analyses, lower diabetes duration, aspirin, alcohol use, younger age, female gender, smoking (Resv 500 arm) and female gender and aspirin use (Resv 40 arm) were associated with higher PTX3 increments. A dose-dependent increment in TAS values in the resveratrol arms (1.4 and 6.4% for Resv 40 and Resv 500, respectively), and a reduction in placebo arm (-8.9%) were observed. Adjusted mean differences of change were 28.5 (95% CI 10.1-46.8) and 44.8 (25.4-64.1) in the Resv 40 and Resv 500 arms, respectively. Resveratrol supplementation increased PTX3 and TAS levels in a dose-dependent manner in T2DM patients. At present, potential clinical implications of these results remain unclear. CLINICALTRIALS. NCT02244879.

Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hakama, Matti; Hemminki, Elina

2012-04-04

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. 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. 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: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98). The results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events. [ISRCTN35338757].

Head-to-head immunogenicity comparison of Edmonston-Zagreb vs. AIK-C measles vaccine strains in infants aged 8-12 months: A randomized clinical trial.

PubMed

Izadi, Shahrokh; Zahraei, Seyed Mohsen; Salehi, Masoud; Mohammadi, Mahdi; Tabatabaei, Seyed Mehdi; Mokhtari-Azad, Talat

2018-01-29

A non-inferiority multi-centre parallel randomized double-blind trial was implemented in Zahedan district, Sistan-va-Baluchestan province, Iran, to compare the performance of the two measles vaccines which are in use in the National Immunization Programme of Iran and are of two different measles virus vaccine strains: Edmonston-Zagreb (EZ) strain vs. AIK-C strain. The main outcome measure was appearance of anti-measles antibody in sera. 200 infants, 8-12 months old, whose parents consented for their children to be included in the study, were randomized in permutation blocks of size 4-8 in four Urban Health Clinics. Having given a pre-vaccination blood sample, they received measles-rubella vaccine containing one of the vaccine strains mentioned before. After 60 days, the second blood sample was taken. The sera of the pre- and post-vaccination blood samples were tested for anti-measles antibodies in the National Reference Measles Laboratory. Parents, laboratory technicians and statistician were blind to groupings. Of the 200 children equally randomized in the two arms, 185 who were seronegative before vaccination (88 in the EZ arm and 97 in the AIK-C arm) were entered in the final analysis. The seroconversion rate in the EZ arm was 76.1% (95% CI: 60.2-85.2%), and that in the AIK-C arm was 58.7%; (95% CI: 48.8-68.7%). The absolute rate difference was 17. 4% (4.1-30.9%; P-value: .012), and the relative seroconversion rate of EZ to AIK-C was 1.3 (95% CI: 1.1-1.6; P-value: .012). No adverse events were reported during the study period. A considerable difference in the seropositivity of different measles containing vaccines could be demonstrated in the first year of life. Iranian Registry of Clinical Trials Registration Number: IRCT2016032827144N1; May 10, 2016 (www.who.int/ictrp/network/irct/en/). Copyright © 2017 Elsevier Ltd. All rights reserved.

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.

PubMed

Moore, R Andrew; Gay-Escoda, C; Figueiredo, R; Tóth-Bagi, Z; Dietrich, T; Milleri, S; Torres-Lagares, D; Hill, C M; García-García, A; Coulthard, P; Wojtowicz, A; Matenko, D; Peñarrocha-Diago, M; Cuadripani, S; Pizà-Vallespir, B; Guerrero-Bayón, C; Bertolotti, M; Contini, M P; Scartoni, S; Nizzardo, A; Capriati, A; Maggi, C A

2015-01-01

Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial

PubMed Central

Lo, Ronson S. L.; Leung, Yuk Ki; Leung, Ling Yan; Man, S. Y.; Woo, W. K.; Cattermole, Giles N.; Rainer, Timothy H.

2018-01-01

Background Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. Objectives To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. Methods Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. Results There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. Conclusion There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. Trial registration The study is registered with ClinicalTrials.gov (no. NCT00528658). PMID:29408866

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

PubMed

Mizuno, Yoshikuni; Nomoto, Masahiro; Hasegawa, Kazuko; Hattori, Nobutaka; Kondo, Tomoyoshi; Murata, Miho; Takeuchi, Masahiro; Takahashi, Masayoshi; Tomida, Takayuki

2014-12-01

To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group. Copyright © 2014. Published by Elsevier Ltd.

A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis.

PubMed

Schiffenbauer, Adam; Garg, Megha; Castro, Christine; Pokrovnichka, Angelina; Joe, Galen; Shrader, Joseph; Cabalar, Imelda Victoria; Faghihi-Kashani, Sara; Harris-Love, Michael O; Plotz, Paul H; Miller, Frederick W; Gourley, Mark

2018-06-01

To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM). A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40. Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab. Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients. Published by Elsevier Inc.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

PubMed

Micallef, J; Soubrouillard, C; Guet, F; Le Guern, M E; Alquier, C; Bruguerolle, B; Blin, O

2001-06-01

This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

Multicenter, double-blind, parallel group study investigating the non-inferiority of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2% ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.

PubMed

Buechner, Stanislaw A

2014-06-01

This study investigated the non-inferiority of efficacy and tolerance of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in the treatment of scalp seborrheic dermatitis. A randomized, double-blind, comparative, parallel group, multicenter study was done. A total of 274 patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice-weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global change [Clinical Global Impressions (CGIs) and Patient Global Impressions (PGIs)]. Miconazole shampoo is at least as effective and safe as ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

TROPICS 1: a phase III, randomized, double-blind, placebo-controlled study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PubMed

Gabrail, Nashat; Sandler, Eric; Charu, Veena; Anas, Nick; Lim, Eduardo; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

2010-12-01

To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. There were 97 patients who received either TNK-TNK-PBO (n = 50) or PBO-TNK-TNK (n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18-55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs. Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.

Iron-Magnesium Hydroxycarbonate (Fermagate): A Novel Non-Calcium-Containing Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Hemodialysis Patients

PubMed Central

McIntyre, Christopher W.; Pai, Pearl; Warwick, Graham; Wilkie, Martin; Toft, Alex J.; Hutchison, Alastair J.

2009-01-01

Background and objectives: This phase II study tested the safety and efficacy of fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for treating hyperphosphatemia in hemodialysis patients. Design, setting, participants, & measurements: A randomized, double-blind, three-arm, parallel-group study compared two doses of fermagate (1 g three times daily or 2 g three times daily with placebo). Sixty-three patients who had been on a stable hemodialysis regimen for ≥3 mo were randomized to the treatment phase. Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period. Results: In the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L, respectively. Adverse event (AE) incidence in the 1-g fermagate arm was statistically comparable to the placebo group. The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm, particularly gastrointestinal AEs, as well as a higher number of discontinuations, complicating interpretation of this dose's efficacy. Both doses were associated with elevations of prehemodialysis serum magnesium levels. Conclusions: The efficacy and tolerability of fermagate were dose dependent. Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study. The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies, or fixed-dose comparisons of more doses. PMID:19158369

Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

PubMed

Glesby, Marshall J; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P

2013-01-01

Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Clinicaltrials.gov NCT00130286.

Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV-Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

PubMed Central

Glesby, Marshall J.; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N.; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P.

2013-01-01

Background Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (−17.5% in rhGH/rosiglitazone and −22.7% in rhGH) but not in the rosiglitazone alone (−2.5%) or control arms (−1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Trial Registration Clinicaltrials.gov NCT00130286 PMID:23593417

Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial.

PubMed

Cicero, A F; Bove, M; Colletti, A; Rizzo, M; Fogacci, F; Giovannini, M; Borghi, C

2017-01-01

The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn't often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice. 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

Improving blood pressure control: increase the dose of diuretic or switch to a fixed-dose angiotensin receptor blocker/diuretic? the valsartan hydrochlorothiazide diuretic for initial control and titration to achieve optimal therapeutic effect (Val-DICTATE) trial.

PubMed

White, William B; Calhoun, David A; Samuel, Rita; Taylor, Addison A; Zappe, Dion H; Purkayastha, Das

2008-06-01

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

PubMed

Rafii, Michael S; Skotko, Brian G; McDonough, Mary Ellen; Pulsifer, Margaret; Evans, Casey; Doran, Eric; Muranevici, Gabriela; Kesslak, Patrick; Abushakra, Susan; Lott, Ira T

2017-01-01

ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia

PubMed Central

Rafii, Michael S.; Skotko, Brian G.; McDonough, Mary Ellen; Pulsifer, Margaret; Evans, Casey; Doran, Eric; Muranevici, Gabriela; Kesslak, Patrick; Abushakra, Susan; Lott, Ira T.

2018-01-01

Background ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer’s disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. Objective To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. Methods This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase 2 study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2:1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. Results There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram (ECG) results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Conclusion Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy. PMID:28453471

The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients - protocol for a double-blind, placebo-controlled randomised trial.

PubMed

Dogar, Omara; Barua, Deepa; Boeckmann, Melanie; Elsey, Helen; Fatima, Razia; Gabe, Rhian; Huque, Rumana; Keding, Ada; Khan, Amina; Kotz, Daniel; Kralikova, Eva; Newell, James N; Nohavova, Iveta; Parrott, Steve; Readshaw, Anne; Renwick, Lottie; Sheikh, Aziz; Siddiqi, Kamran

2018-04-20

Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine - a low-cost plant-derived nicotine substitute - for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomised trial. TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. Newly diagnosed (in the last four weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n= 2,388). The primary outcome measure is biochemically verified continuous abstinence from smoking at six months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and tuberculosis (TB) outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke. This article is protected by copyright. All rights reserved.

The effect of pheniramine on fentanyl-induced cough: a randomized, double blinded, placebo controlled clinical study.

PubMed

Arslan, Zakir; Çalık, Eyup Serhat; Kaplan, Bekir; Ahiskalioglu, Elif Oral

2016-01-01

There are many studies conducted on reducing the frequency and severity of fentayl-induced cough during anesthesia induction. We propose that pheniramine maleate, an antihistaminic, may suppress this cough. We aim to observe the effect of pheniramine on fentanyl-induced cough during anesthesia induction. This is a double-blinded, prospective, three-arm parallel, randomized clinical trial of 120 patients with ASA (American Society of Anesthesiologists) physical status III and IV who aged ≥18 and scheduled for elective open heart surgery during general anesthesia. Patients were randomly assigned to three groups of 40 patients, using computer-generated random numbers: placebo group, pheniramine group, and lidocaine group. Cough incidence differed significantly between groups. In the placebo group, 37.5% of patients had cough, whereas the frequency was significantly decreased in pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p=0.0007 and p=0.0188, respectively). There was no significant change in cough incidence between pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p=0.4325). Cough severity did also change between groups. Post Hoc tests with Bonferroni showed that mean cough severity in placebo differed significantly than that of pheniramine group and lidocaine group (p<0.0001 and p=0.009, respectively). There was no significant change in cough severity between pheniramine group and lidocaine group (p=0.856). Intravenous pheniramine is as effective as lidocaine in preventing fentayl-induced cough. Our results emphasize that pheniramine is a convenient drug to decrease this cough. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Evaluation of intralesional injection of hyaluronic acid compared with verapamil in Peyronie's disease: preliminary results from a prospective, double-blinded, randomized study.

PubMed

Favilla, V; Russo, G I; Zucchi, A; Siracusa, G; Privitera, S; Cimino, S; Madonia, M; Cai, T; Cavallini, G; Liguori, G; D'Achille, G; Silvani, M; Franco, G; Verze, P; Palmieri, A; Torrisi, B; Mirone, V; Morgia, G

2017-07-01

Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid (HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil (ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease (PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function (IIEF-5) score. The difference between post- and pre-treatment plaque size was -1.36 mm (SD ± 1.27) for Group A and -1.80 mm (SD ± 2.47) for Group B (p-value = NS). IIEF-5 increased of 1.46 points (SD ± 2.18) in Group A and 1.78 (SD ± 2.48) in Group B (p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° (SD ± 5.63) from the baseline (p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement (PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I. © 2017 American Society of Andrology and European Academy of Andrology.

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2017-10-01

a randomized sham- controlled double-blind design with the sham- control group receiving slightly pressurized air at the beginning and end of each... controlled ( non -treatment, non -sham) single-arm crossover single-blind study. The scope of the project is to recruit, enroll, test, treat, re-test and...the P.I. conducted a non - controlled pilot trial of hyperbaric oxygen therapy (HBOT 1.5 atmospheres absolute/60 minutes, twice/day, 40 treatments

First experience with particle-in-cell plasma physics code on ARM-based HPC systems

NASA Astrophysics Data System (ADS)

Sáez, Xavier; Soba, Alejandro; Sánchez, Edilberto; Mantsinen, Mervi; Mateo, Sergi; Cela, José M.; Castejón, Francisco

2015-09-01

In this work, we will explore the feasibility of porting a Particle-in-cell code (EUTERPE) to an ARM multi-core platform from the Mont-Blanc project. The used prototype is based on a system-on-chip Samsung Exynos 5 with an integrated GPU. It is the first prototype that could be used for High-Performance Computing (HPC), since it supports double precision and parallel programming languages.

Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial.

PubMed

Walmsley, Sharon; Baumgarten, Axel; Berenguer, Juan; Felizarta, Franco; Florence, Eric; Khuong-Josses, Marie-Aude; Kilby, J Michael; Lutz, Thomas; Podzamczer, Daniel; Portilla, Joaquin; Roth, Norman; Wong, Deborah; Granier, Catherine; Wynne, Brian; Pappa, Keith

2015-12-15

The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of <50 copies per milliliter through W144 (P = 0.01). Superior efficacy was primarily driven by fewer discontinuations due to adverse events in the dolutegravir + abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144.

CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms.

PubMed

Krzysztof, Szwed; Wojciech, Pawliszak; Zbigniew, Serafin; Mariusz, Kowalewski; Remigiusz, Tomczyk; Damian, Perlinski; Magdalena, Szwed; Marta, Tomaszewska; Lech, Anisimowicz; Alina, Borkowska

2017-07-10

Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. NCT03074604; Pre-results. 10-Mar-2017 Original. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol.

PubMed

Allen, Sophia I; Foulds, Jonathan; Pachas, Gladys N; Veldheer, Susan; Cather, Corinne; Azzouz, Nour; Hrabovsky, Shari; Hameed, Ahmad; Yingst, Jessica; Hammett, Erin; Modesto, Jennifer; Krebs, Nicolle M; Zhu, Junjia; Liao, Jason; Muscat, Joshua E; Richie, John; Evins, A Eden

2017-01-19

The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks. Adult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms). Results from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes. TRN: NCT01928758 , registered August 21, 2013.

A randomized controlled trial of intranasal ketamine in migraine with prolonged aura.

PubMed

Afridi, Shazia K; Giffin, Nicola J; Kaube, Holger; Goadsby, Peter J

2013-02-12

The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Eighteen subjects completed the study. Ketamine reduced the severity (p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. This study provides class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.

PubMed

Silberstein, S; Saper, J; Berenson, F; Somogyi, M; McCague, K; D'Souza, J

2008-02-12

To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.

Efficacy and safety of Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Karkon Varnosfaderani, Shahnaz; Hashem-Dabaghian, Fataneh; Amin, Gholamreza; Bozorgi, Mahbubeh; Heydarirad, Ghazaleh; Nazem, Esmaeil; Nasiri Toosi, Mohsen; Mosavat, Seyed Hamdollah

2018-03-01

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society. Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001). This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD. Iranian Registry of Clinical Trials IRCT2016061428469N1. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

PubMed

Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

2016-04-01

1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT's improved bioavailability and absorption. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Leitner, Lorenz; Sybesma, Wilbert; Chanishvili, Nina; Goderdzishvili, Marina; Chkhotua, Archil; Ujmajuridze, Aleksandre; Schneider, Marc P; Sartori, Andrea; Mehnert, Ulrich; Bachmann, Lucas M; Kessler, Thomas M

2017-09-26

Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials. This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥10 4 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern. Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide essential insights into this potentially revolutionizing treatment option. This study has been registered at clinicaltrials.gov ( www.clinicaltrials.gov/ct2/show/NCT03140085 ). April 27, 2017.

Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study.

PubMed

Yozbatiran, Nuray; Keser, Zafer; Davis, Matthew; Stampas, Argyrios; O'Malley, Marcia K; Cooper-Hay, Catherine; Frontera, Joel; Fregni, Felipe; Francisco, Gerard E

2016-07-15

After cervical spinal cord injury, current options for treatment of upper extremity motor functions have been limited to traditional approaches. However, there is a substantial need to explore more rigorous alternative treatments to facilitate motor recovery. To demonstrate whether anodal-primary motor cortex (M1) excitability enhancement (with cathodal-supra orbital area) (atDCS) combined with robot-assisted arm training (R-AAT) will provide greater improvement in contralateral arm and hand motor functions compared to sham stimulation (stDCS) and R-AAT in patients with chronic, incomplete cervical spinal cord injury (iCSCI). In this parallel-group, double-blinded, randomized and sham-controlled trial, nine participants with chronic iCSCI (AIS C and D level) were randomized to receive 10 sessions of atDCS or stDSC combined with R-AAT. Feasibility and tolerability was assessed with attrition rate and occurrence of adverse events, Changes in arm and hand function were assessed with Jebson Taylor Hand Function Test (JTHFT). Amount of Use Scale of Motor Activity Log (AOU-MAL), American Spinal Injury Association Upper Extremity Motor Score and Modified Ashworth Scale (MAS) at baseline, after treatment, and at two-month follow-up. None of the participants missed a treatment session or dropped-out due to adverse events related to the treatment protocol. Participants tended to perform better in JTHFT and AOU-MAL after treatment. Active group at post-treatment and two-month follow-up demonstrated better arm and hand performance compared to sham group. These preliminary findings support that modulating excitatory input of the corticospinal tracts on spinal circuits may be a promising strategy in improving arm and hand functions in persons with incomplete tetraplegia. Further study is needed to explore the underlying mechanisms of recovery.

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project.

PubMed

Bernabeu-Wittel, Máximo; Aparicio, Reyes; Romero, Manuel; Murcia-Zaragoza, José; Monte-Secades, Rafael; Rosso, Clara; Montero, Abelardo; Ruiz-Cantero, Alberto; Melero-Bascones, María

2012-02-21

Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. CLINICALTRIALS.GOV IDENTIFIER: NCT01154491.

Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.

PubMed

Porter, R J; Partiot, A; Sachdeo, R; Nohria, V; Alves, W M

2007-04-10

To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures. A multicenter, randomized, double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing >/=50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population. Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was -23% for 600 mg/day, -29% for 900 mg/day, and -35% for 1,200 mg/day vs -13% for placebo (p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day (p = 0.021), and 33% for 1,200 mg/day (p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia. Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.

PubMed

Beer, Tomasz M; Kwon, Eugene D; Drake, Charles G; Fizazi, Karim; Logothetis, Christopher; Gravis, Gwenaelle; Ganju, Vinod; Polikoff, Jonathan; Saad, Fred; Humanski, Piotr; Piulats, Josep M; Gonzalez Mella, Pablo; Ng, Siobhan S; Jaeger, Dirk; Parnis, Francis X; Franke, Fabio A; Puente, Javier; Carvajal, Roman; Sengeløv, Lisa; McHenry, M Brent; Varma, Arvind; van den Eertwegh, Alfonsus J; Gerritsen, Winald

2017-01-01

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. Trial registration NCT01695850 PMID:24180235

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

PubMed

Zhong, Linda L D; Cheng, Chung Wah; Chan, Yawen; Chan, King Hong; Lam, Ting Wa; Chen, Xiao Rui; Wong, Chi Tak; Wu, Justin C Y; Bian, Zhao Xiang

2013-11-04

Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. NCT01695850.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

PubMed

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

PubMed Central

Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-01-01

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0–10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results. PMID:28716797

Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

PubMed Central

Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

2016-01-01

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial

USDA-ARS?s Scientific Manuscript database

As populations shift to include a larger proportion of older adults, the necessity of research targeting older populations is becoming increasingly apparent. Changes in motor coordination during ‘normal’ aging, in animals and humans, include decrements in balance and locomotion. Parallel to alterati...

The Handbook of Research Impact Assessment. Edition 7. Summer 1997.

DTIC Science & Technology

1997-01-01

Treatment of Patients with Chronic-Schizophrenia - A Multi-National, Multicenter, Double-Blind, Parallel-Group Study Versus Haloperidol ", BRITISH JOURNAL OF...34The Scientific Production and International Reputation of Travassos,Lauro", MEMORIAS DO INSTITUTO OSWALDO CRUZ,1992, Vol 87, Iss S1, pp R7-R10 Courtial

Effect of Piracetam on Dyslexic's Reading Ability.

ERIC Educational Resources Information Center

Wilsher, C.; And Others

1985-01-01

Forty-six dyslexic boys (aged eight to 13) were administered Piracetam or placebo in a double-blind, parallel experiment. Although, overall, there were no significant group effects, the within-subject design revealed improvements in reading speed and accuracy in Piracetam Ss. Dyslexics with higher reading ages improved significantly compared to…

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a Closed-loop System: A Randomized, Double-blinded, Controlled Trial in Major Abdominal Surgery.

PubMed

Joosten, Alexandre; Delaporte, Amelie; Ickx, Brigitte; Touihri, Karim; Stany, Ida; Barvais, Luc; Van Obbergh, Luc; Loi, Patricia; Rinehart, Joseph; Cannesson, Maxime; Van der Linden, Philippe

2018-01-01

The type of fluid and volume regimen given intraoperatively both can impact patient outcome after major surgery. This two-arm, parallel, randomized controlled, double-blind, bi-center superiority study tested the hypothesis that when using closed-loop assisted goal-directed fluid therapy, balanced colloids are associated with fewer postoperative complications compared to balanced crystalloids in patients having major elective abdominal surgery. One hundred and sixty patients were enrolled in the protocol. All patients had maintenance-balanced crystalloid administration of 3 ml · kg · h. A closed-loop system delivered additional 100-ml fluid boluses (patients were randomized to receive either a balanced-crystalloid or colloid solution) according to a predefined goal-directed strategy, using a stroke volume and stroke volume variation monitor. All patients were included in the analysis. The primary outcome was the Post-Operative Morbidity Survey score, a nine-domain scale, at day 2 postsurgery. Secondary outcomes included all postoperative complications. Patients randomized in the colloid group had a lower Post-Operative Morbidity Survey score (median [interquartile range] of 2 [1 to 3] vs. 3 [1 to 4], difference -1 [95% CI, -1 to 0]; P < 0.001) and a lower incidence of postoperative complications. Total volume of fluid administered intraoperatively and net fluid balance were significantly lower in the colloid group. Under our study conditions, a colloid-based goal-directed fluid therapy was associated with fewer postoperative complications than a crystalloid one. This beneficial effect may be related to a lower intraoperative fluid balance when a balanced colloid was used. However, given the study design, the mechanism for the difference cannot be determined with certainty.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day—A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia

PubMed Central

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-01-01

Background Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3–12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. Methods In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Results Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, –11.4 (20.81); paliperidone ER 1.5 mg group, –8.9 (23.31); and paliperidone ER 6 mg group, –15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group—headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group—insomnia (13.6%); and paliperidone ER 6 mg group—headache (11.4%), insomnia (10%), and tremor (10%). Conclusions In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo. PMID:27738355

Repeated tender point injections of granisetron alleviate chronic myofascial pain--a randomized, controlled, double-blinded trial.

PubMed

Christidis, Nikolaos; Omrani, Shahin; Fredriksson, Lars; Gjelset, Mattias; Louca, Sofia; Hedenberg-Magnusson, Britt; Ernberg, Malin

2015-01-01

Serotonin (5-HT) mediates pain by peripheral 5-HT3-receptors. Results from a few studies indicate that intramuscular injections of 5-HT3-antagonists may reduce musculoskeletal pain. The aim of this study was to investigate if repeated intramuscular tender-point injections of the 5-HT3-antagonist granisetron alleviate pain in patients with myofascial temporomandibular disorders (M-TMD). This prospective, randomized, controlled, double blind, parallel-arm trial (RCT) was carried out during at two centers in Stockholm, Sweden. The randomization was performed by a researcher who did not participate in data collection with an internet-based application ( www.randomization.com ). 40 patients with a diagnose of M-TMD according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were randomized to receive repeated injections, one week apart, with either granisetron (GRA; 3 mg) or isotonic saline as control (CTR). The median weekly pain intensities decreased significantly at all follow-ups (1-, 2-, 6-months) in the GRA-group (Friedman test; P < 0.05), but not in the CTR-group (Friedman-test; P > 0.075). The numbers needed to treat (NNT) were 4 at the 1- and 6-month follow-ups, and 3.3 at the 2-month follow-up in favor of granisetron. Repeated intramuscular tender-point injections with granisetron provide a new pharmacological treatment possibility for myofascial pain patients with repeated intramuscular tender-point injections with the serotonin type 3 antagonist granisetron. It showed a clinically relevant pain reducing effect in the temporomandibular region, both in a short- and long-term aspect. European Clinical Trials Database 2005-006042-41 as well as at Clinical Trials NCT02230371 .

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

PubMed

Costello, John M; Dunbar-Masterson, Carolyn; Allan, Catherine K; Gauvreau, Kimberlee; Newburger, Jane W; McGowan, Francis X; Wessel, David L; Mayer, John E; Salvin, Joshua W; Dionne, Roger E; Laussen, Peter C

2014-07-01

We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. http://www.clinicaltrials.gov. Unique identifier: NCT00543309. © 2014 American Heart Association, Inc.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day-A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia.

PubMed

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-05-15

Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3-12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, -11.4 (20.81); paliperidone ER 1.5 mg group, -8.9 (23.31); and paliperidone ER 6 mg group, -15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group-headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group-insomnia (13.6%); and paliperidone ER 6 mg group-headache (11.4%), insomnia (10%), and tremor (10%). In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo.

Transversus abdominis plane block reduces morphine consumption in the early postoperative period following microsurgical abdominal tissue breast reconstruction: a double-blind, placebo-controlled, randomized trial.

PubMed

Zhong, Toni; Ojha, M; Bagher, Shaghayegh; Butler, Kate; Srinivas, Coimbatore; McCluskey, Stuart A; Clarke, Hance; O'Neill, Anne C; Novak, Christine B; Hofer, Stefan O P

2014-11-01

The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial. The authors conducted a double-blind, placebo-controlled, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction. Intraoperatively, epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure. Patients received either bupivacaine (study group) or saline (placebo group) through the catheters for 2 postoperative days. All patients received hydromorphone by means of a patient-controlled analgesic pump. The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups. The secondary outcome measures included the following: total in-hospital opioid; antinausea medication; pain, nausea, and sedation scores; Quality of Recovery Score; time to ambulation; and hospital stay duration. Between September of 2011 and June of 2013, 93 patients were enrolled: 49 received bupivacaine and 44 received saline. There were 11 postoperative complications (13 percent); none were related to the catheter. Primary outcomes were completed by 85 of 93 patients (91.3 percent); the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group (20.7±20.1 mg) compared with 30.0±19.1 mg in the control group (p=0.02). There were no significant differences in secondary outcomes. Following abdominally based breast reconstruction, transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period. Therapeutic, II.

Eicosapentaenoic and docosahexaenoic acids-rich fish oil supplementation attenuates strength loss and limited joint range of motion after eccentric contractions: a randomized, double-blind, placebo-controlled, parallel-group trial.

PubMed

Tsuchiya, Yosuke; Yanagimoto, Kenichi; Nakazato, Koichi; Hayamizu, Kohsuke; Ochi, Eisuke

2016-06-01

This study investigated the effect of eicosapentaenoic and docosahexaenoic acids-rich fish oil (EPA + DHA) supplementation on eccentric contraction-induced muscle damage. Twenty-four healthy men were randomly assigned to consume the EPA + DHA supplement (EPA, n = 12) or placebo (PL, n = 12) by the double-blind method. Participants consumed EPA + DHA or placebo supplement for 8 weeks prior to exercise and continued it until 5 days after exercise. The EPA group consumed EPA + DHA-rich fish oil containing 600 mg EPA and 260 mg DHA per day. Subjects performed five sets of six maximal eccentric elbow flexion exercises. Changes in the maximal voluntary contraction (MVC) torque, range of motion (ROM), upper arm circumference, muscle soreness as well as serum creatine kinase, myoglobin, IL-6, and TNF-α levels in blood were assessed before, immediately after, and 1, 2, 3, and 5 days after exercise. MVC was significantly higher in the EPA group than in the PL group at 2-5 days after exercise (p < 0.05). ROM was also significantly greater in the EPA group than in the PL group at 1-5 days after exercise (p < 0.05). At only 3 days after exercise, muscle soreness of the brachialis was significantly greater in the PL group than in the EPA group (p < 0.05), with a concomitant increase in serum IL-6 levels in the PL group. Eight-week EPA + DHA supplementation attenuates strength loss and limited ROM after exercise. The supplementation also attenuates muscle soreness and elevates cytokine level, but the effect is limited.

Randomized, Double-Blind Study of Emtricitabine (FTC) plus Clevudine versus FTC Alone in Treatment of Chronic Hepatitis B

PubMed Central

Lim, Seng Gee; Krastev, Zahary; Ng, Tay Meng; Mechkov, Grigor; Kotzev, Iskren Andreev; Chan, Sing; Mondou, Elsa; Snow, Andrea; Sorbel, Jeff; Rousseau, Franck

2006-01-01

Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen positive, and the median baseline HBV DNA level was 6 log10 copies/ml. After 24 weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four weeks posttreatment, the mean change in serum HBV DNA levels from baseline was −1.25 log10 copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for FTC alone) (P ≤ 0.025 for all endpoints). The safety profile was similar between arms during treatment, with less posttreatment exacerbation of hepatitis B in the combination arm. In summary, after 24 weeks of treatment, no significant difference between arms was observed, but there was a significantly greater virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm. PMID:16641430

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

2006-01-01

Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men.

PubMed

Cases, Julien; Romain, Cindy; Dallas, Constantin; Gerbi, Alain; Rouanet, Jean Max

2015-01-01

Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial.

PubMed

Caccia, M R; Osio, M; Galimberti, V; Cataldi, G; Mangoni, A

1989-05-01

Accelerometric tremorgrams were recorded from 25 subjects affected by essential tremor and analysed by a Berg-Fourier frequency analyser before and during venous infusion of the following drugs: propranolol (beta-blocker), clonidine (alpha-presynaptic adrenergic agonist), urapidil (alpha-postsynaptic blocker), trazodone (adrenolytic agent) and placebo. The washout interval between infusions was 3 days. Recordings and data analyses were performed in a double-blind crossover trial. Tremor was classified as: at rest; postural (arms hyperextended); and intention (finger-nose test). Analysis of the results showed that propranolol and clonidine reduced significantly (P = 0.01 and P = 0.009, respectively) the power spectrum of postural tremor, but left at rest and intention tremors unchanged. No significant effects on the tremor power spectrum were observed after placebo, urapidil or trazodone administration. None of the drugs had any effect on tremor frequency.

Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma

PubMed Central

Kindler, Hedy L.; Karrison, Theodore G.; Gandara, David R.; Lu, Charles; Krug, Lee M.; Stevenson, James P.; Jänne, Pasi A.; Quinn, David I.; Koczywas, Marianna N.; Brahmer, Julie R.; Albain, Kathy S.; Taber, David A.; Armato, Samuel G.; Vogelzang, Nicholas J.; Chen, Helen X.; Stadler, Walter M.; Vokes, Everett E.

2012-01-01

Purpose Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM. Patients and Methods Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 every 21 days, cisplatin 75 mg/m2 every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression. Results One hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater. Conclusion The addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM. PMID:22665541

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): Interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

PubMed

Magnan, Sindy; Tota, Joseph E; El-Zein, Mariam; Burchell, Ann N; Schiller, John T; Ferenczy, Alex; Tellier, Pierre-Paul; Coutlée, François; Franco, Eduardo L

2018-04-20

We evaluated the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based or a placebo gel to be self-applied every other day for the first month and prior to and following each intercourse during follow-up. Assessments were done at 0·5, 1, 3, 6, 9, and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Analyses were performed by intention-to-treat. Between January 2013 and June 2017, 280 participants were randomly assigned to the carrageenan (n=141) or the placebo (n=139) arm. All participants were included in safety analyses, but 3 (1%) were excluded from efficacy analyses (HPV results unavailable: carrageenan=2, placebo=1). The median follow-up time was 9·2 months (inter-quartile range: 1·9-13·2). 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm got infected by at least one new HPV type (hazard ratio=0·64, 95% confidence interval=0·45-0·89, p=0·009). 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p=0.02); none of which were deemed related to the gels. Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Establishment and rapid detection of a heterozygous missense mutation in the CACNA1F gene by ARMS technique with double-base mismatched primers.

PubMed

Yang, W C; Zhu, L; Zhou, B X; Tania, S; Zhou, Q; Khan, M A; Fu, X L; Cheng, J L; Lv, H B; Fu, J J

2015-09-25

Retinitis pigmentosa (RP) is a retinal degenerative disorder that often causes complete blindness. Mutations of more than 50 genes have been identified as associated with RP, including the CACNA1F gene. In a recent study, by employing next-generation sequencing, we identified a novel mutation in the CACNA1F gene. In this study, we used the amplification refractory mutation system (ARMS) and identified a single nucleotide change c.1555C>T in exon 13 of the CACNA1F gene, leading to the substitution of arginine by tryptophan (p.R519W) in a Chinese individual affected by RP. This study actually confirms this novel mutation, and establishes the ARMS technique for the detection of mutations in RP.

An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.

PubMed

Riedl, Marc A; Bernstein, Jonathan A; Craig, Timothy; Banerji, Aleena; Magerl, Markus; Cicardi, Marco; Longhurst, Hilary J; Shennak, Mustafa M; Yang, William H; Schranz, Jennifer; Baptista, Jovanna; Busse, Paula J

2017-01-01

Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596.

Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

ERIC Educational Resources Information Center

Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

2012-01-01

Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

An elevated plus-maze in mixed reality for studying human anxiety-related behavior.

PubMed

Biedermann, Sarah V; Biedermann, Daniel G; Wenzlaff, Frederike; Kurjak, Tim; Nouri, Sawis; Auer, Matthias K; Wiedemann, Klaus; Briken, Peer; Haaker, Jan; Lonsdorf, Tina B; Fuss, Johannes

2017-12-21

A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.

The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda.

PubMed

Guwatudde, David; Wang, Molin; Ezeamama, Amara E; Bagenda, Danstan; Kyeyune, Rachel; Wamani, Henry; Manabe, Yukari C; Fawzi, Wafaie W

2015-08-19

Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality. Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of -6 · 17 [95 % CI -29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI -0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of -2.16 [95 % CI -4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART. Clinical trials NCT01228578 , registered on 15th October 2010.

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial

PubMed Central

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-01-01

Introduction Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Methods and analysis Inclusion criteria are patients 7–15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). Ethics and dissemination This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. Trial registration number ClinicalTrials.gov NCT02084433. PMID:26163031

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial.

PubMed

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-07-10

Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Inclusion criteria are patients 7-15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. ClinicalTrials.gov NCT02084433. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Randomized, Double-Blind, Split-Face Study Evaluating Fractional Ablative Erbium:YAG Laser-Mediated Trans-Epidermal Delivery of Cosmetic Actives and a Novel Acoustic Pressure Wave Ultrasound Technology for the Treatment of Skin Aging, Melasma, and Acne Scars.

PubMed

Alexiades, Macrene

2015-11-01

Fractional laser resurfacing enhances trans-epidermal delivery (TED), however laser penetration depths >250- μm fail to substantively increase drug delivery. Evaluate the safety and efficacy of a novel acoustic pressure wave ultrasound device following fractional ablative Er:YAG 2940-nm laser (FELR) and topical agents for rhytids, melasma, and acne scars. Randomized, blinded, parallel group split-face side-by-side, controlled study evaluating FELR and topical anti-aging and anti-pigment agents to entire face succeeded by ultrasound to randomized side. Fifteen subjects were enrolled to three treatment arms:rhytids, melasma, and acne scars. Two monthly treatments were administered with 1, 3, and 6 month follow-up. Efficacy was assessed by Comprehensive Grading Scale of Rhytids, Laxity, and Photoaging by Investigator and two blinded physician evaluators. Subject assessments, digital photographs, and reflectance spectroscopic analyses were obtained. Rhytid severity was reduced from a mean of 3.25 to 2.60 on the 4-point grading scale. Spectrophotometric analysis demonstrated increases in lightness (L*) and reductions in redness (a*) and pigment (b*), with greater improvements on the ultrasound side as compared to FELR and topicals alone. Moderate erythema post-treatment resolved in 7 days and no serious adverse events were observed. In this randomized, paired split-face clinical study, FELR-facilitated TED of topical anti-aging actives with ultrasound treatment is safe and effective with improvement in rhytids, melasma, and acne scars. Statistically significant greater improvement in pigment levels was observed on the ultrasound side as compared to FELR-TED and topical agents alone.

Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

PubMed

Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

2016-11-29

Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: A randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults

PubMed Central

2011-01-01

Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein. Methods The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437 PMID:22011460

EFFECT OF A DENTIFRICE CONTAINING ALOE VERA ON PLAQUE AND GINGIVITIS CONTROL. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

PubMed Central

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) – dentifrice containing Aloe vera - or the control group (n=15) – fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice. PMID:19089263

Effect of a dentifrice containing Aloe vera on plaque and gingivitis control. A double-blind clinical study in humans.

PubMed

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) - dentifrice containing Aloe vera - or the control group (n=15) - fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice.

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo].

PubMed

Halaska, M; Raus, K; Bĕles, P; Martan, A; Paithner, K G

1998-10-01

The aim of study presented here was to gather the data about the tolerability and efficacy of Vitex agnus castus (VACS) extract. The study was designed as double-blind, placebo controlled in two parallel groups (each 50 patients). Treatment phase lasted 3 consequent menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or placebo. Mastalgia during at least 5 days of the cycle before the treatment was the strict inclusion condition. For assessment of the efficacy visual analogue scale was used. Altogether 97 patients were included into the statistical analysis (VACS: n = 48, placebo: n = 49). Intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory. We found VACS to be useful in the treatment of cyclical breast pain in women.

Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

2011-01-01

Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Regular consumption of HolisFiit, a polyphenol-rich extract-based food supplement, improves mind and body well-being of overweight and slightly obese volunteers: a randomized, double-blind, parallel trial.

PubMed

Romain, Cindy; Alcaraz, Pedro Emilio; Chung, Linda Haiwon; Cases, Julien

2017-11-01

Modern lifestyles face growing demands for natural solutions to help improve general well-being. Accordingly, mind-body activities such as yoga have considerably grown. However, beneficial effects require regular workout. Besides, literature suggests that polyphenols may demonstrate positive effects on both mental and physical health. Overweight and obese volunteers, for which well-being might be perceived degraded, were included in a 16-week double-blind, randomized and parallel trial with a daily supplementation of HolisFiit ® , a polyphenol-rich food supplement. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) technology; well-being was evaluated with both, Athens Insomnia Scale (AIS) and components from Short Form-36 questionnaire (SF-36). Body composition significantly rebalanced by 7.7% (p = .019) of the lean-to-fat mass ratio. Also, sleep quality significantly improved by 43% (p = .00015) as well as both physical and mental components from SF-36, respectively by 10% (p = .004) and 7% (p = .021). These data altogether, suggest that regular consumption of HolisFiit ® , might significantly improve mind and body well-being.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial.

PubMed

Isiordia-Espinoza, M-A; Pozos-Guillen, A; Martinez-Rider, R; Perez-Urizar, J

2016-09-01

Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. According to the VAS and UAC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

PubMed

Dellinger, Ryan W; Santos, Santiago Roel; Morris, Mark; Evans, Mal; Alminana, Dan; Guarente, Leonard; Marcotulli, Eric

2017-01-01

NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD +) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD + in whole blood demonstrated that NRPT significantly increases the concentration of NAD + in a dose-dependent manner. NAD + levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD + levels was sustained throughout the entire 8-week trial. NAD + levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD + levels sustainably.

A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

PubMed Central

2013-01-01

Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain. PMID:23414938

Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis: a randomized double-blind placebo-controlled trial

PubMed Central

Wills, Anne-Marie; Hubbard, Jane; Macklin, Eric A.; Glass, Jonathan; Tandan, Rup; Simpson, Ericka P; Brooks, Benjamin; Gelinas, Deborah; Mitsumoto, Hiroshi; Mozaffar, Tahseen; Hanes, Gregory P.; Ladha, Shafeeq S.; Heiman-Patterson, Terry; Katz, Jonathan; Lou, Jau-Shin; Mahoney, Katy; Grasso, Daniela; Lawson, Robert; Yu, Hong; Cudkowicz, Merit

2014-01-01

Background Amyotrophic Lateral Sclerosis (ALS) is a rapidly fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in ALS patients and calorie-dense diets increase survival in an ALS mouse model. We therefore hypothesized that hypercaloric diets might lead to weight gain and slow ALS disease progression. Methods In this double-blind, placebo-controlled, multi-center clinical trial, we enrolled adults with ALS without a history of diabetes, significant liver or cardiovascular disease, who were already receiving percutaneous enteral nutrition. We randomly assigned participants to one of three dietary interventions: replacement calories using an isocaloric diet (controls) vs. a high-carbohydrate hypercaloric diet (HC/HC), vs. a high-fat hypercaloric diet (HF/HC). Participants received the intervention diets for four months and were followed for five months. The primary outcomes were safety and tolerability. Secondary outcomes included measures of disease progression, survival, and metabolism. This trial is registered with Clinicaltrials.gov, number NCT00983983. Findings A total of 24 participants were enrolled of whom 20 initiated study diet (six control, eight HC/HC, six HF/HC). Baseline demographics were similar among the three study arms. The HC/HC diet was better tolerated with fewer serious adverse events than the control diet (zero vs. nine, p<0·001) and fewer dose discontinuations due to adverse events (0% vs. 50%). There were no deaths in the HC/HC arm vs. three deaths (43%) in the control arm (logrank p = 0·03). The HF/HC arm was not statistically different from the controls in adverse events, tolerability, deaths or disease progression. Interpretation Our results suggest that hypercaloric enteral nutrition is safe and tolerable in ALS and support the study of nutritional interventions at earlier stages of the disease. Funding The Muscular Dystrophy Association with additional support from the National Center for Research Resources, the National Institutes of Health, and the Harvard NeuroDiscovery Center. PMID:24582471

Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder.

PubMed

Cantillon, Marc; Prakash, Arul; Alexander, Ajay; Ings, Robert; Sweitzer, Dennis; Bhat, Laxminarayan

2017-11-01

The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales. The primary analysis of PANSS Total showed improvement by a mean (SE) of -20.23 (2.65), -15.42 (2.04), and -19.21 (2.39) in the RP5063 15, 30, and 50mg arms, versus -11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15mg (p=0.021) and 50mg (p=0.016) arms. Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels. In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder. Copyright © 2017. Published by Elsevier B.V.

Probiotic administration among free-living older adults: a double blinded, randomized, placebo-controlled clinical trial.

PubMed

Östlund-Lagerström, Lina; Kihlgren, Annica; Repsilber, Dirk; Björkstén, Bengt; Brummer, Robert J; Schoultz, Ida

2016-09-10

Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults. Thus, therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality. The aim of this double-blinded, randomized, placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults. The study enrolled general older adults (>65 years). After eligibility screening qualified subjects (n = 290) participated in a 2-arm study design, with each arm consisting of 12 weeks of intervention of either active or placebo product. Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing, anxiety and stress. Follow up was performed at 8 and 12 weeks. No persistent significant effects were observed on the primary or secondary outcome parameters of the study. A modest effect was observed in the probiotic arm, were levels of stress decreased at week 8 and 12. Similarly, we found that subjects suffering from indigestion and abdominal pain, respectively, showed a significant decrease of anxiety at week 8 after probiotic treatment, but not at week 12. The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri. Neither was any significant improvement in wellbeing, stress or anxiety observed. Even though the RCT had a negative outcome, the study highlights issues important to take into consideration when designing trials among older adults. Clinicaltrials.gov/ NCT01837940 .

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

PubMed Central

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320. PMID:27412105

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting.

PubMed

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-07-13

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). ISRCTN84528320. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed Central

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

2013-01-01

Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. Registry ClinicalTrials.gov. Registry number: NCT00677339 PMID:23967066

Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

PubMed

Krege, Susanne; Rexer, Heidrun; vom Dorp, Frank; de Geeter, Patrick; Klotz, Theodor; Retz, Margitte; Heidenreich, Axel; Kühn, Michael; Kamradt, Joern; Feyerabend, Susan; Wülfing, Christian; Zastrow, Stefan; Albers, Peter; Hakenberg, Oliver; Roigas, Jan; Fenner, Martin; Heinzer, Hans; Schrader, Mark

2014-03-01

To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS. © 2013 The Authors. BJU International © 2013 BJU International.

L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial.

PubMed

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

2013-01-01

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

Clinical Investigation Program Report.

DTIC Science & Technology

1983-10-01

metastatic to liver. (0) H-83-63. Double-blind, randomized parallel comparison of two different dosage regimens of naproxen sodium in patients with...different dosage regimens of naproxen sodium in patients with bone pain due to m etastatic cancer. Start Date: May 83 Est Comp Date: Indefinite Principal...Investigator: Facility: LTC D Gandara, MD LAMC CPT R Mansour, MD D ept/Svc: Associate Investigators: Hematology-Oncology Key Words: naproxen sodium

Forecasting Three-Month Outcomes in a Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR) and Atomoxetine (Strattera) in School-Aged Children with ADHD

ERIC Educational Resources Information Center

Faraone, Stephen V.; Wigal, Sharon B.; Hodgkins, Paul

2007-01-01

Objective: Compare observed and forecasted efficacy of mixed amphetamine salts extended release (MAS-XR; Adderall) with atomoxetine (Strattera) in ADHD children. Method: The authors analyze data from a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study of children ages 6 to 12 with ADHD combined…

A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN® administered orally.

PubMed

Solomon, Todd M; Leech, Jarrett; deBros, Guy B; Murphy, Cynthia A; Budson, Andrew E; Vassey, Elizabeth A; Solomon, Paul R

2016-03-01

Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study. Copyright © 2016 John Wiley & Sons, Ltd.

Lifestyle change recommendations in major depression: Do they work?

PubMed

Serrano Ripoll, M J; Oliván-Blázquez, B; Vicens-Pons, E; Roca, M; Gili, M; Leiva, A; García-Campayo, J; Demarzo, M P; García-Toro, M

2015-09-01

Modifying some lifestyle factors can be useful in depression, at least as an adjuvant treatment. Combining different lifestyle interventions seems to be an adequate strategy to increase their antidepressant efficacy according with preliminary studies, but this issue has not been enough investigated. The present study is a randomized, double-blinded, multicentre, two arm-parallel clinical trials, with a 12 month follow-up. The sample consisted of 273 Primary Care patients. Four combined hygienic-dietary written recommendations were given to the patients about diet, exercise, light exposure and sleep hygiene. Both active and control interventions were associated with improvement on BDI (Beck Depression Inventory) scores. However, there were not statistically significant differences (7.0 vs. 7.6; p=0.594). We were unable to monitor whether patients carry out recommendations. Intervention could be too difficult to accomplish for depressed patients without enough support and supervision. Just giving written lifestyle recommendations are not enough for depressive patients to benefit from them, so perhaps lifestyle change recommendations work or do not work on Depression depending on how they are presented to patients and on monitoring systems of their implementation. Copyright © 2015 Elsevier B.V. All rights reserved.

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

PubMed

Garcia-del-Muro, X; Vadell, C; Pérez Manga, G; Bover, I; Rifá, J; Beltrán, M; Barros, M M; Germá, J R; Fabregat, X; Moreno, V; Salvador, A; Viladiu, P

1998-01-01

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study.

PubMed

Haroyan, Armine; Mukuchyan, Vahan; Mkrtchyan, Nana; Minasyan, Naira; Gasparyan, Srbuhi; Sargsyan, Aida; Narimanyan, Mikael; Hovhannisyan, Areg

2018-01-09

The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with boswellic acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients' global assessment of disease severity. Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin® compared to placebo was observed both in physical performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin® group. The treatments were well tolerated. Twelve-week use of curcumin complex or its combination with boswellic acid reduces pain-related symptoms in patients with OA. Curcumin in combination with boswellic acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin® increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and boswellic acid. This trial is registered at the database www.clinicaltrials.gov . https://clinicaltrials.gov/ct2/show/NCT02390349?term=EuroPharma&rank=1 . Study registration number: NCT02390349 .

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-06-17

Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes. A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis. Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences. Clinicaltrials.gov: NCT01748929. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy.

PubMed

Moore, R A; McQuay, H J; Tomaszewski, J; Raba, G; Tutunaru, D; Lietuviete, N; Galad, J; Hagymasy, L; Melka, D; Kotarski, J; Rechberger, T; Fülesdi, B; Nizzardo, A; Guerrero-Bayón, C; Cuadripani, S; Pizà-Vallespir, B; Bertolotti, M

2016-01-22

Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain. Randomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8). The efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients. The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed. EU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013).

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study.

PubMed

Jadoon, Khalid A; Ratcliffe, Stuart H; Barrett, David A; Thomas, E Louise; Stott, Colin; Bell, Jimmy D; O'Sullivan, Saoirse E; Tan, Garry D

2016-10-01

Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = -1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = -44.51 points; P < 0.01]), adiponectin (ETD = -5.9 × 10(6) pg/mL; P < 0.01), and apolipoprotein A (ETD = -6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (-898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes. © 2016 by the American Diabetes Association.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

PubMed

Yang, Chao-Chun; Wong, Tak-Wah; Lee, Chih-Hung; Hong, Chien-Hui; Chang, Chung-Hsing; Lai, Feng-Jie; Lin, Shang-Hung; Chi, Ching-Chi; Lin, Tzu-Kai; Yen, Hsi; Wu, Chin-Han; Sheu, Hamm-Ming; Lan, Cheng-Che E

2018-06-01

Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Further analysis of PREVAIL: enzalutamide use in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

PubMed Central

Aragon-Ching, Jeanny B

2014-01-01

PREVAIL was a phase III multinational, double-blind, placebo-controlled trial that enrolled chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC), which showed remarkable improvement in co-primary endpoints with an overall 81% reduction in the risk of radiographic progression, as well as 29% reduction in the risk of death in favor of the enzalutamide arm over placebo. All secondary endpoints including time to subsequent chemotherapy initiation and prostate specific antigen (PSA) progression were in favor of the enzalutamide arm. The results of PREVAIL shows the utility of enzalutamide that would likely soon expand the indication to asymptomatic or minimally symptomatic men with mCRPC not previously treated with chemotherapy. PMID:25080931

Further analysis of PREVAIL: enzalutamide use in chemotherapy-naïve men with metastatic castration-resistant prostate cancer.

PubMed

Aragon-Ching, Jeanny B

2014-01-01

PREVAIL was a phase III multinational, double-blind, placebo-controlled trial that enrolled chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC), which showed remarkable improvement in co-primary endpoints with an overall 81% reduction in the risk of radiographic progression, as well as 29% reduction in the risk of death in favor of the enzalutamide arm over placebo. All secondary endpoints including time to subsequent chemotherapy initiation and prostate specific antigen (PSA) progression were in favor of the enzalutamide arm. The results of PREVAIL shows the utility of enzalutamide that would likely soon expand the indication to asymptomatic or minimally symptomatic men with mCRPC not previously treated with chemotherapy.

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

PubMed

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

2017-06-01

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

Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

Bupropion and Naltrexone for Smoking Cessation: A Double-Blind Randomized Placebo-Controlled Clinical Trial

PubMed Central

Mooney, Marc E.; Schmitz, Joy M.; Allen, Sharon; Grabowski, John; Pentel, Paul; Oliver, Andrew; Hatsukami, Dorothy K.

2016-01-01

Combination of non-nicotine pharmacotherapies has been under-examined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + Placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically-verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP+NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP+NTX, 54.1%; BUP+PBO, 33.3%), p = 0.0210, but not at 6-month follow-up (BUP+NTX, 27.9%; BUP+PBO, 15.0%), p = 0.09. Continuous abstinence rates did not differ, p = 0.0740 (BUP+NTX, 26.2%; BUP+PBO, 13.3%). Those receiving BUP+NTX reported reduced nicotine withdrawal, p = 0.0364. The BUP+NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups. PMID:27213949

Department of Clinical Investigation Annual Progress Report: Fiscal Year 1989

DTIC Science & Technology

1989-01-01

Between Plasma Oxygen Permeability 10 and Atherosclerotic Coronary Artery Disease as Determined by Cardiac Catheterization C89-03 A Double-Blind, Parallel...Local Anesthetic Administration During Cardiac Catheterization C89-05 Intravenous Sotalol for the Termination of P3 Paroxysmal Supraventricular... History and Treatment of Patients with Non- Invasive Intraductal Adenocarcinoma H85-09 (**8H-85-I) Phase III Study of Subtotal Lymphoid Irradiation or

A Phase III Randomized, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of Acarmet (Metformin HCl 500 mg Plus Acarbose 50 mg Tablets) Versus Acarbose Alone in Subjects With Type 2 Diabetes Mellitus

ClinicalTrials.gov

2010-11-19

The Objectives of the Study is to Evaluate the Efficacy and Safety of Acarmet (Metformin HCl 500 mg; Plus Acarbose 50 mg Tablets) Thrice Daily Versus Acarbose 50 mg Thrice Daily Over 16 Weeks in; Subjects With Type 2 Diabetes Mellitus.

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.

PubMed

Moore, Nicholas; Verdoux, Hélène; Fantino, Bruno

2005-05-01

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum Study (TEOSS)

PubMed Central

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). METHOD Patients (age 8–19 years) who had improved during an 8-week, randomized double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS. PMID:20494268

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial

PubMed Central

Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

2016-01-01

Background Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. Material and Methods A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

Probiotics for standard triple Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial.

PubMed

Hauser, Goran; Salkic, Nermin; Vukelic, Karina; JajacKnez, Alenka; Stimac, Davor

2015-05-01

The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori.The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration.A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001).Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease.

Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus

PubMed Central

Kreuzer, Peter M.; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B.; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790

Reductions of intimate partner violence resulting from supplementing children with omega-3 fatty acids: A randomized, double-blind, placebo-controlled, stratified, parallel-group trial.

PubMed

Portnoy, Jill; Raine, Adrian; Liu, Jianghong; Hibbeln, Joseph R

2018-05-20

Omega-3 supplementation has been found to reduce externalizing behavior in children. Reciprocal models of parent-child behavior suggest that improving child behavior could lead to improvements in parent behavior, however no study has examined whether omega-3 supplementation in children could reduce intimate partner violence or child maltreatment by their adult caregivers. In this randomized, double-blind, placebo-controlled, stratified, parallel group trial, a community sample of children were randomized to receive either a fruit drink containing 1 gm of omega-3 fats (Smartfish Recharge; Omega-3 group, n = 100) or the same fruit drink without omega-3's (Placebo group, n = 100). Child participants, adult caregivers, and research staff were blinded to group assignment. Adult caregivers reported inter-partner and child-directed physical assault and psychological aggression at baseline, 6 months (end of treatment) and 12 months (6 months post-treatment) using the Conflicts Tactics Scale. Caregivers of children in the omega-3 group reported long-term reductions in psychological aggression in a group × time interaction. Improvements in adult psychological aggression were correlated with improvements in child externalizing behavior scores. No differences were reported for child maltreatment. This study is the first to show that omega-3 supplementation in children can reduce inter-partner psychological aggression among adult caregivers not receiving supplements. Findings suggest that improving child behavior through omega-3 supplementation could have long-term benefits to the family system as a whole. © 2018 Wiley Periodicals, Inc.

True Shear Parallel Plate Viscometer

NASA Technical Reports Server (NTRS)

Ethridge, Edwin; Kaukler, William

2010-01-01

This viscometer (which can also be used as a rheometer) is designed for use with liquids over a large temperature range. The device consists of horizontally disposed, similarly sized, parallel plates with a precisely known gap. The lower plate is driven laterally with a motor to apply shear to the liquid in the gap. The upper plate is freely suspended from a double-arm pendulum with a sufficiently long radius to reduce height variations during the swing to negligible levels. A sensitive load cell measures the shear force applied by the liquid to the upper plate. Viscosity is measured by taking the ratio of shear stress to shear rate.

Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle-controlled, Left-right Comparison Study.

PubMed

Angelova-Fischer, Irena; Rippke, Frank; Richter, Daniel; Filbry, Alexander; Arrowitz, Craig; Weber, Teresa; Fischer, Tobias W; Zillikens, Detlef

2018-04-27

Prevention of the flares is a main goal in the long-term treatment of atopic dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and glycerol, for prevention of the flares in adults with mild to moderately severe AD, treated with topical steroids, that led to clearing of the inflammatory lesions and had been discontinued prior to inclusion. The study was a 12-week, double-blind, randomized, vehicle-controlled, left-right comparison test with the number of relapses, defined as re-occurrence of erythema for at least 3 consecutive days, considered the primary outcome. Compared with the vehicle, the active formulation significantly reduced the number of relapses and maintained the barrier homeostasis of the respective arm. To the best of knowledge, this is the first study to show prevention of the AD flares by the use of stand-alone emollient treatment, based on comparison with the corresponding vehicle while excluding concomitant/rescue medications.

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis

PubMed Central

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-01-01

Introduction Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. Methods and analysis The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Ethics and dissemination Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. PMID:28554913

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis.

PubMed

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-05-29

Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial.

PubMed

van Doorn, Eva; Pleguezuelos, Olga; Liu, Heng; Fernandez, Ana; Bannister, Robin; Stoloff, Gregory; Oftung, Fredrik; Norley, Stephen; Huckriede, Anke; Frijlink, Henderik W; Hak, Eelko

2017-04-04

Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses. In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18-60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity. Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated. EudraCT number 2015-001932-38 ; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).

Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma.

PubMed

Hari, Parameswaran; Lin, Huamao Mark; Zhu, Yanyan; Berg, Deborah; Richardson, Paul G; Moreau, Philippe

2018-05-29

The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM). In this double-blind, placebo-controlled, randomized study (NCT01564537), 722 patients with RRMM following 1-3 prior lines of therapy received Rd plus ixazomib (ixazomib-Rd; n = 360) or matching placebo (placebo-Rd; n = 362) until disease progression or unacceptable toxicity. Healthcare resource utilization data were captured on Day 1 of each 28-day cycle, every 4 weeks during follow-up for progression-free survival, and every 12 weeks during subsequent follow-up, and included medical encounters (length of stay, inpatient, outpatient, and reason) and number of missing days from work or other activities for patients and caregivers. Exposure-adjusted rates of hospitalization were similar between the ixazomib-Rd and placebo-Rd arms, at 0.530 and 0.564 per patient year (ppy), respectively, as were outpatient visit rates (3.305 and 3.355 ppy). Mean length of hospitalization per patient was 10.0 and 10.8 days, respectively. In both arms, hospitalization and outpatient visit rates were higher in patients with two or three prior lines of treatment (ixazomib-Rd: 0.632 and 3.909 ppy; placebo-Rd: 0.774 and 3.539 ppy) compared with patients with one prior line (ixazomib-Rd: 0.460 and 2.888 ppy; placebo-Rd: 0.436 and 3.243 ppy). Patients and their caregivers who missed any work or other activity missed a median of 7 and 5 days in the ixazomib-Rd arm, respectively, vs 8 and 4 days with placebo-Rd. The study was not powered for a statistical comparison of healthcare resource utilization between treatment arms, nor did it capture costs associated with utilization of the identified healthcare resources. This pre-specified analysis demonstrated that the all-oral triplet regimen of ixazomib added to Rd did not increase healthcare resource utilization compared with placebo-Rd.

A pilot randomized double-blind placebo-controlled trial on topical chamomile (Matricaria chamomilla L.) oil for severe carpal tunnel syndrome.

PubMed

Hashempur, Mohammad Hashem; Lari, Zeinab Nasiri; Ghoreishi, Parissa Sadat; Daneshfard, Babak; Ghasemi, Mohammad Sadegh; Homayouni, Kaynoosh; Zargaran, Arman

2015-11-01

To assess the effectiveness of standardized topical Chamomile (Matricaria chamomilla L.) oil in patients with severe carpal tunnel syndrome, as a complementary treatment. A pilot randomized double-blind placebo-controlled trial was conducted. Twenty six patients with documented severe carpal tunnel syndrome were treated in two parallel groups with a night splint plus topical chamomile oil or placebo. They were instructed to use their prescribed oil for 4 weeks, twice daily. Symptomatic and functional status of the patients and their electrodiagnostic parameters were evaluated when enrolled and after the trial period, as our outcome measures. A significant improvement of symptomatic and functional status of patients in the chamomile oil group was observed (p = 0.019 and 0.016, respectively) compared with those in the placebo group. However, electrodiagnostic parameters showed no significant changes between the two groups. Chamomile oil improved symptomatic and functional status of patients with severe carpal tunnel syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Myorelaxant Effect of Bee Venom Topical Skin Application in Patients with RDC/TMD Ia and RDC/TMD Ib: A Randomized, Double Blinded Study

PubMed Central

Baron, Stefan

2014-01-01

The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with Clinicaltrials.gov NCT02101632. PMID:25050337

Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hemminki, Elina; Hovi, Sirpa-Liisa; Hakama, Matti

2016-10-18

To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. 3 clinical centres in Estonia. Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. The proportion of willingness, eligibility and attendance. Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. ISRCTN35338757. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Characteristics of women with nausea and vomiting of pregnancy who chose to continue compassionate use of placebo after a randomised trial.

PubMed

Matok, I; Umans, J; Feghali, M N; Clark, S; Caritis, S; Miodovnik, M; Hankins, G; Mattison, D R; Nordeng, H; Koren, G

2013-08-01

The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.

Slow-release L-Cysteine (Acetium®) Lozenge Is an Effective New Method in Smoking Cessation. A Randomized, Double-blind, Placebo-controlled Intervention.

PubMed

Syrjänen, Kari; Eronen, Katja; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Bäckström, Anna; Suovaniemi, Osmo

2017-07-01

Because of the major health problems and annual economic burden caused by cigarette smoking, effective new tools for smoking intervention are urgently needed. Our previous randomized controlled trial (RCT) provided promising results on the efficacy of slow-release L-cysteine lozenge in smoking intervention, but the study was not adequately powered. To confirm in an adequately-powered study the results of the previous RCT implicating that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium® lozenge, Biohit Oyj, Helsinki), would assist in smoking cessation by reducing acetaldehyde-enhanced nicotine addiction. On this matter, we undertook a double-blind, randomized, placebo-controlled trial comparing Acetium® lozenge and placebo in smoking intervention. A cohort of 1,998 cigarette smokers were randomly allocated to intervention (n=996) and placebo arms (n=1,002). At baseline, smoking history was recorded by a questionnaire, with nicotine dependence testing according to the Fagerström scale (FTND). The subjects used smoking diary recording the daily numbers of cigarettes, lozenges and subjective sensations of smoking. The data were analysed separately for point prevalence of abstinence (PPA) and prolonged abstinence (PA) endpoints. Altogether, 753 study subjects completed the trial per protocol (PP), 944 with violations (mITT), and the rest (n=301) were lost to follow-up (LTF). During the 6-month intervention, 331 subjects stopped smoking; 181 (18.2%) in the intervention arm and 150 (15.0%) in the placebo arm (OR=1.43; 95%CI=1.09-1.88); p=0.010). In the PP group, 170 (45.3%) quitted smoking in the intervention arm compared to 134 (35.4%) in the placebo arm (OR=1.51, 95%CI=1.12-2.02; p=0.006). In multivariate (Poisson regression) model, decreased level of smoking pleasure (p=0.010) and "smoking sensations changed" were powerful independent predictors of quit events (IRR=12.01; 95%CI=1.5-95.6). Acetium® lozenge, herein confirmed in an adequately powered study to be an effective means to aid smoking quit, represents a major breakthrough in the development of smoking intervention methods, because slow-release L-cysteine is non-toxic, with no side-effects or limitations of use. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effects of Gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation. Methods This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3rd, 4th and 5th menstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks. Discussion This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis. Trial registration Current Controlled Trials: ISRCTN30426947 PMID:22217258

Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.

PubMed

Eziefula, Alice Chijioke; Staedke, Sarah G; Yeung, Shunmay; Webb, Emily; Kamya, Moses; White, Nicholas J; Bousema, Teun; Drakeley, Chris

2013-03-26

For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status. In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine. These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.

Prospective randomized double-blinded trial comparing 2 anti-MRSA agents with supplemental coverage of cefazolin before lower extremity revascularization.

PubMed

Stone, Patrick A; AbuRahma, Ali F; Campbell, James R; Hass, Stephen M; Mousa, Albeir Y; Nanjundappa, Aravinda; Srivastiva, Mohit; Modak, Asmita; Emmett, Mary

2015-09-01

To compare with antibiotics with methicillin-resistant microbial coverage in a prospective fashion. Current antibiotic prophylaxis for vascular procedures includes a first generation cephalosporin. No changes in recommendations have occurred despite changes in reports of incidence of MRSA related surgical site infections. Does supplemental anti-MRSA prophylactic coverage provide a significant reduction in Gram-positive or MRSA infections? Single center prospective double blinded randomized study of patients undergoing lower extremity vascular procedures from 2011 to 2014. One hundred seventy-eight (178) patients were evaluated at 90 days for surgical site infection. Infections were categorized as early infections less than 30 days of the index procedure and late after 90 days. Early vascular surgical site infection occurred in 7(8.24%) of patients in the Vancomycin arm, and 11 (11.83%) in the Daptomycin arm (P = 0.43). Gram-positive related infections and MRSA infections occurred in 1(1.18%)/0(0%) of Vancomycin patients and 9 (9.68%)/1 (1.08%) of Daptomycin patients, respectively (P < 0.02 and P = 1.00). Readmissions related to surgical site infections occurred in 4(4.71%) in the Vancomycin group and 11 (11.8%) in the Daptomycin group (P = 0.11). Patients undergoing operative exploration occurred in 5 (5.88%) in the Vancomycin group and 10 (10.75%) of the Daptomycin group (P = 0.17). Late infections were reported in 3 patients, 2 of which were in the combined Daptomycin group. Median hospital charges related to readmissions due to a surgical site infection was $50,823 in the combination Vancomycin arm and $110,920 in the combination Daptomycin group; however, no statistical significance was appreciated (P = 0.11). Vancomycin supplemental prophylaxis seems to reduce the incidence of Gram-positive infection compared with adding supplemental Daptomycin prophylaxis. The Incidence of MRSA-related surgical site infections is low with the addition of either anti-MRSA agents compared with historical incidence of MRSA-related infection.

Efficacy and safety of a natural mineral water rich in magnesium and sulphate for bowel function: a double-blind, randomized, placebo-controlled study.

PubMed

Bothe, Gordana; Coh, Aljaz; Auinger, Annegret

2017-03-01

The present placebo-controlled, double-blind, randomized trial aimed to investigate whether a natural mineral water rich in magnesium sulphate and sodium sulphate (Donat Mg) may help to improve bowel function. A total of 106 otherwise healthy subjects with functional constipation were randomly assigned to consume 300 or 500 mL of a natural mineral water as compared to placebo water, over a course of 6 weeks. The 300-mL arms were terminated due to the results of a planned interim analysis. Subjects documented the complete spontaneous bowel movements, spontaneous and overall bowel movements/week, stool consistency, gastrointestinal symptoms and general well-being in a diary. Change in the number of complete spontaneous bowel movements was defined as the primary outcome. For the 75 subjects in the 500-mL arms, the change in the number of complete spontaneous bowel movements per week tended to be higher in the active group when compared to placebo after 6 weeks (T2 = 1.8; p value  = 0.036; one-sided). The mean number of spontaneous bowel movements significantly increased over the course of the study, with significant differences between study arms considering the whole study time (F test = 4.743; p time × group  = 0.010, 2-sided). Stool consistency of spontaneous bowel movements (p < 0.001) and the subjectively perceived symptoms concerning constipation (p = 0.005) improved significantly with the natural mineral water as compared to placebo. The daily consumption of a natural mineral water rich in magnesium sulphate and sodium sulphate improved bowel movement frequency and stool consistency in subjects with functional constipation. Moreover, the subjects' health-related quality of life improved. EudraCT No 2012-005130-11.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Chemokine Receptor 5 (CCR5) Antagonist to Decrease the Occurrence of Immune Reconstitution Inflammatory Syndrome in HIV-Infection: The CADIRIS Study.

PubMed

Sierra-Madero, Juan G; Ellenberg, Susan; Rassool, Mohammed S; Tierney, Ann; Belaunzarán-Zamudio, Pablo F; López-Martínez, Alondra; Piñeirúa-Menéndez, Alicia; Montaner, Luis J; Azzoni, Livio; Benítez, César Rivera; Sereti, Irini; Andrade-Villanueva, Jaime; Mosqueda-Gómez, Juan L; Rodriguez, Benigno; Sanne, Ian; Lederman, Michael M

2014-11-01

Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in HIV-infected patients. IRIS is associated with an increased risk of hospitalization and death. We ascertained whether CCR5 blockade using maraviroc reduces the risk of IRIS. The CADIRIS study was a randomized, double-blind, placebo-controlled, clinical trial that accrued subjects from five clinical sites in Mexico and one in South Africa between November 2009 and January 2012, and followed them for one year. The primary outcome was occurrence of IRIS by 24 weeks. HIV-infected adults, naïve to ART, with CD4 cells <100/μL, and HIVRNA >1,000 copies/mL were eligible. We screened 362 subjects; 279 met inclusion criteria, 3 refused participation, and 276 were randomized. Participants received maraviroc 600 mg twice daily or placebo added to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. There were 276 patients randomized (140 received maraviroc and 136 placebo). There was no difference in the time to IRIS events between treatment arms (HR 1·08, 95% CI (0·66, 1·77), log-rank test p =0·743). In total, 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc arm and 31 (23%) in the placebo arm ( p =0·88). Maraviroc had no significant effect on frequency, time or severity of IRIS events after ART initiation. Including a CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in persons with advanced HIV infection. The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA. ClinicalTrials.gov . ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780).

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Chemokine Receptor 5 (CCR5) Antagonist to Decrease the Occurrence of Immune Reconstitution Inflammatory Syndrome in HIV-Infection: The CADIRIS Study

PubMed Central

Sierra-Madero, Juan G.; Ellenberg, Susan; Rassool, Mohammed S.; Tierney, Ann; Belaunzarán-Zamudio, Pablo F.; López-Martínez, Alondra; Piñeirúa-Menéndez, Alicia; Montaner, Luis J.; Azzoni, Livio; Benítez, César Rivera; Sereti, Irini; Andrade-Villanueva, Jaime; Mosqueda-Gómez, Juan L.; Rodriguez, Benigno; Sanne, Ian; Lederman, Michael M.

2015-01-01

Background Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in HIV-infected patients. IRIS is associated with an increased risk of hospitalization and death. We ascertained whether CCR5 blockade using maraviroc reduces the risk of IRIS. Methods The CADIRIS study was a randomized, double-blind, placebo-controlled, clinical trial that accrued subjects from five clinical sites in Mexico and one in South Africa between November 2009 and January 2012, and followed them for one year. The primary outcome was occurrence of IRIS by 24 weeks. HIV-infected adults, naïve to ART, with CD4 cells <100/μL, and HIVRNA >1,000 copies/mL were eligible. We screened 362 subjects; 279 met inclusion criteria, 3 refused participation, and 276 were randomized. Participants received maraviroc 600 mg twice daily or placebo added to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Findings There were 276 patients randomized (140 received maraviroc and 136 placebo). There was no difference in the time to IRIS events between treatment arms (HR 1·08, 95% CI (0·66, 1·77), log-rank test p=0·743). In total, 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc arm and 31 (23%) in the placebo arm (p=0·88). Interpretation Maraviroc had no significant effect on frequency, time or severity of IRIS events after ART initiation. Including a CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in persons with advanced HIV infection. Funding The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA. Trial Registration ClinicalTrials.gov. ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780) PMID:26366430

A low-fat yoghurt supplemented with a rooster comb extract on muscle joint function in adults with mild knee pain: a randomized, double blind, parallel, placebo-controlled, clinical trial of efficacy.

PubMed

Solà, Rosa; Valls, Rosa-Maria; Martorell, Isabel; Giralt, Montserrat; Pedret, Anna; Taltavull, Núria; Romeu, Marta; Rodríguez, Àurea; Moriña, David; Lopez de Frutos, Victor; Montero, Manuel; Casajuana, Maria-Carmen; Pérez, Laura; Faba, Jenny; Bernal, Gloria; Astilleros, Anna; González, Roser; Puiggrós, Francesc; Arola, Lluís; Chetrit, Carlos; Martinez-Puig, Daniel

2015-11-01

Preliminary results suggested that oral-administration of rooster comb extract (RCE) rich in hyaluronic acid (HA) was associated with improved muscle strength. Following these promising results, the objective of the present study was to evaluate the effect of low-fat yoghurt supplemented with RCE rich in HA on muscle function in adults with mild knee pain; a symptom of early osteoarthritis. Participants (n = 40) received low-fat yoghurt (125 mL d(-1)) supplemented with 80 mg d(-1) of RCE and the placebo group (n = 40) consumed the same yoghurt without the RCE, in a randomized, controlled, double-blind, parallel trial over 12 weeks. Using an isokinetic dynamometer (Biodex System 4), RCE consumption, compared to control, increased the affected knee peak torque, total work and mean power at 180° s(-1), at least 11% in men (p < 0.05) with no differences in women. No dietary differences were noted. These results suggest that long-term consumption of low-fat yoghurt supplemented with RCE could be a dietary tool to improve muscle strength in men, associated with possible clinical significance. However, further studies are needed to elucidate reasons for these sex difference responses observed, and may provide further insight into muscle function.

Comparative efficacy and safety of two 0.025% tretinoin gels: results from a multicenter double-blind, parallel study.

PubMed

Lucky, A W; Cullen, S I; Jarratt, M T; Quigley, J W

1998-04-01

The addition of polyolprepolymer-2 in tretinoin formulations may reduce tretinoin-induced cutaneous irritation. This study compared the efficacy and safety of a new 0.025% tretinoin gel containing polyolprepolymer-2, its vehicle, and a commercially-available 0.025% tretinoin gel in patients with mild to moderate acne vulgaris. In this 12-week multicenter, double-blind, parallel group study, efficacy was evaluated by objective lesion counts and the investigators' global evaluations. Subjective assessment of cutaneous irritation by the investigators and patients evaluated safety. The efficacy of the two active treatments in this 215 patient study was comparable, and both treatments were statistically significantly more effective than vehicle. When compared with the commercially-available tretinoin gel, the formulation containing polyolprepolymer-2 demonstrated statistically significantly less peeling at days 28, 56, and 84, statistically significantly less dryness by day 84, and statistically significantly less itching at day 14. Irritation scores for the formulation containing polyolprepolymer-2 were numerically lower but not statistically different from those of the commercially-available gel for erythema and burning. The number of cutaneous and noncutaneous adverse events were similar for both active medications. The two 0.025% gels studied demonstrated comparable efficacy. However, the gel formulation containing polyolprepolymer-2 caused significantly less peeling and drying than the commercially-available formulation by day 84 of the study.

Treatment assignment guesses by study participants in a double-blind dose escalation clinical trial of saw palmetto.

PubMed

Lee, Jeannette Y; Moore, Page; Kusek, John; Barry, Michael

2014-01-01

This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Participants randomized to receive saw palmetto were instructed to take one 320 mg gelcap daily for the first 24 weeks, two 320 mg gelcaps daily for the second 24 weeks, and three 320 mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. The study was conducted at 11 clinical centers in North America. Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N=151) or placebo (N=155). Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p=0.823) or placebo (p=0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto.

Intraoperative Nerve Blocks Fail to Improve Quality of Recovery after Tissue Expander Breast Reconstruction: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.

PubMed

Lanier, Steven T; Lewis, Kevin C; Kendall, Mark C; Vieira, Brittany L; De Oliveira, Gildasio; Nader, Anthony; Kim, John Y S; Alghoul, Mohammed

2018-03-01

The authors' study represents the first level I evidence to assess whether intraoperative nerve blocks improve the quality of recovery from immediate tissue expander/implant breast reconstruction. A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in which patients undergoing immediate tissue expander/implant breast reconstruction were randomized to either (1) intraoperative intercostal and pectoral nerve blocks with 0.25% bupivacaine with 1:200,000 epinephrine and 4 mg of dexamethasone or (2) sham nerve blocks with normal saline. The 40-item Quality of Recovery score, pain score, and opioid use in the postoperative period were compared statistically between groups. Power analysis ensured 80 percent power to detect a 10-point (clinically significant) difference in the 40-item Quality of Recovery score. Forty-seven patients were enrolled. Age, body mass index, laterality, mastectomy type, and lymph node dissection were similar between groups. There were no statistical differences in quality of recovery, pain burden as measured by visual analogue scale, opioid consumption, antiemetic use, or length of hospital stay between groups at 24 hours after surgery. Mean global 40-item Quality of Recovery scores were 169 (range, 155 to 182) for the treatment arm and 165 (range, 143 to 179) for the placebo arm (p = 0.36), indicating a high quality of recovery in both groups. Although intraoperative nerve blocks can be a safe adjunct to a comprehensive postsurgical recovery regimen, the authors' results indicate no effect on overall quality of recovery from tissue expander/implant breast reconstruction. Therapeutic, I.

The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.

PubMed

Dummer, Reinhard; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Chang, Anne Lynn S; Cornélis, Frank; Kudchadkar, Ragini; Trefzer, Uwe; Lear, John T; Sellami, Dalila; Migden, Michael R

2016-07-01

The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

PubMed

Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

2009-05-01

Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Catalog of Observed Tangents to the Spiral Arms in the Milky Way Galaxy

NASA Astrophysics Data System (ADS)

Vallée, Jacques P.

2014-11-01

From the Sun's location in the Galactic disk, one can use different arm tracers (CO, H I, thermal or ionized or relativistic electrons, masers, cold and hot dust, etc.) to locate a tangent to each spiral arm in the disk of the Milky Way. We present a master catalog of the astronomically observed tangents to the Galaxy's spiral arms, using different arm tracers from the literature. Some arm tracers can have slightly divergent results from several papers, so a mean value is taken—see the Appendix for CO, H II, and masers. The catalog of means currently consists of 63 mean tracer entries, spread over many arms (Carina, Crux-Centaurus, Norma, Perseus origin, near 3 kpc, Scutum, Sagittarius), stemming from 107 original arm tracer entries. Additionally, we updated and revised a previous statistical analysis of the angular offset and linear separation from the mid-arm for each different mean arm tracer. Given enough arm tracers, and summing and averaging over all four spiral arms, one could determine if arm tracers have separate and parallel lanes in the Milky Way. This statistical analysis allows a cross-cut of a Galactic spiral arm to be made, confirming a recent discovery of a linear separation between arm tracers. Here, from the mid-arm's CO to the inner edge's hot dust, the arm halfwidth is about 340 pc doubling would yield a full arm width of 680 pc. We briefly compare these observations with the predictions of many spiral arm theories, notably the density wave theory.

CATALOG OF OBSERVED TANGENTS TO THE SPIRAL ARMS IN THE MILKY WAY GALAXY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vallée, Jacques P., E-mail: jacques.vallee@nrc-cnrc.gc.ca

2014-11-01

From the Sun's location in the Galactic disk, one can use different arm tracers (CO, H I, thermal or ionized or relativistic electrons, masers, cold and hot dust, etc.) to locate a tangent to each spiral arm in the disk of the Milky Way. We present a master catalog of the astronomically observed tangents to the Galaxy's spiral arms, using different arm tracers from the literature. Some arm tracers can have slightly divergent results from several papers, so a mean value is taken—see the Appendix for CO, H II, and masers. The catalog of means currently consists of 63 meanmore » tracer entries, spread over many arms (Carina, Crux-Centaurus, Norma, Perseus origin, near 3 kpc, Scutum, Sagittarius), stemming from 107 original arm tracer entries. Additionally, we updated and revised a previous statistical analysis of the angular offset and linear separation from the mid-arm for each different mean arm tracer. Given enough arm tracers, and summing and averaging over all four spiral arms, one could determine if arm tracers have separate and parallel lanes in the Milky Way. This statistical analysis allows a cross-cut of a Galactic spiral arm to be made, confirming a recent discovery of a linear separation between arm tracers. Here, from the mid-arm's CO to the inner edge's hot dust, the arm halfwidth is about 340 pc; doubling would yield a full arm width of 680 pc. We briefly compare these observations with the predictions of many spiral arm theories, notably the density wave theory.« less

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

A phase II trial of tideglusib in Alzheimer's disease.

PubMed

Lovestone, Simon; Boada, Mercè; Dubois, Bruno; Hüll, Michael; Rinne, Juha O; Huppertz, Hans-Jürgen; Calero, Miguel; Andrés, María V; Gómez-Carrillo, Belén; León, Teresa; del Ser, Teodoro

2015-01-01

The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients.

Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with uterine fibroids: a protocol for a randomised controlled trial.

PubMed

Jung, Jeeyoun; Lee, Ju Ah; Ko, Mi Mi; You, Sooseong; Lee, Eunhee; Choi, Jiae; Kang, Byoung-Kab; Lee, Myeong Soo

2016-11-24

Gyejibongneyong-hwan (GBH), or the Guizhi Fuling Formula in Chinese, is widely used to treat uterine fibroids in East Asian countries including Korea, China and Japan. This study will assess the efficacy and safety of the GBH formula for the treatment of dysmenorrhoea. This study will be a randomised double-blind controlled trial with two parallel arms: the GBH group and the placebo group. This trial will recruit 38 women between 18 and 45 years of age with secondary dysmenorrhoea with uterine fibroids. The investigational drugs, either GBH or placebo, will be administered to the participants three times per day for two menstrual periods (8 weeks). The participants will be followed up for three menstrual cycles after administration of the drugs. The primary outcome will be the Numeric Rating Scale score of average menstrual pain. All analyses will be performed with SAS (V.9.1.3; SAS Institute, Cary, North Carolina, USA) by a statistician blinded to the allocation of the groups. Statistical analysis will be undertaken on the intent-to-treat (ITT) basis with a 95% CI using the last observation carried forward for missing values. The ITT analysis will include all randomised patients. This research protocol has been reviewed and approved by the institutional review boards of the trial centre (number WSOH IRB 1606-03). Written informed consent will be obtained from all study participants prior to enrolment in the study. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print. KCT0001967. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Efficient two-stage dual-beam noncollinear optical parametric amplifier

NASA Astrophysics Data System (ADS)

Cheng, Yu-Hsiang; Gao, Frank Y.; Poulin, Peter R.; Nelson, Keith A.

2018-06-01

We have constructed a noncollinear optical parametric amplifier with two signal beams amplified in the same nonlinear crystal. This dual-beam design is more energy-efficient than operating two amplifiers in parallel. The cross-talk between two beams has been characterized and discussed. We have also added a second amplification stage to enhance the output of one of the arms, which is then frequency-doubled for ultraviolet generation. This single device provides two tunable sources for ultrafast spectroscopy in the ultraviolet and visible region.

Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study

PubMed Central

2014-01-01

Background Split-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. However, carry-over effects may induce bias in split- mouth RCTs. We aimed to assess whether intervention effect estimates differ between split- mouth and parallel-arm RCTs investigating the same questions. Methods We performed a meta-epidemiological study. We systematically reviewed meta- analyses including both split-mouth and parallel-arm RCTs with binary or continuous outcomes published up to February 2013. Two independent authors selected studies and extracted data. We used a two-step approach to quantify the differences between split-mouth and parallel-arm RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for dichotomous data and differences in standardized mean differences (∆SMD) for continuous data; second, we pooled RORs or ∆SMDs across meta-analyses by random-effects meta-analysis models. Results We selected 18 systematic reviews, for 15 meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and 19 meta-analyses with continuous outcomes (28 split-mouth and 28 parallel-arm RCTs). Effect estimates did not differ between split-mouth and parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52–1.80; mean ∆SMD, 0.08, -0.14–0.30). Conclusions Our study did not provide sufficient evidence for a difference in intervention effect estimates derived from split-mouth and parallel-arm RCTs. Authors should consider including split-mouth RCTs in their meta-analyses with suitable and appropriate analysis. PMID:24886043

Magnetic resonance therapy for knee osteoarthritis: a randomized, double blind placebo controlled trial.

PubMed

Gökşen, Nurgül; Çaliş, Mustafa; Doğan, Serap; Çaliş, Havva T; Özgöçmen, Salih

2016-08-01

Therapeutic nuclear magnetic resonance therapy (MRT) works based on the electromagnetic fields. To investigate efficacy of MRT in knee osteoarthritis (OA). Prospective, randomized, double-blind, placebo controlled trial. Outpatient clinic, university hospital. Patients who had mild to moderate knee OA at a single knee joint and between 30-75-years-old were randomized by blinded chip cards (1:1). The treatment group received ten sessions of one hour daily MRT, controls received placebo MRT. All patients underwent clinical examination at baseline, after 2 weeks, and 12 weeks. Imaging included blindly assessed ultrasonography and magnetic resonance (MR) of the knee. Ninety-seven patients completed the study. Both groups improved significantly but the average change from baseline in outcome parameters was similar in MRT group (on VAS-pain,-2.6; WOMAC-pain, -2.09; WOMAC-stiffness, -1.81; WOMAC-physical, -1.96) compared to placebo after two weeks (VAS-pain,-1.6; WOMAC-pain, -1.91; WOMAC-stiffness, -1.27; WOMAC-physical, -1.54). Also changes were quite similar at the 12th week after the treatment. SF-36 components at 12th week improved but changes were not significant. Imaging arm also failed to show significant differences between groups in terms of cartilage thickness on US and MR scores. No adverse events were recorded. MRT is safe, but not superior to placebo in terms of improvement in clinical or imaging parameters after a 10-day course of treatment in mild to moderate knee OA. The present study does not promote use of a 10-day course of MRT in mild to moderate knee OA.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

PubMed Central

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-01-01

Objective To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Methods Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity. Results AUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Conclusions Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. Trial registration number EudraCT number 2012-000785-37; Results. PMID:27466231

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

PubMed

Evans, Malkanthi; Antony, Joseph; Guthrie, Najla; Landes, Bernie; Aruoma, Okezie I

2018-01-01

The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A Double-blind, Randomized Controlled Trial.

PubMed

Lemoel, Fabien; Contenti, Julie; Giolito, Didier; Boiffier, Mathieu; Rapp, Jocelyn; Istria, Jacques; Fournier, Marc; Ageron, François-Xavier; Levraut, Jacques

2017-12-01

The goal of our study was to compare the frequency and severity of recovery reactions between ketamine and ketamine-propofol 1:1 admixture ("ketofol"). We performed a multicentric, randomized, double-blind trial in which adult patients received emergency procedural sedations with ketamine or ketofol. Our primary outcome was the proportion of unpleasant recovery reactions. Other outcomes were frequency of interventions required by these recovery reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction of patients as well as providers. A total of 152 patients completed the study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic interventions required by these reactions. There was no serious adverse event in both groups. Rates in hemodynamic or respiratory events as well as satisfaction scores were similar. Significantly fewer patients experienced emesis with ketofol, with a threefold reduction in incidence compared with ketamine. We found a significant reduction in recovery reactions and emesis frequencies among adult patients receiving emergency procedural sedations with ketofol, compared with ketamine. © 2017 by the Society for Academic Emergency Medicine.

HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery.

PubMed

Jahr, Jonathan S; Mackenzie, Colin; Pearce, L Bruce; Pitman, Arkadiy; Greenburg, A Gerson

2008-06-01

The ability of hemoglobin based oxygen carrier-201 (HBOC-201) to safely reduce and/or eliminate perioperative transfusion was studied in orthopedic surgery patients. A randomized, single-blind, packed red blood cell (PRBC)-controlled, parallel-group multicenter study was conducted. Six hundred eighty-eight patients were randomized to treatment with HBOC-201 (H, n = 350) or PRBC (R, n = 338) at the first transfusion decision. Primary endpoints were transfusion avoidance and blinded assessment [Mann-Whitney estimator (MW)] of safety noninferiority. Groups were compared directly and by paired/matching group analyses predicated on a prospectively defined dichotomy [treatment success (HH) vs. failure (HR)] in the H arm and an equivalently defined dichotomy [3 (R3+) units PRBC] in the R arm, based on need (moderate vs. high) for additional oxygen carrying capacity. A total of 59.4% of patients in the H arm avoided PRBC transfusion. Adverse events (8.47 vs. 5.88), and serious adverse events (SAEs) (0.35 vs. 0.25) per patient were higher in the H versus R arms (p < 0.001 and p < 0.01) with MW = 0.561 (95 CI 0.528-0.594). HH versus R3- had identical (0.14) serious adverse events/patient and a MW = 0.519 (95% confidence limit 0.481-0.558), whereas the incidence was higher (0.63 vs. 0.47) for HR versus R3+ with a MW = 0.605 (95% confidence limit 0.550-0.662). Age (>80 years), volume overload and undertreatment contributed to this imbalance. HBOC-201 eliminated transfusion in the majority of subjects. The between arms (H vs. R) safety analysis was unfavorable and likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone. However, patients <80 years old with moderate clinical need may safely avoid transfusion when treated with up to 10 units of HBOC-201.

A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia.

PubMed

Kollef, Marin H; Chastre, Jean; Clavel, Marc; Restrepo, Marcos I; Michiels, Bart; Kaniga, Koné; Cirillo, Iolanda; Kimko, Holly; Redman, Rebecca

2012-11-13

The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. ClinicalTrials.gov: NCT00589693.

A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia

PubMed Central

2012-01-01

Introduction The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. Methods This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). Results The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). Conclusions Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. Trial Registration ClinicalTrials.gov: NCT00589693 PMID:23148736

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

PubMed

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-06-01

To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren's contracture.

PubMed

Räisänen, Mikko P; Karjalainen, Teemu; Göransson, Harry; Reito, Aleksi; Kautiainen, Hannu; Malmivaara, Antti; Leppänen, Olli V

2018-03-28

Dupuytren's contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques. We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I-III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed. The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals. NCT03192020; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis

PubMed Central

Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

2011-01-01

OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975

Idelalisib or Placebo in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL - Interim Results of a Phase 3 Randomized, Double-blind Placebo-Controlled Trial

PubMed Central

Zelenetz, Andrew D.; Barrientos, Jacqueline C.; Brown, Jennifer R.; Coiffier, Bertrand; Delgado, Julio; Egyed, Miklós; Ghia, Paolo; Illés, Árpád; Jurczak, Wojciech; Marlton, Paula; Montillo, Marco; Morschhauser, Franck; Pristupa, Alexander S.; Robak, Tadeusz; Sharman, Jeff P.; Simpson, David; Smolej, Lukáš; Tausch, Eugen; Adewoye, Adeboye H.; Dreiling, Lyndah K.; Kim, Yeonhee; Stilgenbauer, Stephan; Hillmen, Peter

2017-01-01

Summary Background Bendamustine and rituximab (BR) has been a standard of care for the management of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). We evaluated the efficacy and safety of adding idelalisib, a first-in-class targeted PI3Kδ inhibitor, to BR in patients with R/R CLL Methods This trial was a global, multicenter, double-blind, placebo -controlled trial in adult patients (≥18 years) with R/R CLL requiring treatment for their disease. Patients had to have measurable lymphadenopathy (≥1 nodal lesion ≥2.0 cm in the longest diameter and ≥1.0 cm in the longest perpendicular diameter) by computer tomography or magnetic resonance imaging, disease progression within <36 months since last prior therapy, a Karnofsky Performance Status score ≥60 and adequate bone marrow, liver and kidney function. Key exclusion criteria included histological transformation to an aggressive lymphoma (eg, Richter transformation) or disease refractory to bendamustine. Patients were randomised 1:1 using a central interactive web response system that assigned a unique treatment code for each patient, to receive intravenous BR infusions for a maximum of 6 cycles in addition to blinded study drug matching the assigned treatment of either twice-daily oral idelalisib 150 mg or placebo administered continuously until disease progression or intolerable study drug-related toxicity. Randomisation was stratified based on high-risk features (IGHV, del(17p)/TP53 mutation) and refractory vs relapsed disease. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee in the intent-to-treat population. Overall survival was a key secondary endpoint. Crossover was not permitted to the idelalisib arm at progression. The trial is ongoing (ClinicalTrials.gov # NCT01569295). Findings Between 26 June 2012 and 21 August 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomised to the idelalisib and 209 to the placebo arm. After the prespecified interim analysis, the Independent Data Monitoring Committee (IDMC) recommended discontinuation and unblinding of the trial due to efficacy. Updated data are presented in this manuscript with a cutoff date of 07 October 2015. Median (95% CI) PFS was 20·8 (16·6, 26·4) and 11·1 (8·9, 11·1) months in the idelalisib and placebo arms, respectively (hazard ratio [HR], 0·33; 95% CI, 0·25, 0·44; P<0·0001) at a median (Q1, Q3) follow-up of 14 (7, 18) months. The most frequent grade 3 or greater AEs were neutropenia (124/207 [60%]) and febrile neutropenia (48/207 [23%]) in the idelalisib arm and neutropenia (99/209 [47%]) and thrombocytopenia (27/209 [13%]) in the placebo arm. Serious AEs included febrile neutropenia, pneumonia and pyrexia and were common in both treatment arms. An increased risk of infection was observed in the idelalisib vs placebo arm. Interpretation Idelalisib plus BR is superior to BR alone, improving PFS and OS. This regimen represents an important new treatment option for patients with R/R CLL. PMID:28139405

Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial.

PubMed

Agar, Meera R; Lawlor, Peter G; Quinn, Stephen; Draper, Brian; Caplan, Gideon A; Rowett, Debra; Sanderson, Christine; Hardy, Janet; Le, Brian; Eckermann, Simon; McCaffrey, Nicola; Devilee, Linda; Fazekas, Belinda; Hill, Mark; Currow, David C

2017-01-01

Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14). In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added. anzctr.org.au Identifier: ACTRN12607000562471.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial

PubMed Central

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-01-01

Introduction Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. Methods and analysis This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics and dissemination Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. Trial registration number NCT02198924. PMID:27609846

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

PubMed

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-09-08

Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. NCT02198924. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

PubMed

Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

2015-11-01

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative pain and was well tolerated in a Taiwanese population. ClinicalTrials.gov identifier: NCT01813890.

Conceptual design and kinematic analysis of a novel parallel robot for high-speed pick-and-place operations

NASA Astrophysics Data System (ADS)

Meng, Qizhi; Xie, Fugui; Liu, Xin-Jun

2018-06-01

This paper deals with the conceptual design, kinematic analysis and workspace identification of a novel four degrees-of-freedom (DOFs) high-speed spatial parallel robot for pick-and-place operations. The proposed spatial parallel robot consists of a base, four arms and a 1½ mobile platform. The mobile platform is a major innovation that avoids output singularity and offers the advantages of both single and double platforms. To investigate the characteristics of the robot's DOFs, a line graph method based on Grassmann line geometry is adopted in mobility analysis. In addition, the inverse kinematics is derived, and the constraint conditions to identify the correct solution are also provided. On the basis of the proposed concept, the workspace of the robot is identified using a set of presupposed parameters by taking input and output transmission index as the performance evaluation criteria.

A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study): Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness

PubMed Central

Kim, Jinyoung; Cho, Jae-Heung

2017-01-01

This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD), in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere's disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale) and frequency of dizziness, balance function (Berg Balance Scale), fatigue (Fatigue Severity Scale) and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire) levels, and depression (Korean version of Beck's Depression Inventory) and anxiety (State-Trait Anxiety Inventory) levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions' questionnaire) and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided). This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017. PMID:29387128

Naked-eye fingerprinting of single nucleotide polymorphisms on psoriasis patients

NASA Astrophysics Data System (ADS)

Valentini, Paola; Marsella, Alessandra; Tarantino, Paolo; Mauro, Salvatore; Baglietto, Silvia; Congedo, Maurizio; Paolo Pompa, Pier

2016-05-01

We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics.We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02200f

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

PubMed

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

2004-01-01

The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells. Copyright 2004 S. Karger AG, Basel

Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials.

PubMed

Tinahones, Francisco J; Gallwitz, Baptist; Nordaby, Matias; Götz, Sophia; Maldonado-Lutomirsky, Mario; Woerle, Hans J; Broedl, Uli C

2017-02-01

To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated. © 2016 John Wiley & Sons Ltd.

Comparison of anti-plaque efficacy between a low and high cost dentifrice: A short term randomized double-blind trial

PubMed Central

Ganavadiya, Rahul; Shekar, B. R. Chandra; Goel, Pankaj; Hongal, Sudheer G.; Jain, Manish; Gupta, Ruchika

2014-01-01

Objective: The aim of this study was to compare the anti-plaque efficacy of a low and high cost commercially available tooth paste among 13-20 years old adolescents in a Residential Home, Bhopal, India. Materials and Methods: The study was randomized double-blind parallel clinical trial conducted in a Residential Home, Bhopal, India. A total of 65 patients with established dental plaque and gingivitis were randomly assigned to either low cost or high cost dentifrice group for 4 weeks. The plaque and gingival scores at baseline and post-intervention were assessed and compared. Statistical analysis was performed using paired t-test and the independent sample t-test. The statistical significance was fixed at 0.05. Results: Results indicated a significant reduction in plaque and gingival scores in both groups post-intervention compared with the baseline. Difference between the groups was not significant. No adverse events were reported and both the dentifrices were well-tolerated. Conclusion: Low cost dentifrice is equally effective to the high cost dentifrice in reducing plaque and gingival inflammation. PMID:25202220

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Dietary Wolfberry Extract Modifies Oxidative Stress by Controlling the Expression of Inflammatory mRNAs in Overweight and Hypercholesterolemic Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Lee, You Jin; Ahn, Youngsook; Kwon, Oran; Lee, Mee Youn; Lee, Choong Hwan; Lee, Sungyoung; Park, Taesung; Kwon, Sung Won; Kim, Ji Yeon

2017-01-18

In the present study, we evaluated the antioxidative and anti-inflammatory effects of an aqueous extract of wolfberry fruit (WBE) in mild hypercholesterolemic and overweight subjects. This study was a double-blind randomized trial of two parallel groups of free-living subjects (n = 53). The participants consumed the contents of an 80 mL pouch containing 13.5 g WBE or placebo after one meal per day over an 8-week period. Following 8 weeks of WBE supplementation, we observed a slight but significant decrease in erythrocyte superoxide dismutase activity and an increase in catalase activity. Furthermore, to assess endogenous DNA damage in lymphocytes, the alkaline comet assay was performed, showing that the percentage of DNA in the tail was significantly decreased by 8-week WBE intake. Additionally, the proportion of significantly deregulated mRNAs related to oxidative or inflammatory stress was considerably higher in the WBE intake group. The present data indicate that WBE intake has antioxidative and anti-inflammatory effects in overweight and hypercholesterolemic subjects by modulating mRNA expression.

Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase 3 Double-Blind, Randomized Trial from the North Central Cancer Treatment Group N06C4

PubMed Central

Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

2010-01-01

Purpose A 2-arm, double-blinded, randomized trial to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma receiving external beam radiotherapy to breast or chest wall were randomly assigned to daily apply 0.1% MMF or placebo cream. Primary study end point was provider-assessed maximum grade of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation dermatitis. Secondary end points included provider-assessed CTCAE grade 3 or greater radiation dermatitis and adverse-event monitoring. Patient-reported outcome (PRO) measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and quality of life self-assessment. Assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results In total, 176 patients were enrolled from September 21, 2007 through December 7, 2007. The provider-assessed primary end point showed no difference in mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs 1.3 for placebo; P=.18). CTCAE toxicity was greater in placebo group (P=.04), primarily from pruritus. For PRO measures, the maximum Skindex-16 score for MMF group showed less itching (P=.008), less irritation (P=.01), less symptom persistence or recurrence (P=.02), and less annoyance with skin problems (P=.04); the group's maximum Skin Toxicity Assessment Tool score showed less burning sensation (P=.02) and less itching (P=.002). Conclusion Patients receiving daily MMF during radiotherapy may experience reduced acute skin toxicity in comparison to placebo. PMID:20800381

A comparison of the efficacy and safety of intravenous followed by oral delafloxacin with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections: a phase 3, multinational, double-blind, randomized study.

PubMed

O'Riordan, William; McManus, Alison; Teras, Juri; Poromanski, Ivan; Cruz-Saldariagga, Maria; Quintas, Megan; Lawrence, Laura; Liang, ShuJui; Cammarata, Sue

2018-03-06

Delafloxacin is an IV/oral anionic fluoroquinolone with activity against Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms. It is approved in the US for acute bacterial skin and skin structure infections caused by designated susceptible Gram-positive and Gram-negative organisms, and is in development for the treatment of community-acquired bacterial pneumonia. A multicenter, randomized, double-blind trial of 850 adults with ABSSSI compared delafloxacin 300 mg IV Q12h for 3 days with a switch to 450 mg oral delafloxacin, to vancomycin 15 mg/kg IV with aztreonam for 5-14 days. The primary endpoint was objective response (OR) at 48-72 hours. Investigator‑assessed response based on resolution of signs and symptoms at Follow up (FU [Day 14±1]), and Late Follow up (LFU [Day 21- 28]) were secondary endpoints. In the intent-to-treat analysis set, the OR was 83.7% in the delafloxacin arm and 80.6% in the comparator arm. Investigator-assessed success was similar at FU (87.2% versus 84.4%) and LFU (83.5% versus 82.2%). Delafloxacin was comparable to vancomycin + aztreonam in eradication of MRSA at 96.0% vs 97.0% at FU. Frequency of treatment-emergent adverse events (TEAEs) between the groups was similar. TEAEs leading to study drug discontinuation was higher in the vancomycin + aztreonam group (1.2% vs 2.4%). In ABSSSI patients, IV/oral delafloxacin monotherapy was noninferior to IV vancomycin + aztreonam combination therapy for both the OR and the investigator-assessed response at FU and LFU. Delafloxacin was well tolerated as monotherapy in treatment of ABSSSI.

Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial.

PubMed

Villar-García, Judit; Hernández, Juan J; Güerri-Fernández, Robert; González, Alicia; Lerma, Elisabet; Guelar, Ana; Saenz, David; Sorlí, Lluisa; Montero, Milagro; Horcajada, Juan P; Knobel Freud, Hernando

2015-03-01

Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of <20 copies per milliliter for at least 2 years. Patients were randomized to oral supplementation with probiotics or placebo during 12 weeks. Markers of microbial translocation (lipopolysaccharide-binding protein [LBP] and soluble CD14), inflammation (interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, high-sensitivity C-reactive protein), and immunological and clinical data were determined before and after the intervention and 3 months after treatment discontinuation. Quantitative variables were compared using the Mann-Whitney U test, and categorical variables were compared using the Fisher exact test. After 12 weeks of treatment, differences between the probiotic arm and the placebo arm were observed in LBP values (-0.30 vs +0.70 pg/mL) and IL-6 (-0.60 vs +0.78 pg/mL). These differences were also noted at 3 months after treatment withdrawal. Qualitative analysis was performed, defining a variable as "decreased" or "increased" from baseline LBP. A significant decrease of LBP at 12 weeks of treatment was observed (57.9% patients in the probiotic group vs 6.2% in the placebo group, P = 0.002). Treatment with S. boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1-infected patients with long-term virologic suppression.

Prophylactic tetracycline does not diminish the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash: results from the North Central Cancer Treatment Group (Supplementary N03CB).

PubMed

Jatoi, Aminah; Dakhil, Shaker R; Sloan, Jeff A; Kugler, John W; Rowland, Kendrith M; Schaefer, Paul L; Novotny, Paul J; Wender, Donald B; Gross, Howard M; Loprinzi, Charles L

2011-10-01

Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings. Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided). Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated. Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors.

Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial.

PubMed

Bonelli, Luigina; Puntoni, Matteo; Gatteschi, Beatrice; Massa, Paolo; Missale, Guido; Munizzi, Francesco; Turbino, Laura; Villanacci, Vincenzo; De Censi, Andrea; Bruzzi, Paolo

2013-06-01

Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention. To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 μg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group). After a median follow-up of 4 years (range 1-15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3% in the intervention and 64.5% in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39% reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95% CI 0.41-0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95% CI 0.37-0.99) and advanced adenomas (adjusted HR = 0.50; 95% CI 0.24-1.01). Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver.

PubMed

Biffi, Roberto; Fattori, Luca; Bertani, Emilio; Radice, Davide; Rotmensz, Nicole; Misitano, Pasquale; Cenciarelli, Sabine; Chiappa, Antonio; Tadini, Liliana; Mancini, Marina; Pesenti, Giovanni; Andreoni, Bruno; Nespoli, Angelo

2012-05-23

An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery. We decided to test this finding in a randomized, double-blind trial. Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were randomly assigned to have the surgical incision dressed with Aquacel Ag Hydrofiber dressing or a common dressing. To blind the patient and the nursing and medical staff to the nature of the dressing used, scrub nurses covered Aquacel Ag Hydrofiber with a common wound dressing in the experimental arm, whereas a double common dressing was applied to patients of control group. The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery. A total of 112 patients (58 in the experimental arm and 54 in the control group) qualified for primary end-point analysis. The characteristics of the patient population and their surgical procedures were similar. The overall rate of surgical-site infection was lower in the experimental group (11.1% center 1, 17.5% center 2; overall 15.5%) than in controls (14.3% center 1, 24.2% center 2, overall 20.4%), but the observed difference was not statistically significant (P = 0.451), even with respect to surgical-site infection grade 1 (superficial) versus grades 2 and 3, or grade 1 and 2 versus grade 3. This randomized trial did not confirm a statistically significant superiority of Aquacel Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery. Clinicaltrials.gov: NCT00981110.

Preoperative flap-site injection with ropivacaine and epinephrine in BABA robotic and endoscopic thyroidectomy safely reduces postoperative pain: A CONSORT-compliant double-blinded randomized controlled study (PAIN-BREKOR trial).

PubMed

Lee, Joon-Hyop; Suh, Yong Joon; Song, Ra-Yeong; Yi, Jin Wook; Yu, Hyeong Won; Kwon, Hyungju; Choi, June Young; Lee, Kyu Eun

2017-06-01

Clinical trials on bilateral axillo-breast approach (BABA) thyroidectomy show that levobupivacaine and ropivacaine significantly reduce postoperative pain, but they focused on BABA robotic thyroidectomy only and did not identify specific sites of significant pain relief. Our objective was to assess the pain reduction at various sites and safety of ropivacaine-epinephrine flap injection in BABA thyroidectomy. This prospective double-blinded randomized controlled trial was conducted in compliance with the revised CONSORT statement (ClinicalTrials.gov registration no. NCT02112370). Patients were randomized into the ropivacaine-epinephrine arm or control (normal saline) arm. From January 2014 to May 2016, 148 patients participated. The primary endpoint was site-specific pain, as measured by numeric rating scale 12 hours after surgery. The ropivacaine-epinephrine group exhibited significantly less swallowing difficulty (P = .008), anterior neck pain (P = .016), and right (P = .019) and left (P = .035) chest pain. Secondary endpoints were systolic (P = .402), diastolic (P = .827) blood pressure, and pulse rate (P = .397) after injection before incision and during surgery. The vital signs of the groups just after injection did not differ. During surgery, the ropivacaine-epinephrine patients had higher pulse rates (99 ± 13.3 vs 88 ± 16.1, P < .001) but within normal range. There were no adverse events such as postoperative nausea and vomiting. There was no significant difference in pain scores in either patient group between patients who underwent robotic or endoscopic interventions. BABA flap-site injection with ropivacaine and epinephrine mix before incision effectively and safely reduced postoperative pain. Future studies should focus on tailoring ropivacaine and epinephrine dosage for individuals.

The effect of combined somatosensory stimulation and task-specific training on upper limb function in chronic stroke: a double-blind randomized controlled trial.

PubMed

Fleming, Melanie K; Sorinola, Isaac O; Roberts-Lewis, Sarah F; Wolfe, Charles D; Wellwood, Ian; Newham, Di J

2015-02-01

Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus-response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear. © The Author(s) 2014.

Effects of repetitive peripheral magnetic stimulation on upper-limb spasticity and impairment in patients with spastic hemiparesis: a randomized, double-blind, sham-controlled study.

PubMed

Krewer, Carmen; Hartl, Sandra; Müller, Friedemann; Koenig, Eberhard

2014-06-01

To investigate short-term and long-term effects of repetitive peripheral magnetic stimulation (rpMS) on spasticity and motor function. Monocentric, randomized, double-blind, sham-controlled trial. Neurologic rehabilitation hospital. Patients (N=66) with severe hemiparesis and mild to moderate spasticity resulting from a stroke or a traumatic brain injury. The average time ± SD since injury for the intervention groups was 26 ± 71 weeks or 37 ± 82 weeks. rpMS for 20 minutes or sham stimulation with subsequent occupational therapy for 20 minutes, 2 times a day, over a 2-week period. Modified Tardieu Scale and Fugl-Meyer Assessment (arm score), assessed before therapy, at the end of the 2-week treatment period, and 2 weeks after study treatment. Additionally, the Tardieu Scale was assessed after the first and before the third therapy session to determine any short-term effects. Spasticity (Tardieu >0) was present in 83% of wrist flexors, 62% of elbow flexors, 44% of elbow extensors, and 10% of wrist extensors. Compared with the sham stimulation group, the rpMS group showed short-term effects on spasticity for wrist flexors (P=.048), and long-term effects for elbow extensors (P<.045). Arm motor function (rpMS group: median 5 [4-27]; sham group: median 4 [4-9]) did not significantly change over the study period in either group, whereas rpMS had a positive effect on sensory function. Therapy with rpMS increases sensory function in patients with severe limb paresis. The magnetic stimulation, however, has limited effect on spasticity and no effect on motor function. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

PubMed

Miwa, Hiroto; Osada, Taro; Nagahara, Akihito; Ohkusa, Toshifumi; Hojo, Mariko; Tomita, Toshihiko; Hori, Kazutoshi; Matsumoto, Takayuki; Sato, Nobuhiro

2006-12-01

Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.

The efficacy of SMART Arm training early after stroke for stroke survivors with severe upper limb disability: a protocol for a randomised controlled trial.

PubMed

Brauer, Sandra G; Hayward, Kathryn S; Carson, Richard G; Cresswell, Andrew G; Barker, Ruth N

2013-07-02

Recovery of upper limb function after stroke is poor. The acute to subacute phase after stroke is the optimal time window to promote the recovery of upper limb function. The dose and content of training provided conventionally during this phase is however, unlikely to be adequate to drive functional recovery, especially in the presence of severe motor disability. The current study concerns an approach to address this shortcoming, through evaluation of the SMART Arm, a non-robotic device that enables intensive and repetitive practice of reaching by stroke survivors with severe upper limb disability, with the aim of improving upper limb function. The outcomes of SMART Arm training with or without outcome-triggered electrical stimulation (OT-stim) to augment movement and usual therapy will be compared to usual therapy alone. A prospective, assessor-blinded parallel, three-group randomised controlled trial is being conducted. Seventy-five participants with a first-ever unilateral stroke less than 4 months previously, who present with severe arm disability (three or fewer out of a possible six points on the Motor Assessment Scale [MAS] Item 6), will be recruited from inpatient rehabilitation facilities. Participants will be randomly allocated to one of three dose-matched groups: SMART Arm training with OT-stim and usual therapy; SMART Arm training without OT-stim and usual therapy; or usual therapy alone. All participants will receive 20 hours of upper limb training over four weeks. Blinded assessors will conduct four assessments: pre intervention (0-weeks), post intervention (4-weeks), 26 weeks and 52 weeks follow-up. The primary outcome measure is MAS item 6. All analyses will be based on an intention-to-treat principle. By enabling intensive and repetitive practice of a functional upper limb task during inpatient rehabilitation, SMART Arm training with or without OT-stim in combination with usual therapy, has the potential to improve recovery of upper limb function in those with severe motor disability. The immediate and long-term effects of SMART Arm training on upper limb impairment, activity and participation will be explored, in addition to the benefit of training with or without OT-stim to augment movement when compared to usual therapy alone. ACTRN12608000457347.

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Viner, Jaye L.; Pentland, Alice P.; Cantrell, Wendy; Bailey, Howard; Kang, Sewon; Linden, Kenneth G.; Heffernan, Michael; Duvic, Madeleine; Richmond, Ellen; Elewski, Boni E.; Umar, Asad; Bell, Walter; Gordon, Gary B.

2010-01-01

Background Preclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs). Methods A double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided. Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma skin cancer history, and patient time on study, the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm (RR = 0.41, 95% CI = 0.23 to 0.72, P = .002) as were the numbers of BCCs (RR = 0.40, 95% CI = 0.18 to 0.93, P = .032) and SCCs (RR = 0.42, 95% CI = 0.19 to 0.93, P = .032). Serious and cardiovascular adverse events were similar in the two groups. Conclusions Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers. PMID:21115882

A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults.

PubMed

Lewis, John E; Melillo, Angelica B; Tiozzo, Eduard; Chen, Lawrence; Leonard, Susanna; Howell, Mark; Diaz, Janelle; Gonzalez, Kathy; Woolger, Judi M; Konefal, Janet; Paterson, Elaine; Barnes, David

2014-02-04

Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity. This study investigated the effect of Ginkgo Synergy(®) plus Choline (n = 33) and OPC Synergy(®) plus Catalyn(®) (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling. No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy(®) plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy(®) plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy(®) plus Catalyn(®) arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy(®) plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001). Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with clinicaltrials.gov (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc.

Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone

PubMed Central

Piller, Linda B; Davis, Barry R; Cutler, Jeffrey A; Cushman, William C; Wright, Jackson T; Williamson, Jeff D; Leenen, Frans HH; Einhorn, Paula T; Randall, Otelio S; Golden, John S; Haywood, L Julian

2002-01-01

Background The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17–1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79–2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P < .05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67–1.38; P = 0.83). Conclusion Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm. PMID:12459039

TEFLON BELLOWS PULSE GENERATORS FOR SOLVENT EXTRACTION PULSE COLUMNS

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCarthy, P.B.

1954-01-01

A Teflon bellows-type pulse generator is described which consists of two 3-in. nominal diameter Teflon bellows mounted on either end of a flanged spool piece and rigidly connected internally by a push rod so that the two of bellows move in tandem. The ends of the two bellows are closed by means of blind flanges. Tne spool piece is designed for insertion in a 6-in. diameter nozzle on a solvent extraction pulse column. The double bellows arrangement constitutes a safety feature to prevent loss of the column contents in the event of failure of the inner bellows in contact withmore » column solution. Failure of the inner bellows may be detected by a conductivity probe mounted in the air space inside of the double bellows assembly. Reciprocating motion is imcrank arm rigidly connected through a cross head and push rod to the face of the external bellows flange. The push rod is guided by means of linear ball bushings. Frequency variation over a range of 30 to 100 cycles/ min.was obtained by use of a Thymotrol-controlled electric motor to drive the crank arm. Variable stroke adjustment (0 to 1-in. range) was possible by adjustment of linkages on the crank arm. A load compensating spring was founnd desirable to counteract the thrust on the push rod resulting tom the static pressure at the bottom of the solvent extraction column. Without the spring, accelerated wear of the bearing on the crank arm occured. The pulse generator operated uneventfully for 1776 hours (6.61x lO/sup 6/ cycles) at a frequency of 62 cycles/min. and a bellows travel of l-in. (equivalent to a displacement of 1.6 in. in a 3-in. diam. column). (auth)« less

Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery

PubMed Central

Stevinson, C; Devaraj, V S; Fountain-Barber, A; Hawkins, S; Ernst, E

2003-01-01

Homeopathic arnica is widely believed to control bruising, reduce swelling and promote recovery after local trauma; many patients therefore take it perioperatively. To determine whether this treatment has any effect, we conducted a double-blind, placebo-controlled, randomized trial with three parallel arms. 64 adults undergoing elective surgery for carpal tunnel syndrome were randomized to take three tablets daily of homeopathic arnica 30C or 6C or placebo for seven days before surgery and fourteen days after surgery. Primary outcome measures were pain (short form McGill Pain Questionnaire) and bruising (colour separation analysis) at four days after surgery. Secondary outcome measures were swelling (wrist circumference) and use of analgesic medication (patient diary). 62 patients could be included in the intention-to-treat analysis. There were no group differences on the primary outcome measures of pain (P=0.79) and bruising (P=0.45) at day four. Swelling and use of analgesic medication also did not differ between arnica and placebo groups. Adverse events were reported by 2 patients in the arnica 6C group, 3 in the placebo group and 4 in the arnica 30C group. The results of this trial do not suggest that homeopathic arnica has an advantage over placebo in reducing postoperative pain, bruising and swelling in patients undergoing elective hand surgery. PMID:12562974

Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery.

PubMed

Stevinson, C; Devaraj, V S; Fountain-Barber, A; Hawkins, S; Ernst, E

2003-02-01

Homeopathic arnica is widely believed to control bruising, reduce swelling and promote recovery after local trauma; many patients therefore take it perioperatively. To determine whether this treatment has any effect, we conducted a double-blind, placebo-controlled, randomized trial with three parallel arms. 64 adults undergoing elective surgery for carpal tunnel syndrome were randomized to take three tablets daily of homeopathic arnica 30C or 6C or placebo for seven days before surgery and fourteen days after surgery. Primary outcome measures were pain (short form McGill Pain Questionnaire) and bruising (colour separation analysis) at four days after surgery. Secondary outcome measures were swelling (wrist circumference) and use of analgesic medication (patient diary). 62 patients could be included in the intention-to-treat analysis. There were no group differences on the primary outcome measures of pain (P=0.79) and bruising (P=0.45) at day four. Swelling and use of analgesic medication also did not differ between arnica and placebo groups. Adverse events were reported by 2 patients in the arnica 6C group, 3 in the placebo group and 4 in the arnica 30C group. The results of this trial do not suggest that homeopathic arnica has an advantage over placebo in reducing postoperative pain, bruising and swelling in patients undergoing elective hand surgery.

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder.

PubMed

Findling, Robert L; Quinn, Declan; Hatch, Simon J; Cameron, Sara J; DeCory, Heleen H; McDowell, Michael

2006-12-01

To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.

Effects and Safety of Gyejibongnyeong-Hwan on Dysmenorrhea Caused by Blood Stagnation: A Randomized Controlled Trial

PubMed Central

Park, Jeong-Su; Park, Sunju; Cheon, Chun-Hoo; Jo, Seong-Cheon; Cho, Han Baek; Lim, Eun-Mee; Lim, Hyung Ho; Shin, Yong-Cheol; Ko, Seong-Gyu

2013-01-01

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration. Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group. Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles. Trial Registration. This trial is registered with Current Controlled Trials no. ISRCTN30426947. PMID:24191165

Donepezil and flight simulator performance: effects on retention of complex skills.

PubMed

Yesavage, J A; Mumenthaler, M S; Taylor, J L; Friedman, L; O'Hara, R; Sheikh, J; Tinklenberg, J; Whitehouse, P J

2002-07-09

We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention.

PubMed

Syrjänen, Kari; Salminen, Johanna; Aresvuo, Ulla; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Salaspuro, Mikko; Suovaniemi, Osmo

2016-05-01

Harmans are condensation products of acetaldehyde and biogenic amines in saliva. Like other monoamine oxidase inhibitors, harmans help maintain behavioral sensitization to nicotine and mediate the addictive potential of cigarette smoke-derived acetaldehyde. The aim of this study was to test the hypothesis that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium™ lozenge; Biohit Oyj, Helsinki, Finland) blocks the formation of harmans and eliminates acetaldehyde-enhanced nicotine addiction in smokers. A double-blind, randomized, placebo-controlled trial comparing Acetium lozenges and placebo in smoking intervention was undertaken. A cohort of 423 cigarette smokers were randomly allocated to intervention (n=212) and placebo arms (n=211). Smoking-related data were recorded by questionnaires, together with nicotine dependence testing by Fagerström scale. The participants used a smoking diary to record the daily number of cigarettes, test lozenges and sensations of smoking. The data were analyzed separately for point prevalence of abstinence and prolonged abstinence endpoints. Altogether, 110 study participants completed the trial per protocol, 234 had minor violations, and the rest (n=79) were lost to follow-up. During the 6-month trial, 65 participants quit smoking; 38 (17.9%) in the intervention arm and 27 (12.8%) in the placebo arm [odds ratio (OR)=1.48; 95% confidence intervals (CI)=0.87-2.54; p=0.143]. Success in the per protocol group was better (42.9% vs. 31.1%, respectively; OR=1.65, 95% CI=0.75-3.62; p=0.205) than in the modified intention-to-treat group: 13.5% vs. 7.4% (p=0.128). If the efficacy of Acetium lozenge can be confirmed in an adequately powered study, this new approach would represent a major breakthrough in smoking quit intervention because slow-release L-cysteine is non-toxic with no side-effects or limitations of use. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment.

PubMed

Montero-Odasso, Manuel; Almeida, Quincy J; Burhan, Amer M; Camicioli, Richard; Doyon, Julien; Fraser, Sarah; Li, Karen; Liu-Ambrose, Teresa; Middleton, Laura; Muir-Hunter, Susan; McIlroy, William; Morais, José A; Pieruccini-Faria, Frederico; Shoemaker, Kevin; Speechley, Mark; Vasudev, Akshya; Zou, G Y; Berryman, Nicolas; Lussier, Maxime; Vanderhaeghe, Leanne; Bherer, Louis

2018-04-16

Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

Prospective Randomized Double-blinded Trial Comparing 2 Anti-MRSA Agents With Supplemental Coverage of Cefazolin Before Lower Extremity Revascularization

PubMed Central

Stone, Patrick A.; AbuRahma, Ali F.; Campbell, James R.; Hass, Stephen M.; Mousa, Albeir Y.; Nanjundappa, Aravinda; Srivastiva, Mohit; Modak, Asmita; Emmett, Mary

2015-01-01

Objective To compare with antibiotics with methicillin-resistant microbial coverage in a prospective fashion. Background Current antibiotic prophylaxis for vascular procedures includes a first generation cephalosporin. No changes in recommendations have occurred despite changes in reports of incidence of MRSA related surgical site infections. Does supplemental anti-MRSA prophylactic coverage provide a significant reduction in Gram-positive or MRSA infections? Methods Single center prospective double blinded randomized study of patients undergoing lower extremity vascular procedures from 2011 to 2014. One hundred seventy-eight (178) patients were evaluated at 90 days for surgical site infection. Infections were categorized as early infections less than 30 days of the index procedure and late after 90 days. Results Early vascular surgical site infection occurred in 7(8.24%) of patients in the Vancomycin arm, and 11 (11.83%) in the Daptomycin arm (P = 0.43). Gram-positive related infections and MRSA infections occurred in 1(1.18%)/0(0%) of Vancomycin patients and 9 (9.68%)/1 (1.08%) of Daptomycin patients, respectively (P < 0.02 and P = 1.00). Readmissions related to surgical site infections occurred in 4(4.71%) in the Vancomycin group and 11 (11.8%) in the Daptomycin group (P = 0.11). Patients undergoing operative exploration occurred in 5 (5.88%) in the Vancomycin group and 10 (10.75%) of the Daptomycin group (P = 0.17). Late infections were reported in 3 patients, 2 of which were in the combined Daptomycin group. Median hospital charges related to readmissions due to a surgical site infection was $50,823 in the combination Vancomycin arm and $110,920 in the combination Daptomycin group; however, no statistical significance was appreciated (P = 0.11). Conclusions Vancomycin supplemental prophylaxis seems to reduce the incidence of Gram-positive infection compared with adding supplemental Daptomycin prophylaxis. The Incidence of MRSA-related surgical site infections is low with the addition of either anti-MRSA agents compared with historical incidence of MRSA-related infection. PMID:26258318

Treatment Assignment Guesses by Study Participants in a Double-Blind Dose Escalation Clinical Trial of Saw Palmetto

PubMed Central

Moore, Page; Kusek, John; Barry, Michael

2014-01-01

Abstract Objectives: This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Design: Participants randomized to receive saw palmetto were instructed to take one 320 mg gelcap daily for the first 24 weeks, two 320 mg gelcaps daily for the second 24 weeks, and three 320 mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. Settings: The study was conducted at 11 clinical centers in North America. Participants: Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N=151) or placebo (N=155). Outcome measures: Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. Results: For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p=0.823) or placebo (p=0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Conclusions: Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto. PMID:23383975

Effect of the patient education - Learning and Coping strategies - in cardiac rehabilitation on return to work at one year: a randomised controlled trial show (LC-REHAB).

PubMed

Bitsch, Birgitte Laier; Nielsen, Claus Vinther; Stapelfeldt, Christina Malmose; Lynggaard, Vibeke

2018-05-21

Personal resources are identified as important for the ability to return to work (RTW) for patients with ischaemic heart disease (IHD) or heart failure (HF) undergoing cardiac rehabilitation (CR). The patient education 'Learning and Coping' (LC) addresses personal resources through a pedagogical approach. This trial aimed to assess effect of adding LC strategies in CR compared to standard CR measured on RTW status at one-year follow-up after CR. In an open parallel randomised controlled trial, patients with IHD or HF were block-randomised in a 1:1 ratio to the LC arm (LC plus CR) or the control arm (CR alone) across three Danish hospital units. Eligible patients were aged 18 to ≤60 and had not left the labour market. The intervention was developed from an inductive pedagogical approach consisting of individual interviews and group based teaching by health professionals with experienced patients as co-educators. The control arm consisted of deductive teaching (standard CR). RTW status was derived from the Danish Register for Evaluation of Marginalisation (DREAM). Blinding was not possible. The effect was evaluated by logistic regression analysis and reported as crude and adjusted odds ratios (OR) with 95% confidence interval (CI). The population for the present analysis was N = 244 (LC arm: n = 119 versus control arm: n = 125). No difference in RTW status was found at one year across arms (LC arm: 64.7% versus control arm: 68.8%, adjusted odds ratio OR: 0.76, 95% CI: 0.43-1.31). Addition of LC strategies in CR showed no improvement in RTW at one year follow-up. www.clinicaltrials.gov identifier NCT01668394. First Posted: August 20, 2012.

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis

PubMed Central

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-01-01

Introduction Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. Trial registration number NCT023528702; Pre-results. PMID:27072573

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis.

PubMed

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-04-12

Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. NCT023528702; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

PubMed

Koike, Haruki; Akiyama, Kazuo; Saito, Toyokazu; Sobue, Gen

2015-03-01

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease.

Curcumin for Radiation Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Thirty Breast Cancer Patients

PubMed Central

Ryan, Julie L.; Heckler, Charles E.; Ling, Marilyn; Katz, Alan; Williams, Jacqueline P.; Pentland, Alice P.; Morrow, Gary R.

2014-01-01

Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS =2.6 vs. 3.4; P =0.008). Fisher’s exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P =0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients. PMID:23745991

A double-blind, randomized clinical study to determine the efficacy of benzocaine 10% on histamine-induced pruritus and UVB-light induced slight sunburn pain.

PubMed

Bauer, Martin; Schwameis, Richard; Scherzer, Thomas; Lang-Zwosta, Isabelle; Nishino, Kanako; Zeitlinger, Markus

2015-01-01

This study aims to explore the efficacy of the topical application of 10% benzocaine for treating pruritus and pain as compared to vehicle ointment. Twenty male subjects were treated in a randomized double-blind fashion with the investigational medicinal product (IMPD) and vehicle. Immediately after the injection of 100 µg histamine on both arms, subjects received topical treatment and pruritus was subsequently assessed with visual analogue scale (VASpruritus) and Eppendorfer questionnaire. Ultraviolet B radiation (UVB) was administered on the back to induce slight sunburn. Twelve hours after UVB application again the IMPD was applied on the right or left upper back and vehicle on the other side and pain related to sunburn was measured with VASpain and pressure algometry. A trend towards better reduction of pruritus was shown for benzocaine in VASpruritus. For the VASpain significant differences in group comparison (p = 0.02) were observed. Algometer measurements showed onset of pain reduction in the verum group after 20 min whereas in the vehicle-treated area pain relief occurred only after 60 min after application. The topically administered ointment containing 10% benzocaine was found superior over vehicle for treating pain, but not pruritus.

Naproxen Sodium for Pain Control With Intrauterine Device Insertion: A Randomized Controlled Trial.

PubMed

Ngo, Lynn L; Braaten, Kari P; Eichen, Eva; Fortin, Jennifer; Maurer, Rie; Goldberg, Alisa B

2016-12-01

To evaluate whether 550 mg oral naproxen sodium given 1 hour before intrauterine device (IUD) insertion is effective for pain relief as compared with placebo. This was a randomized, double-blind, placebo-controlled trial. The primary outcome was pain with IUD insertion measured on a 100-mm visual analog scale (VAS). Our sample size was calculated to detect a 15-mm difference in VAS scores with 80% power (α=0.05). Secondary outcomes included pain with tenaculum placement, uterine sounding, and 5 and 15 minutes postinsertion. A total of 118 women were enrolled and analyzed (58 in the naproxen sodium arm, 60 in the placebo arm, 97% nulliparous) between May 11, 2015, and March 25, 2016. There were no differences in baseline demographics or reproductive characteristics between arms. There were no differences in median VAS pain scores for the primary outcome of pain with IUD insertion between the naproxen sodium arm compared with the placebo arm (69 compared with 66 mm, P=.89). There were no differences in the secondary outcomes of median VAS pain scores with tenaculum placement (37 compared with 32 mm, P=.97) or uterine sounding (60 compared with 58 mm, P=.66). However, median pain scores postprocedure were lower in the naproxen arm as compared with the placebo arm: 17 compared with 26 mm (P=.01) at 5 minutes and 13 compared with 24 mm (P=.01) at 15 minutes postinsertion. Oral naproxen sodium does not reduce pain with IUD insertion but does reduce pain after insertion and should be considered as a premedication. ClinicalTrials.gov, http://clinicaltrials.gov, NCT02388191.

Evaluation of pulsing magnetic field effects on paresthesia in multiple sclerosis patients, a randomized, double-blind, parallel-group clinical trial.

PubMed

Afshari, Daryoush; Moradian, Nasrin; Khalili, Majid; Razazian, Nazanin; Bostani, Arash; Hoseini, Jamal; Moradian, Mohamad; Ghiasian, Masoud

2016-10-01

Evidence is mounting that magnet therapy could alleviate the symptoms of multiple sclerosis (MS). This study was performed to test the effects of the pulsing magnetic fields on the paresthesia in MS patients. This study has been conducted as a randomized, double-blind, parallel-group clinical trial during the April 2012 to October 2013. The subjects were selected among patients referred to MS clinic of Imam Reza Hospital; affiliated to Kermanshah University of Medical Sciences, Iran. Sixty three patients with MS were included in the study and randomly were divided into two groups, 35 patients were exposed to a magnetic pulsing field of 4mT intensity and 15-Hz frequency sinusoidal wave for 20min per session 2 times per week over a period of 2 months involving 16 sessions and 28 patients was exposed to a magnetically inactive field (placebo) for 20min per session 2 times per week over a period of 2 months involving 16 sessions. The severity of paresthesia was measured by the numerical rating scale (NRS) at 30, 60days. The study primary end point was NRS change between baseline and 60days. The secondary outcome was NRS change between baseline and 30days. Patients exposing to magnetic field showed significant paresthesia improvement compared with the group of patients exposing to placebo. According to our results pulsed magnetic therapy could alleviate paresthesia in MS patients .But trials with more patients and longer duration are mandatory to describe long-term effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

PubMed

Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-07-01

A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

PubMed

Howie, Stephen; Bottomley, Christian; Chimah, Osaretin; Ideh, Readon; Ebruke, Bernard; Okomo, Uduak; Onyeama, Charles; Donkor, Simon; Rodrigues, Onike; Tapgun, Mary; Janneh, Marie; Oluwalana, Claire; Kuti, Bankole; Enwere, Godwin; Esangbedo, Pamela; Doherty, Conor; Mackenzie, Grant; Greenwood, Brian; Corrah, Tumani; Prentice, Andrew; Adegbola, Richard; Zaman, Syed

2018-06-01

The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared. Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P  = 0.011 and 18.7 vs 11.0 hours; P  = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P  = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment. In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children. ISRCTN33548493.

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial

PubMed Central

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-01-01

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

PubMed

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-08-23

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents' quality of life: a multicenter, randomized trial.

PubMed

Staab, Doris; Kaufmann, Roland; Bräutigam, Matthias; Wahn, Ulrich

2005-09-01

Atopic eczema begins primarily in infancy or early childhood, and sleep loss due to night-time pruritus can have a considerable impact on patients' and parents' quality of life (QoL). In this study, infants (n = 196) with mild to severe atopic eczema were randomized 2:1, double-blind, to receive either pimecrolimus cream 1% (Elidel, Novartis Pharma, Nürnberg, Germany) or the corresponding vehicle bid for 4 wk, followed by a 12 wk, open-label phase and a 4 wk, treatment-free, follow-up period. The parents' QoL was measured at baseline and at the end of the double-blind phase, using the questionnaire 'QoL in Parents of Children with Atopic Dermatitis' (PQoL-AD), thus data presented here refer to the initial 4-wk treatment phase only. After 4 wk of double-blind treatment, an increase in the mean percentage change from baseline in eczema area and severity index of 71.5% was observed with pimecrolimus, compared with 19.4% with vehicle. The increase in efficacy was paralleled by the following mean percentage changes from baseline in the five domains of the questionnaire in pimecrolimus and vehicle, respectively: psychosomatic well-being: 14.6% vs. 6.2%; effects on social life: 6.7% vs. 2.3%; confidence in medical treatment: 10.0% vs. 3.7%; emotional coping: 16.1% vs. 6.5%; acceptance of disease: 19.6% vs. 7.0%. Analysis (ancova) of the dependent variable difference from baseline and the covariate baseline value revealed values of p < 0.05 for all five domains, despite the very short duration of the study. It is concluded that improvements in atopic eczema in infants achieved by treatment with pimecrolimus have a significant beneficial effect on the QoL of parents.

A randomized double-blind placebo-controlled clinical trial on efficacy and safety of association of simethicone and Bacillus coagulans (Colinox®) in patients with irritable bowel syndrome.

PubMed

Urgesi, R; Casale, C; Pistelli, R; Rapaccini, G L; de Vitis, I

2014-01-01

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that affects 15-20% of the Western population. There are currently few therapeutic options available for the treatment of IBS. The aim of this study is to evaluate the efficacy and the safety of a medical device containing a combination of Simethicone and Bacillus coagulans in the treatment of IBS. This is a monocentric double-blind, placebo-controlled parallel group clinical trial. Adult subjects suffering from IBS as defined by Rome III criteria were enrolled. Bloating, discomfort, abdominal pain were assessed as primary end point. Subjects received the active treatment or placebo 3 time a day after each meal for 4 weeks of study period. Subjects were submitted to visit at Day 0 (T1), at Days 14 (T2) and 29 (T3). Fifty-two patients were included into the study. Intragroup analysis showed a significant reduction of the bloating, discomfort and pain in Colinox® group (CG) compared to placebo group (PG). Between group analysis confirmed, at T1-T3, significant differences between CG and PG in bloating and discomfort. Simethicone is an inert antifoaming able to reduce bloating, abdominal discomfort. Literature offers increasing evidence linking alterations in the gastrointestinal microbiota and IBS and it is well known that probiotics are important to restore the native gut microbiota. The Colinox medical device is specifically targeted against most intrusive symptom of IBS (bloating) and it is also able to counteract the most accredited ethiopathogenetic factor in IBS (alterations of intestinal microbiota). This is the first randomized double-blind placebo-controlled clinical trial demonstrating the efficacy and safety of a combination of simethicone and Bacillus coagulans in treatment of IBS.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

2018-06-01

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

PubMed

Coyle, Christopher; Cafferty, Fay H; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C S; Gilbert, Duncan; Kynaston, Howard; Cameron, David; Wilson, Richard H; Ring, Alistair; Langley, Ruth E

2016-11-01

There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy. Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk. The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures. The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

PubMed

Wallace, Carol A; Giannini, Edward H; Spalding, Steven J; Hashkes, Philip J; O'Neil, Kathleen M; Zeft, Andrew S; Szer, Ilona S; Ringold, Sarah; Brunner, Hermine I; Schanberg, Laura E; Sundel, Robert P; Milojevic, Diana; Punaro, Marilynn G; Chira, Peter; Gottlieb, Beth S; Higgins, Gloria C; Ilowite, Norman T; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J

2012-06-01

To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms. Copyright © 2012 by the American College of Rheumatology.

Effect of two contrasting interventions on upper limb chronic pain and disability: a randomized controlled trial.

PubMed

Sundstrup, Emil; Jakobsen, Markus D; Andersen, Christoffer H; Jay, Kenneth; Persson, Roger; Aagaard, Per; Andersen, Lars L

2014-01-01

Chronic pain and disability of the arm, shoulder, and hand severely affect labor market participation. Ergonomic training and education is the default strategy to reduce physical exposure and thereby prevent aggravation of pain. An alternative strategy could be to increase physical capacity of the worker by physical conditioning. To investigate the effect of 2 contrasting interventions, conventional ergonomic training (usual care) versus resistance training, on pain and disability in individuals with upper limb chronic pain exposed to highly repetitive and forceful manual work. Examiner-blinded, parallel-group randomized controlled trial with allocation concealment. Slaughterhouses located in Denmark, Europe. Sixty-six adults with chronic pain in the shoulder, elbow/forearm, or hand/wrist and work disability were randomly allocated to 10 weeks of specific resistance training for the shoulder, arm, and hand muscles for 3 x 10 minutes per week, or ergonomic training and education (usual care control group). Pain intensity (average of shoulder, arm, and hand, scale 0 - 10) was the primary outcome, and disability (Work module of DASH questionnaire) as well as isometric shoulder and wrist muscle strength were secondary outcomes. Pain intensity, disability, and muscle strength improved more following resistance training than usual care (P < 0.001, P = 0.05, P <0.0001, respectively [corrected]). Pain intensity decreased by 1.5 points (95% confidence interval -2.0 to -0.9) following resistance training compared with usual care, corresponding to an effect size of 0.91 (Cohen's d). Blinding of participants is not possible in behavioral interventions. However, at baseline outcome expectations of the 2 interventions were similar. Resistance training at the workplace results in clinical relevant improvements in pain, disability, and muscle strength in adults with upper limb chronic pain exposed to highly repetitive and forceful manual work. NCT01671267.

Uniform magnetic fields and double-wrapped coil systems: improved techniques for the design of bioelectromagnetic experiments.

PubMed

Kirschvink, J L

1992-01-01

A common mistake in biomagnetic experimentation is the assumption that Helmholtz coils provide uniform magnetic fields; this is true only for a limited volume at their center. Substantial improvements on this design have been made during the past 140 years with systems of three, four, and five coils. Numerical comparisons of the field uniformity generated by these designs are made here, along with a table of construction details and recommendations for their use in experiments in which large volumes of uniform intensity magnetic exposures are needed. Double-wrapping, or systems of bifilar windings, can also help control for the non-magnetic effects of the electric coils used in many experiments. In this design, each coil is wrapped in parallel with two separate, adjacent strands of copper wire, rather than the single strand used normally. If currents are flowing in antiparallel directions, the magnetic fields generated by each strand will cancel and yield virtually no external magnetic field, whereas parallel currents will yield an external field. Both cases will produce similar non-magnetic effects of ohmic heating, and simple measures can reduce the small vibration and electric field differences. Control experiments can then be designed such that the only major difference between treated and untreated groups is the presence or absence of the magnetic field. Double-wrapped coils also facilitate the use of truly double-blind protocol, as the same apparatus can be used either for experimental or control groups.

Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

PubMed

Lindholm, Asa; Bixo, Marie; Björn, Inger; Wölner-Hanssen, Pål; Eliasson, Mats; Larsson, Anders; Johnson, Owe; Poromaa, Inger Sundström

2008-05-01

To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS). Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial. Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice. Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study. Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification. The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors. After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels. Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

[Randomized double-blind comparative study of minaprine (200mg/j) and of placebo on memory loss].

PubMed

Allain, H; Belliard, S; Lieury, A; Menard, G; Patat, A; Le Coz, F; Gandon, J M

1996-01-01

Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study.

PubMed

Draelos, Zoe Diana; Elewski, Boni; Staedtler, Gerald; Havlickova, Blanka

2013-12-01

Rosacea is a common chronic inflammatory skin disease that primarily affects facial skin. Its etiology is unknown, and currently there is no cure. Rosacea can be associated with severe symptoms, including transient erythema (flushing), nontransient erythema, papules, pustules, and telangiectases, leading to substantial discomfort and an unattractive appearance. This randomized, double-blind, vehicle-controlled, multicenter, parallel-group study conducted over 12 weeks with a 4-week follow-up period evaluated the efficacy and safety of a new formulation of azelaic acid (AzA) foam in a 15% concentration compared to vehicle alone in patients with papulopustular rosacea (PPR). Primary efficacy variables assessed were investigator global assessment (IGA) dichotomized into success and failure, and nominal change in inflammatory lesion count from baseline to end of treatment. Results indicated that the new foam formulation of AzA is effective and well-tolerated in a population of patients with PPR. Although no single formulation is appropriate for all patients, the development of a new foam formulation in addition to other available vehicles provides patients with options and allows health care providers to match the needs as well as preferences of individual patients and skin types with appropriate delivery modalities.

Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

PubMed

Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

2009-01-01

To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

PubMed Central

Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

2013-01-01

Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study.

PubMed

Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

2017-01-01

Bilastine, a novel non-sedating second-generation H 1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.

PubMed

Espay, Alberto J; Norris, Matthew M; Eliassen, James C; Dwivedi, Alok; Smith, Matthew S; Banks, Christi; Allendorfer, Jane B; Lang, Anthony E; Fleck, David E; Linke, Michael J; Szaflarski, Jerzy P

2015-02-24

To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease. © 2015 American Academy of Neurology.

[Effectiveness of Vitex agnus-castus preparations].

PubMed

Gorkow, C; Wuttke, W; März, R W

2002-01-01

The prolactin-inhibiting effect of ACF-preparations, which is due to dopaminergic activities, has been shown in humans too and gives a pharmacological rationale for the clinical effects observed in the different indications (2, 11, 25, 26, 35, 41). Confirmation of efficacy in the treatment of mastalgia has been best endorsed by two recently published double-blind studies conducted according to the principles of GCP (14, 41). One double-blind study, several open and postmarketing surveillance studies have shown that the premenstrual syndrome, or individual symptoms, can be influenced positively (3, 6, 7, 9, 19, 21, 37). Design shortcomings in a second double-blind study should be eliminated in future studies in this indication to improve the body of evidence (18). Hither to there has been one controlled double-blind study of cycle disorders in the case of corpus luteum insufficiency with significant results and a number of non-controlled open studies (1, 4, 15, 16, 20, 24, 26, 27, 32, 35, 36). The high success rates in the open studies indicate therapeutic effects, and it should be possible to reproduce these results under double-blind conditions. The success rates on fertility disorders should be confirmed in controlled double-blind studies (10, 33, 34).

Effects of amphetamine and/or L-dopa and physiotherapy after stroke - a blinded randomized study.

PubMed

Sonde, L; Lökk, J

2007-01-01

Major therapeutic advances in the rehabilitation of subacute stroke are lacking. A promising approach is treatment with facilitating drugs like amphetamine or levodopa in combination with physiotherapy. In a randomized, double-blind, placebo-controlled clinical trail, the effect of 10 sessions with either 20 mg of D-amphetamine, 100 mg of L-dopa or 10 mg of D-amphetamine + 50 mg of L-dopa combined with physiotherapy during a 2-week period was investigated in 25 patients admitted to a stroke rehabilitation unit. Motor function (Fugl-Meyer score) and activities of daily living (Barthel's index) were assessed. All patients improved significantly over the intervention period. Drug-treated patients did not show any additional increase in motor function or ADL. It is feasible and safe to perform larger clinical trials with this type of four-arm design. However, the lack of significant effects could be because of type, dosage, and time of drugs as well as the physical intervention strategy.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.

PubMed

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-03-01

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary end points included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometrical mean ratio (GMR) of AUC inf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C max was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC inf and C max were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. EudraCT number 2012-000785-37; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial.

PubMed

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-02-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep variables at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings. The side effect profile was low and not significantly different between the two arms.

Systematic review of blinding assessment in randomized controlled trials in schizophrenia and affective disorders 2000-2010.

PubMed

Baethge, Christopher; Assall, Oliver P; Baldessarini, Ross J

2013-01-01

Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports. Copyright © 2013 S. Karger AG, Basel.

A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.

PubMed

Peterson, P K; Pheley, A; Schroeppel, J; Schenck, C; Marshall, P; Kind, A; Haugland, J M; Lambrecht, L J; Swan, S; Goldsmith, S

1998-04-27

To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome. A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone. An outpatient clinical trials unit. Twenty-five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%] women; mean duration of illness, 7.0 years) were recruited from a research and clinic registry. Five patients withdrew from the trial. All participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks in each treatment. Self-administered questionnaires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale. The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time test, and a treadmill exercise test were used to assess functional status. Blood pressure, heart rate, and plasma norepinephrine levels were obtained at baseline. Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits. At baseline, the study participants reported symptom severity greater than 5 for most symptoms, and all had evidence of marked functional impairments. No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial. Blood pressure and heart rate readings were unaffected by treatment, and plasma norepinephrine levels did not differ from those of a healthy control group. The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial. Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.

A Prospective, Randomized, Double-Blind Multicenter Study Comparing Continuous Diffusion of Oxygen Therapy to Sham Therapy in the Treatment of Diabetic Foot Ulcers.

PubMed

Niederauer, Mark Q; Michalek, Joel E; Armstrong, David G

2017-09-01

Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs). We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up. There were no significant differences in assessed descriptive characteristics between the treatment arms ( P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham ( P < .001). The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).

Safety and Pharmacokinetics of Multiple 750-Milligram Doses of Intravenous Levofloxacin in Healthy Volunteers

PubMed Central

Chow, Andrew T.; Fowler, Cynthia; Williams, R. Rex; Morgan, Nancy; Kaminski, Susan; Natarajan, Jaya

2001-01-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation. PMID:11408234

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

PubMed

Chow, A T; Fowler, C; Williams, R R; Morgan, N; Kaminski, S; Natarajan, J

2001-07-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial.

PubMed

Breau, Rodney H; Lavallée, Luke T; Cnossen, Sonya; Witiuk, Kelsey; Cagiannos, Ilias; Momoli, Franco; Bryson, Gregory; Kanji, Salmaan; Morash, Christopher; Turgeon, Alexis; Zarychanski, Ryan; Mallick, Ranjeeta; Knoll, Greg; Fergusson, Dean A

2018-05-02

Radical cystectomy for bladder cancer is associated with a high risk of needing red blood cell transfusion. Tranexamic acid reduces blood loss during cardiac and orthopedic surgery, but no study has yet evaluated tranexamic acid use during cystectomy. A randomized, double-blind (surgeon-, anesthesiologist-, patient-, data-monitor-blinded), placebo-controlled trial of tranexamic acid during cystectomy was initiated in June 2013. Prior to incision, the intervention arm participants receive a 10 mg/kg loading dose of intravenously administered tranexamic acid, followed by a 5 mg/kg/h maintenance infusion. In the control arm, the patient receives an identical volume of normal saline that is indistinguishable from the intervention. The primary outcome is any blood transfusion from the start of surgery up to 30 days post operative. There are no strict criteria to mandate the transfusion of blood products. The decision to transfuse is entirely at the discretion of the treating physicians who are blinded to patient allocation. Physicians are allowed to utilize all resources to make transfusion decisions, including serum hemoglobin concentration and vital signs. To date, 147 patients of a planned 354 have been randomized to the study. This protocol reviews pertinent data relating to blood transfusion during radical cystectomy, highlighting the need to identify methods for reducing blood loss and preventing transfusion in patients receiving radical cystectomy. It explains the clinical rationale for using tranexamic acid to reduce blood loss during cystectomy, and outlines the study methods of our ongoing randomized controlled trial. Canadian Institute for Health Research (CIHR) Protocol: MOP-342559; ClinicalTrials.gov, ID: NCT01869413. Registered on 5 June 2013.

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.

PubMed

Langford, R M; Mares, J; Novotna, A; Vachova, M; Novakova, I; Notcutt, W; Ratcliffe, S

2013-04-01

Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of -0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.

A randomized, double-blind, placebo-controlled clinical trial on the treatment of vitamin D insufficiency in postmenopausal women

PubMed Central

Hansen, Karen E.; Johnson, R. Erin; Chambers, Kaitlin R.; Johnson, Michael G.; Lemon, Christina C.; Thuy Vo, Tien Nguyen; Marvdashti, Sheeva

2015-01-01

Importance Experts debate optimal 25(OH)D levels for musculoskeletal health. Objective To compare effects of placebo, low-dose and high-dose vitamin D on one-year changes in total fractional calcium absorption, bone mineral density, Timed-Up-and-Go and 5-sit-to-stand tests and muscle mass in postmenopausal women with vitamin D insufficiency. Design Randomized, double-blind, placebo-controlled, clinical trial conducted from May 2010 to August 2014. Setting Single-center trial conducted in Madison, Wisconsin. Participants 230 postmenopausal women ≤75 years old with baseline 25(OH)D levels 14-27 ng/mL and no osteoporosis. Intervention Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=76), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL. Main Outcome Measures One year change in total fractional calcium absorption using two stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed-Up-and-Go and 5-Sit-to-Stand tests, functional status (Health Assessment Questionnaire) and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of p-values to control the false discovery rate. Results After controlling for baseline absorption, calcium absorption increased 1% (10 mg/day) in the high-dose arm, but decreased by 2% in low-dose (p=0.005 vs. high-dose) and by 1.3% placebo (p=0.03 vs. high-dose) arms. We found no between-arm changes in spine, mean total hip, mean femoral neck or total body bone mineral density, trabecular bone score, muscle mass, 5-sit-to-stand or Timed-Up-and-Go test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity or functional status. Conclusion and Relevance High-dose vitamin D therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels ≥30 ng/mL in postmenopausal women. Instead, we found that low and high-dose vitamin D were equivalent to placebo, in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels <30 ng/mL. ClinicalTrials.gov.Identifier:NCT00933244 PMID:26237520

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study

PubMed Central

Beer, Tomasz M.; Armstrong, Andrew J.; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N.; Higano, Celestia S.; Iversen, Peter; Evans, Christopher P.; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S.; Borre, Michael; Mulders, Peter; Tammela, Teuvo L.; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-01-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28–0.37; p < 0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67–0.88; p = 0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9–22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1–5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2–not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8–34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PMID:27477525

Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome.

PubMed

Aubuchon, Mira; Kunselman, Allen R; Schlaff, William D; Diamond, Michael P; Coutifaris, Christos; Carson, Sandra A; Steinkampf, Michael P; Carr, Bruce R; McGovern, Peter G; Cataldo, Nicholas A; Gosman, Gabriella G; Nestler, John E; Myers, Evan R; Legro, Richard S

2011-10-01

Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004. This multi-center clinical trial was conducted in academic centers. Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, -14.7 to -21.3%) as well as creatinine (-4.2 to -6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (-10% in bilirubin, -9 to -11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.

A randomized phase 2 study comparing two doses of delafloxacin with tigecycline in adults with complicated skin and skin-structure infections.

PubMed

O'Riordan, William; Mehra, Purvi; Manos, Paul; Kingsley, Jeff; Lawrence, Laura; Cammarata, Sue

2015-01-01

A randomized, double-blind, multicenter trial was done to compare two doses of delafloxacin with tigecycline in patients with various complicated skin and skin-structure infections (wound infections following surgery, trauma, burns, or animal/insect bites, abscesses, and cellulitis). Patients were randomized 1:1:1 to receive delafloxacin 300mg intravenous (IV) every 12h, delafloxacin 450mg IV every 12h, or tigecycline 100mg IV×1, followed by 50mg IV every 12h; randomization was stratified by infection type. Duration of therapy was 5-14 days. The primary efficacy analysis, performed on the clinically evaluable (CE) population at the test-of-cure (TOC) visit (14-21 days after the final dose of study drug), compared clinical response rates in the delafloxacin and tigecycline arms. Clinical response rates in the two delafloxacin arms were also compared. Among CE patients, clinical cure rates at TOC visit were similar in the delafloxacin and tigecycline arms (94.3%, 92.5%, and 91.2%, respectively in delafloxacin 300-mg, delafloxacin 450-mg, and tigecycline arms). Overall, the most frequent adverse events were nausea, vomiting, and diarrhea; the 300-mg delafloxacin arm was the best-tolerated regimen. Delafloxacin was similarly effective as tigecycline for a variety of complicated skin and skin-structure infections and was well tolerated. (Clinicaltrials.gov NCT 0719810). Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of the effect of two sugar-substituted chewing gums on different caries- and gingivitis-related variables: a double-blind, randomized, controlled clinical trial.

PubMed

Martínez-Pabón, María C; Duque-Agudelo, Lucas; Díaz-Gil, Juan D; Isaza-Guzmán, Diana M; Tobón-Arroyave, Sergio I

2014-01-01

The aim of this study was to compare the effect of two sugar-substituted chewing gums besides toothbrushing on different clinical, microbiological, and biochemical caries- and gingivitis-related variables. The study was designed as a double-blind, randomized, controlled trial with three parallel arms. A total of 130 dental students, who volunteered after signing an informed consent, were randomly allocated to receive one of the following interventions: hexitol-sweetened gum containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), pentitol-sweetened gum containing no CPP-ACP, and control group with no gum. Subjects within the experimental groups chewed two gum pellets for 20 min three times a day after meals. The daily consumption level of both polyols was 6.0 g. Clinical examinations and salivary samplings were conducted at baseline and after 30 days of gum use. Pre- and post-intervention stimulated whole saliva samples were quantified for calcium/phosphate ionic concentration, total facultative bacterial load, Streptococcus mutans/Lactobacillus spp. counts, and Gram-negative percentage. A statistically significant reduction in visible plaque score was displayed in the hexitol/CPP-ACP gum group after the intervention when compared with baseline, but the order of the effect was in the same order as the differences between the groups at baseline. A similar tendency was seen in both the pentitol/non-CPP-ACP gum and control groups regarding total salivary facultative bacterial load and S. mutans count, but median values of these parameters were more significantly reduced in the pentitol/non-CPP-ACP gum group in comparison with those of the control group. Alterations of salivary Lactobacillus spp. were demonstrated only in the pentitol/non-CPP-ACP gum group. Although these findings might indicate that a 30-day protocol of daily chewing of pentitol-sweetened gum containing no CPP-ACP might have some a reducing effect on the salivary levels of facultative bacteria, S. mutans and Lactobacillus spp., there was only a marginal, if any, benefit from the chewing gums under study on some microbiological caries- and gingivitis-related variables. Taking into account that for transferring results into clinically relevant conclusions the findings need to be strong and consistent, adhering to single significant differences appears not appropriate. Hence, the clinical significance of chewing gums as an adjunctive tool for daily oral care remained questionable.

Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.

PubMed

Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

2016-01-01

The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg ( P <0.05), and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg ( P <0.006). A decrease in vWF was seen in the female population consuming nattokinase ( P <0.1). In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h), an increase was seen for 66% of the people after 8-week consumption of nattokinase ( P <0.1), in contrast to only 8% in the placebo group. The data suggest that nattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

PubMed Central

Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

2016-01-01

Objective The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. Materials and methods A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Results Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05), and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006). A decrease in vWF was seen in the female population consuming nattokinase (P<0.1). In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h), an increase was seen for 66% of the people after 8-week consumption of nattokinase (P<0.1), in contrast to only 8% in the placebo group. Conclusion The data suggest that nattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase’s effect on vWF and hypertension. PMID:27785095

The impact of arm position on the measurement of orthostatic blood pressure.

PubMed

Guss, David A; Abdelnur, Diego; Hemingway, Thomas J

2008-05-01

Blood pressure is a standard vital sign in patients evaluated in an Emergency Department. The American Heart Association has recommended a preferred position of the arm and cuff when measuring blood pressure. There is no formal recommendation for arm position when measuring orthostatic blood pressure. The objective of this study was to assess the impact of different arm positions on the measurement of postural changes in blood pressure. This was a prospective, unblinded, convenience study involving Emergency Department patients with complaints unrelated to cardiovascular instability. Repeated blood pressure measurements were obtained using an automatic non-invasive device with each subject in a supine and standing position and with the arm parallel and perpendicular to the torso. Orthostatic hypotension was defined as a difference of >or= 20 mm Hg systolic or >or= 10 mm Hg diastolic when subtracting standing from supine measurements. There were four comparisons made: group W, arm perpendicular supine and standing; group X, arm parallel supine and standing; group Y, arm parallel supine and perpendicular standing; and group Z, arm perpendicular supine and parallel standing. There were 100 patients enrolled, 55 men, mean age 44 years. Four blood pressure measurements were obtained on each patient. The percentage of patients meeting orthostatic hypotension criteria in each group was: W systolic 6% (95% CI 1%, 11%), diastolic 4% (95% CI 0%, 8%), X systolic 8% (95% CI 3%, 13%), diastolic 9% (95% CI 3%, 13%), Y systolic 19% (95% CI 11%, 27%), diastolic 30% (95% CI 21%, 39%), Z systolic 2% (95% CI 0%, 5%), diastolic 2% (95% CI 0%, 5%). Comparison of Group Y vs. X, Z, and W was statistically significant (p < 0.0001). Arm position has a significant impact on determination of postural changes in blood pressure. The combination of the arm parallel when supine and perpendicular when standing may significantly overestimate the orthostatic change. Arm position should be held constant in supine and standing positions when assessing for orthostatic change in blood pressure.

Improvement in health-related quality of life after therapy with omeprazole in patients with coronary artery disease and recurrent angina-like chest pain. A double-blind, placebo-controlled trial of the SF-36 survey

PubMed Central

2011-01-01

Background Many patients with coronary artery disease (CAD) have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs). The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL) in patients with CAD. Study 48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy. Results Patients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health), as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being. Conclusions A double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo. PMID:21939510

Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief depression: results from an exploratory randomized, double-blind, placebo-controlled treatment study.

PubMed

Baldwin, David S; Green, Mary; Montgomery, Stuart A

2014-11-01

'Recurrent brief depression' (RBD) is a common, distressing and impairing depressive disorder for which there is no current proven pharmacological or psychological treatment. This multicentre, randomized, fixed-dose, parallel-group, placebo-controlled study of the reversible inhibitor of monoamine oxidase moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day) evaluated the potential efficacy of active medication, when compared with placebo, in patients with recurrent brief depression, recruited in the mid-1990s. After a 2-4-week single-blind placebo run-in period, a total of 35 patients were randomized to receive double-blind medication for 4 months, but only 16 completed the active treatment period. An intention-to-treat analysis of the 34 evaluable patients found no evidence for the efficacy of moclobemide or imipramine, when compared with placebo, in significantly reducing the severity, duration or frequency of depressive episodes. A total of 28 patients experienced at least one adverse event, and four patients engaged in nonfatal self-harm. Limitations of the study include the small sample size and the high rate of participant withdrawal. The lack of efficacy of these antidepressant drugs and the previous finding of the lack of efficacy of the selective serotonin reuptake inhibitor fluoxetine together indicate that medications other than antidepressant drugs should be investigated as potential treatments for what remains a common, distressing and potentially hazardous condition.

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

PubMed

Verlaet, Annelies A J; Ceulemans, Berten; Verhelst, Helene; Van West, Dirk; De Bruyne, Tess; Pieters, Luc; Savelkoul, Huub F J; Hermans, Nina

2017-03-28

Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.

Treatment of Diabetic Foot Ulcers through Systemic Effects of Extremely Low Frequency Electromagnetic Fields

NASA Astrophysics Data System (ADS)

Trejo-Núñez, A. D.; Pérez-Chávez, F.; García-Sánchez, C.; Serrano-Luna, G.; Cañendo-Dorantes, L.

2008-08-01

This study was designed to, investigate the healing effects of extremely low frequency electromagnetic fields (ELF-EMF) on diabetic foot ulcers and test two different exposure systems aimed at reducing the ELF-EMF exposure time of patients. In the first system the ELF-EMF were applied to the arm where only 3% of the total blood volume/min circulates at any given time. In the second system the ELF-EMF were applied to the thorax where more than 100% of the total blood volume/minute circulates at any given time. Twenty-six diabetic patients, with superficial neuropathic ulcers unresponsive to medical treatment were included in this preliminary report. In the first group (17 patients), the arm was exposed two hours twice a week to a extremely low frequency electromagnetic field of 0.45-0.9 mTrms, 120 Hz generated inside a solenoid coil of 10.1 cm by 20.5 cm long. In the second group the thorax of 7 patients was exposed 25 minutes twice a week to an electromagnetic field of 0.4-0.85 mTrms, 120 Hz generated in the center of a squared quasi-Helmholtz coil 52 cm by side. One patient was assigned to a placebo configuration of each exposure system with identical appearance as the active equipment but without magnetic field. Patients with deep ulcers, infected ulcers, cancer, or auto-immune disease were excluded. These preliminary results showed that the two exposure systems accelerate the healing process of neuropathic ulcers. Complete healing of the ulcer had a median duration of 90 days in both exposure systems. Therefore thorax exposure where more blood is exposed to ELF-EMF per unit of time was able to reduce 4.8 times the patient treatment time. In those patients assigned to the placebo equipment no healing effects were observed. This study will continue with a parallel, double blind placebo controlled protocol.

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

A novel submucosal injection solution for endoscopic resection of large colorectal lesions: a randomized, double-blind trial.

PubMed

Repici, Alessandro; Wallace, Michael; Sharma, Prateek; Bhandari, Pradeep; Lollo, Gianluca; Maselli, Roberta; Hassan, Cesare; Rex, Douglas K

2018-05-08

SIC-8000 (Eleview) is a new FDA-approved solution for submucosal injection developed to provide long-lasting cushion to facilitate endoscopic resection maneuvers. Our aim was to compare the efficacy and safety of SIC-8000 with those of saline solution, when performing endoscopic mucosal resection (EMR) of large colorectal lesions. In a randomized double-blind trial, patients undergoing EMR for ≥20 mm colorectal non-pedunculated lesions were randomized in a 1:1 ratio between SIC-8000 and saline solution as control solution in 5 tertiary centers. Endoscopists and patients were blinded to the type of submucosal solution used. Total volume to complete EMR and per lesion size and time of resection were primary end-points, whereas the Sydney Resection Quotient (SRQ), as well as other EMR outcomes, and the rate of adverse events were secondary. A 30-day telephone follow up was performed. An alpha level <0.05 was considered as statistically significant (NCT 02654418). Of the 327 patients screened, 226 (mean age: 66±10; males: 56%) were enrolled in the study and randomized between the 2 submucosal agents. Of these, 211 patients (mean size of the lesions 33±13 mm; I-s: 36%; proximal colon: 74%) entered in the final analysis (SIC-8000: 102; saline solution: 109). EMR was complete in all cases. The total volume needed for EMR was significantly less in the SIC-8000 arm compared with saline solution (16.1±9.8 mL vs 31.6±32.0 mL; p<0.001). This corresponded to an average volume per lesion size of 0.5±0.3 mL/mm and 0.9±0.6 mL/mm with SIC-8000 and saline solution, respectively, (p<0.001). The mean time to completely resect the lesion tended to be lower with SIC-8000 as compared with saline solution (19.1±16.8 minutes vs 29.7±68.9 minutes; p=0.1). The SRQ was significantly higher with SIC-8000 as compared with saline solution (10.3±8.1 vs 8.0±5.7; p=0.04) with a trend for a lower number of resected pieces (5.7±6.0 vs 6.5±5.04; p=0.052) and a higher rate of en bloc resections (19/102, 18.6% vs 12/111, 11.0%; p=0.1). The rate of adverse events was similar between the 2 arms (SIC-8000: 18.6%, saline solution: 17%), and none of the serious adverse events (SIC-8000: 8.8%; saline solution: 10.7%) was related with study treatment. In a double-blind, randomized clinical trial, a new FDA approved agent for sub-mucosal injection appeared to be a more effective and equally safe submucosal agent for EMR injection than saline solution. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Structural Studies of Three-Arm Star Block Copolymers Exposed to Extreme Stretch Suggests a Persistent Polymer Tube

NASA Astrophysics Data System (ADS)

Mortensen, Kell; Borger, Anine L.; Kirkensgaard, Jacob J. K.; Garvey, Christopher J.; Almdal, Kristoffer; Dorokhin, Andriy; Huang, Qian; Hassager, Ole

2018-05-01

We present structural small-angle neutron scattering studies of a three-armed polystyrene star polymer with short deuterated segments at the end of each arm. We show that the form factor of the three-armed star molecules in the relaxed state agrees with that of the random phase approximation of Gaussian chains. Upon exposure to large extensional flow conditions, the star polymers change conformation resulting in a highly stretched structure that mimics a fully extended three-armed tube model. All three arms are parallel to the flow, one arm being either in positive or negative stretching direction, while the two other arms are oriented parallel, right next to each other in the direction opposite to the first arm.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

A Randomized Double-Blinded Trial on the Effects of Ultrasound Transducer Orientation on Teaching and Learning Ultrasound-Guided Regional Anesthesia.

PubMed

Lam, Nicholas C K; Baker, Elizabeth B; Fishburn, Steven J; Hammer, Angie R; Petersen, Timothy R; Mariano, Edward R

2016-07-01

Learning ultrasound-guided regional anesthesia skills, especially needle/ beam alignment, can be especially difficulty for trainees, who can often become frustrated. We hypothesized that teaching novices to orient the transducer and needle perpendicular to their shoulders will improve performance on a standardized task, compared to holding the transducer and needle parallel to the shoulders. This study compared the effects of transducer orientation on trainees' ability to complete a standardized ultrasound-guided nerve block simulation. The time to task completion and percentage of the attempt time without adequate needle visualization were measured. Participants were right-handed healthy adults with no previous ultrasound experience and were randomly assigned to training in either transducer and needle alignment in a coronal plane, parallel to the shoulders (parallel group) or transducer and needle alignment in a sagittal plane, perpendicular to the shoulders (perpendicular group). Participants used ultrasound to direct a needle to 3 targets in a standardized gelatin phantom and repeated this task 3 times. Their efforts were timed and evaluated by an assessor, who was blinded to group assignment. Data were analyzed on 28 participants. The perpendicular group was able to complete the task more quickly (P < .001) and with a smaller proportion of time lost to inadequate needle visualization (P < .001). Ultrasound-guided regional anesthesia trainees complete a standardized task more quickly and efficiently when instructed to hold the transducer and needle in an orientation perpendicular to their shoulders.

Randomized trial of the effectiveness of combined behavioral/pharmacological smoking cessation treatment in Syrian primary care clinics.

PubMed

Ward, Kenneth D; Asfar, Taghrid; Al Ali, Radwan; Rastam, Samer; Weg, Mark W Vander; Eissenberg, Thomas; Maziak, Wasim

2013-02-01

Effectiveness of nicotine replacement therapy (NRT) for smoking cessation has not been evaluated in low income countries, such as Syria, where it is expensive and not widely available. We evaluated whether nicotine patch boosts smoking cessation rates when used in conjunction with behavioral support in primary care clinics in Aleppo, Syria. Two arm, parallel group, randomized, placebo controlled, double-blinded multi-site trial. Four primary care clinics in Aleppo, Syria.  Two hundred and sixty-nine adult primary care patients received behavioral cessation counseling from a trained primary care physician and were randomized to receive six weeks of treatment with nicotine versus placebo patch. Primary end-points were prolonged abstinence (no smoking after a 2-week grace period) at end of treatment, and 6 and 12 months post-quit day, assessed by self-report and exhaled carbon monoxide levels of <10 p.p.m. Treatment adherence was excellent and nicotine patch produced expected reductions in urges to smoke and withdrawal symptoms, but no treatment effect was observed. The proportion of patients in the nicotine and placebo groups with prolonged abstinence was 21.6% and 20.0%, respectively, at end of treatment, 13.4% and 14.1% at 6 months, and 12.7% and 11.9% at 12 months.  Nicotine patches may not be effective in helping smokers in low-income countries to stop when given as an adjunct to behavioural support. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Euiiyin-tang in the treatment of obesity: study protocol for a randomised controlled trial.

PubMed

Cheon, Chunhoo; Jang, Soobin; Park, Jeong-Su; Ko, Youme; Kim, Doh Sun; Lee, Byung Hoon; Song, Hyun Jong; Song, Yun-Kyung; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

2017-06-21

Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity. This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory. The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine. ClinicalTrials.gov, NCT01724099 . Registered on 2 November 2012.

Effect of a chlorhexidine-containing brush-on gel on peri-implant mucositis.

PubMed

Hallström, H; Lindgren, S; Twetman, S

2017-05-01

The aim was to evaluate the effect of a chlorhexidine-containing brush-on gel when used as supplement to oral hygiene instructions and mechanical debridement, on peri-implant mucositis in adults. The study group consisted of 38 adults (48-87 years.) with peri-implant mucositis that were consecutively enrolled in three private clinics after informed consent. The study employed a double-blind controlled design with two parallel arms. After baseline registrations, oral hygiene reinforcement and mechanical debridement, the patients were randomly allocated to either a test group with once daily tooth brushing with an oral care brush-on gel containing 0.2% chlorhexidine digluconate (Cervitec Gel) or a control gel group. The duration of the intervention was 12 weeks. The primary outcome was bleeding on probing (BOP) and secondary endpoints were local plaque score (LPS) and pocket probing depth (PPD). The groups were balanced at baseline. The daily use of the chlorhexidine-containing gel resulted in reduced BOP after 4 and 12 weeks compared with the control group (P < 0.05). The PPD was significantly reduced (P < 0.05) after 12 weeks compared to baseline in the test group, but not in the control group. No side effects or adverse events were reported. The present findings indicated moderate but significant improvements of clinical parameters when mechanical debridement was combined with a self-applied oral care brush-on gel for the management of peri-implant mucositis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation

PubMed Central

Salimpour, Yousef; Mari, Zoltan K.

2015-01-01

In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via noninvasive cortical stimulation. In addition to reducing effort costs associated with the affected arm, the cortical stimulation also improved clinical motor symptoms of the disease. PMID:26338339

Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: a Phase 3, double-blind, randomized study.

PubMed

Pullman, J; Gardovskis, J; Farley, B; Sun, E; Quintas, M; Lawrence, L; Ling, R; Cammarata, S

2017-12-01

Delafloxacin is an investigational anionic fluoroquinolone in development for oral or intravenous administration for the treatment of infections caused by Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms. To establish the non-inferiority of delafloxacin compared with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections and to compare the safety of the two antimicrobials. A Phase 3, multicentre, randomized, double-blind, active-controlled study with 660 patients compared delafloxacin 300 mg or vancomycin 15 mg/kg plus aztreonam 2 g each administered twice daily intravenously for 5-14 days. Non-inferiority was evaluated by objective response (≥20% erythema reduction) at 48-72 h after initiation of study drug, investigator subjective assessment of outcome and microbiological responses. Clinical Trials Registration: NCT01811732. EudraCT number: 2012-001767-71. In the ITT analysis set, the objective response was 78.2% in the delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment difference, -2.6%; 95% CI, -8.78% to 3.57%). Investigator-assessed cure was similar between the two groups at follow-up (52.0% versus 50.5%) and late follow-up (70.4% versus 66.6%). Bacterial eradication of MRSA was 100% and 98.5% in the delafloxacin group and the vancomycin/aztreonam group, respectively. Frequency of treatment-emergent adverse events in the delafloxacin and vancomycin/aztreonam groups was similar. Treatment-emergent adverse events leading to study drug discontinuation were higher in the vancomycin/aztreonam group compared with the delafloxacin group (4.3% versus 0.9%). Delafloxacin, an anionic fluoroquinolone, was statistically non-inferior to vancomycin/aztreonam at 48-72 h following the start of therapy and was well tolerated as monotherapy in the treatment of acute bacterial skin and skin structure infections. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: a Phase 3, double-blind, randomized study

PubMed Central

Pullman, J; Gardovskis, J; Farley, B; Sun, E; Quintas, M; Lawrence, L; Ling, R; Cammarata, S

2017-01-01

Abstract Background Delafloxacin is an investigational anionic fluoroquinolone in development for oral or intravenous administration for the treatment of infections caused by Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms. Objectives To establish the non-inferiority of delafloxacin compared with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections and to compare the safety of the two antimicrobials. Patients and methods A Phase 3, multicentre, randomized, double-blind, active-controlled study with 660 patients compared delafloxacin 300 mg or vancomycin 15 mg/kg plus aztreonam 2 g each administered twice daily intravenously for 5–14 days. Non-inferiority was evaluated by objective response (≥20% erythema reduction) at 48–72 h after initiation of study drug, investigator subjective assessment of outcome and microbiological responses. Clinical Trials Registration: NCT01811732. EudraCT number: 2012-001767-71. Results In the ITT analysis set, the objective response was 78.2% in the delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment difference, −2.6%; 95% CI, −8.78% to 3.57%). Investigator-assessed cure was similar between the two groups at follow-up (52.0% versus 50.5%) and late follow-up (70.4% versus 66.6%). Bacterial eradication of MRSA was 100% and 98.5% in the delafloxacin group and the vancomycin/aztreonam group, respectively. Frequency of treatment-emergent adverse events in the delafloxacin and vancomycin/aztreonam groups was similar. Treatment-emergent adverse events leading to study drug discontinuation were higher in the vancomycin/aztreonam group compared with the delafloxacin group (4.3% versus 0.9%). Conclusions Delafloxacin, an anionic fluoroquinolone, was statistically non-inferior to vancomycin/aztreonam at 48–72 h following the start of therapy and was well tolerated as monotherapy in the treatment of acute bacterial skin and skin structure infections. PMID:29029278

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

PubMed Central

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

2014-01-01

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

Randomized, double-blind, placebo controlled pilot study of intradetrusor injections of onabotulinumtoxinA for the treatment of refractory overactive bladder persisting following surgical management of benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Dunphy, Claire; Lee, Richard; Lee, Daniel; Sheth, Seema; Marks, Leonard; Kaplan, Steven A; Te, Alexis E

2014-04-01

We assessed the efficacy of onabotulinumtoxinA (BOTOX, Allergan Inc., Irvine, CA, USA) in patients with refractory overactive bladder (OAB) after treatment for benign prostatic hyperplasia (BPH). This was a two-center, randomized, double-blinded pilot study conducted in patients with OAB secondary to bladder outlet obstruction (BOO), refractory to anticholinergic medication and persistent for greater than 3 months after surgical intervention to relieve obstruction, with an International Prostate Symptom Score (IPSS) > 12. Patients were randomized in 1:1 fashion to either 200 units of onabotulinumtoxinA versus placebo. Fifteen patients received onabotulinumtoxinA versus 13 who received placebo. Follow up was performed at 1 week and then 1, 3, 6, and 9 months. The primary endpoint was reduction in the frequency of micturition per 24 hours by 3-day voiding diary. Secondary endpoints were maximum flow rate (Qmax), post-void residual (PVR), and IPSS scores. Patients receiving onabotulinumtoxinA demonstrated significantly improved quality of life scores at 180 and 270 days after treatment (p = 0.02 and 0.03, respectively) as well as significantly lower International Consultation on Incontinence Questionnaire (ICIQ) scores (p < 0.05). Baseline urinary frequency was 10.5 versus 11.0 voids/day (p = 0.47). Frequency episodes improved from 11 episodes per day to 8 episodes per day in the treatment arm. The placebo arm did not have a decrease in frequency episodes. This response was durable up to 90 days, although this was not statistically significant. IPSS, PVR, and urgency were unchanged postoperatively in both groups. OnabotulinumtoxinA was safe in patients with refractory irritative lower urinary tracts symptoms after surgical treatment of BPH. There were improvements in daily frequency, although the results were not statistically significant. Larger trials are needed to help characterize the utility of onabotulinumtoxinA in the treatment of OAB secondary to BPH.

The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome.

PubMed

Legro, Richard S; Kunselman, Allen R; Brzyski, Robert G; Casson, Peter R; Diamond, Michael P; Schlaff, William D; Christman, Gregory M; Coutifaris, Christos; Taylor, Hugh S; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-05-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Jacobson, Sandra W; Carter, R Colin; Molteno, Christopher D; Stanton, Mark E; Herbert, Jane; Lindinger, Nadine M; Lewis, Catherine E; Dodge, Neil C; Hoyme, H Eugene; Zeisel, Steven H; Meintjes, Ernesta M; Duggan, Christopher P; Jacobson, Joseph L

2018-05-11

We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this paper, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure on infant growth and cognitive function. 69 Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months; recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy prenatal alcohol exposure on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.

PubMed

Wozniak, Janet; Faraone, Stephen V; Chan, James; Tarko, Laura; Hernandez, Mariely; Davis, Jacqueline; Woodworth, K Yvonne; Biederman, Joseph

2015-11-01

We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05). Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. ClinicalTrials.gov identifier: NCT01396486. © Copyright 2015 Physicians Postgraduate Press, Inc.

Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital.

PubMed

Knudson, Rachel A; Dunlavy, Paul W; Franko, Jan; Raman, Shankar R; Kraemer, Soren R

2016-09-01

Prior industry conducted studies have shown that long acting liposomal bupivacaine injection improves pain control postoperatively. To evaluate whether liposomal bupivacaine reduced the use of postoperative opioid (http://links.lww.com/DCR/A253) pain medication as compared to standard bupivacaine following colorectal surgery. A double blinded, prospective, randomized controlled trial comparing liposomal bupivacaine versus standard bupivacaine in patients undergoing elective colon resection. Community hospital with general surgery residency program with all cases performed by colorectal surgeons. Fifty-seven patients were randomized and reported as intention-to-treat analysis with 6 protocol violations. Sensitivity analysis excluding these 6 patients demonstrated no change in study results or conclusion. Mean age was 67 ± 2 years and 56% were male. There were 36 patients who underwent minimally invasive surgery, and 21 patients had an open colon resection. Experimental arm received liposomal bupivacaine while control arm received standard bupivacaine. Primary outcome measure was intravenous hydromorphone equivalent used via PCA during first 48 hours after operation. There was no significant difference between the two groups in the amount of opioid used orally or intravenously in the postoperative period. The primary outcome measure was PCA hydromorphone consumption during first two postoperative days after operation (hydromorphone equivalent use in standard bupivacaine group 11.3 ± 8.9 mg versus 13.3 ± 11.9 mg in liposomal bupivacaine group, p = 0.58 Mann-Whitney test). Small pragmatic trials typically remain underpowered for secondary analyses. A larger study could help to further delineate other outcomes that are impacted by postoperative pain. Liposomal bupivacaine did not change the amount of opioid used postoperatively. Based on our study, liposomal bupivacaine does not provide any added benefit over conventional bupivacaine after colon resection. (ClinicalTrials.gov: NCT02052557).

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

PubMed

Powell, Jerry; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Maas Enriquez, Monika; Schwartz, Lawrence; Ingerslev, Jørgen

2012-11-01

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME II (PPCOS II) TRIAL: RATIONALE AND DESIGN OF A DOUBLE-BLIND RANDOMIZED TRIAL OF CLOMIPHENE CITRATE AND LETROZOLE FOR THE TREATMENT OF INFERTILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

PubMed Central

Legro, Richard S.; Kunselman, Allen R.; Brzyski, Robert G.; Casson, Peter R.; Diamond, Michael P.; Schlaff, William D.; Christman, Gregory M.; Coutifaris, Christos; Taylor, Hugh S.; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-01-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50 mg every day for 5 days (day 3–7 of cycle), or B) letrozole 2.5 mg every day for 5 days (day 3–7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (× 5 days) or 7.5 mg of letrozole a day (× 5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. PMID:22265923

A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis.

PubMed

Turner, Abigail Norris; Carr Reese, Patricia; Fields, Karen S; Anderson, Julie; Ervin, Melissa; Davis, John A; Fichorova, Raina N; Roberts, Mysheika Williams; Klebanoff, Mark A; Jackson, Rebecca D

2014-11-01

Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban sexually transmitted disease clinic (clinicaltrials.gov registration NCT01450462). All participants received 500 mg of oral metronidazole twice daily for 7 days. Intervention participants (n = 59) also received 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks; control women (n = 59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12, and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not associated with decreased BV recurrence in this high-risk sexually transmitted disease clinic population. Copyright © 2014 Elsevier Inc. All rights reserved.

A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis

PubMed Central

TURNER, Abigail Norris; REESE, Patricia CARR; FIELDS, Karen S.; ANDERSON, Julie; ERVIN, Melissa; DAVIS, John A.; FICHOROVA, Raina N.; ROBERTS, Mysheika Williams; KLEBANOFF, Mark A.; JACKSON, Rebecca D.

2014-01-01

Objective Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. Study design This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban STD clinic (clinicaltrials.gov registration NCT01450462). All participants received 500mg oral metronidazole twice daily for seven days. Intervention participants (n=59) also received nine doses of 50,000 international units of cholecalciferol (vitamin D3) over 24 weeks; control women (n=59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12 and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Results Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Conclusions Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not associated with decreased BV recurrence in this high-risk STD clinic population. PMID:24949544

Technique of Axillary Use of a Combat Ready Clamp to Stop Junctional Bleeding

DTIC Science & Technology

2013-01-01

compressed parallel to—but not on—the clavicle (Fig. 4). 5. Adjust the horizontal arm length by using its locking pin. 6. Adjust the vertical arm by...arm adjustment for square disk head contact atop the target. Fig. 4. Placing the square disk head atop the target, parallel to—but not on—the clavicle

A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

PubMed

Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

2012-07-01

Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

2012-06-01

Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P < 0.001) and at Weeks 1, 2, and 4 (P < 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the lixivaptan group vs. placebo. The TMT-B and MOS-6 showed no significant differences between groups. Lixivaptan was well tolerated-thirst and polyuria occurred more frequently vs. placebo. In outpatients with HF and volume overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

The effect of a corticosteroid cream and a barrier-strengthening moisturizer in hand eczema. A double-blind, randomized, prospective, parallel group clinical trial.

PubMed

Lodén, M; Wirén, K; Smerud, K T; Meland, N; Hønnås, H; Mørk, G; Lützow-Holm, C; Funk, J; Meding, B

2012-05-01

Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment. The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema. The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1%) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient's skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale. Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion. Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Choi, Ji-Young; Paik, Doo-Jin; Kwon, Dae Young; Park, Yongsoon

2014-04-22

The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/μL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

PubMed

Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen; Nielsen, René Ernst; Berk, Michael; Dean, Olivia May; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee

2018-04-05

Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial

PubMed Central

Meyer-Gerspach, Anne Christin; Cajacob, Lucian; Riva, Daniele; Herzog, Raphael; Drewe, Juergen; Beglinger, Christoph; Wölnerhanssen, Bettina K.

2016-01-01

Background/Objectives The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. Subjects/Methods The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water. Results Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects. Conclusions It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance. Trial Registration ClinicalTrials.gov NCT01875575 PMID:26942445

Effect of Probiotic Curd on Salivary pH and Streptococcus mutans: A Double Blind Parallel Randomized Controlled Trial.

PubMed

Srivastava, Shivangi; Saha, Sabyasachi; Kumari, Minti; Mohd, Shafaat

2016-02-01

Dairy products like curd seem to be the most natural way to ingest probiotics which can reduce Streptococcus mutans level and also increase salivary pH thereby reducing the dental caries risk. To estimate the role of probiotic curd on salivary pH and Streptococcus mutans count, over a period of 7 days. This double blind parallel randomized clinical trial was conducted at the institution with 60 caries free volunteers belonging to the age group of 20-25 years who were randomly allocated into two groups. Test Group consisted of 30 subjects who consumed 100ml of probiotic curd daily for seven days while an equal numbered Control Group were given 100ml of regular curd for seven days. Saliva samples were assessed at baseline, after ½ hour 1 hour and 7 days of intervention period using pH meter and Mitis Salivarius Bacitracin agar to estimate salivary pH and S. mutans count. Data was statistically analysed using Paired and Unpaired t-test. The study revealed a reduction in salivary pH after ½ hour and 1 hour in both the groups. However after 7 days, normal curd showed a statistically significant (p< 0.05) reduction in salivary pH while probiotic curd showed a statistically significant (p< 0.05) increase in salivary pH. Similarly with regard to S. mutans colony counts probiotic curd showed statistically significant reduction (p< 0.05) as compared to normal curd. Short-term consumption of probiotic curds showed marked salivary pH elevation and reduction of salivary S. mutans counts and thus can be exploited for the prevention of enamel demineralization as a long-term remedy keeping in mind its cost effectiveness.

Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in overweight adults: a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

PubMed

Cho, Young-Gyu; Jung, Ji-Hye; Kang, Jae-Heon; Kwon, Jin Soo; Yu, Seung Pil; Baik, Tae Gon

2017-07-28

YY-312 is a herbal extract powder from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode, which have health promoting effects, including body fat reduction. We aimed to evaluate the efficacy and safety of YY-312 for body fat reduction in overweight adults. This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial performed in overweight Korean adults aged 19-60 years with a body mass index of 25.0-29.9 kg/m 2 . The daily dose of YY-312 was 2400 mg (containing 1800 mg of active herbal extract and 600 mg of cyclodextrin). Primary outcomes were reductions in body fat mass (BFM) and body fat percentage (BF%) after 12 weeks. Secondary outcomes included reductions in body weight and waist circumference (WC) after 12 weeks. After 12 weeks, BFM (1.6 kg vs. 0.1 kg; P = 0.023) and BF% (1.5% vs. -0.2%; P = 0.018) decreased significantly more in the YY-312 group than in the placebo group, as did body weight (2.7 kg vs. 1.0 kg; P = 0.014) and WC (2.2 cm vs. 0.8 cm; P = 0.049). All safety parameters were within normal limits; no serious adverse events occurred in either group. In a 12-week clinical trial in overweight adults, YY-312 resulted in significantly greater reduction in body fat vs. placebo, while being safe and well tolerated. cris.nih.go.kr: ( KCT0001225 ).

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

PubMed

Gao, Jian-Wei; Gao, Xue-Min; Zou, Ting; Zhao, Tian-Meng; Wang, Dong-Hua; Wu, Zong-Gui; Ren, Chang-Jie; Wang, Xing; Geng, Nai-Zhi; Zhao, Ming-Jun; Liang, Qiu-Ming; Feng, Xing; Yang, Bai-Song; Shi, Jun-Ling; Hua, Qi

2018-03-01

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group. Copyright© by the Chinese Pharmaceutical Association.

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

PubMed

Serpell, M; Ratcliffe, S; Hovorka, J; Schofield, M; Taylor, L; Lauder, H; Ehler, E

2014-08-01

Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ(9) -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study. In total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co-primary efficacy endpoints were the 30% responder rate in PNP 0-10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated. At the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention-to-treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05-3.70]. There was also a reduction in mean PNP 0-10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0-10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment. These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified. © 2014 European Pain Federation - EFIC®

The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.

PubMed

Tian, Jinzhou; Shi, Jing; Wei, Mingqing; Qin, Renan; Ni, Jingnian; Zhang, Xuekai; Li, Ting; Wang, Yongyan

2016-06-08

Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.

Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial

PubMed Central

Usall, Judith; Huerta-Ramos, Elena; Labad, Javier; Cobo, Jesús; Núñez, Christian; Creus, Marta; Parés, Gemma García; Cuadras, Daniel; Franco, José; Miquel, Eva; Reyes, Julio César; Roca, Mercedes

2016-01-01

The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. Trial registration: NCT01573637. PMID:26591005

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

PubMed Central

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

2007-01-01

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

Adjunctive daily supplementation with encapsulated fruit, vegetable and berry juice powder concentrates and clinical periodontal outcomes: a double-blind RCT

PubMed Central

Chapple, Iain L C; Milward, Michael R; Ling-Mountford, Nicola; Weston, Paul; Carter, Kevin; Askey, Keeley; Dallal, Gerard E; De Spirt, Silke; Sies, Helmut; Patel, Dina; Matthews, John B

2012-01-01

Aim A double-blind randomized controlled trial to determine whether dietary supplementation with fruit/vegetable/berry juice powder concentrates, simultaneously with non-surgical periodontal therapy, improved 2-month treatment outcomes. Methods Volunteers with chronic periodontitis were randomly assigned to one of three groups: fruit/vegetable (FV), fruit/vegetable/berry (FVB) or placebo. Supplements were taken daily during non-surgical debridement and maintenance and outcomes assessed at 2, 5 and 8 months after completion. Primary outcomes were mean probing pocket depth (PPD), clinical attachment gain, % sites bleeding on probing (% BOP) at 2 months. Adherence and plasma β-carotene were determined. Results Sixty-one nutritionally replete (by serum biochemistry) volunteers enrolled and 60 (n = 20 per arm) completed the 2-month review. Clinical outcomes improved in all groups at 2 months, with additional improvement in PPD versus placebo for FV (p < 0.03). Gingival crevicular fluid volumes diminished more in supplement groups than placebo (FVB; p < 0.05) at 2 months, but not at later times. The % BOP (5 months) and cumulative plaque scores (8 months) were lowered more in the FV group (p < 0.05). Conclusions Adjunctive juice powder concentrates appear to improve initial pocket depth reductions in nutritionally replete patients, where plasma micronutrient bioavailability is attainable. Definitive multicentre studies in untreated and treated patients are required to ascertain the clinical significance of such changes. PMID:22093005

A Comparison of Genicular Nerve Treatment Using Either Radiofrequency or Analgesic Block with Corticosteroid for Pain after a Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Study.

PubMed

Qudsi-Sinclair, Salima; Borrás-Rubio, Enrique; Abellan-Guillén, Juan F; Padilla Del Rey, María Luz; Ruiz-Merino, Guadalupe

2017-06-01

Knee osteoarthritis is a disease that affects a third of the population over 65 years of age, and it is increasingly becoming a motive for consultation and a source of pain and disability. The gold standard surgical treatment is a total knee arthroplasty; however, 15% to 30% of patients who have undergone surgery continue to experience pain and functional limitation. A double-blind, randomized clinical study compared neurolysis using traditional radiofrequency (RF) to local anesthetic and corticosteroid block of the superolateral, superomedial, and inferomedial branches of the knee genicular nerves in patients who had total knee arthroplasty but still experience pain. Twenty-eight patients, 14 on each treatment arm, were followed for over a 1-year period. A reduction in pain and significant joint function improvement during the first 3 to 6 months was shown, with similar results using both techniques. No adverse effects were noted. An improvement in both disability and quality of life was observed, as well as a reduction in the need for analgesics in both treatment groups. Further clinical trials need to be undertaken, with a larger sample size, in order to demonstrate the efficacy of this technique and to detect the possible appearance of any long-term adverse effects. © 2016 World Institute of Pain.

Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

PubMed

Ghaleiha, Ali; Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Tabrizi, Mina; Hajiaghaee, Reza; Hassanzadeh, Elmira; Akhondzadeh, Shahin

2013-05-01

Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.

PubMed

Drijgers, Rosa L; Verhey, Frans R J; Tissingh, Gerrit; van Domburg, Peter H M F; Aalten, Pauline; Leentjens, Albert F G

2012-09-15

In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population. Copyright © 2012 Elsevier B.V. All rights reserved.

Toward evidence-based medical statistics: a Bayesian analysis of double-blind placebo-controlled antidepressant trials in the treatment of anxiety disorders.

PubMed

Monden, Rei; de Vos, Stijn; Morey, Richard; Wagenmakers, Eric-Jan; de Jonge, Peter; Roest, Annelieke M

2016-12-01

The Food and Drug Administration (FDA) uses a p < 0.05 null-hypothesis significance testing framework to evaluate "substantial evidence" for drug efficacy. This framework only allows dichotomous conclusions and does not quantify the strength of evidence supporting efficacy. The efficacy of FDA-approved antidepressants for the treatment of anxiety disorders was re-evaluated in a Bayesian framework that quantifies the strength of the evidence. Data from 58 double-blind placebo-controlled trials were retrieved from the FDA for the second-generation antidepressants for the treatment of anxiety disorders. Bayes factors (BFs) were calculated for all treatment arms compared to placebo and were compared with the corresponding p-values and the FDA conclusion categories. BFs ranged from 0.07 to 131,400, indicating a range of no support of evidence to strong evidence for the efficacy. Results also indicate a varying strength of evidence between the trials with p < 0.05. In sum, there were large differences in BFs across trials. Among trials providing "substantial evidence" according to the FDA, only 27 out of 59 dose groups obtained strong support for efficacy according to the typically used cutoff of BF ≥ 20. The Bayesian framework can provide valuable information on the strength of the evidence for drug efficacy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in Children with Autism.

PubMed

Tumuluru, Rameshwari V; Corbett-Dick, Patricia; Aman, Michael G; Smith, Tristram; Arnold, L Eugene; Pan, Xueliang; Buchan-Page, Kristin A; Brown, Nicole V; Ryan, Melissa M; Hyman, Susan L; Hellings, Jessica; Williams, Craig; Hollway, Jill A; Lecavalier, Luc; Rice, Robert R; McAuliffe-Bellin, Sarah; Handen, Benjamin L

2017-10-01

Attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention and over activity, occur in approximately one-third of children with autism spectrum disorder (ASD). We describe the rate and duration of adverse events in a randomized controlled trial of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance in children with ASD. We conducted a 10-week, double-blind, 2 × 2 trial of ATX and PT with 128 children (ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6 weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8 mg/(kg·day) and maintained for an additional 4 weeks. An average of seven PT sessions were conducted in the two PT arms. Adverse events (AEs) were assessed through parent ratings of common symptoms on a seven-point Likert severity scale and through direct interviews with study medical staff. ATX was associated with decreased appetite and fatigue, but was otherwise well tolerated. Most reported AEs lasted 4 weeks or less. Unlike reports with typically developing (TD) children, there were no concerns with QTc changes or suicidal ideation. This study extends the findings of previous studies of ATX in ASD by documenting that the type of AEs was similar to that of TD children, with no significant safety concerns.

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.

PubMed

Choung, R S; Talley, N J; Peterson, J; Camilleri, M; Burton, D; Harmsen, W S; Zinsmeister, A R

2007-03-01

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

Randomized trial for superiority of high field strength intra-operative magnetic resonance imaging guided resection in pituitary surgery.

PubMed

Tandon, Vivek; Raheja, Amol; Suri, Ashish; Chandra, P Sarat; Kale, Shashank S; Kumar, Rajinder; Garg, Ajay; Kalaivani, Mani; Pandey, Ravindra M; Sharma, Bhawani S

2017-03-01

Till date there are no randomized trials to suggest the superiority of intra-operative magnetic resonance imaging (IOMRI) guided trans-sphenoidal pituitary resection over two dimensional fluoroscopic (2D-F) guided resections. We conducted this trial to establish the superiority of IOMRI in pituitary surgery. Primary objective was to compare extent of tumor resection between the two study arms. It was a prospective, randomized, outcome assessor and statistician blinded, two arm (A: IOMRI, n=25 and B: 2D-F, n=25), parallel group clinical trial. 4 patients from IOMRI group cross-over to 2D-F group and were consequently analyzed in latter group, based on modified intent to treat method. A total of 50 patients were enrolled till completion of trial (n=25 in each study arm). Demographic profile and baseline parameters were comparable among the two arms (p>0.05) except for higher number of endoscopic procedures and experienced neurosurgeons (>10years) in arm B (p=0.02, 0.002 respectively). Extent of resection was similar in both study arms (A, 94.9% vs B, 93.6%; p=0.78), despite adjusting for experience of operating surgeon and use of microscope/endoscope for surgical resection. We observed that use of IOMRI helped optimize the extent of resection in 5/20 patients (25%) for pituitary tumor resection in-group A. Present study failed to observe superiorty of IOMRI over conventional 2D-F guided resection in pituitary macroadenoma surgery. By use of this technology, younger surgeons could validate their results intra-operatively and hence could increase EOR without causing any increase in complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

How "Blind" Are Double-Blind Studies?

ERIC Educational Resources Information Center

Margraf, Jurgen; And Others

1991-01-01

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

Reliability and Usefulness of Intraoperative 3-Dimensional Imaging by Mobile C-Arm With Flat-Panel Detector.

PubMed

Fujimori, Takahito; Iwasaki, Motoki; Nagamoto, Yukitaka; Kashii, Masafumi; Takao, Masaki; Sugiura, Tsuyoshi; Yoshikawa, Hideki

2017-02-01

Reliability and agreement study. To assess the reliability of intraoperative 3-dimensional imaging with a mobile C-arm (3D C-arm) equipped with a flat-panel detector. Pedicle screws are widely used in spinal surgery. Postoperative computed tomography (CT) is the most reliable method to detect screw misplacement. Recent advances in imaging devices have enabled surgeons to acquire 3D images of the spine during surgery. However, the reliability of these imaging devices is not known. A total of 203 screws were used in 22 consecutive patients who underwent surgery for scoliosis. Screw position was read twice with a 3D C-arm and twice with CT in a blinded manner by 2 independent observers. Screw positions were classified into 4 categories at every 2 mm and then into 2 simpler categories of acceptable or unacceptable. The degree of agreement with respect to screw positions between the double readings was evaluated by κ value. With unanimous agreement between 2 observers regarding postoperative CT readings considered the gold standard, the sensitivity of the 3D C-arm for determining screw misplacement was calculated. A total 804 readings were performed. For the 4-category classification, the mean κ value for the 2 interobserver readings was 0.52 for the 3D C-arm and 0.46 for CT. For the 2-category classification, the mean κ value for the 2 interobserver readings was 0.80 for the 3D C-arm and 0.66 for CT. The sensitivity, specificity, positive predictive value, and negative predictive value of intraoperative imaging with the 3D C-arm were 70%, 95%, 44%, and 98%, respectively. With respect to screws with perforation ≥4 mm, the sensitivity was 83%. No revision surgery was performed. Intraoperative imaging with a 3D C-arm was reliable for detecting screw misplacement and helpful in decreasing the rate of revision surgery for screw misplacement.

Safety and Effectiveness of BufferGel and 0.5% PRO2000 Gel for the Prevention of HIV Infection in Women

PubMed Central

Karim, Salim S Abdool; Richardson, Barbra A; Ramjee, Gita; Hoffman, Irving F; Chirenje, Zvavahera M; Taha, Taha; Kapina, Muzala; Maslankowski, Lisa; Coletti, Anne; Profy, Albert; Moench, Thomas R.; Piwowar-Manning, Estelle; Mâsse, Benoît; Hillier, Sharon L.; Soto-Torres, Lydia

2011-01-01

Objective To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male to female HIV transmission Design Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open label no gel arm. Methods Study participants from Malawi, South Africa, Zambia, Zimbabwe and USA were instructed to apply study gel ≤1 hour before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up. Results The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 Gel, BufferGel, Placebo Gel and No Gel arms were 2.70, 4.14, 3.91 and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 Gel arm was lower than the Placebo Gel arm (Hazard Ratio (HR)=0.7; p=0.10) and the No Gel arm (HR=0.67; p=0.06). HIV incidence rates were similar in the BufferGel and both Placebo Gel (HR=1.10; p=0.63) and No Gel control arms (HR=1.05; p=0.78). HIV incidence was similar in the Placebo Gel and No Gel arms (HR=0.97; p=0.89). Conclusions 0.5% PRO2000 Gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the MDP 301 trial have confirmed that 0.5% PRO2000 has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were safe. PMID:21330907

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study.

PubMed

Shi, Victor; Senni, Michele; Streefkerk, Hendrik; Modgill, Vikas; Zhou, Wenchun; Kaplan, Allen

2018-08-01

PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC). Of the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support. The number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study.

PubMed

Aramwit, Pornanong; Keongamaroon, Orathai; Siritientong, Tippawan; Bang, Nipaporn; Supasyndh, Ouppatham

2012-09-24

Uremic pruritus (UP) is a significant complication in ESRD patients and substantially impairs their quality of life. UP is considered to be a skin manifestation of chronic inflammation. Because sericin can suppress the release of pro-inflammatory cytokines, the purpose of this study was to investigate the short-term safety and efficacy of sericin cream for treating UP in hemodialysis patients. This study used a double-blind design to investigate the effects of random topical administration of sericin cream and cream base (placebo) on either the right or left extremities of hemodialysis patients for 6 weeks. Skin hydration, irritation and pigmentation were evaluated every 2 weeks using Skin Diagnostic SD27. The visual analog scale for itching was also evaluated every 2 weeks, and the Kidney Disease Quality of Life Short Form was performed on the day of each patient's enrollment and after 6 weeks of treatment. Fifty dialysis patients were enrolled, 47 of which completed the study. The hydration of the skin of the patients' extremities increased significantly after administration of sericin cream; significant differences were found between sericin treatment and control after 6 weeks of treatment (p = 0.041 for arms and p = 0.022 for legs, respectively). Moreover, a significant difference was also found in skin irritation between the two treatments (p = 0.013 for arms and p = 0.027 for legs, respectively). At the end of the study, the skin pigmentation level was significantly reduced on both the arms (p = 0.032) and legs (p = 0.021) of the sericin-treated side compared with the side treated with cream base. The mean itching score decreased significantly from moderate to severe at the time of enrollment to mild pruritus after 6 weeks of treatment (p = 0.002). A better quality of life was found in all domains tested although statistically significant differences before and after treatment was found only in the patients' pain scores, the effect of kidney disease on daily life, sleep quality and symptoms or problems related to kidney disease. We conclude that sericin cream has a high potential for reducing UP in hemodialysis patients.The trial registration number of this study is ISRCTN16019033; its public title is "sericin cream reduces pruritus in hemodialysis patients".

Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study

PubMed Central

2012-01-01

Background Uremic pruritus (UP) is a significant complication in ESRD patients and substantially impairs their quality of life. UP is considered to be a skin manifestation of chronic inflammation. Because sericin can suppress the release of pro-inflammatory cytokines, the purpose of this study was to investigate the short-term safety and efficacy of sericin cream for treating UP in hemodialysis patients. Methods This study used a double-blind design to investigate the effects of random topical administration of sericin cream and cream base (placebo) on either the right or left extremities of hemodialysis patients for 6 weeks. Skin hydration, irritation and pigmentation were evaluated every 2 weeks using Skin Diagnostic SD27. The visual analog scale for itching was also evaluated every 2 weeks, and the Kidney Disease Quality of Life Short Form was performed on the day of each patient’s enrollment and after 6 weeks of treatment. Results Fifty dialysis patients were enrolled, 47 of which completed the study. The hydration of the skin of the patients’ extremities increased significantly after administration of sericin cream; significant differences were found between sericin treatment and control after 6 weeks of treatment (p = 0.041 for arms and p = 0.022 for legs, respectively). Moreover, a significant difference was also found in skin irritation between the two treatments (p = 0.013 for arms and p = 0.027 for legs, respectively). At the end of the study, the skin pigmentation level was significantly reduced on both the arms (p = 0.032) and legs (p = 0.021) of the sericin-treated side compared with the side treated with cream base. The mean itching score decreased significantly from moderate to severe at the time of enrollment to mild pruritus after 6 weeks of treatment (p = 0.002). A better quality of life was found in all domains tested although statistically significant differences before and after treatment was found only in the patients’ pain scores, the effect of kidney disease on daily life, sleep quality and symptoms or problems related to kidney disease. Conclusions We conclude that sericin cream has a high potential for reducing UP in hemodialysis patients. The trial registration number of this study is ISRCTN16019033; its public title is “sericin cream reduces pruritus in hemodialysis patients”. PMID:23006933

The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Iafrati, Mark D; Asher, Enrico; Bandyk, Dennis F; Hallett, John W; Lumsden, Alan B; Pearl, Gregory J; Roddy, Sean P; Vijayaraghavan, Krishnaswami; Patel, Amit N

2011-09-27

Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which is usually combined with mortality for AMP-free survival (AFS). Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control) of 48 patients treated with site of service obtained bone marrow cells (BMAC) as well as a systematic review of the literature. Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood). Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6%) and those with tissue loss (46.7%), irrespective of treatment group, was significant (p = 0.0029). In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337). The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067). Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. BMAC shows promise in improving AMP-free survival if the trends in this pilot study are validated in a larger pivotal trial. The difference in amp rate between Rutherford 4 & 5 patients suggests that these patients should be stratified in future RCTs.

Treatment of Opioid Dependent Pregnant Women: Clinical and Research Issues

PubMed Central

Jones, H.E.; Martin, P.R.; Heil, S.H.; Stine, S.M.; Kaltenbach, K.; Selby, P.; Coyle, M.G.; O’Grady, K.E.; Arria, A.M.; Fischer, G.

2008-01-01

This paper addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance is provided to aid clinical decision-making, based on both research evidence and the collective clinical experience of the authors which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project. MOTHER is a double-blind, double-dummy, flexible–dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the opioid dependence treatment among pregnant women and their neonates. The paper begins with a discussion of appropriate assessment during pregnancy, and then addresses clinical management stages, including maintenance medication selection, induction and stabilization, opioid agonist medication management before, during and after delivery, pain management, breast-feeding, and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed. PMID:18248941

Colchicine in Behçet syndrome: a longterm survey of patients in a controlled trial.

PubMed

Hamuryudan, Vedat; Hatemi, Gulen; Tascilar, Koray; Yurdakul, Sebahattin; Mat, Cem; Ozyazgan, Yilmaz; Seyahi, Emire; Ugurlu, Serdal; Yazici, Hasan

2014-04-01

To test the hypothesis that colchicine use during early disease decreases immunosuppressive use in Behçet syndrome (BS) in the long term. Patients with BS who participated in a double-blind, placebo-controlled trial of colchicine 16.6±1.1 years ago were evaluated for immunosuppressive use during the posttrial period. We could contact 90/116 patients; 28 (31%) received immunosuppressives during the posttrial period, 14 being from the colchicine arm. Posttrial colchicine use and cumulative duration were similar between patients who received immunosuppressives and those who did not. Continuous use of colchicine, even when initiated at an early disease stage, does not seem to decrease the use of immunosuppressives in the long term.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

PubMed

Sergiyenko, Nikolay; Sukhina, Ludmila; Bezdetko, Pavel; Kovalenko, Yuriy; Nikitin, Nikolai; Merzbacher, Matthias; Gross, Dorothea; Kohnen, Ralf

2014-05-10

The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. Current Controlled Trials ISRCTN15464650.

Inorganic nitrate as a treatment for acute heart failure: a protocol for a single center, randomized, double-blind, placebo-controlled pilot and feasibility study.

PubMed

Falls, Roman; Seman, Michael; Braat, Sabine; Sortino, Joshua; Allen, Jason D; Neil, Christopher J

2017-08-08

Acute heart failure (AHF) is a frequent reason for hospitalization worldwide and effective treatment options are limited. It is known that AHF is a condition characterized by impaired vasorelaxation, together with reduced nitric oxide (NO) bioavailability, an endogenous vasodilatory compound. Supplementation of inorganic sodium nitrate (NaNO 3 ) is an indirect dietary source of NO, through bioconversion. It is proposed that oral sodium nitrate will favorably affect levels of circulating NO precursors (nitrate and nitrite) in AHF patients, resulting in reduced systemic vascular resistance, without significant hypotension. We propose a single center, randomized, double-blind, placebo-controlled pilot trial, evaluating the feasibility of sodium nitrate as a treatment for AHF. The primary hypothesis that sodium nitrate treatment will result in increased systemic levels of nitric oxide pre-cursors (nitrate and nitrite) in plasma, in parallel with improved vasorelaxation, as assessed by non-invasively derived systemic vascular resistance index. Additional surrogate measures relevant to the known pathophysiology of AHF will be obtained in order to assess clinical effect on dyspnea and renal function. The results of this study will provide evidence of the feasibility of this novel approach and will be of interest to the heart failure community. This trial may inform a larger study.

Pain relief by transcutaneous electric nerve stimulation with bidirectional modulated sine waves in patients with chronic back pain: a randomized, double-blind, sham-controlled study.

PubMed

Shimoji, Koki; Takahashi, Norio; Nishio, Yasuyuki; Koyanagi, Mika; Aida, Sumihisa

2007-01-01

Objectives.  Newly developed bidirectional modulated sine waves (BMW) might provide some derived benefit to patients with low back pain. Pain relief by transcutaneous electric nerve stimulation (TENS) with BMWs was tested. Materials and Methods.  Analgesic effects of BMWs and conventional bidirectional pulsed waves on chronic back pain in 28 patients were compared, and effects of repeated TENS using BMWs on chronic back pain were investigated in 21 patients by means of a randomized double-blind, sham-controlled, parallel-group method. Pain intensity was assessed using numerical rating scale (NRS). Results.  There was significant immediate reduction in NRS in patients receiving BMWs, and 60 min after treatment compared to sham TENS. Weekly repeated treatments using massage and TENS with BMWs for 5 weeks resulted in a decrease of NRS, but there were no significant differences between the TENS plus massage and sham TENS plus massage groups. Conclusions.  This study shows that TENS with BMWs significantly inhibits chronic back pain, and treatment effects are attained within a day. The results also suggest that there were no statistically significant long-term effects of TENS with BMW in the repeated treatment.

Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.

PubMed

Wade, Derick T; Makela, Petra; Robson, Philip; House, Heather; Bateman, Cynthia

2004-08-01

The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.

Diaper dermatitis: a therapeutic dilemma. Results of a double-blind placebo controlled trial of miconazole nitrate 0.25%.

PubMed

Concannon, P; Gisoldi, E; Phillips, S; Grossman, R

2001-01-01

Diaper dermatitis, an acute inflammation of the skin in the diaper area, is the most common dermatologic disorder of infancy. This placebo-controlled, randomized, double-blind, parallel-group trial compared the efficacy and safety of miconazole nitrate 0.25% in a zinc oxide/petrolatum base with that of the ointment base alone in treating acute diaper dermatitis in infants and evaluated the role of Candida albicans in the response to treatment. Infants age 2-13 months with diaper rash were treated with either miconazole nitrate 0.25% (N = 101) or ointment base (N = 101) for 7 days. Although improvement in rash from baseline was seen in both treatment groups on days 3, 5, and 7, patients receiving miconazole nitrate 0.25% had significantly fewer rash sites and lower mean total rash scores on days 5 and 7 (p < 0.001). In the miconazole nitrate 0.25% group, improvement was most marked among those with moderate or severe diaper dermatitis at baseline and among patients whose baseline rashes were positive for C. albicans. Treatment with miconazole nitrate 0.25% was as safe as with ointment base alone. Miconazole nitrate 0.25% ointment is a safe and effective treatment for diaper dermatitis in infants.

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

PubMed

Henderson, V W; Paganini-Hill, A; Miller, B L; Elble, R J; Reyes, P F; Shoupe, D; McCleary, C A; Klein, R A; Hake, A M; Farlow, M R

2000-01-25

AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

PubMed

Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

2004-08-01

Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

Use of honey associated with Ananas comosus (Bromelin) in the treatment of acute irritative cough

PubMed Central

Peixoto, Décio Medeiros; Rizzo, José Angelo; Schor, Deborah; Silva, Almerinda Rêgo; de Oliveira, Dinaldo Cavalcanti; Solé, Dirceu; Sarinho, Emanuel

2016-01-01

Abstract Objective: To evaluate the immediate improvement rate of irritative cough in patients treated with the combination of Ananas comosus extract and honey (Bromelin®) compared with the use of honey alone (placebo group). Methods: Pragmatic, double-blind, randomized, parallel-group study with children aged between 2 and 15 years, with irritative cough for at least 24hours. The double-blind assessment of cough was through the number of observed coughing episodes and intensity score for a period of 10minutes of observation. The decrease of one point in the mean total score was considered as a therapeutic effect. Results: There was a reduction in coughing episodes in both groups, as well as in the cough score after 30minutes of drug or honey administration. The change in clinical score above two points, which could indicate marked improvement, occurred in five patients in the bromelin group and only in one in the placebo group, but without significant difference. There were no adverse events. Conclusions: The immediate improvement rate of irritative cough was similar in patients treated with combination of Ananas comosus extract and honey (Bromelin®) compared with the use of honey alone (placebo group). It is possible that honey has a therapeutic effect on mucus and cough characteristics (Clinical Trials: NCT01356693). PMID:27181342

[Treatment of chronic postinfectious fatigue: randomized double-blind study of two doses of sulbutiamine (400-600 mg/day) versus placebo].

PubMed

Tiev, K P; Cabane, J; Imbert, J C

1999-10-01

Chronic fatigue remains a medical mystery and a therapeutic failure. The subgroup of chronic fatigue postinfectious fatigue (CPIF) is an interesting one since it is quite frequent in general practice. We studied sulbutiamine (Su), isobutyryl-thiamine disulfide in this context. We included 326 general-practice patients suffering from CPIF: they received randomly either Su, 400 mg daily (n = 106), or Su, 600 mg daily (n = 111), or placebo (n = 109) for 28 days in a double-blind, parallel-group study. 315 patients completed the study. The evaluation of fatigue, by multiple means including mainly MFI, a validated multidimensional fatigue scale, showed overall no significant difference between the groups. On the 7th day, however, women receiving Su, 600 mg had less fatigue (P < 0.01), but the figures were quite diverse and no persistent effect was noted at the 28th day. Thus, we showed for the first time that a high level general-practice study of fatigue is feasible using specific tools. Whether the effect observed after 1 week in women represents a true finding needs additional research. Further studies are in progress in order to characterize better the potential usefulness of Su in chronic fatigue.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

PubMed

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-08-02

To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Double blind randomised placebo controlled parallel group study. Hospital in Hampshire. 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Enzyme potentiated desensitisation showed no treatment effect in this study.

[Double-blind randomized comparative study of nicergoline naftidrofuryl on the quality of life in chronic obliterative arteriopathy of lower limbs with intermittent claudication].

PubMed

Meilhac, B; Montestruc, F; Aubin, F; Djian, F; Rouffy, J

1997-01-01

The functional limitation of patients with obliterative arterial disease, and with intermittent claudication, damages their quality of life. The purpose of this trial was to compare the effects of nicergoline and naftidrofuryl on the quality of life and the functional discomfort of the 131 patients with claudication. It was a multicentre, randomised, double-blind trial with parallel groups. The patients were asked to complete a quality of life questionnaire and a Visual Analogue Scale, and to evaluate the number of steps on flat ground before the pain began. After 6 months of treatment, we observed, for all treatments combined, a significant improvement (p = 0.0001) in the quality of life and in the functional discomfort. Three variables favoured nicergoline: the estimated time before the onset of the pain (p = 0.003), the functional discomfort quantified by the Visual Analogue Scale (p < 0.05), the distance covered on flat ground (p = 0.013). The other variables, and especially the total score on the self-questionnaire, confirmed this impression, without reaching significance (p = 0.136). The data suggest that in terms of quality of life nicergoline is superior. The clinical tolerance is good and comparable between the two treatments.

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

PubMed Central

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

2015-01-01

Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

PubMed

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

2015-08-07

Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥ 140 mm Hg and home BP ≥ 130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K(+), clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy

PubMed Central

Lee, Hee Yeon; Lee, Kyung Hee; Kim, Bong-Seog; Song, Hong Suk; Yang, Sung Hyun; Kim, Joon Hee; Kim, Yeul Hong; Kim, Jong Gwang; Kim, Sang-We; Kim, Dong-Wan; Kim, Si-Young; Park, Hee Sook

2014-01-01

Purpose This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. Results Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. Conclusion In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups. PMID:24520219

Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial

PubMed Central

Rawal, Narinder; Macquaire, Valery; Catalá, Elena; Berti, Marco; Costa, Rui; Wietlisbach, Markus

2011-01-01

This randomized, double-blind, double-dummy, multicenter trial compared efficacy and safety of tramadol HCL 37.5 mg/paracetamol 325 mg combination tablet with tramadol HCL 50 mg capsule in the treatment of postoperative pain following ambulatory hand surgery with iv regional anesthesia. Patients received trial medication at admission, immediately after surgery, and every 6 hours after discharge until midnight of the first postoperative day. Analgesic efficacy was assessed by patients (n = 128 in each group, full analysis set) and recorded in a diary on the evening of surgery day and of the first postoperative day. They also documented the occurrence of adverse events. By the end of the first postoperative day, the proportion of treatment responders based on treatment satisfaction (primary efficacy variable) was comparable between the groups (78.1% combination, 71.9% tramadol; P = 0.24) and mean pain intensity (rated on a numerical scale from 0 = no pain to 10 = worst imaginable pain) had been reduced to 1.7 ± 2.0 for both groups. Under both treatments, twice as many patients experienced no pain (score = 0) on the first postoperative day compared to the day of surgery (35.9% vs 16.4% for tramadol/paracetamol and 36.7% vs 18% for tramadol treatment). Rescue medication leading to withdrawal (diclofenac 50 mg) was required by 17.2% patients with tramadol/paracetamol and 13.3% with tramadol. Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004). Tramadol/paracetamol combination tablets provided comparable analgesic efficacy with a better safety profile to tramadol capsules in patients experiencing postoperative pain following ambulatory hand surgery. PMID:21559356

Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease.

PubMed

Thomas, E; Wade, A; Crawford, G; Jenner, B; Levinson, N; Wilkinson, J

2014-03-01

The alginate-antacid, Gaviscon Double Action (Gaviscon DA; Reckitt Benckiser, Slough, UK) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction. The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design. A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease (GERD) patients. A randomised, double-blind, parallel group study was performed in 110 patients with symptoms of GERD. Patients received Gaviscon DA or placebo tablets for 7 consecutive days. The primary endpoint compared the change in overall Reflux Disease Questionnaire (RDQ) symptom score (combined heartburn/regurgitation/dyspepsia). Secondary endpoints assessed individual dimensions, GERD dimension (heartburn and regurgitation) and overall treatment evaluation (OTE). There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group (Least Squares Mean difference -0.55; P = 0.0033), and for each of the dimensions independently. Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [mean (standard deviation) OTE 4.1 (2.44) vs. 1.9 (3.34); P = 0.0005]. No differences in the incidence of adverse events were observed between treatment groups. Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance. Larger scale clinical investigations of medications targeting the acid pocket are warranted. (EudraCT, 2012-002188-84). © 2014 John Wiley & Sons Ltd.

An arginine-rich motif of ring finger protein 4 (RNF4) oversees the recruitment and degradation of the phosphorylated and SUMOylated Krüppel-associated box domain-associated protein 1 (KAP1)/TRIM28 protein during genotoxic stress.

PubMed

Kuo, Ching-Ying; Li, Xu; Kong, Xiang-Qian; Luo, Cheng; Chang, Che-Chang; Chung, Yiyin; Shih, Hsiu-Ming; Li, Keqin Kathy; Ann, David K

2014-07-25

Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM) in RNF4 acts as a novel recognition motif for selective target recruitment. Results from combined mutagenesis and computational modeling studies suggest that RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1 (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated degradation of promyelocytic leukemia protein (PML) under stress. In parallel, results of bimolecular fluorescence complementation assays validated the role of the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks. The conservation of such a motif may possibly explain the requirement for timely substrate selectivity determination among a myriad of SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates the SIM-dependent recruitment of targets to RNF4, which could be critical to dynamically fine-tune the abundance of Ser(P)-824-SUMO-KAP1 and, potentially, other SUMOylated proteins during DNA damage response. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

An Arginine-rich Motif of Ring Finger Protein 4 (RNF4) Oversees the Recruitment and Degradation of the Phosphorylated and SUMOylated Krüppel-associated Box Domain-associated Protein 1 (KAP1)/TRIM28 Protein during Genotoxic Stress*

PubMed Central

Kuo, Ching-Ying; Li, Xu; Kong, Xiang-Qian; Luo, Cheng; Chang, Che-Chang; Chung, Yiyin; Shih, Hsiu-Ming; Li, Keqin Kathy; Ann, David K.

2014-01-01

Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM) in RNF4 acts as a novel recognition motif for selective target recruitment. Results from combined mutagenesis and computational modeling studies suggest that RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1 (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated degradation of promyelocytic leukemia protein (PML) under stress. In parallel, results of bimolecular fluorescence complementation assays validated the role of the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks. The conservation of such a motif may possibly explain the requirement for timely substrate selectivity determination among a myriad of SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates the SIM-dependent recruitment of targets to RNF4, which could be critical to dynamically fine-tune the abundance of Ser(P)-824-SUMO-KAP1 and, potentially, other SUMOylated proteins during DNA damage response. PMID:24907272

Adding a PECS II block for proximal arm arteriovenous access - a randomised study.

PubMed

Quek, K H; Low, E Y; Tan, Y R; Ong, A S C; Tang, T Y; Kam, J W; Kiew, A S C

2018-05-01

Brachial plexus block is often utilised for proximal arm arteriovenous access creation. However, the medial upper arm and axilla are often inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic supplementation, or conversion into general anaesthesia. We hypothesised that the addition of a PECS II block would improve anaesthesia and analgesia for proximal arm arteriovenous access surgery. In this prospective, double-blinded, randomised proof-of-concept study, 36 consenting adults with end-stage renal disease aged between 21 and 90 years received either a combined supraclavicular and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary outcome was whether patients required intraoperative local anaesthetic supplementation by the surgeon. In Group PECS, 33.3% (6/18) needed local anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative local anaesthetic supplementation. Group PECS required lower volume of supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs. 15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1-4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There were no significant differences between the groups with respect to postoperative visual analogue scale pain scores, time to first rescue analgesia or patient satisfaction. The results suggest that adding a PECS II block to a supraclavicular block improves regional anaesthesia for patients with end-stage renal disease undergoing proximal arm arteriovenous access surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Metformin and/or Clomiphene Do Not Adversely Affect Liver or Renal Function in Women with Polycystic Ovary Syndrome

PubMed Central

Aubuchon, Mira; Kunselman, Allen R.; Schlaff, William D.; Diamond, Michael P.; Coutifaris, Christos; Carson, Sandra A.; Steinkampf, Michael P.; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Myers, Evan R.

2011-01-01

Context: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. Objective: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. Design: This was a secondary analysis of a randomized, doubled-blind trial from 2002–2004. Setting: This multi-center clinical trial was conducted in academic centers. Patients: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. Interventions: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. Main Outcome Measure: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. Results: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, −14.7 to −21.3%) as well as creatinine (−4.2 to −6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (−10% in bilirubin, −9 to −11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. Conclusion: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function. PMID:21832111

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

PubMed Central

Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah

2013-01-01

Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Brown, Paul D; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H; Roberge, David; Kavadi, Vivek; Bentzen, Soren M; Mehta, Minesh P; Watkins-Bruner, Deborah

2013-10-01

To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

PubMed

Goetz, Matthew P; Toi, Masakazu; Campone, Mario; Sohn, Joohyuk; Paluch-Shimon, Shani; Huober, Jens; Park, In Hae; Trédan, Olivier; Chen, Shin-Cheh; Manso, Luis; Freedman, Orit C; Garnica Jaliffe, Georgina; Forrester, Tammy; Frenzel, Martin; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Di Leo, Angelo

2017-11-10

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial.

PubMed

Rabadi, Meheroz H; Aston, Christopher E

2017-10-01

The aim of this article was to determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm hand in patients after an acute ischemic stroke compared with sham transcranial direct current stimulation plus conventional OT. In this prospective, randomized, double-blinded, sham-controlled trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n = 8) or control (sham transcranial direct current stimulation plus OT; n = 8) groups. All patients received a standard 3-hr in-patient rehabilitation therapy, plus an additional ten 30-min sessions of tDCS. During each session, 1 mA of cathodal stimulation to the unaffected PMC is performed followed by the patient's scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and subscores on discharge. Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared with a 2-point improvement in the control group. Application of 30-min of c-tDCS to the unaffected PMC showed a 10-point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistically significant, this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study.

PubMed

Bokde, Arun L W; Cavedo, Enrica; Lopez-Bayo, Patricia; Lista, Simone; Meindl, Thomas; Born, Christine; Galluzzi, Samantha; Faltraco, Frank; Dubois, Bruno; Teipel, Stefan J; Reiser, Maximilian; Möller, Hans-Jürgen; Hampel, Harald

2016-03-30

A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

First-Line Therapy for Human Cutaneous Leishmaniasis in Peru Using the TLR7 Agonist Imiquimod in Combination with Pentavalent Antimony

PubMed Central

Miranda-Verastegui, Cesar; Tulliano, GianFranco; Gyorkos, Theresa W.; Calderon, Wessmark; Rahme, Elham; Ward, Brian; Cruz, Maria; Llanos-Cuentas, Alejandro; Matlashewski, Greg

2009-01-01

Background Current therapies for cutaneous leishmaniasis are limited by poor efficacy, long-term course of treatment, and the development of resistance. We evaluated if pentavalent antimony (an anti-parasitic drug) combined with imiquimod (an immunomodulator) was more effective than pentavalent antimony alone in patients who had not previously been treated. Methods A randomized double-blind clinical trial involving 80 cutaneous leishmaniasis patients was conducted in Peru. The study subjects were recruited in Lima and Cusco (20 experimental and 20 control subjects at each site). Experimental arm: Standard dose of pentavalent antimony plus 5% imiquimod cream applied to each lesion three times per week for 20 days. Control arm: Standard dose of pentavalent antimony plus placebo (vehicle cream) applied as above. The primary outcome was cure defined as complete re-epithelization with no inflammation assessed during the 12 months post-treatment period. Results Of the 80 subjects enrolled, 75 completed the study. The overall cure rate at the 12-month follow-up for the intention-to-treat analysis was 75% (30/40) in the experimental arm and 58% (23/40) in the control arm (p = 0.098). Subgroup analyses suggested that combination treatment benefits were most often observed at the Cusco site, where L. braziliensis is the prevalent species. Over the study period, only one adverse event (rash) was recorded, in the experimental arm. Conclusion The combination treatment of imiquimod plus pentavalent antimony performed better than placebo plus pentavalent antimony, but the difference was not statistically significant. Trial Registration Clinical Trials.gov NCT00257530 PMID:19636365

Moxifloxacin in Pediatric Patients with Complicated Intra-Abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study.

PubMed

Wirth, Stefan; Emil, Sherif G S; Engelis, Arnis; Digtyar, Valeri; Criollo, Margarita; DiCasoli, Carl; Stass, Heino; Willmann, Stefan; Nkulikiyinka, Richard; Grossmann, Ulrike

2018-01-18

This study was designed to evaluate primarily the safety and also the efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal infections (cIAIs). In this multicenter, randomized, double-blind, controlled study, 451 pediatric patients aged 3 months to 17 years with cIAIs were treated with intravenous/oral MXF (N = 301) or comparator (COMP, intravenous ertapenem followed by oral amoxicillin/clavulanate; N = 150) for 5 to 14 days. Doses of MXF were selected based on the results of a Phase 1 study in pediatric patients (NCT01049022). The primary endpoint was safety, with particular focus on cardiac and musculoskeletal safety; clinical and bacteriological efficacy at test of cure were also investigated. The proportion of patients with adverse events (AEs) was comparable between the two treatment arms (MXF: 58.1% and COMP: 54.7%). The incidence of drug-related AEs was higher in the MXF arm than the COMP arm (14.3% and 6.7%, respectively). No cases of QTc interval prolongation-related morbidity or mortality were observed. The proportion of patients with musculoskeletal AEs was comparable between treatment arms; no drug-related events were reported. Clinical cure rates were 84.6% and 95.5% in the MXF and COMP arms, respectively, in patients with confirmed pathogen(s) at baseline. MXF treatment was well tolerated in children with cIAIs. However, a lower clinical cure rate was observed with MXF treatment compared with COMP. This study does not support a recommendation of MXF for children with cIAIs when alternative more efficacious antibiotics with better safety profile are available.

Brief Report: Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception.

PubMed

Balkus, Jennifer E; Palanee-Phillips, Thesla; Reddy, Krishnaveni; Siva, Samantha; Harkoo, Ishana; Nakabiito, Clemensia; Kintu, Kenneth; Nair, Gonasangrie; Chappell, Catherine; Kiweewa, Flavia Matovu; Kabwigu, Samuel; Naidoo, Logashvari; Jeenarain, Nitesha; Marzinke, Mark; Soto-Torres, Lydia; Brown, Elizabeth R; Baeten, Jared M

2017-10-01

To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use. A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention. Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection. Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm and 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods. Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially because of poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.

Parallelization of a blind deconvolution algorithm

NASA Astrophysics Data System (ADS)

Matson, Charles L.; Borelli, Kathy J.

2006-09-01

Often it is of interest to deblur imagery in order to obtain higher-resolution images. Deblurring requires knowledge of the blurring function - information that is often not available separately from the blurred imagery. Blind deconvolution algorithms overcome this problem by jointly estimating both the high-resolution image and the blurring function from the blurred imagery. Because blind deconvolution algorithms are iterative in nature, they can take minutes to days to deblur an image depending how many frames of data are used for the deblurring and the platforms on which the algorithms are executed. Here we present our progress in parallelizing a blind deconvolution algorithm to increase its execution speed. This progress includes sub-frame parallelization and a code structure that is not specialized to a specific computer hardware architecture.

A robot arm simulation with a shared memory multiprocessor machine

NASA Technical Reports Server (NTRS)

Kim, Sung-Soo; Chuang, Li-Ping

1989-01-01

A parallel processing scheme for a single chain robot arm is presented for high speed computation on a shared memory multiprocessor. A recursive formulation that is derived from a virtual work form of the d'Alembert equations of motion is utilized for robot arm dynamics. A joint drive system that consists of a motor rotor and gears is included in the arm dynamics model, in order to take into account gyroscopic effects due to the spinning of the rotor. The fine grain parallelism of mechanical and control subsystem models is exploited, based on independent computation associated with bodies, joint drive systems, and controllers. Efficiency and effectiveness of the parallel scheme are demonstrated through simulations of a telerobotic manipulator arm. Two different mechanical subsystem models, i.e., with and without gyroscopic effects, are compared, to show the trade-off between efficiency and accuracy.

New prototype of acousto-optical radio-wave spectrometer with parallel frequency processing for astrophysical applications

NASA Astrophysics Data System (ADS)

Shcherbakov, Alexandre S.; Chavez Dagostino, Miguel; Arellanes, Adan O.; Aguirre Lopez, Arturo

2016-09-01

We develop a multi-band spectrometer with a few spatially parallel optical arms for the combined processing of their data flow. Such multi-band capability has various applications in astrophysical scenarios at different scales: from objects in the distant universe to planetary atmospheres in the Solar system. Each optical arm exhibits original performances to provide parallel multi-band observations with different scales simultaneously. Similar possibility is based on designing each optical arm individually via exploiting different materials for acousto-optical cells operating within various regimes, frequency ranges and light wavelengths from independent light sources. Individual beam shapers provide both the needed incident light polarization and the required apodization to increase the dynamic range of a system. After parallel acousto-optical processing, data flows are united by the joint CCD matrix on the stage of the combined electronic data processing. At the moment, the prototype combines still three bands, i.e. includes three spatial optical arms. The first low-frequency arm operates at the central frequencies 60-80 MHz with frequency bandwidth 40 MHz. The second arm is oriented to middle-frequencies 350-500 MHz with frequency bandwidth 200-300 MHz. The third arm is intended for ultra-high-frequency radio-wave signals about 1.0-1.5 GHz with frequency bandwidth <300 MHz. To-day, this spectrometer has the following preliminary performances. The first arm exhibits frequency resolution 20 KHz; while the second and third arms give the resolution 150-200 KHz. The numbers of resolvable spots are 1500- 2000 depending on the regime of operation. The fourth optical arm at the frequency range 3.5 GHz is currently under construction.

Ambulatory Treatment of Fast Breathing in Young Infants Aged <60 Days: A Double-Blind, Randomized, Placebo-Controlled Equivalence Trial in Low-Income Settlements of Karachi

PubMed Central

Muhammad, Amber A.; Shafiq, Yasir; Shah, Saima; Kumar, Naresh; Ahmed, Imran; Azam, Iqbal; Pasha, Omrana; Zaidi, Anita K. M.

2017-01-01

Abstract Background. Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible. Methods. This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1–8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis. Results. Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms. Conclusions. This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants. Clinical Trials Registration. NCT01533818. PMID:27941119

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

PubMed

Chen, Grace; Nomikos, George G; Affinito, John; Zhao, Zhen

2016-09-01

Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Effect of Transcranial Direct Current Stimulation on Neurorehabilitation of Task-Specific Dystonia: A Double-Blind, Randomized Clinical Trial.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Álvaro

2015-09-01

Task-specific focal hand dystonia can disable affected individuals. Although neurorehabilitation techniques such as sensory motor retuning can result in complete recovery in some patients, it requires many months of treatment. Combining transcranial direct current stimulation (tDCS) with neurorehabilitation is a new and promising approach that can help these patients. However, the results in different studies are contradictory. Analyze whether delivering tDCS (cathode over left and anode over right parietal region) during the neurorehabilitation process for musicians with dystonia can increase the effectiveness of therapy. A parallel double-blind randomized design was used to study 30 musicians with right-hand primary focal dystonia. All patients underwent a 2-week course of neurorehabilitation based on sensory motor retuning therapy coupled with either real or sham tDCS for the first 30 minutes of each daily 1-hour therapy session (total 10 sessions). The therapist and patient were blind to the tDCS condition. A dystonia severity score was obtained before and after the 2-week protocol. The therapist also rated the evolution of each patient. Both groups significantly improved their dystonia severity score during the 2 weeks. Score differences were 88.23 (±40.51) and 63.36 (±30.57) for the active and sham groups, respectively. The active group showed a statistically significant greater improvement. Biparietal tDCS with left-sided cathode is a safe technique that does not interfere with the neurorehabilitation procedure and can increase therapy effectiveness in rehabilitation patients with right-hand task-specific focal dystonia.

Parallel processing architecture for computing inverse differential kinematic equations of the PUMA arm

NASA Technical Reports Server (NTRS)

Hsia, T. C.; Lu, G. Z.; Han, W. H.

1987-01-01

In advanced robot control problems, on-line computation of inverse Jacobian solution is frequently required. Parallel processing architecture is an effective way to reduce computation time. A parallel processing architecture is developed for the inverse Jacobian (inverse differential kinematic equation) of the PUMA arm. The proposed pipeline/parallel algorithm can be inplemented on an IC chip using systolic linear arrays. This implementation requires 27 processing cells and 25 time units. Computation time is thus significantly reduced.

The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

PubMed Central

Black, Jed; Pardi, Daniel; Hornfeldt, Carl S.; Inhaber, Neil

2010-01-01

Objective: To further explore the effects of sodium oxybate (SXB) administration on nocturnal sleep in narcolepsy patients during a double-blind, placebo-controlled, parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States, Canada, and Europe. Method: Patients were withdrawn from antidepressants and sedative/hypnotics, and then randomized to receive 4.5, 6, or 9 g SXB or placebo nightly for 8 weeks. Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments, while patients receiving placebo were randomized to undergo a similar mock dose titration. The use of stimulant therapy continued unchanged. Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms. Daily diaries were used to record changes in narcolepsy symptoms and adverse events. Results: Following 8 weeks of SXB treatment, study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep, reaching a median increase of 52.5 minutes in patients receiving 9 g nightly. Compared to placebo-treated patients, delta power was significantly increased in all dose groups. Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses. The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms. Conclusions: The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep, wake after sleep onset, awakenings, total sleep time, and stage 1 sleep in a dose-related manner. The frequency and severity of narcolepsy symptoms decreased with treatment. Citation: Black J; Pardi D; Hornfeldt CS; Inhaber N. The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption: a double-blind, placebo-controlled study in patients with narcolepsy. J Clin Sleep Med 2010;6(6):596-602. PMID:21206549

Post-hoc analysis of MCI186-17, the extension study to MCI186-16, the confirmatory double-blind, parallel-group, placebo-controlled study of edaravone in amyotrophic lateral sclerosis.

PubMed

Takahashi, Fumihiro; Takei, Koji; Tsuda, Kikumi; Palumbo, Joseph

2017-10-01

In the 24-week double-blind study of edaravone in ALS (MCI186-16), edaravone did not show a statistically significant difference versus placebo for the primary efficacy endpoint. For post-hoc analyses, two subpopulations were identified in which edaravone might be expected to show efficacy: the efficacy-expected subpopulation (EESP), defined by scores of ≥2 points on all 12 items of the ALS Functional Rating Scale-Revised (ALSFRS-R) and a percent predicted forced vital capacity (%FVC) ≥80% at baseline; and the definite/probable EESP 2 years (dpEESP2y) subpopulation which, in addition to EESP criteria, had definite or probable ALS diagnosed by El Escorial revised criteria, and disease duration of ≤2 years. In the 36-week extension study of MCI186-16, a 24-week double-blind comparison followed by 12 weeks of open-label edaravone (MCI186-17; NCT00424463), analyses of ALSFRS-R scores of the edaravone-edaravone group and edaravone-placebo group for the full analysis set (FAS) and EESP, as prospectively defined, were reported in a previous article. Here we additionally report results in patients who met dpEESP2y criteria at the baseline of MCI186-16. In the dpEESP2y, the difference in ALSFRS-R changes from 24 to 48 weeks between the edaravone-edaravone and edaravone-placebo groups was 2.79 (p = 0.0719), which was greater than the differences previously reported for the EESP and the FAS. The pattern of adverse events in the dpEESP2y did not show any additional safety findings to those from the earlier prospective study. In conclusion, this post-hoc analysis suggests a potential effect of edaravone between 24 and 48 weeks in patients meeting dpEESP2y criteria at baseline.

Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation.

PubMed

Johanson, John F; Morton, Dan; Geenen, Joseph; Ueno, Ryuji

2008-01-01

To assess the efficacy and safety of lubiprostone in adults with chronic constipation. This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements (SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement (BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/discomfort; global treatment effectiveness ratings; and safety assessments. The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients (5.69 vs 3.46, P= 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 (P

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

PubMed

Lindsay, Cameron; Simpson, Julie; Ispoglou, Sissi; Sturman, Steve G; Pandyan, Anand D

2014-01-08

Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. ISRCTN57435427, EudraCT2010-021257-39, NCT01882556.

Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.

PubMed

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2010-08-26

Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or arabinogalactan on salivary IgA, white blood cell count, inflammatory cytokines or complement. The proprietary arabinogalactan extract (ResistAid), tested in this randomized, double-blind, placebo-controlled, parallel-group pilot study, increased the antibody response of healthy volunteers to the 23-valent pneumococcal vaccine compared to placebo. ISRCTN98817459.

Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

PubMed Central

2010-01-01

Background Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or arabinogalactan on salivary IgA, white blood cell count, inflammatory cytokines or complement. Conclusions The proprietary arabinogalactan extract (ResistAid™), tested in this randomized, double-blind, placebo-controlled, parallel-group pilot study, increased the antibody response of healthy volunteers to the 23-valent pneumococcal vaccine compared to placebo. Trial Registration ISRCTN98817459 PMID:20796315

Displacement and deformation measurement for large structures by camera network

NASA Astrophysics Data System (ADS)

Shang, Yang; Yu, Qifeng; Yang, Zhen; Xu, Zhiqiang; Zhang, Xiaohu

2014-03-01

A displacement and deformation measurement method for large structures by a series-parallel connection camera network is presented. By taking the dynamic monitoring of a large-scale crane in lifting operation as an example, a series-parallel connection camera network is designed, and the displacement and deformation measurement method by using this series-parallel connection camera network is studied. The movement range of the crane body is small, and that of the crane arm is large. The displacement of the crane body, the displacement of the crane arm relative to the body and the deformation of the arm are measured. Compared with a pure series or parallel connection camera network, the designed series-parallel connection camera network can be used to measure not only the movement and displacement of a large structure but also the relative movement and deformation of some interesting parts of the large structure by a relatively simple optical measurement system.

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

PubMed Central

Evans, E Glyn V; Sigurgeirsson, Bárdur

1999-01-01

Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatmentContinuous terbinafine should be the current treatment of choice for onychomycosis PMID:10205099

Electroacupuncture for chemotherapy-induced peripheral neuropathy: study protocol for a pilot multicentre randomized, patient-assessor-blinded, controlled trial

PubMed Central

2013-01-01

Background Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting side effect of neurotoxic chemotherapeutic agents. CIPN can lead not only to loss of physical function, difficulties in activities of daily living (ADLs), and decreased quality of life, but also to dose reduction, delay or even cessation of treatment. Currently, there are few proven effective treatments for CIPN. This randomized controlled clinical trial is designed to evaluate the effects and safety of electroacupuncture (EA) for patients with CIPN. Methods/design This is a multicenter, two-armed, parallel-design, patient-assessor-blinded, randomized, sham-controlled clinical trial. Forty eligible patients with CIPN will be randomized in a ratio of 1:1 to the EA or sham EA arms. During the treatment phase, patients will undergo eight sessions of verum EA or sham EA twice weekly for four weeks, and then will be followed-up for eight weeks. Electrical stimulation in the EA group will consist of a mixed frequency of 2/120 Hz and 80% of bearable intensity. Sham EA will be applied to non-acupoints, with shallow needle insertion and no current. All outcomes and analyses of results will be assessed by researchers blinded to treatment allocation. The effects of EA on CIPN will be evaluated according to both subjective and objective outcome measures. The primary outcome measure will be the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to assess CIPN (QLQ-CIPN20). The secondary outcome measures will be the results on the numerical rating scale, the Semmes-Weinstein monofilament test, the nerve conduction study, and the EORTC QLQ-C30, as well as the patient’s global impression of change and adverse events. Safety will be assessed at each visit. Discussion The results of this on-going study will provide clinical evidence for the effects and safety of EA for CIPN compared with sham EA. Trial registration Clinical Research Information Service: KCT0000506 PMID:23945074

Intraocular pressure decrease with preservative-free fixed and unfixed combination of tafluprost and timolol in pseudoexfoliative glaucoma.

PubMed

Holló, Gábor; Ropo, Auli

2015-01-01

We investigated the intraocular pressure (IOP) lowering efficacy of preservative-free fixed and non-fixed combination of tafluprost 0.0015% and timolol 0.5% in pseudoexfoliative glaucoma (XFG). A per protocol worse eye analysis was made on all XFG patients who participated in a recent 6 month, prospective, randomized, double-masked, parallel group, multicenter phase III study. The mean time-wise IOP decreased by 8.62 to 10.25 mmHg (31.8 to 36.7%) in the fixed dose combination arm (15 patients) and by 5.38 to 11.35 mmHg (21.3 to 41.2%) in the non-fixed combination arm (13 patients), respectively (p < 0.001 for all comparisons). The results show that a preservative-free fixed dose combination of tafluprost and timolol provides a clinically significant IOP reduction in XFG, and may offer an advantage for the XFG patients with dry eye, due to its preservative-free nature.

A pilot randomized controlled trial comparing effectiveness of prism glasses, visual search training and standard care in hemianopia.

PubMed

Rowe, F J; Conroy, E J; Bedson, E; Cwiklinski, E; Drummond, A; García-Fiñana, M; Howard, C; Pollock, A; Shipman, T; Dodridge, C; MacIntosh, C; Johnson, S; Noonan, C; Barton, G; Sackley, C

2017-10-01

Pilot trial to compare prism therapy and visual search training, for homonymous hemianopia, to standard care (information only). Prospective, multicentre, parallel, single-blind, three-arm RCT across fifteen UK acute stroke units. Stroke survivors with homonymous hemianopia. Arm a (Fresnel prisms) for minimum 2 hours, 5 days per week over 6 weeks. Arm b (visual search training) for minimum 30 minutes, 5 days per week over 6 weeks. Arm c (standard care-information only). Adult stroke survivors (>18 years), stable hemianopia, visual acuity better than 0.5 logMAR, refractive error within ±5 dioptres, ability to read/understand English and provide consent. Primary outcomes were change in visual field area from baseline to 26 weeks and calculation of sample size for a definitive trial. Secondary measures included Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual, Short Form-12 questionnaires and Radner reading ability. Measures were post-randomization at baseline and 6, 12 and 26 weeks. Randomization block lists stratified by site and partial/complete hemianopia. Allocations disclosed to patients. Primary outcome assessor blind to treatment allocation. Eighty-seven patients were recruited: 27-Fresnel prisms, 30-visual search training and 30-standard care; 69% male; mean age 69 years (SD 12). At 26 weeks, full results for 24, 24 and 22 patients, respectively, were compared to baseline. Sample size calculation for a definitive trial determined as 269 participants per arm for a 200 degree 2 visual field area change at 90% power. Non-significant relative change in area of visual field was 5%, 8% and 3.5%, respectively, for the three groups. Visual Function Questionnaire responses improved significantly from baseline to 26 weeks with visual search training (60 [SD 19] to 68.4 [SD 20]) compared to Fresnel prisms (68.5 [SD 16.4] to 68.2 [18.4]: 7% difference) and standard care (63.7 [SD 19.4] to 59.8 [SD 22.7]: 10% difference), P=.05. Related adverse events were common with Fresnel prisms (69.2%; typically headaches). No significant change occurred for area of visual field area across arms over follow-up. Visual search training had significant improvement in vision-related quality of life. Prism therapy produced adverse events in 69%. Visual search training results warrant further investigation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Treatment outcomes and patient-reported quality of life after orthognathic surgery with computer-assisted 2- or 3-dimensional planning: A randomized double-blind active-controlled clinical trial.

PubMed

Bengtsson, Martin; Wall, Gert; Larsson, Pernilla; Becktor, Jonas P; Rasmusson, Lars

2018-06-01

Thorough treatment planning is essential for a good clinical outcome in orthognathic treatment. The planning is often digital. Both 2-dimensional (2D) and 3-dimensional (3D) software options are available. The aim of this randomized 2-arm parallel double-blinded active-controlled clinical trial was to compare the outcomes of computer-based 2D and 3D planning techniques according to patient-reported health related quality of life. The hypothesis was that a 3D technique would give a better treatment outcome compared with a 2D technique. Orthognathic treatment for 62 subjects, aged 18 to 28 years, with severe Class III malocclusion was planned with both 2D and 3D techniques. After treatment planning but before surgery, the patients were randomly allocated via blind collection of 1 enveloped card for each subject in a 1:1 ratio to the test (3D) or the control (2D) group. Thus, the intervention was according to which planning technique was used. The primary outcome was patient-reported outcome measures. The secondary outcome was relationship between patient-reported outcome measures and cephalometric accuracy. Questionnaires on the patient's health-related quality of life (HRQoL) were distributed preoperatively and 12 months after surgical treatment. The questionnaires were coded, meaning blinding throughout the analysis. Differences between groups were tested with the Fisher permutation test. The HRQoL was also compared with measurements of cephalometric accuracy for the 2 groups. Three subjects were lost to clinical follow-up, leaving 57 included. Of these, 55 subjects completed the questionnaires, 28 in the 2D and 27 in the 3D groups. No statistically significant difference regarding HRQoL was found between the studied planning techniques: the Oral Health Impact Profile total showed -3.69 (95% confidence interval, -19.68 to 12.30). Consistent results on HRQoL and cephalometric accuracy showed a difference between pretreatment and posttreatment that increased in both groups but to a higher level in the 3D group. A difference between pretreatment and posttreatment HRQoL was shown for both groups, indicating increased quality of life after treatment. This supports recent findings comparing 3D and 2D planning techniques. No serious harm was observed during the study. Improvements of HRQoL were shown after treatment independent of which planning technique, 2D or 3D, was used. No statistically significant difference was found between the planning techniques. This trial was not registered. The protocol was not published before trial commencement. This project was supported by personal grants to Martin Bengtsson from the Scandinavian Association of Oral and Maxillofacial Surgeons (25000 SEK), the Southern Region of the Swedish Dental Association (50000 SEK), and the Swedish Association of Oral and Maxillofacial Surgeons (25000 SEK). The sponsors had no influence on the study design, analysis of the data, or the writing of the article. Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-01-01

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

Mirror therapy in children with hemiparesis: a randomized observer-blinded trial.

PubMed

Bruchez, Roselyn; Jequier Gygax, Marine; Roches, Sylvie; Fluss, Joel; Jacquier, David; Ballabeni, Pierluigi; Grunt, Sebastian; Newman, Christopher J

2016-09-01

To determine the efficacy of mirror therapy in children with hemiparesis. The design was an observer-blinded parallel-group randomized controlled trial (International Standard Randomised Controlled Trial Number 48748291). Randomization was computer-generated, 1:1 allocation to mirror therapy or comparison groups. The settings were home-based intervention and tertiary centre assessments. Participants were 90 children with hemiparesis aged 7 to 17 years. Intervention was 15 minutes per day of simultaneous arm training, 5 days a week, for 5 weeks. The mirror therapy group used a mirror; those in the comparison group looked at their paretic limb. Assessments comprised measures of upper limb strength, function (Melbourne Assessment 2), daily performance (ABILHAND-Kids), and sensory function at weeks 0 (T0 ), 5 (T1 ), and 10 (T2 ). There were no significant differences in outcomes and their progression over time between the mirror therapy and comparison groups. Post-hoc intention-to-treat analyses showed significant improvements in both groups for grasp strength (T0 -T1 +12.6%), pinch strength (T0 -T2 +9.1%), upper limb function in terms of accuracy (T0 -T2 +2.7%) and fluency (T0 -T2 +5.0%), as well as daily performance (T0 -T2 +16.6%). Per protocol analyses showed additional improvements in dexterity (T0 -T2 +4.0%). The use of the mirror illusion during therapy had no significant effect on treatment outcomes. However, 5 weeks of daily simultaneous arm training significantly improved paretic upper limb strength, function, and daily use. © 2016 Mac Keith Press.

Calcipotriene plus betamethasone dipropionate topical suspension for the treatment of mild to moderate psoriasis vulgaris on the body: a randomized, double-blind, vehicle-controlled trial.

PubMed

Menter, Alan; Gold, Linda Stein; Bukhalo, Michael; Grekin, Steven; Kempers, Steven; Boyce, Brent M; Ganslandt, Cecilia; Villumsen, John; Lebwohl, Mark

2013-01-01

A combination topical suspension/gel containing calcipotriene plus betamethasone dipropionate has been developed as a safe and effective treatment for patients with psoriasis vulgaris of the scalp. This same preparation has the potential to be a convenient, effective, and cosmetically appealing formulation for psoriasis on the body. This trial evaluated the efficacy and safety of a topical suspension containing calcipotriene plus betamethasone dipropionate compared with its constituent components and topical suspension vehicle in the treatment of mild to moderate psoriasis on the trunk and limbs. This was a randomized, double-blind, vehicle-controlled, 4-arm trial in 1,152 subjects. The co-primary efficacy end points were the proportion of subjects achieving controlled disease based on the Investigators' Global Assessment of disease severity at weeks 4 and 8. Adverse events, vital signs, and clinical laboratory measurements were also assessed. At week 4, a greater proportion of subjects in the calcipotriene plus betamethasone group achieved controlled disease compared with subjects in the calcipotriene-only and vehicle-only treatment groups. At week 8, a statistically significantly (P<.01) greater proportion of subjects in the calcipotriene plus betamethasone group achieved controlled disease compared with subjects in the 3 other treatment groups. Adverse events and other safety assessments were similar between the groups. The topical suspension containing calcipotriene plus betamethasone dipropionate traditionally used for scalp psoriasis is also a safe and effective once-daily treatment for psoriasis vulgaris on the body.

Plasma urolithin metabolites correlate with improvements in endothelial function after red raspberry consumption: A double-blind randomized controlled trial.

PubMed

Istas, Geoffrey; Feliciano, Rodrigo P; Weber, Timon; Garcia-Villalba, Rocio; Tomas-Barberan, Francisco; Heiss, Christian; Rodriguez-Mateos, Ana

2018-05-24

Raspberries are a rich source of ellagitannins and anthocyanins. The aim of this work was to investigate whether raspberry consumption can improve vascular function and to understand which phenolic metabolites may be responsible for the effects. A 3 arm double-blind randomized controlled crossover human intervention trial was conducted in 10 healthy males. Flow-mediated dilation (FMD) was measured at baseline, 2 h, and 24 h post-consumption of 200 g and 400 g of red raspberries containing 201 or 403 mg of total (poly)phenols, or a matched control drink. Raspberry (poly)phenol metabolites were analyzed in plasma and urine by UPLC-QTOF mass spectrometry using authentic standards. Significant improvements in FMD were observed at 2 h (1.6% (95%CI 1.2, 1.9) and 1.2% (95% CI 0.8, 1.5)) and 24 h (1.0% (95% CI 0.6, 1.2) and 0.7% (95%CI 0.2, 0.9)) post-consumption of the 200 and 400 g raspberry drinks as compared to control, respectively. Plasma ellagic acid, urolithin A-3-glucuronide and urolithin A-sulfate correlated with the improvements in FMD at 2 and 24 h post consumption, respectively. Consumption of dietary achievable amounts of red raspberries acutely improves endothelial function up to 24 h and ellagitannins may be responsible for the observed effect. Copyright © 2018 Elsevier Inc. All rights reserved.

Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up

PubMed Central

Morales, Alicia; Gandolfo, Alessandro; Bravo, Joel; Carvajal, Paola; Silva, Nora; Godoy, Claudia; Garcia-Sesnich, Jocelyn; Hoare, Anilei; Diaz, Patricia; Gamonal, Jorge

2018-01-01

ABSTRACT Objective The aim of this double-blind, placebo-controlled and parallel- arm randomized clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1-containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical therapy in clinical parameters and in presence and levels of Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Material and Methods Forty-seven systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically and microbiologically at baseline for 3, 6 and 9 months after therapy. Subgingival plaque samples were collected from four periodontal sites with clinical attachment level ≥1 mm, probing pocket depth ≥4 mm and bleeding on probing, one site in each quadrant. Samples were cultivated and processed using the PCR technique. Patients received nonsurgical therapy including scaling and root planing (SRP) and were randomly assigned to a probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1 was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5 days. Results All groups showed improvements in clinical and microbiological parameters at all time points evaluated. Probiotic and antibiotic groups showed greater reductions in cultivable microbiota compared with baseline. The placebo group showed greater reduction in number of subjects with P. gingivalis compared with baseline. However, there were no significant differences between groups. Conclusions The adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial therapy resulted in similar clinical and microbiological improvements compared with the placebo group. PMID:29364340

Controlled release nifedipine and valsartan combination therapy in patients with essential hypertension: the adalat CR and valsartan cost-effectiveness combination (ADVANCE-combi) study.

PubMed

Saito, Ikuo; Saruta, Takao

2006-10-01

This study was designed to compare the clinical efficacy of two calcium channel blocker-based combination therapies with an angiotensin receptor blocker in Japanese patients with essential hypertension. A 16-week, double-blind, parallel-arm, randomized clinical trial was performed to compare the efficacy and safety of the combination therapy of controlled release nifedipine (nifedipine CR) plus valsartan vs. that of amlodipine plus valsartan. The primary endpoint was the target blood pressure achievement rate. Eligible patients were randomly allocated to nifedipine CR-based or amlodipine-based treatment groups. Patients were examined every 4 weeks to determine whether the blood pressure had reached the target level. When the target level was not achieved, the drug regimen was changed; when the target blood pressure was achieved, the same study medication was continued. A total of 505 patients were enrolled in the study (nifedipine CR group: 245 cases; amlodipine group: 260 cases). After 16 weeks of treatment, blood pressure was significantly reduced in both groups, but to a larger extent in the nifedipine CR group than in the amlodipine group (p < 0.01). The target blood pressure achievement rate was also significantly higher in the nifedipine CR group (p < 0.001). There was no significant difference in the incidence of drug-related adverse events between the groups. These results indicate that the nifedipine CR-based combination therapy was superior to the amlodipine-based therapy for decreasing blood pressure and achieving the target blood pressure in patients with essential hypertension.

Econazole Nitrate Foam 1% Improves the Itch of Tinea Pedis.

PubMed

Fleischer, Alan B; Raymond, Isabelle

2016-09-01

Econazole nitrate topical foam, 1%, is indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older. The symptom of itch or pruritus was evaluated in two randomized, double-blind, parallel-group, vehicle-controlled, multicenter Phase III studies in which econazole foam was compared with foam vehicle in subjects with interdigital tinea pedis. A thin, uniform layer of study treatment was applied once daily to all clinically affected interdigital regions of both feet for four weeks. At baseline, at least 69% of all subjects had moderate to severe itch. Throughout the duration of both studies, numerically econazole foam was numerically superior to vehicle in achieving absence of itch. After the cessation of treatment, from day 29, itching continues to improve until day 43 in the active treatment group, whereas there is no evident continued improvement within the vehicle foam groups. At day 43, in the active treatment groups, 83% in Study 1 and 71% in Study 2 achieved complete absence of itching. Using less stringent criteria, for the econazole nitrate foam arm, achieving no itch or mild itch (0 or 1), in Study 1, 95% and 86.8% in Study 2 achieved this outcome. Tolerability of the products was excellent with few treatment-related adverse events. In summary, econazole foam decreased the burden of itch as early as day 8 in patients with interdigital tinea pedis, and this improvement continued after cessation of treatment.

J Drugs Dermatol. 2016;15(9):1111-1114.

Safety assessment of Bacillus subtilis CU1 for use as a probiotic in humans.

PubMed

Lefevre, Marie; Racedo, Silvia M; Denayrolles, Muriel; Ripert, Gabrielle; Desfougères, Thomas; Lobach, Alexandra R; Simon, Ryan; Pélerin, Fanny; Jüsten, Peter; Urdaci, Maria C

2017-02-01

Bacillus subtilis CU1 is a recently described probiotic strain with beneficial effects on immune health in elderly subjects. The following work describes a series of studies supporting the safety of the strain for use as an ingredient in food and supplement preparations. Using a combination of 16S rDNA and gyrB nucleotide analyses, the species was identified as a member of the Bacillus subtilis complex (B. subtilis subsp. spizizenii). Further characterization of the organism at the strain level was achieved using random amplified polymorphic DNA polymerase chain reaction (RAPD PCR) and pulsed field gel electrophoresis (PFGE) analyses. B. subtilis CU1 did not demonstrate antibiotic resistance greater than existing regulatory cutoffs against clinically important antibiotics, did not induce hemolysis or produce surfactant factors, and was absent of toxigenic activity in vitro. Use of B. subtilis CU1 as a probiotic has recently been evaluated in a 16-week randomized, double-blind, placebo-controlled, parallel-arm study, in which 2 × 10 9 spores per day of B. subtilis CU1 were administered for a total 40 days to healthy elderly subjects (4 consumption periods of 10 days separated by 18-day washouts). This work describes safety related endpoints not previously reported. B. subtilis CU1 was safe and well-tolerated in the clinical subjects without undesirable physiological effects on markers of liver and kidney function, complete blood counts, hemodynamic parameters, and vital signs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

PubMed Central

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

2015-01-01

Introduction The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Methods Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Results Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Conclusion Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. PMID:26077603

Effect of Chlorella Ingestion on Oxidative Stress and Fatigue Symptoms in Healthy Men.

PubMed

Okada, Hirotaka; Yoshida, Noriko; Kakuma, Tatsuyuki; Toyomasu, Kouji

2018-05-21

We examined the effects of dietary chlorella ingestion on oxidative stress and fatigue symptoms in healthy men under resting and fatigue conditions. We conducted a double-blind, parallel-arm controlled study. Twenty-seven healthy male volunteers (mean age, 35.4±10.4 years) were randomly divided into the chlorella and placebo groups, and received chlorella (6 g/day) and lactose as placebo (7.2 g/day), respectively, for 4 weeks. To simulate mild fatigue, subjects underwent exercise (40% of the heart rate reserve) for 30 minutes. Fatigue was measured using the visual analog scale of fatigue (F-VAS) pre- and post-exercise. Serum antioxidant capacity (AC), malondialdehyde levels, and other indices of oxidative stress were measured pre- and post-exercise. All measurements were repeated after the intervention period and the results were compared with baseline measurements. Under resting conditions, AC significantly increased after the intervention period in the chlorella group, but not in the placebo group. Malondialdehyde levels after the intervention period were significantly lower in the chlorella group than in the placebo group. There were no significant differences in any of the oxidative-stress indices measured pre- and post-exercise, either before or after intervention, in either group. F-VAS significantly increased after exercise at all measurement time-points in both groups, except after the intervention period in the chlorella group. Under fatigue conditions, there were no significant differences in oxidative stress indices between the groups. Our results suggest that chlorella ingestion has the potential to relieve oxidative stress and enhance tolerance for fatigue under resting conditions.

Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience.

PubMed

Marcinak, John F; Munsaka, Melvin S; Watkins, Paul B; Ohira, Takashi; Smith, Neila

2018-06-01

Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical trials due to liver safety concerns. The liver safety of fasiglifam was assessed from data based on six phase II and nine phase III double-blind studies and two open-label studies with emphasis on pooled data from 15 double-blind studies from both global and Japanese development programs. Taking into consideration different daily doses of fasiglifam administered in clinical studies, the primary comparisons were between all patients exposed to fasiglifam (any dose) versus placebo, and, where applicable, versus the two active comparators, sitagliptin or glimepiride. A Liver Safety Evaluation Committee consisting of hepatologists blinded to treatment assignments evaluated hepatic adverse events (AEs) and serious AEs (SAEs) for causal relationship to study drug. The analysis included data from 9139 patients with T2DM in 15 double-blind controlled studies who received either fasiglifam (n = 5359, fasiglifam group), fasiglifam and sitagliptin (n = 123), or a comparator agent (n = 3657, non-exposed group consisting of placebo and other antidiabetic agents). Exposure to treatment for more than 1 year ranged from 249 patients in the placebo arm, to 370 patients in the glimepiride arm and 617 patients in the fasiglifam 50 mg arm. The primary focus of the analysis was on the hepatic safety of fasiglifam. The overall safety profile based on treatment-emergent AEs (TEAEs), SAEs, deaths, and withdrawal due to AEs was similar between fasiglifam and placebo (excluding liver test abnormalities). However, there was an increased incidence rate of serum alanine aminotransferase (ALT) elevations > 3 × upper limit of normal (ULN), 5 × ULN, and 10 × ULN in fasiglifam-treated patients compared with those treated with placebo or active comparators. ALT elevations > 3 × ULN for fasiglifam were 2.7% compared with 0.8 and 0.5% for the active comparators and placebo. There did not appear to be a clear dose response in incidence of ALT elevations between patients receiving 25 or 50 mg daily. The cumulative incidence of elevations in serum ALT > 3 × ULN was higher in the first 6 months of treatment with fasiglifam compared with both placebo and the active comparators, but the rate of new ALT elevations appeared to be similar across all treatment groups thereafter. No demographic or baseline patient characteristics were identified to predict elevations exceeding ALT > 3 × ULN in fasiglifam-treated patients. The pattern of liver injury with fasiglifam was hepatocellular, and there were no reports of liver-related deaths, liver failure or life-threatening liver injury. Most fasiglifam-associated ALT elevations were asymptomatic and resolved promptly upon discontinuing treatment, but in two patients the recovery was prolonged. Importantly, three important serious liver injury cases were identified among fasiglifam-treated patients; one case was adjudicated to be a clear Hy's Law case and the two remaining cases were considered to closely approximate Hy's Law cases. Although the incidence of overall AEs, SAEs, and deaths was similar between fasiglifam and placebo, a liver signal was identified based primarily on the difference in liver chemistry values in the fasiglifam group compared with the placebo and active comparator groups. Three serious liver injuries were attributed to fasiglifam treatment. Clinical development of fasiglifam was halted due to these liver safety concerns.

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

PubMed Central

2013-01-01

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

End-tidal concentration of sevoflurane for preventing rocuronium-induced withdrawal of the arm in pediatric patients.

PubMed

Yeom, Jong Hoon; Kim, Yong Oh; Lee, Jae Min; Jeon, Woo Jae

2014-04-01

During induction of general anesthesia, the intravenous injection of rocuronium is often associated with withdrawal movement of the arm due to pain, and this abrupt withdrawal may result in dislodgement of the venous catheter, injury, or inadequate injection of rocuronium. We performed this study to evaluate the 50 and 95% effective end-tidal concentrations of sevoflurane (ETsev) for preventing rocuronium-induced withdrawal of the arm. We conducted a prospective double-blind study in 31 pediatric patients. After free flow of lactated Ringer's IV fluid was confirmed, anesthesia was induced in the patients by using 2.5% thiopental sodium (4 mg/kg) and sevoflurane (4 vol%) with 6 L/min of oxygen. When the target ETsev was reached, preservative-free 1% lidocaine (1.5 mg/kg) was intravenously injected during manual venous occlusion and rocuronium (0.6 mg/kg) was injected after lidocaine injection under free-flow intravenous fluid. A nurse who was an investigator and was blinded to the ETsev injected the rocuronium. The nurse evaluated the response. Non-withdrawal movement was observed in 5 out of 11 patients with ETsev 3.0 vol% and in 5 out of 6 patients with ETsev 3.5 vol%. By Dixon's up-and-down method, the 50% effective concentration (EC50) of sevoflurane for non-withdrawal movement at rocuronium injection was 3.1 ± 0.4 vol%. A logistic regression curve of the probability of non-withdrawal movements showed that the 50% effective ETsev for abolishing withdrawal movement at rocuronium injection was 2.9 vol% (95% confidence interval [CI] 2.4-3.8 vol%) and the 95% effective ETsev was 4.3 vol% (95% CI 3.6-9.8 vol%). This study showed that the 50 and 95% effective ETsev that prevent withdrawal movement at rocuronium injection are 2.9 and 4.3 vol%, respectively.

Effect of single-dose Ginkgo biloba and Panax ginseng on driving performance.

PubMed

LaSala, Gregory S; McKeever, Rita G; Patel, Urvi; Okaneku, Jolene; Vearrier, David; Greenberg, Michael I

2015-02-01

Panax ginseng and Gingko biloba are commonly used herbal supplements in the United States that have been reported to increase alertness and cognitive function. The objective of this study was to investigate the effects of these specific herbals on driving performance. 30 volunteers were tested using the STISIM3® Driving Simulator (Systems Technology Inc., Hawthorne, CA, USA) in this double-blind, placebo-controlled study. The subjects were randomized into 3 groups of 10 subjects per group. After 10-min of simulated driving, subjects received either ginseng (1200 mg), Gingko (240 mg), or placebo administered orally. The test herbals and placebo were randomized and administered by a research assistant outside of the study to maintain blinding. One hour following administration of the herbals or placebo, the subjects completed an additional 10-min of simulated driving. Standard driving parameters were studied including reaction time, standard deviation of lateral positioning, and divided attention. Data collected for the divided attention parameter included time to response and number of correct responses. The data was analyzed with repeated-measures analysis of variance (ANOVA) and Kruskal-Wallis test using SPSS 22 (IBM, Armonk, NY, USA). There was no difference in reaction time or standard deviation of lateral positioning for both the ginseng and Ginkgo arms. For the divided attention parameter, the response time in the Ginkgo arm decreased from 2.9 to 2.5 s. The ginseng arm also decreased from 3.2 to 2.4 s. None of these values were statistically significant when between group differences were analyzed. The data suggests there was no statistically significant difference between ginseng, Ginkgo or placebo on driving performance. We postulate this is due to the relatively small numbers in our study. Further study with a larger sample size may be needed in order to elucidate more fully the effects of Ginkgo and ginseng on driving ability.

Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective, single-blinded, two-arm parallel, clinical field trial

PubMed Central

2014-01-01

Background Despite its wide acceptance as a treatment for canine chronic enteropathies, the macrolide antibiotic tylosin lacks official oral dosage recommendations. Not even textbooks share consensus about the dose; daily recommendations vary from 25 to 80 mg/kg and dosing intervals from one to three times daily. The objective of this prospective, single-blinded, two-arm parallel, clinical field trial was to determine whether doses of 5 mg/kg or 15 mg/kg tylosin administered orally once daily for seven days would have a similar effect on fecal consistency in diarrhea relapses to that of a 25 mg/kg dose of tylosin administered once daily for seven days, a dosage that has proved effective in controlling canine tylosin-responsive diarrhea (TRD). A further objective was to compare the efficacy of the 5 mg/kg and 15 mg/kg tylosin dosages. Fifteen client-owned dogs diagnosed with TRD that had responded to a dose of 25 mg/kg tylosin once daily for seven days were enrolled in the study. After a relapse of diarrhea the dogs were allocated into two groups receiving tylosin orally in doses of either 5 mg/kg or 15 mg/kg once daily for seven days. The owners were blinded to the dosage. The elimination of diarrhea was the main criterion in assessing treatment success. The mean fecal consistency score of the last three treatment days for all dosages, including 25 mg/kg, as evaluated by the owners according to a standardized fecal scoring system, served as the primary outcome measures. Results All eight dogs responded to the 5 mg/kg dose, and six of seven dogs responded to the 15 mg/kg dose. The mean fecal consistency scores at the 25 mg/kg tylosin dosage were no significantly different from scores at the 5 mg/kg or 15 mg/kg tylosin dosages (P = 0.672, P = 0.345). Conclusions Interestingly, 14/15 (93%) of the dogs responding to a dose of 25 mg/kg tylosin once daily for seven days also responded to the lower dosages at diarrhea relapse. The data indicate that a suitable dose of tylosin for treating diarrhea relapse in canine TRD could be as low as 5 mg/kg once daily for seven days. PMID:25096196

Six Months of Diazoxide Treatment at Bedtime in Newly Diagnosed Subjects With Type 1 Diabetes Does Not Influence Parameters of β-Cell Function and Autoimmunity but Improves Glycemic Control

PubMed Central

Radtke, Maria Anita; Nermoen, Ingrid; Kollind, Magnus; Skeie, Svein; Sørheim, Jan Inge; Svartberg, Johan; Hals, Ingrid; Moen, Torolf; Dørflinger, Gry Høst; Grill, Valdemar

2010-01-01

OBJECTIVE Continuous β-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control, and autoimmunity markers in the absence of side effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients were randomized to 6 months of treatment with placebo or 100 mg diazoxide at bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3+ regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention. RESULTS Of six dropouts, three were due to perceived side effects; one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3, and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean −0.30 and −0.18 nmol/l in the diazoxide arm and −0.08 and −0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms and remained stable during intervention but was significantly lower compared with nondiabetic subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects and did not measurably affect insulin production but was associated with improved metabolic control. PMID:20028939

Patient-reported outcomes in a phase iii study of everolimus versus placebo in patients with metastatic carcinoma of the kidney that has progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

PubMed

Beaumont, Jennifer L; Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients.

Patient-Reported Outcomes in a Phase III Study of Everolimus Versus Placebo in Patients with Metastatic Carcinoma of the Kidney That Has Progressed on Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

PubMed Central

Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J.; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

Purpose. A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Methods. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Results. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. Conclusions. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients. PMID:21459902

Safety and efficacy of a traditional herbal medicine (Throat Coat) in symptomatic temporary relief of pain in patients with acute pharyngitis: a multicenter, prospective, randomized, double-blinded, placebo-controlled study.

PubMed

Brinckmann, Josef; Sigwart, Herbert; van Houten Taylor, Leslie

2003-04-01

To investigate the safety and efficacy of Throat Coat) (Traditional Medicinals,) Sebastopol, CA), a traditional demulcent herbal tea, in comparison with a placebo tea in the symptomatic treatment of acute pharyngitis. Multicenter, prospective, randomized, double-blinded, placebo-controlled, two-armed, parallel-group clinical trial. Three primary care clinics in Duluth, MN, Madison, WI, and Middleton, WI. Patients of both genders (>or=18 years of age) with clinical diagnoses of acute pharyngitis. Patients (n = 60) were randomly assigned to receive 5-8 oz of Throat Coat (n = 30) or a placebo (n = 30), four to six times daily. The study period was 2 to 7 days with a window for the follow-up visit of 2-10 days accounting for the variable duration of sore throat symptoms. Primary efficacy parameter: sum of pain intensity differences (SPID) for pain in throat on swallowing, calculated as the area under the curve (AUC) of pain intensity difference scores (assessed at 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 30 minutes after treatment). Secondary efficacy parameter: total pain relief (TOTPAR), calculated as the AUC from time 0 (baseline) to 30 minutes of pain relief (assessed at 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 30 minutes). Compared to placebo, intensity of throat pain when swallowing was significantly reduced by Throat Coat in intention to treat and valid for efficacy analysis (VEA). Significant differences in change from baseline pain were observed at 5 min (p = 0.007), 10 min (p = 0.005), 15 minutes (p = 0.01), 20 minutes (p = 0.05), and 30 minutes (p = 0.04) after completion of the first dose (VEA analysis). There was a statistically significant improvement of SPID in the Throat Coat-treated group: Least square means +/- standard error of the means (SEM) of SPID were -16.5 +/- 13.9 in the placebo group and -43.8 +/- 11.9 in the Throat Coat-treated group (p = 0.012). TOTPAR was also significantly higher in the Throat Coat-treated group: Least square means +/- SEM of TOTPAR were 32.4 +/- 12.8 in the placebo group and 53.6 +/- 10.9 in the Throat Coat-treated group (p = 0.031). This study shows that Throat Coat is significantly superior to placebo and provided a rapid, temporary relief of sore throat pain in patients with pharyngitis.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

PubMed

Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Nobuko; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kanouchi, Tadashi; Kohara, Nobuo; Kawamoto, Michi; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Hirata, Koichi; Kokubun, Norito; Masuda, Ray; Kaneko, Juntaro; Yabe, Ichiro; Sasaki, Hidenao; Kaida, Ken-Ichi; Takazaki, Hiroshi; Suzuki, Norihiro; Suzuki, Shigeaki; Nodera, Hiroyuki; Matsui, Naoko; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu

2018-06-01

Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 5. Speech outcomes in 5-year-olds - consonant proficiency and errors.

PubMed

Willadsen, Elisabeth; Lohmander, Anette; Persson, Christina; Lundeborg, Inger; Alaluusua, Suvi; Aukner, Ragnhild; Bau, Anja; Boers, Maria; Bowden, Melanie; Davies, Julie; Emborg, Berit; Havstam, Christina; Hayden, Christine; Henningsson, Gunilla; Holmefjord, Anders; Hölttä, Elina; Kisling-Møller, Mia; Kjøll, Lillian; Lundberg, Maria; McAleer, Eilish; Nyberg, Jill; Paaso, Marjukka; Pedersen, Nina Helen; Rasmussen, Therese; Reisæter, Sigvor; Andersen, Helene Søgaard; Schöps, Antje; Tørdal, Inger-Beate; Semb, Gunvor

2017-02-01

Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocols for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Norway, Sweden, and the UK. Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with non-syndromic UCLP. Speech audio- and video-recordings of 391 children (136 girls and 255 boys) were available and transcribed phonetically. The main outcome measure was Percent Consonants Correct (PCC) from blinded assessments. In Trial 1, arm A showed statistically significant higher PCC scores (82%) than arm B (78%) (p = .045). No significant differences were found between prevalences in Trial 2, A: 79%, C: 82%; or Trial 3, A: 80%, D: 85%. Across all trials, girls achieved better PCC scores, excluding s-errors, than boys (91.0% and 87.5%, respectively) (p = .01). PCC scores were higher in arm A than B in Trial 1, whereas no differences were found between arms in Trials 2 or 3. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed. ISRCTN29932826.

Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

PubMed Central

Assadi, Seyed Mohammad; Radgoodarzi, Reza; Ahmadi-Abhari, Seyed Ali

2003-01-01

Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence. PMID:14624703

Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: a double-blind, placebo-controlled trial.

PubMed

Narula, Preeta Kaur; Rehan, H S; Unni, K E S; Gupta, Neeraj

2010-05-01

Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters. In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12 weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects. Topiramate resulted in a weight loss of 1.27+/-2.28 kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated. Topiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Effects of green tea (Camellia sinensis) mouthwash containing 1% tannin on dental plaque and chronic gingivitis: a double-blinded, randomized, controlled trial.

PubMed

Radafshar, Golpar; Ghotbizadeh, Mahshid; Saadat, Farshid; Mirfarhadi, Nastaran

2017-02-01

The aim of the present study was to explore the effects of Iranian green tea mouthwash containing 1% tannin on dental plaque and chronic gingivitis. In this randomized, double-blinded, parallel, controlled clinical trial, 40 volunteer dental students with a gingival index ≥1 were enrolled. At baseline, gingival, plaque, and bleeding indices were recorded and all the participants received dental polishing. Based on random allocation, 20 participants used the test and 20 used chlorhexidine mouthwash with no change in regular toothbrushing methods. The participants were asked to use 15 mL of the respective mouthwash for 1 min, twice a day for 28 days. All indices, as well as stain index, were recorded after 1 and 4 weeks post-rinsing. Data were analyzed using repeated-measures ANOVA and Bonferroni tests. Significant in-group differences, but not between-group differences, were observed in all indices after 1 and 4 weeks compared to baseline. The test mouthwash resulted in significantly less tooth staining than the control. The 1% tannin green tea mouthwash could be a safe and feasible adjunct to mechanical plaque control. The tested green tea mouthwash could be considered a good alternative for chlorhexidine in contraindicating situations. © 2015 Wiley Publishing Asia Pty Ltd.

Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Udani, Jay K.; George, Annie A.; Musthapa, Mufiza; Pakdaman, Michael N.; Abas, Azreena

2014-01-01

Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40–65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers. PMID:24550993

Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Udani, Jay K; George, Annie A; Musthapa, Mufiza; Pakdaman, Michael N; Abas, Azreena

2014-01-01

Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients.

PubMed

Shahmansouri, Nazila; Farokhnia, Mehdi; Abbasi, Seyed-Hesammeddin; Kassaian, Seyed Ebrahim; Noorbala Tafti, Ahmad-Ali; Gougol, Amirhossein; Yekehtaz, Habibeh; Forghani, Saeedeh; Mahmoodian, Mehran; Saroukhani, Sepideh; Arjmandi-Beglar, Akram; Akhondzadeh, Shahin

2014-02-01

A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial. Relatively small sample size and short observational period were the major limitations of this study. Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression. © 2013 Published by Elsevier B.V.

Neuropsychological Training of Attention Improves MS-Related Fatigue: Results of a Randomized, Placebo-Controlled, Double-Blind Pilot Study.

PubMed

Flachenecker, Peter; Meissner, Heike; Frey, Rebecca; Guldin, Wolfgang

2017-01-01

Attentional deficits may be pathophysiologically relevant in MS-associated fatigue. Thirty MS patients with fatigue and attentional deficits in neuropsychological testing participated in this randomized, placebo-controlled, double-blind trial. The intervention group (IG; n = 14) was treated with 10 h of computerized, specific neuropsychological training performing simple reaction time tasks, whereas the control group (CG; n = 16) also runs through computerized, but unspecific neuropsychological training using tasks without time components. The subjective feeling of fatigue was assessed with the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) questionnaire, and testing of alertness was used as an objective measure at baseline and after the 2-week study period. Reaction times of alertness were significantly decreased in IG but not CG after 2 weeks. The subjective feeling of fatigue was ameliorated in both groups but more pronounced in IG. Effect sizes were below 0.7 for alertness and WEIMuS scores in CG but large and clinically meaningful in IG for both measures. Our pilot study suggests that neuropsychological training of attention may improve both measures of fatigue. The parallel improvement of attentional deficits and subjective fatigue after specific neuropsychological training support previous findings that fatigue may be at least partially caused by impaired intensity of attention. © 2017 S. Karger AG, Basel.

Use of honey associated with Ananas comosus (Bromelin) in the treatment of acute irritative cough.

PubMed

Peixoto, Décio Medeiros; Rizzo, José Angelo; Schor, Deborah; Silva, Almerinda Rêgo; Oliveira, Dinaldo Cavalcanti de; Solé, Dirceu; Sarinho, Emanuel

2016-12-01

To evaluate the immediate improvement rate of irritative cough in patients treated with the combination of Ananas comosus extract and honey (Bromelin ® ) compared with the use of honey alone (placebo group). Pragmatic, double-blind, randomized, parallel-group study with children aged between 2 and 15 years, with irritative cough for at least 24hours. The double-blind assessment of cough was through the number of observed coughing episodes and intensity score for a period of 10minutes of observation. The decrease of one point in the mean total score was considered as a therapeutic effect. There was a reduction in coughing episodes in both groups, as well as in the cough score after 30minutes of drug or honey administration. The change in clinical score above two points, which could indicate marked improvement, occurred in five patients in the bromelin group and only in one in the placebo group, but without significant difference. There were no adverse events. The immediate improvement rate of irritative cough was similar in patients treated with combination of Ananas comosus extract and honey (Bromelin ® ) compared with the use of honey alone (placebo group). It is possible that honey has a therapeutic effect on mucus and cough characteristics (Clinical Trials: NCT01356693). Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study

PubMed Central

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-01-01

Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Design Double blind randomised placebo controlled parallel group study. Setting Hospital in Hampshire. Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Interventions Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of β glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Main outcome measures Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. Results The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study. PMID:12896934

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

PubMed Central

2014-01-01

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

Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study.

PubMed

Battaglia, A; Bruni, G; Ardia, A; Sacchetti, G

1989-04-01

In view of some controversies still existing about the real efficacy of ergot derivatives in the management of dementia, a double-blind, randomized, parallel group trial extending up to 6 months was carried out to compare the effects of nicergoline, 60 mg daily, and placebo in 315 patients suffering from mild to moderate dementia. Clinical evaluation was performed by the SCAG scale. The trial, which included a 1-month placebo run-in period, showed that both placebo and nicergoline were associated with some degree of improvement. The effect of nicergoline, however, was significantly greater and more sustained, steadily increasing with time. In particular, the difference between nicergoline and placebo in mean total SCAG score was 5.5 at 3 months (95% confidence interval: 3.6-7.4) and increased to 9.8 at 6 months (95% confidence interval: 7.8-11.8). A comparison of nicergoline versus placebo in the frequencies of changes in each item of the SCAG showed also a significant difference at 6 months, the percent of patients displaying an improvement by at least 2 points ranging from 13.5 (bothersome) to 30.2 (disorientation) in nicergoline group, against 4.1 (self-care) to 14.3 (fatigue) in placebo group. The safety of nicergoline, as judged by hemodynamic changes and drug-related adverse reactions, was quite satisfactory.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial.

PubMed

Maenthaisong, Ratree; Chaiyakunapruk, Nathorn; Tiyaboonchai, Waree; Tawatsin, Apiwat; Rojanawiwat, Archawin; Thavara, Usavadee

2014-02-01

Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions. All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes. There were no significant differences between treatment and reference arms on any outcome at any time of measurement. Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design.

PubMed

Anywaine, Zacchaeus; Abaasa, Andrew; Levin, Jonathan; Kasirye, Ronnie; Kamali, Anatoli; Grosskurth, Heiner; Munderi, Paula; Nunn, Andrew

2015-07-01

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design. COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events. Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations. This paper describes the design and methodological considerations important for the conduct of CTX cessation studies. Copyright © 2015. Published by Elsevier Inc.

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

PubMed

de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

2016-09-01

Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

PubMed

Faught, E; Ayala, R; Montouris, G G; Leppik, I E

2001-11-27

Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.

Maternal kisses are not effective in alleviating minor childhood injuries (boo-boos): a randomized, controlled and blinded study.

PubMed

2015-12-01

The practice of maternal kissing of minor injuries of childhood (boo-boos), though widely endorsed and practised, has never been demonstrated to be of benefit to children. To determine the efficacy, if any, of maternal kissing of boo-boos in toddlers. Randomized, controlled and double-blinded study of children with experimentally induced minor injuries. Control arms included both no intervention group and 'sham' (non-maternal) kissing. Children were blinded to the identity of the kisser in both the maternal and sham control groups. Outpatient research clinics in Ottawa, Canada. 943 maternal-toddler pairs recruited from the community. Toddler Discomfort Index (TDI) pre-injury, 1 and 5 minutes post-injury. One-minute and 5-minute TDI scores did not differ significantly between the maternal and sham kiss groups. Both of these groups had significantly higher TDI scores at 5 minutes compared to the no intervention group. Maternal kissing of boo-boos confers no benefit on children with minor traumatic injuries compared to both no intervention and sham kissing. In fact, children in the maternal kissing group were significantly more distressed at 5 minutes than were children in the no intervention group. The practice of maternal kissing of boo-boos is not supported by the evidence and we recommend a moratorium on the practice. © 2015 John Wiley & Sons, Ltd.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

PubMed

Suzuki, K; Yamanaka, T; Hashimoto, H; Shimada, Y; Arata, K; Matsui, R; Goto, K; Takiguchi, T; Ohyanagi, F; Kogure, Y; Nogami, N; Nakao, M; Takeda, K; Azuma, K; Nagase, S; Hayashi, T; Fujiwara, K; Shimada, T; Seki, N; Yamamoto, N

2016-08-01

There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. UMIN000004863. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.

PubMed

Tomasik, Andrzej; Jacheć, Wojciech; Wojciechowska, Celina; Kawecki, Damian; Białkowska, Beata; Romuk, Ewa; Gabrysiak, Artur; Birkner, Ewa; Kalarus, Zbigniew; Nowalany-Kozielska, Ewa

2015-05-01

Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker. A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804). Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.

PubMed

Pakdaman, Michael N; Udani, Jay K; Molina, Jhanna Pamela; Shahani, Michael

2016-05-20

Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption. Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties. Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance. The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance. The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance. Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms. Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover. The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California). The placebo was formulated from maltodextrin. Study participants were instructed to take the product once daily for 4 weeks. Data collected included subjective symptom scores related to lactose intolerance. Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0.033), abdominal cramping (p = 0.012), vomiting (p = 0.0002), and overall symptom score (p = 0.037). No adverse events were reported. The present study has found that this unique DDS-1 strain of Lactobacillus acidophilus, manufactured by Nebraska Cultures, is safe to consume and improves abdominal symptom scores compared to placebo with respect to diarrhea, cramping, and vomiting during an acute lactose challenge.

A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial.

PubMed

Welsh, Robert C; Rao, Sunil V; Zeymer, Uwe; Thompson, Vivian P; Huber, Kurt; Kochman, Janusz; McClure, Matthew W; Gretler, Daniel D; Bhatt, Deepak L; Gibson, C Michael; Angiolillo, Dominick J; Gurbel, Paul A; Berdan, Lisa G; Paynter, Gayle; Leonardi, Sergio; Madan, Mina; French, William J; Harrington, Robert A

2012-06-01

We evaluated the safety, efficacy, and tolerability of elinogrel, a competitive, reversible intravenous and oral P2Y(12) inhibitor that does not require metabolic activation, in patients undergoing nonurgent percutaneous coronary intervention. In a randomized, double-blind, dose-ranging phase 2b trial, 652 patients received either 300 or 600 mg of clopidogrel pre-percutaneous coronary intervention followed by 75 mg daily or 80 or 120 mg of IV elinogrel followed by 50, 100, or 150 mg oral elinogrel twice daily. Numerous exploratory safety and efficacy end points were assessed and, as such, had no prespecified primary end point, and the study was not powered to conclusively evaluate its objectives. Thrombolysis in myocardial infarction combined bleeding was increased with elinogrel (hazard ratio, 1.98; 95% confidence interval, 1.10 to 3.57), related largely to increased bleeding requiring medical attention (elinogrel 47/408 [11.5%] versus clopidogrel 13/208 [6.3%]) and occurring primarily at the percutaneous coronary intervention access site. Efficacy end points and postprocedure cardiac enzyme were similar, but there was a nonsignificant higher frequency of periprocedural myocardial infarctions in the elinogrel arms (OR, 1.59; 95% confidence interval, 0.79 to 3.48). There was an increased incidence of dyspnea (elinogrel 50/408 [12.3%] versus clopidogrel 8/208 [3.8%]) and transaminase elevation (alanine transferase/aspartate transferase >3× the upper limit of normal; elinogrel 18/408 [4.4%] versus clopidogrel 2/208 [1.0%]) in the elinogrel arms, but there were no cases of heart block, bradycardia, hypotension, or liver failure. In patients undergoing nonurgent percutaneous coronary intervention and in comparison with clopidogrel, intravenous and oral elinogrel therapy did not significantly increase thrombolysis in myocardial infarction major or minor bleeding, although bleeding requiring medical attention was more common. The significance of these findings will need to be more definitively determined in future Phase 3 studies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751231.

A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.

PubMed

Fukuda, Mark M; Krudsood, Srivicha; Mohamed, Khadeeja; Green, Justin A; Warrasak, Sukhuma; Noedl, Harald; Euswas, Ataya; Ittiverakul, Mali; Buathong, Nillawan; Sriwichai, Sabaithip; Miller, R Scott; Ohrt, Colin

2017-01-01

Tafenoquine is an investigational 8-aminoquinoline for the prevention of Plasmodium vivax relapse. Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen. This randomized, active-control, double-blind trial was conducted in Bangkok, Thailand. Seventy patients with microscopically confirmed P. vivax were randomized (2:1) to tafenoquine 400 mg once daily for 3 days or 2500 mg total dose chloroquine phosphate (1500 mg chloroquine base) given over 3 days plus primaquine 15 mg daily for 14 days. Patients were followed to day 120. Day 28 adequate clinical response rate in the per-protocol population was 93% (40/43) (90%CI 83-98%) with tafenoquine, and 100% (22/22) (90%CI 87-100%) with chloroquine/primaquine. Day 120 relapse prevention was 100% (35/35) with tafenoquine (90%CI 92-100%), and 95% (19/20) (90%CI 78-100%) with chloroquine/primaquine. Mean (SD) parasite, gametocyte and fever clearance times with tafenoquine were 82.5 h (32.3), 49.1 h (33.0), and 41.1 h (31.4) versus 40.0 h (15.7), 22.7 h (16.4), and 24.7 h (17.7) with chloroquine/primaquine, respectively. Peak methemoglobin was 1.4-25.6% (median 7.4%, mean 9.1%) in the tafenoquine arm, and 0.5-5.9% (median 1.5%, mean 1.9%) in the chloroquine/primaquine arm. There were no clinical symptoms of methemoglobinemia in any patient. Although there was no difference in efficacy in this study, the slow rate of parasite, gametocyte and fever clearance indicates that tafenoquine should not be used as monotherapy for radical cure of P. vivax malaria. Also, monotherapy increases the potential risk of resistance developing to this long-acting agent. Clinical trials of single-dose tafenoquine 300 mg combined with standard 3-day chloroquine or artemisinin-based combination therapy are ongoing. Clinicaltrials.gov NCT01290601.

A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria

PubMed Central

Krudsood, Srivicha; Mohamed, Khadeeja; Green, Justin A.; Warrasak, Sukhuma; Noedl, Harald; Euswas, Ataya; Ittiverakul, Mali; Buathong, Nillawan; Sriwichai, Sabaithip; Miller, R. Scott; Ohrt, Colin

2017-01-01

Background Tafenoquine is an investigational 8-aminoquinoline for the prevention of Plasmodium vivax relapse. Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen. Methods This randomized, active-control, double-blind trial was conducted in Bangkok, Thailand. Seventy patients with microscopically confirmed P. vivax were randomized (2:1) to tafenoquine 400 mg once daily for 3 days or 2500 mg total dose chloroquine phosphate (1500 mg chloroquine base) given over 3 days plus primaquine 15 mg daily for 14 days. Patients were followed to day 120. Results Day 28 adequate clinical response rate in the per-protocol population was 93% (40/43) (90%CI 83–98%) with tafenoquine, and 100% (22/22) (90%CI 87–100%) with chloroquine/primaquine. Day 120 relapse prevention was 100% (35/35) with tafenoquine (90%CI 92–100%), and 95% (19/20) (90%CI 78–100%) with chloroquine/primaquine. Mean (SD) parasite, gametocyte and fever clearance times with tafenoquine were 82.5 h (32.3), 49.1 h (33.0), and 41.1 h (31.4) versus 40.0 h (15.7), 22.7 h (16.4), and 24.7 h (17.7) with chloroquine/primaquine, respectively. Peak methemoglobin was 1.4–25.6% (median 7.4%, mean 9.1%) in the tafenoquine arm, and 0.5–5.9% (median 1.5%, mean 1.9%) in the chloroquine/primaquine arm. There were no clinical symptoms of methemoglobinemia in any patient. Discussion Although there was no difference in efficacy in this study, the slow rate of parasite, gametocyte and fever clearance indicates that tafenoquine should not be used as monotherapy for radical cure of P. vivax malaria. Also, monotherapy increases the potential risk of resistance developing to this long-acting agent. Clinical trials of single-dose tafenoquine 300 mg combined with standard 3-day chloroquine or artemisinin-based combination therapy are ongoing. Trial registration Clinicaltrials.gov NCT01290601 PMID:29121061

Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial.

PubMed

Madhi, S A; Kirsten, M; Louw, C; Bos, P; Aspinall, S; Bouckenooghe, A; Neuzil, K M; Steele, A D

2012-04-27

Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Confidence interval: 56-88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children. A prospective, double-blind, placebo controlled multi-centered trial in South Africa and Malawi randomly assigned infants in a 1:1:1 ratio to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. 1339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1-83%). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homeopathy for Depression: A Randomized, Partially Double-Blind, Placebo-Controlled, Four-Armed Study (DEP-HOM)

PubMed Central

Adler, Ubiratan C.; Krüger, Stephanie; Teut, Michael; Lüdtke, Rainer; Schützler, Lena; Martins, Friederike; Willich, Stefan N.; Linde, Klaus; Witt, Claudia M.

2013-01-01

Background The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated. Aims To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks. Methods A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed. Results A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI −1.2;5.2) for Q-potencies vs. placebo and −3.1 (−5.9;−0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups. Conclusions Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Trial registration clinicaltrials.gov identifier NCT01178255. Protocol publication: http://www.trialsjournal.com/content/12/1/43 PMID:24086352

Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

PubMed

Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

2017-07-01

Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited. ClinicalTrials.gov identifier: NCT01280305. © Copyright 2017 Physicians Postgraduate Press, Inc.

Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choo, Richard; Lukka, Himu; Cheung, Patrick

Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5more » on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.« less

Homeopathy for Depression - DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study

PubMed Central

2011-01-01

Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the challenges of homeopathic research and the results might be useful information in the current discussion about the evidence on homeopathy Trial registration ClinicalTrials.gov: NCT01178255 PMID:21320338

A pilot single-blind multicentre randomized controlled trial to evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on the arm function of children with spastic cerebral palsy.

PubMed

Preston, Nick; Weightman, Andrew; Gallagher, Justin; Levesley, Martin; Mon-Williams, Mark; Clarke, Mike; O'Connor, Rory J

2016-10-01

To evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on arm function of children with spastic cerebral palsy. A single-blind randomized controlled trial design. Power calculations indicated that 58 children would be required to demonstrate a clinically important difference. Intervention was home-based; recruitment took place in regional spasticity clinics. A total of 15 children with cerebral palsy aged five to 12 years were recruited; eight to the device group. Both study groups received 'usual follow-up treatment' following spasticity treatment with botulinum toxin; the intervention group also received a rehabilitation gaming device. ABILHAND-kids and Canadian Occupational Performance Measure were performed by blinded assessors at baseline, six and 12 weeks. An analysis of covariance showed no group differences in mean ABILHAND-kids scores between time points. A non-parametric analysis of variance on Canadian Occupational Performance Measure scores showed a statistically significant improvement across time points (χ 2 (2,15) = 6.778, p = 0.031), but this improvement did not reach minimal clinically important difference. Mean daily device use was seven minutes. Recruitment did not reach target owing to unanticipated staff shortages in clinical services. Feedback from children and their families indicated that the games were not sufficiently engaging to promote sufficient use that was likely to result in functional benefits. This study suggests that computer-assisted arm rehabilitation gaming does not benefit arm function, but a Type II error cannot be ruled out. © The Author(s) 2015.

A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged > or =65 years with community-acquired pneumonia.

PubMed

Shorr, Andrew F; Zadeikis, Neringa; Xiang, Jim X; Tennenberg, Alan M; Wes Ely, E

2005-08-01

This subgroup analysis sought to determine the efficacy and tolerability of a 5-day regimen of levofloxacin 750 mg/d compared with a 10-day regimen of levofloxacin 500 mg/d in the treatment of community-acquired pneumonia (CAP) in elderly patients (aged > or =65 years). This subgroup analysis was based on the outcomes in patients aged > or =65 years from a randomized, double-blind, controlled trial conducted at 70 US centers. Patients in Pneumonia Severity Index (PSI) class I/II and III/IV were randomized to receive levofloxacin 750 mg/d for 5 days or levofloxacin 500 mg/d for 10 days. Study investigators assessed clinical and microbiologic outcomes 7 to 14 days after administration of the last dose of medication and collected adverse events for 30 days after the last dose. This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache. This subgroup analysis found that levofloxacin 750 mg/d for 5 days was well tolerated in the treatment of CAP in elderly patients. Undajusted and adjusted rates of clinical success were statistically similar between levofloxacin 750 mg/d for 5 days and levofloxacin 500 mg/d for 10 days.

Review of science issues, deployment strategy, and status for the ARM north slope of Alaska-Adjacent Arctic Ocean climate research site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stamnes, K.; Ellingson, R.G.; Curry, J.A.

1999-01-01

Recent climate modeling results point to the Arctic as a region that is particularly sensitive to global climate change. The Arctic warming predicted by the models to result from the expected doubling of atmospheric carbon dioxide is two to three times the predicted mean global warming, and considerably greater than the warming predicted for the Antarctic. The North Slope of Alaska-Adjacent Arctic Ocean (NSA-AAO) Cloud and Radiation Testbed (CART) site of the Atmospheric Radiation Measurement (ARM) Program is designed to collect data on temperature-ice-albedo and water vapor-cloud-radiation feedbacks, which are believed to be important to the predicted enhanced warming inmore » the Arctic. The most important scientific issues of Arctic, as well as global, significance to be addressed at the NSA-AAO CART site are discussed, and a brief overview of the current approach toward, and status of, site development is provided. ARM radiometric and remote sensing instrumentation is already deployed and taking data in the perennial Arctic ice pack as part of the SHEBA (Surface Heat Budget of the Arctic ocean) experiment. In parallel with ARM`s participation in SHEBA, the NSA-AAO facility near Barrow was formally dedicated on 1 July 1997 and began routine data collection early in 1998. This schedule permits the US Department of Energy`s ARM Program, NASA`s Arctic Cloud program, and the SHEBA program (funded primarily by the National Science Foundation and the Office of Naval Research) to be mutually supportive. In addition, location of the NSA-AAO Barrow facility on National Oceanic and Atmospheric Administration land immediately adjacent to its Climate Monitoring and Diagnostic Laboratory Barrow Observatory includes NOAA in this major interagency Arctic collaboration.« less

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

PubMed

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

2013-10-01

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). 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. 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. 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.

Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans.

PubMed

Beaumont, Martin; Portune, Kevin Joseph; Steuer, Nils; Lan, Annaïg; Cerrudo, Victor; Audebert, Marc; Dumont, Florent; Mancano, Giulia; Khodorova, Nadezda; Andriamihaja, Mireille; Airinei, Gheorghe; Tomé, Daniel; Benamouzig, Robert; Davila, Anne-Marie; Claus, Sandrine Paule; Sanz, Yolanda; Blachier, François

2017-10-01

Background: Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context. Objective: The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans. Design: A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by 1 H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays. Results: HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death. Conclusions: This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis. This trial was registered at clinicaltrials.gov as NCT02351297. © 2017 American Society for Nutrition.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

PubMed

Bousser, M G; Amarenco, P; Chamorro, A; Fisher, M; Ford, I; Fox, K; Hennerici, M G; Mattle, H P; Rothwell, P M

2009-01-01

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event. Copyright 2009 S. Karger AG, Basel.

Effect of L-Tryptophan and L-Leucine on Gut Hormone Secretion, Appetite Feelings and Gastric Emptying Rates in Lean and Non-Diabetic Obese Participants: A Randomized, Double-Blind, Parallel-Group Trial

PubMed Central

Meyer-Gerspach, Anne Christin; Häfliger, Simon; Meili, Julian; Doody, Alison; Rehfeld, Jens F; Drewe, Jürgen; Beglinger, Christoph; Wölnerhanssen, Bettina

2016-01-01

Background/Objectives Gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance satiation peptide secretion could provide a therapeutic approach for obesity. Carbohydrates and lipids have been extensively investigated in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion. Participants/Methods The study was conducted as a randomized (balanced), double-blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese participants were included. Participants received intragastric loads of L-trp (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g glucose and 300 mL tap water served as control treatments. Results Results of the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018), and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii) neither of the amino acids modulated subjective appetite feelings; and iv) the two amino acids did not alter insulin or glucose concentrations. Conclusions L-trp is a luminal regulator of CCK release with effects on gastric emptying, an effect that could be mediated by CCK. L-trp’s effect on GLP-1 secretion is only minor. At the doses given, the two amino acids did not affect subjective appetite feelings. Trial Registration ClinicalTrials.gov NCT02563847 PMID:27875537

Immunogenicity and safety of a high-dose hepatitis B vaccine among patients receiving methadone maintenance treatment: A randomized, double-blinded, parallel-controlled trial.

PubMed

Shi, Jing; Feng, Yongliang; Gao, Linying; Feng, Dan; Yao, Tian; Shi, Shan; Zhang, Yawei; Liang, Xiaofeng; Wang, Suping

2017-04-25

To explore whether the immunization with high-dose (60μg) hepatitis B vaccines in patients receiving methadone maintenance treatment (MMT) could yield a superior protection against hepatitis B infection than did the standard dose (20μg). We conducted a randomized, double-blinded, parallel-controlled trial in MMT patients. Patients with serologically negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were randomized in a ratio of 1:1 to receive three intramuscular injections of 20μg or 60μg recombinant hepatitis B vaccine at months 0, 1, and 6. Serum HBsAg and anti-HBs were measured at months 7 and 12 post-vaccination to assess the immunogenicity. A total of 196 MMT patients were randomized and 195 received at least one injection (98 and 97 in 20 and 60μg vaccine groups, respectively). The 60μg vaccine group showed a seroconversion of anti-HBs of 87.3%, high-level response rate of 56.3%, and GMC of 742.9mIU/mL at month 7. While these results were numerically higher than the 20μg group, a statistical difference was not found. HIV infection and concomitant drug abuse were negatively associated with the robust immune responses. 7.7% of MMT patients receiving at least one dose of vaccine reported solicited adverse reactions within 7days after vaccination, 2.6% reported unsolicited adverse reactions within 28days after vaccination. None of the MMT patients reported serious adverse events or became HBsAg positive during the follow-up. The three-dose regimen of 60μg recombinant hepatitis B vaccine at months 0, 1, and 6 can yield a similar immunogenicity among MMT patients as compared to the 20μg vaccine. ClinicalTrials.gov identifier: NCT02991599. Copyright © 2017. Published by Elsevier Ltd.

Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial.

PubMed

Usall, Judith; Huerta-Ramos, Elena; Labad, Javier; Cobo, Jesús; Núñez, Christian; Creus, Marta; Parés, Gemma García; Cuadras, Daniel; Franco, José; Miquel, Eva; Reyes, Julio César; Roca, Mercedes

2016-03-01

The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. NCT01573637. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Association of Efavirenz Hypersusceptibility with Virologic Response in ACTG 368, a Randomized Trial of Abacavir (ABC) in Combination with Efavirenz (EFV) and Indinavir (IDV) in HIV-infected Subjects with Prior Nucleoside Analog Experience

PubMed Central

Demeter, Lisa M.; DeGruttola, Victor; Lustgarten, Stephanie; Bettendorf, Daniel; Fischl, Margaret; Eshleman, Susan; Spreen, William; Nguyen, Bach-Yen; Koval, Christine E.; Eron, Joseph J.; Hammer, Scott; Squires, Kathleen

2010-01-01

Purpose To evaluate the association of efavirenz hypersusceptibility (EFV-HS) with clinical outcome in a double-blind, placebo-controlled, randomized trial of EFV plus indinavir (EFV+IDV) vs. EFV+IDV plus abacavir (ABC) in 283 nucleoside-experienced HIV-infected patients. Methods and Results Rates of virologic failure were similar in the 2 arms at week 16 (p=0.509). Treatment discontinuations were more common in the ABC arm (p=0.001). Using logistic regression, there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score. Using 3 different genotypic scoring systems, EFV-HS was significantly associated with reduced virologic failure at week 16, independent of treatment assignment. In some patients on the nucleoside-sparing arm, the nucleoside-resistant mutant L74V was selected for in combination with the uncommonly occurring EFV-resistant mutant K103N+L100I; L74V was not detected as a minority variant, using clonal sequence analysis, when the nucleoside-sparing regimen was initiated. Conclusions Premature treatment discontinuations in the ABC arm and the presence of EFV-hypersusceptible HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV. In addition, L74V, when combined with K103N+L100I, may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance. PMID:18215978

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies

PubMed Central

Hollis, Sally; Jorup, Carin; Lythgoe, Dan; Martensson, Gunnar; Regnell, Pontus; Eckerwall, Göran

2017-01-01

Background Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors. Methods AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study. Results Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38). Conclusion This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments. However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. PMID:28435240

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies.

PubMed

Hollis, Sally; Jorup, Carin; Lythgoe, Dan; Martensson, Gunnar; Regnell, Pontus; Eckerwall, Göran

2017-01-01

Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors. AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks' duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study. Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38). This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments. However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

PubMed

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

PubMed

Kothny, Wolfgang; Lukashevich, Valentina; Foley, James E; Rendell, Marc S; Schweizer, Anja

2015-09-01

There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR <30 ml min(-1) [1.73 m](-2) were randomised (via interactive voice response technology) to vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events. In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles. At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI. ClinicalTrials.gov NCT00616811 (completed) This study was planned and conducted by Novartis.

Journeys in The Country of The Blind: Entanglement Theory and The Effects of Blinding on Trials of Homeopathy and Homeopathic Provings

PubMed Central

2007-01-01

The idea of quantum entanglement is borrowed from physics and developed into an algebraic argument to explain how double-blinding randomized controlled trials could lead to failure to provide unequivocal evidence for the efficacy of homeopathy, and inability to distinguish proving and placebo groups in homeopathic pathogenic trials. By analogy with the famous double-slit experiment of quantum physics, and more modern notions of quantum information processing, these failings are understood as blinding causing information loss resulting from a kind of quantum superposition between the remedy and placebo. PMID:17342236

Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial.

PubMed

Mogollon, Jaime Andres; Boivin, Catherine; Lemieux, Simone; Blanchet, Claudine; Claveau, Joël; Dodin, Sylvie

2014-06-27

Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20-65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Our study failed to demonstrate a statistically-significant protective effect of HFC vs. LFC consumption on skin sensitivity to UV radiation as measured by MED. ClinicalTrials.gov identifier: NCT01444625.

A neural-network-based approach to the double traveling salesman problem.

PubMed

Plebe, Alessio; Anile, Angelo Marcello

2002-02-01

The double traveling salesman problem is a variation of the basic traveling salesman problem where targets can be reached by two salespersons operating in parallel. The real problem addressed by this work concerns the optimization of the harvest sequence for the two independent arms of a fruit-harvesting robot. This application poses further constraints, like a collision-avoidance function. The proposed solution is based on a self-organizing map structure, initialized with as many artificial neurons as the number of targets to be reached. One of the key components of the process is the combination of competitive relaxation with a mechanism for deleting and creating artificial neurons. Moreover, in the competitive relaxation process, information about the trajectory connecting the neurons is combined with the distance of neurons from the target. This strategy prevents tangles in the trajectory and collisions between the two tours. Results of tests indicate that the proposed approach is efficient and reliable for harvest sequence planning. Moreover, the enhancements added to the pure self-organizing map concept are of wider importance, as proved by a traveling salesman problem version of the program, simplified from the double version for comparison.

A single dose desensitization for summer hay fever. Results of a double blind study-1988.

PubMed

Fell, P; Brostoff, J

1990-01-01

A new type of desensitising vaccine, enzyme potentiated was subjected to a double-blind randomised study during the hay fever season. The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season.

Effects of baking-soda-containing dentifrices on oral malodor.

PubMed

Brunette, D M

1997-01-01

Oral malodor, also known as bad breath or halitosis, is an extremely common problem. Bad breath can arise from many sources in the body, but most frequently is produced in the mouth by the action of gram-negative anaerobic bacteria on sulfur-containing proteinaceous substrates in the saliva, such as debris and plaque. The primary molecules responsible for oral malodor are volatile sulfur compounds (VSC), such as hydrogen sulfide and methylmercaptan. Increased malodor production is related to greater bacterial numbers, reducing conditions, availability of protein substrates, and a pH above neutral. Bad breath is more common in the elderly, as well as those with unhygienic mouths, gingivitis, and periodontitis, but bad breath can also be found in some individuals who are periodontally healthy. The major source of oral malodor is the tongue. Approaches to controlling malodor have included masking, oral hygiene, antibacterial agents, conversion of VSC to nonodorous forms, oxidizing agents, and traditional approaches, including the use of backing soda. Results of controlled double-blind crossover studies, using both organoleptic (sensory) and gas chromatographic analysis of mouth air VSC, indicate that two dentifrices with high baking-soda concentrations, Arm & Hammer Dental Care and Arm & Hammer PeroxiCare, reduce oral malodor.

Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes.

PubMed

Ostojic, Sergej M; Calleja, Julio; Jourkesh, Morteza

2010-02-28

Dehydroepiandrosterone (DHEA) is often promoted as a slimming and weight/fat loss agent and ingestion of DHEA may have hypolipidemic and anti-obesity properties. The main aim of this study was to examine the effects of acute DHEA intake on body composition and serum steroid hormones in young athletes. Twenty young (19 to 22 years) male soccer players were allocated into two randomly assigned trials in double-blind design by ingesting 100-mg daily oral DHEA or as placebo (PLA) for 28 days. Body mass was not affected by 4 weeks of DHEA supplementation (P > 0.05). No significant changes in body mass index (BMI), waist-to-hip ratio (WHR) and body fat or total muscle mass for the two groups were detected at the end of the trial (P > 0.05). There was no within- or between-group difference in arm fat index (AFI) and corrected mid-upper-arm muscle area (cAMA) (P > 0.05). Treatment with DHEA resulted in a significant increase of total testosterone, estradiol and DHEA-S levels in treated subjects versus the placebo group (P < 0.05). Results of this study suggest that DHEA supplementation has no beneficial effects on body composition in young competitive athletes.

Tolerability of extended-release quetiapine fumarate compared with immediate-release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double-blind, parallel-group study.

PubMed

De Deyn, Peter Paul; Eriksson, Hans; Svensson, Hanna

2012-03-01

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR. Copyright © 2011 John Wiley & Sons, Ltd.

A randomized controlled trial to evaluate the feasibility of the Wii Fit for improving walking in older adults with lower limb amputation.

PubMed

Imam, Bita; Miller, William C; Finlayson, Heather; Eng, Janice J; Jarus, Tal

2017-01-01

To assess the feasibility of Wii.n.Walk for improving walking capacity in older adults with lower limb amputation. A parallel, evaluator-blind randomized controlled feasibility trial. Community-living. Individuals who were ⩾50 years old with a unilateral lower limb amputation. Wii.n.Walk consisted of Wii Fit training, 3x/week (40 minute sessions), for 4 weeks. Training started in the clinic in groups of 3 and graduated to unsupervised home training. Control group were trained using cognitive games. Feasibility indicators: trial process (recruitment, retention, participants' perceived benefit from the Wii.n.Walk intervention measured by exit questionnaire), resources (adherence), management (participant processing, blinding), and treatment (adverse event, and Cohen's d effect size and variance). Primary clinical outcome: walking capacity measured using the 2 Minute Walk Test at baseline, end of treatment, and 3-week retention. Of 28 randomized participants, 24 completed the trial (12/arm). Median (range) age was 62.0 (50-78) years. Mean (SD) score for perceived benefit from the Wii.n.Walk intervention was 38.9/45 (6.8). Adherence was 83.4%. The effect sizes for the 2 Minute Walk Test were 0.5 (end of treatment) and 0.6 (3-week retention) based on intention to treat with imputed data; and 0.9 (end of treatment) and 1.2 (3-week retention) based on per protocol analysis. The required sample size for a future larger RCT was deemed to be 72 (36 per arm). The results suggested the feasibility of the Wii.n.Walk with a medium effect size for improving walking capacity. Future larger randomized controlled trials investigating efficacy are warranted.

Diet and anthropometry at 2 years of age following an oral health promotion programme for Australian Aboriginal children and their carers: a randomised controlled trial.

PubMed

Smithers, Lisa G; Lynch, John; Hedges, Joanne; Jamieson, Lisa M

2017-12-01

There are marked disparities between indigenous and non-indigenous children's diets and oral health. Both diet and oral health are linked to longer-term health problems. We aimed to investigate whether a culturally appropriate multi-faceted oral health promotion intervention reduced Aboriginal children's intake of sugars from discretionary foods at 2 years of age. We conducted a single-blind, parallel-arm randomised controlled trial involving women who were pregnant or had given birth to an Aboriginal child in the previous 6 weeks. The treatment group received anticipatory guidance, Motivational Interviewing, health and dental care for mothers during pregnancy and children at 6, 12 and 18 months. The control group received usual care. The key dietary outcome was the percent energy intake from sugars in discretionary foods (%EI), collected from up to three 24-h dietary recalls by trained research officers who were blind to intervention group. Secondary outcomes included intake of macronutrients, food groups, anthropometric z scores (weight, height, BMI and mid-upper arm circumference) and blood pressure. We enrolled 224 children to the treatment group and 230 to the control group. Intention-to-treat analyses showed that the %EI of sugars in discretionary foods was 1·6 % lower in the treatment group compared with control (95 % CI -3·4, 0·2). This culturally appropriate intervention at four time-points from pregnancy to 18 months resulted in small changes to 2-year-old Aboriginal children's diets, which was insufficient to warrant broader implementation of the intervention. Further consultation with Aboriginal communities is necessary for understanding how to improve the diet and diet-related health outcomes of young Aboriginal children.

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

PubMed Central

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

2015-01-01

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

Interpreting Breast International Group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer.

PubMed

Regan, Meredith M; Price, Karen N; Giobbie-Hurder, Anita; Thürlimann, Beat; Gelber, Richard D

2011-05-26

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205.

Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer

PubMed Central

2011-01-01

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205. PMID:21635709

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.

PubMed

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Evans, Christopher P; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S; Borre, Michael; Mulders, Peter; Tammela, Teuvo L; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-02-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p<0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

PubMed

Ning, Yang-Min; Brave, Michael; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard

2015-08-01

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14-0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30-0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. ©AlphaMed Press.

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

GPU-based parallel algorithm for blind image restoration using midfrequency-based methods

NASA Astrophysics Data System (ADS)

Xie, Lang; Luo, Yi-han; Bao, Qi-liang

2013-08-01

GPU-based general-purpose computing is a new branch of modern parallel computing, so the study of parallel algorithms specially designed for GPU hardware architecture is of great significance. In order to solve the problem of high computational complexity and poor real-time performance in blind image restoration, the midfrequency-based algorithm for blind image restoration was analyzed and improved in this paper. Furthermore, a midfrequency-based filtering method is also used to restore the image hardly with any recursion or iteration. Combining the algorithm with data intensiveness, data parallel computing and GPU execution model of single instruction and multiple threads, a new parallel midfrequency-based algorithm for blind image restoration is proposed in this paper, which is suitable for stream computing of GPU. In this algorithm, the GPU is utilized to accelerate the estimation of class-G point spread functions and midfrequency-based filtering. Aiming at better management of the GPU threads, the threads in a grid are scheduled according to the decomposition of the filtering data in frequency domain after the optimization of data access and the communication between the host and the device. The kernel parallelism structure is determined by the decomposition of the filtering data to ensure the transmission rate to get around the memory bandwidth limitation. The results show that, with the new algorithm, the operational speed is significantly increased and the real-time performance of image restoration is effectively improved, especially for high-resolution images.

Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

PubMed

Schmidt, Simone; Gocheva, Vanya; Zumbrunn, Thomas; Rubino-Nacht, Daniela; Bonati, Ulrike; Fischer, Dirk; Hafner, Patricia

2017-03-09

Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.

2008-01-01

Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dosemore » distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.« less

The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study.

PubMed

Bagel, Jerry; Duffin, Kristina Callis; Moore, Angela; Ferris, Laura K; Siu, Kimberly; Steadman, Jennifer; Kianifard, Farid; Nyirady, Judit; Lebwohl, Mark

2017-10-01

Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P < .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P < .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies. There was no active comparator arm. Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial.

PubMed

Stengel, Joel Z; Jones, David P

2008-09-01

Proper colonic cleansing prior to colonoscopy is paramount to ensuring complete mucosal visualization and polyp identification. In a double-blind fashion, we compared single-dose lubiprostone (24 microg) versus placebo pretreatment prior to a split-dose polyethylene glycol electrolyte (PEG-E) bowel preparation without dietary restriction to determine the efficacy, safety, and patient tolerability. Two hundred patients referred for outpatient colorectal cancer screening were randomized to receive a single-dose of unlabeled lubiprostone (24 microg) or placebo prior to a split-dose PEG-E bowel preparation without dietary restriction. The patients were surveyed prior to the colonoscopy on the tolerability of the bowel preparation, and any adverse events were recorded. The cleanliness of the colon was graded by the endoscopist during the procedure utilizing the Ottawa bowel preparation scale. One hundred ninety-one patients completed the study (95%). Split-dose PEG-E with lubiprostone pretreatment was found to be more effective at bowel cleansing in each segment of the colon when compared with split-dose PEG-E with placebo (P < 0.001). Patients enrolled in the lubiprostone treatment arm rated the overall experience as more tolerable (P 0.003) and complained of less abdominal bloating (P 0.049). No differences were observed between the groups for treatment-emergent side effects or adverse events (P > 0.05). Single-dose lubiprostone prior to split-dose PEG-E without dietary restriction significantly improves colonic mucosa visualization during colonoscopy and is well tolerated by patients.

Warming and humidification of insufflation carbon dioxide in laparoscopic colonic surgery: a double-blinded randomized controlled trial.

PubMed

Sammour, Tarik; Kahokehr, Arman; Hayes, Julian; Hulme-Moir, Mike; Hill, Andrew G

2010-06-01

We aimed to test the hypothesis that warming and humidification of insufflation CO2 would lead to reduced postoperative pain and improved recovery by reducing peritoneal inflammation in laparoscopic colonic surgery. Warming and humidification of insufflation gas is thought be beneficial in laparoscopic surgery, but evidence in prolonged laparoscopic procedures is lacking. We used a multicenter, double-blinded, randomized controlled design. The Study Group received warmed (37 degrees C), humidified (98% RH) insufflation carbon dioxide, and the Control Group received standard gas (19 degrees C, 0% RH). Anesthesia and analgesia were standardized. Intraoperative oesophageal temperature was measured at 15 minutes intervals. At the conclusion of surgery, the primary surgeon was asked to rate camera fogging on a Likert scale. Postoperative opiate usage was determined using Morphine Equivalent Daily Dose (MEDD), and pain was measured using visual analogue scores. Peritoneal and plasma cytokine concentrations were measured at 20 hours postoperatively. Postoperative recovery was measured using defined discharge and complication criteria, and the Surgical Recovery Score. Eighty-two patients were randomized, with 41 in each arm. Groups were well matched at baseline. Intraoperative core temperature was similar in both groups. Median camera fogging score was significantly worse in the Study group (4 vs. 2, P = 0.040). There were marginal differences in pain scores, but no significant differences were detected in MEDD usage, cytokine concentrations, or any recovery parameters measured. Warming and humidification of insufflation CO2 does not attenuate the early inflammatory cytokine response, and confers no clinically significant benefit in laparoscopic colonic surgery.

Rationale and methods of the iFightDepression study: A double-blind, randomized controlled trial evaluating the efficacy of an internet-based self-management tool for moderate to mild depression.

PubMed

Justicia, Azucena; Elices, Matilde; Cebria, Ana Isabel; Palao, Diego J; Gorosabel, Jesús; Puigdemont, Dolors; de Diego-Adeliño, Javier; Gabilondo, Andrea; Iruin, Alvaro; Hegerl, Ulrich; Pérez, Víctor

2017-04-19

During the last decade online interventions have emerged as a promising approach for patients with mild/moderate depressive symptoms, reaching at large populations and representing cost-effective alternatives. The main objective of this double-blind, randomized controlled trial is to examine the efficacy of an internet-based self-management tool (iFightDepression) for mild to moderate depression as an add-on to treatment as usual (TAU) versus internet-based psychoeducation plus TAU. A total of 310 participants with major depression disorder (MDD) will be recruited at four different mental-health facilities in Spain. Participants will be randomly allocated to one of two study arms: iFightDepression (iFD) tool + TAU vs. internet-based psychoeducation + TAU. Both interventions last for 8 weeks and there is a 12 weeks follow up. The primary outcome measure is changes in depressive symptoms assessed with the Hamilton Depression Rating Scale. Additionally, pre-post interventions assessments will include socio-demographic data, a brief medical and clinical history and self-reported measures of depressive symptoms, quality of life, functional impairments and satisfaction with the iFD tool. iFightDepression is an easy-prescribed tool that could increase the efficacy of conventional treatment and potentially reach untreated patients, shortening waiting lists to receive psychological treatment. Confirming the efficacy of the iFD internet-based self-management tool as an add-on treatment for individuals with mild to moderate depression will be clinically-relevant. Registration number NCT02312583 . Clinicaltrials.gov . December 4, 2014.

A randomized, double-blind, placebo-controlled trial of oral procyanidin with vitamins A, C, E for melasma among Filipino women.

PubMed

Handog, Evangeline B; Galang, Dulce Amor Vivan F; de Leon-Godinez, Maria Azirrel; Chan, Gertrude P

2009-08-01

Melasma is a common, acquired, symmetric hypermelanosis characterized by irregular brown to gray-brown macules on the cheeks, forehead, nasal bridge, cutaneous part of the upper lip, mandible, and the upper arms. Few trials have been conducted regarding the potential benefits of oral procyanidin in melasma. To assess the safety and efficacy of oral procyanidin + vitamins A, C, E among Filipino patients with epidermal melasma. A randomized, double-blind, placebo-controlled trial lasting 8 weeks, involving 60 adult female volunteers with bilateral epidermal melasma, Fitzpatrick skin types III-V, was conducted at the Section of Dermatology, Research Institute for Tropical Medicine, Department of Health, Manila, Philippines. Patients received either the test drug or placebo, twice daily with meals. Changes in pigmentation were measured using a mexameter, the melasma area and severity index (MASI), and a global evaluation by the patient and investigator. Safety evaluations were performed at each follow-up visit. Fifty-six patients completed the trial. Mexameter results demonstrated a significant decrease in the degree of pigmentation in the left malar (165.85 +/- 70.909) and right malar (161.33 +/- 61.824) regions (P < 0.0001). MASI scores showed a significant improvement in the left malar (2.4862 +/- 1.67816) and right malar (1.8889 +/- 1.67110) regions (P = 0.001). Procyanidin + vitamins A, C, E proved to be safe and well tolerated, with minimal adverse events. In this 8-week trial period, oral procyanidin + vitamins A, C, E proved to be safe and effective among Filipino women with epidermal melasma.

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities.

PubMed Central

McNamara, Rachel; Randell, Elizabeth; Gillespie, David; Wood, Fiona; Felce, David; Romeo, Renee; Angel, Lianna; Espinasse, Aude; Hood, Kerry; Davies, Amy; Meek, Andrea; Addison, Katy; Jones, Glyn; Deslandes, Paul; Allen, David; Knapp, Martin; Thapar, Ajay; Kerr, Michael

2017-01-01

BACKGROUND Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. OBJECTIVES To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. DESIGN A two-arm individually randomised double-blind placebo-controlled drug reduction trial. SETTING Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. PARTICIPANTS Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. INTERVENTION A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. MAIN OUTCOME MEASURES Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use. RESULTS Of the 22 participants randomised (intervention, n = 11; control, n = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, n = 10; and control, n = 7; 77% of those randomised). There were no clinically important changes in participants' levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial. LIMITATIONS Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study. CONCLUSIONS The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development. FUTURE WORK We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication. TRIAL REGISTRATION Current Controlled Trials ISRCTN38126962. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 47. See the NIHR Journals Library website for further project information. PMID:28857740

Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE): a randomized controlled trial protocol.

PubMed

Winstein, Carolee J; Wolf, Steven L; Dromerick, Alexander W; Lane, Christianne J; Nelsen, Monica A; Lewthwaite, Rebecca; Blanton, Sarah; Scott, Charro; Reiss, Aimee; Cen, Steven Yong; Holley, Rahsaan; Azen, Stanley P

2013-01-11

Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting.The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC. Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure.The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05. ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose. www.ClinicalTrials.gov Identifier: NCT00871715

The Effect of Three Methods of Supporting the Double Bass on Muscle Tension.

ERIC Educational Resources Information Center

Dennis, Allan

1984-01-01

Using different methods of holding the double bass, college students performed Beethoven's Symphony No. 9. Audio recordings of performance were rated. Muscle tension readings from the left arm, right arm, upper back, and lower back were taken, using electromyography. Results suggest nonsignificant differences in both performance quality and muscle…

Twist limits for late twisting double somersaults on trampoline.

PubMed

Yeadon, M R; Hiley, M J

2017-06-14

An angle-driven computer simulation model of aerial movement was used to determine the maximum amount of twist that could be produced in the second somersault of a double somersault on trampoline using asymmetrical movements of the arms and hips. Lower bounds were placed on the durations of arm and hip angle changes based on performances of a world trampoline champion whose inertia parameters were used in the simulations. The limiting movements were identified as the largest possible odd number of half twists for forward somersaulting takeoffs and even number of half twists for backward takeoffs. Simulations of these two limiting movements were found using simulated annealing optimisation to produce the required amounts of somersault, tilt and twist at landing after a flight time of 2.0s. Additional optimisations were then run to seek solutions with the arms less adducted during the twisting phase. It was found that 3½ twists could be produced in the second somersault of a forward piked double somersault with arms abducted 8° from full adduction during the twisting phase and that three twists could be produced in the second somersault of a backward straight double somersault with arms fully adducted to the body. These two movements are at the limits of performance for elite trampolinists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

USDA-ARS?s Scientific Manuscript database

This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

ERIC Educational Resources Information Center

Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

1997-01-01

Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

Treatment of Menorrhagia with Tranexamic Acid. A Double-blind Trial

PubMed Central

Callender, Shei La T.; Warner, G. T.; Cope, E.

1970-01-01

In a double-blind trial tranexamic acid (Cyclokapron) 1 g. four times a day for the first four days of menstruation, significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found. No difference in side-effects was noted between the active and placebo treatment. PMID:4919554

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

2010-01-01

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

Multi-arm spectrometer for parallel frequency analysis of radio-wave signals oriented to astronomical observations

NASA Astrophysics Data System (ADS)

Shcherbakov, Alexandre S.; Chavez Dagostino, Miguel; Arellanes, Adan Omar; Tepichin Rodriguez, Eduardo

2017-08-01

We describe a potential prototype of modern spectrometer based on acousto-optical technique with three parallel optical arms for analysis of radio-wave signals specific to astronomical observations. Each optical arm exhibits original performances to provide parallel multi-band observations with different scales simultaneously. Similar multi-band instrument is able to realize measurements within various scenarios from planetary atmospheres to attractive objects in the distant Universe. The arrangement under development has two novelties. First, each optical arm represents an individual spectrum analyzer with its individual performances. Such an approach is conditioned by exploiting various materials for acousto-optical cells operating within various regimes, frequency ranges, and light wavelengths from independent light sources. Individually produced beam shapers give both the needed incident light polarization and the required apodization for light beam to increase the dynamic range of the system as a whole. After parallel acousto-optical processing, a few data flows from these optical arms are united by the joint CCD matrix on the stage of the combined extremely high-bit rate electronic data processing that provides the system performances as well. The other novelty consists in the usage of various materials for designing wide-aperture acousto-optical cells exhibiting the best performances within each of optical arms. Here, one can mention specifically selected cuts of tellurium dioxide, bastron, and lithium niobate, which overlap selected areas within the frequency range from 40 MHz to 2.0 GHz. Thus one yields the united versatile instrument for comprehensive studies of astronomical objects simultaneously with precise synchronization in various frequency ranges.

Memory strength and lineup presentation moderate effects of administrator influence on mistaken identifications.

PubMed

Zimmerman, David M; Chorn, Jacqueline Austin; Rhead, Lindsey M; Evelo, Andrew J; Kovera, Margaret Bull

2017-12-01

Administrator/witness pairs (N = 313) were randomly assigned to target-absent lineups in a 2 (Suspect/Perpetrator Similarity: High Suspect Similarity vs. Low Suspect Similarity) × 2 (Retention Interval: 30 min vs. 1 week) × 2 (Lineup Presentation: Simultaneous vs. Sequential) × 2 (Administrator Knowledge: Single-Blind vs. Double-Blind) factorial design to test whether suspect similarity and memory strength constrain interpersonal expectancy effects on eyewitness identification accuracy. Administrators who knew which lineup member was the suspect (single-blind) or who administered simultaneous lineups were more likely to emit verbal and nonverbal behaviors that suggested to the witness who the suspect was. Additionally, single-blind administrators exerted more pressure on witnesses to choose the suspect as opposed to fillers. Administrator knowledge interacted with retention interval and lineup presentation to influence mistaken identifications of innocent suspects; witnesses were more likely to mistakenly identify an innocent suspect from single-blind than double-blind lineups when witness retention intervals were long and photographs were presented simultaneously. Contrary to our predictions, suspect/perpetrator similarity did not interact with other manipulated variables to influence identification decisions. Both sequential and double-blind procedures should be used to reduce the use of suggestive behavior during lineup administration. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A Randomized, Double-Blind, Placebo-Controlled Trial of Eszopiclone for the Treatment of Insomnia in Patients with Chronic Low Back Pain

PubMed Central

Goforth, Harold W.; Preud'homme, Xavier A.; Krystal, Andrew D.

2014-01-01

Study Objectives: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. Design: Double-blind, placebo-controlled, parallel-group, 1-mo trial. Setting: Duke University Medical Center Outpatient Sleep Clinic. Patients: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). Interventions: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. Measurements and Results: ESZ significantly improved total sleep time (mean increase: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. Conclusions: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. Trial Registration: clinicaltrials.gov identifier: NCT00365976 Citation: Goforth HW, Preud'homme XA, Krystal AD. A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain. SLEEP 2014;37(6):1053-1060. PMID:24882900

A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief).

PubMed

Inoue, Satoshi; Saito, Yoji; Tsuneto, Satoru; Aruga, Etsuko; Ide, Azusa; Kakurai, Yasuyuki

2017-01-01

In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics. This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment. The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was -0.4 mm (95% CI -5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics. The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.

Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST): A Pilot Randomized Trial.

PubMed

Kosa, S Daisy; Gafni, Amiram; House, Andrew A; Lawrence, JulieAnn; Moist, Louise; Nathoo, Bharat; Tam, Paul; Sarabia, Alicia; Thabane, Lehana; Wu, George; Lok, Charmaine E

2017-03-01

We developed the Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST) to permit hemodialysis (HD) patients with central venous catheters (catheters) to shower without additional infection risk. Our primary objective was to determine the feasibility of conducting a parallel randomized controlled trial (RCT) to evaluate the impact of HIPPO-ST on catheter-related bacteremia (CRB) in adult HD patients. Adult HD patients using catheters were recruited from 11 HD units. Patients were randomized to receive HIPPO-ST or standard care and were followed up for 6 months. Only CRB-outcome assessors were blinded. For the study to be considered feasible, 4 of 5 feasibility outcomes, each with its own statistical threshold for success, must have been achieved. A total of 68 patients were randomized (33 HIPPO-ST and 35 control) and were followed up to 6 months. Of 5 measures of feasibility, 4 were achieved: (1) accurate CRB rate documented (threshold: κ level >0.80); (2) 97.8% (279/285) of satellite HD patients with catheters were screened (threshold: >95%); (3) 88% (23/26) in the HIPPO-ST arm were successfully educated by 6 months (threshold: >80%); and (4) 0% (0/29) patients in the control arm were "contaminated," that is, using HIPPO-ST (threshold: <5%). However, only 44.2% (72/163) of eligible patients consented to participate (threshold: >80%). The rate of CRB was similarly low in HIPPO-ST and control groups (0.68 vs. 0.88/1000 catheter days). This HIPPO-ST pilot study demonstrated the feasibility of the larger HIPPO-ST study, especially given the high levels of education success with the HIPPO-ST arm and the low levels of contamination in the control arm.

Accelerated resolution of laser-induced bruising with topical 20% arnica: a rater-blinded randomized controlled trial.

PubMed

Leu, S; Havey, J; White, L E; Martin, N; Yoo, S S; Rademaker, A W; Alam, M

2010-09-01

Dermatological procedures can result in disfiguring bruises that resolve slowly. To assess the comparative utility of topical formulations in hastening the resolution of skin bruising. Healthy volunteers, age range 21-65 years, were enrolled for this double (patient and rater) blinded randomized controlled trial. For each subject, four standard bruises of 7 mm diameter each were created on the bilateral upper inner arms, 5 cm apart, two per arm, using a 595-nm pulsed-dye laser (Vbeam; Candela Corp., Wayland, MA, U.S.A.). Randomization was used to assign one topical agent (5% vitamin K, 1% vitamin K and 0·3% retinol, 20% arnica, or white petrolatum) to exactly one bruise per subject, which was then treated under occlusion twice a day for 2 weeks. A dermatologist not involved with subject assignment rated bruises [visual analogue scale, 0 (least)-10 (most)] in standardized photographs immediately after bruise creation and at week 2. There was significant difference in the change in the rater bruising score associated with the four treatments (anova, P=0·016). Pairwise comparisons indicated that the mean improvement associated with 20% arnica was greater than with white petrolatum (P=0·003), and the improvement with arnica was greater than with the mixture of 1% vitamin K and 0·3% retinol (P=0·01). Improvement with arnica was not greater than with 5% vitamin K cream, however. Topical 20% arnica ointment may be able to reduce bruising more effectively than placebo and more effectively than low-concentration vitamin K formulations, such as 1% vitamin K with 0·3% retinol. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

New validated recipes for double-blind placebo-controlled low-dose food challenges.

PubMed

Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

2013-05-01

Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

A randomized controlled trial of very early rehabilitation in speech after stroke.

PubMed

Godecke, Erin; Armstrong, Elizabeth A; Rai, Tapan; Middleton, Sandy; Ciccone, Natalie; Whitworth, Anne; Rose, Miranda; Holland, Audrey; Ellery, Fiona; Hankey, Graeme J; Cadilhac, Dominique A; Bernhardt, Julie

2016-07-01

The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population. © 2016 World Stroke Organization.

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

Individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized, double-dummy, double-blind, placebo-controlled trial.

PubMed

Macías-Cortés, Emma Del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. ClinicalTrials.gov NCT01635218. https://clinicaltrials.gov/ct2/show/NCT01635218 [corrected].

Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial

PubMed Central

Macías-Cortés, Emma del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Background Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. Trial Registration ClinicalTrials.gov NCT01635218 Protocol Publication http://www.trialsjournal.com/content/14/1/105. PMID:25768800

Effect of Exogenous Albumin on the Incidence of Postoperative Acute Kidney Injury in Patients Undergoing Off-pump Coronary Artery Bypass Surgery with a Preoperative Albumin Level of Less Than 4.0 g/dl.

PubMed

Lee, Eun-Ho; Kim, Wook-Jong; Kim, Ji-Yeon; Chin, Ji-Hyun; Choi, Dae-Kee; Sim, Ji-Yeon; Choo, Suk-Jung; Chung, Cheol-Hyun; Lee, Jae-Won; Choi, In-Cheol

2016-05-01

Hypoalbuminemia may increase the risk of acute kidney injury (AKI). The authors investigated whether the immediate preoperative administration of 20% albumin solution affects the incidence of AKI after off-pump coronary artery bypass surgery. In this prospective, single-center, randomized, parallel-arm double-blind trial, 220 patients with preoperative serum albumin levels less than 4.0 g/dl were administered 100, 200, or 300 ml of 20% human albumin according to the preoperative serum albumin level (3.5 to 3.9, 3.0 to 3.4, or less than 3.0 g/dl, respectively) or with an equal volume of saline before surgery. The primary outcome measure was AKI incidence after surgery. Postoperative AKI was defined by maximal AKI Network criteria based on creatinine changes. Patient characteristics and perioperative data except urine output during surgery were similar between the two groups studied, the albumin group and the control group. Urine output (median [interquartile range]) during surgery was higher in the albumin group (550 ml [315 to 980]) than in the control group (370 ml [230 to 670]; P = 0.006). The incidence of postoperative AKI in the albumin group was lower than that in the control group (14 [13.7%] vs. 26 [25.7%]; P = 0.048). There were no significant between-group differences in severe AKI, including renal replacement therapy, 30-day mortality, and other clinical outcomes. There were no significant adverse events. Administration of 20% exogenous albumin immediately before surgery increases urine output during surgery and reduces the risk of AKI after off-pump coronary artery bypass surgery in patients with a preoperative serum albumin level of less than 4.0 g/dl.

Effects of two eye drop products on computer users with subjective ocular discomfort.

PubMed

Skilling, Francis C; Weaver, Tony A; Kato, Kenneth P; Ford, Jerry G; Dussia, Elyse M

2005-01-01

An increasing number of people seek medical attention for symptoms of visual discomfort due to computer vision syndrome (CVS). We compared the efficacy and adverse event rates of a new eye lubricant, OptiZen (InnoZen, Inc., polysorbate 80 0.5%) and Visine Original (Pfizer Consumer Healthcare, tetrahydrozoline HCl 0.05%). In this double-blind parallel arm trial, 50 healthy men and women, ages 18 to 65 years, with symptoms of CVS who use a video display terminal for a minimum of 4 hours per day were randomized to OptiZen (n = 25) or Visine Original (n= 25), 1 to 2 drops b.i.d. for 5 days. The primary end-points were ocular discomfort and adverse events. OptiZen and Visine Original had similar efficacy in alleviating symptoms of ocular discomfort (odds ratio of 1.23 [95% confidence interval, 0.63 to 2.42], P= 0.55). OptiZen and Visine Original were very similar with respect to odds ratios and 95% confidence interval (CI) for each of the measurement times (P= 0.72). Visine Original users reported a significantly higher incidence of temporary ocular stinging/burning immediately after drug instillation (28%, 7/25) than did OptiZen users (4%, 1/24) (P= 0.05). Patients using OptiZen were 89% less likely to have stinging/burning effects than those patients using Visine Original (95% CI: 0.01 to 0.95). OptiZen and Visine Original are effective at alleviating ocular discomfort associated with prolonged computer use. Adverse event findings suggest that OptiZen causes less ocular discomfort on instillation, potentially attributable to its milder ingredient profile.

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.

PubMed

McAndrew, Amy; Lawn, Will; Stevens, Tobias; Porffy, Lilla; Brandner, Brigitta; Morgan, Celia J A

2017-04-04

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

PubMed

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Soy protein and bone mineral density in older men and women: a randomized trial.

PubMed

Newton, K M; LaCroix, A Z; Levy, L; Li, S S; Qu, P; Potter, J D; Lampe, J W

2006-10-20

Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50-80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the comparison group (-ISO) received soy protein containing 3mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior-anterior spine (L1-L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. Among all participants, mean percent change in spine BMD (+/-S.E.) was 0.16+/-0.44 in -ISO (P=0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men (P=0.01). At 12 months, in women, mean percent change was 0.58+/-0.70 in +ISO and -1.84+/-0.86 in -ISO (P=0.05); among men it was 1.32+/-0.53 in +ISO and 0.31+/-0.48 in -ISO (P=0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54+/-0.38 in +ISO and -0.13+/-0.36 in -ISO (P=0.20) among all participants. Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.

Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial.

PubMed

Tassonyi, Edömér; Pongrácz, Adrienn; Nemes, Réka; Asztalos, László; Lengyel, Szabolcs; Fülesdi, Béla

2015-08-01

Pipecuronium is a steroidal neuromuscular blocking agent. Sugammadex, a relaxant binding γ-cyclodextrin derivative, reverses the effect of rocuronium, vecuronium, and pancuronium. We investigated whether sugammadex reverses moderate pipecuronium-induced neuromuscular blockade (NMB) and the doses required to achieve reversal. This single-center, randomized, double-blind, 5-group parallel-arm study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX) according to international standards. When the NMB recovered spontaneously to train-of-four count 2, patients randomly received 1.0, 2.0, 3.0, or 4.0 mg/kg of sugammadex or placebo. Recovery time from sugammadex injection to normalized train-of-four (TOF) ratio 0.9 was the primary outcome variable. The recovery time from the sugammadex injection to final T1 was the secondary end point. Postoperative neuromuscular functions were also assessed. Each patient who received sugammadex recovered to a normalized TOF ratio of 0.9 within 5.0 minutes (95% lower confidence interval for the lowest dose 70.1%; for all doses 90.8%) and 79% of these patients reached a normalized TOF ratio 0.9 within 2.0 minutes (95% lower confidence interval for the lowest dose 26.7%; for all doses 63.7%). T1 recovered several minutes after the TOF ratio. No residual postoperative NMB was observed. Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.

I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life

PubMed Central

Lorenzo-Zúñiga, Vicente; Llop, Elba; Suárez, Cristina; Álvarez, Beatriz; Abreu, Luis; Espadaler, Jordi; Serra, Jordi

2014-01-01

AIM: To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). METHODS: A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. RESULTS: During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. CONCLUSION: A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea. PMID:25024629

I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life.

PubMed

Lorenzo-Zúñiga, Vicente; Llop, Elba; Suárez, Cristina; Alvarez, Beatriz; Abreu, Luis; Espadaler, Jordi; Serra, Jordi

2014-07-14

To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea.

Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies.

PubMed

Bugarski-Kirola, Dragana; Blaettler, Thomas; Arango, Celso; Fleischhacker, Wolfgang W; Garibaldi, George; Wang, Alice; Dixon, Mark; Bressan, Rodrigo A; Nasrallah, Henry; Lawrie, Stephen; Napieralski, Julie; Ochi-Lohmann, Tania; Reid, Carol; Marder, Stephen R

2017-07-01

There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 mg and 20 mg [FlashLyte]) or placebo once daily for 24 weeks. The primary efficacy end point was mean change from baseline in Positive and Negative Syndrome Scale negative symptom factor score at week 24. The intent-to-treat population in DayLyte and FlashLyte included 605 and 594 patients, respectively. At week 24, mean change from baseline showed improvement in all treatment arms but no statistically significant separation from placebo in Positive and Negative Syndrome Scale negative symptom factor score and all other end points. Bitopertin was well tolerated. These studies provide no evidence for superior efficacy of adjunctive bitopertin in any of the doses tested over placebo in patients with persistent predominant negative symptoms of schizophrenia. Copyright © 2017. Published by Elsevier Inc.

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.

PubMed

Acosta, Andrés; Camilleri, Michael; Shin, Andrea; Linker Nord, Sara; O'Neill, Jessica; Gray, Amber V; Lueke, Alan J; Donato, Leslie J; Burton, Duane D; Szarka, Lawrence A; Zinsmeister, Alan R; Golden, Pamela L; Fodor, Anthony

2016-05-26

Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose-mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.