Research: Treatment Study to determine the durability of glycaemic control with early treatment with a vildagliptin–metformin combination regimen vs. standard-of-care metformin monotherapy—the VERIFY trial: a randomized double-blind trial

PubMed Central

Del Prato, S; Foley, J E; Kothny, W; Kozlovski, P; Stumvoll, M; Paldánius, P M; Matthews, D R

2014-01-01

Aims Durability of good glycaemic control (HbA1c) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows β-cell deterioration as measured by HbA1c. Methods Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48–58 mmol/mol (6.5–7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin–metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. Summary VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria. PMID:24863949

Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

PubMed Central

Trenkwalder, Claudia; Kies, Bryan; Rudzinska, Monika; Fine, Jennifer; Nikl, Janos; Honczarenko, Krystyna; Dioszeghy, Peter; Hill, Dennis; Anderson, Tim; Myllyla, Vilho; Kassubek, Jan; Steiger, Malcolm; Zucconi, Marco; Tolosa, Eduardo; Poewe, Werner; Surmann, Erwin; Whitesides, John; Boroojerdi, Babak; Chaudhuri, Kallol Ray

2011-01-01

In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society PMID:21322021

Towards evidence-based medicine in specific grass pollen immunotherapy.

PubMed

Calderon, M; Mösges, R; Hellmich, M; Demoly, P

2010-04-01

When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality.

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

PubMed

Christensen, E; Neuberger, J; Crowe, J; Altman, D G; Popper, H; Portmann, B; Doniach, D; Ranek, L; Tygstrup, N; Williams, R

1985-11-01

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment. Using Cox multiple regression analysis and adjusting for slight imbalance between the two treatment groups, the therapeutic effect of azathioprine was statistically significant (p = 0.01), with azathioprine reducing the risk of dying to 59% of that observed during placebo treatment (95% confidence interval 40%-90%) or improving survival time by 20 mo in the average patient. Furthermore, azathioprine slowed down progressing incapacitation. Side effects of azathioprine were relatively few. The analysis revealed that the following five variables independently implied poor prognosis: high serum bilirubin, old age, cirrhosis, low serum albumin, and central cholestasis. These factors were combined to a "prognostic index" for prediction of outcome in new patients. The index was validated on independent patient data. On the basis of these results we recommend azathioprine as a routine treatment of primary biliary cirrhosis.

Vardenafil orodispersible tablet.

PubMed

Sanford, Mark

2012-01-01

Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ≥65 years, and adverse events were mostly mild or moderate in severity.

Health-related quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder.

PubMed

Banaschewski, Tobias; Johnson, Mats; Lecendreux, Michel; Zuddas, Alessandro; Adeyi, Ben; Hodgkins, Paul; Squires, Liza A; Coghill, David R

2014-12-01

The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD. Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively. Patients aged 6-17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons. The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard deviation below the normative mean in four of the five domains, and there was significant improvement across all domains from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores deteriorated in all domains in the placebo group, but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Risk Avoidance (effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction (0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the Family domain and the Learning and School domain. WFIRS-P total score and scores in all domains improved significantly from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean scores deteriorated in the placebo group but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Family, Learning and School, and Risky Activities domains and in total (effect size 0.908; p < 0.001). Using parent-rated instruments, long-term maintenance of the beneficial effect of LDX in multiple domains of health-related quality of life and functional impairment was demonstrated by comparison of treatment continuation and withdrawal under randomized, double-blind, placebo-controlled conditions.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

PubMed

Chin, Melanie P; Bakris, George L; Block, Geoffrey A; Chertow, Glenn M; Goldsberry, Angie; Inker, Lesley A; Heerspink, Hiddo J L; O'Grady, Megan; Pergola, Pablo E; Wanner, Christoph; Warnock, David G; Meyer, Colin J

2018-01-01

Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. © 2018 The Author(s) Published by S. Karger AG, Basel.

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial.

PubMed

Berger, Jeffrey S; Katona, Brian G; Jones, W Schuyler; Patel, Manesh R; Norgren, Lars; Baumgartner, Iris; Blomster, Juuso; Mahaffey, Kenneth W; Held, Peter; Millegård, Marcus; Heizer, Gretchen; Reist, Craig; Fowkes, F Gerry; Hiatt, William R

2016-05-01

Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur. The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A randomized, placebo‐controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis

PubMed Central

Ratziu, Vlad; Harrison, Stephen A.; Abdelmalek, Manal F.; Aithal, Guruprasad P.; Caballeria, Juan; Francque, Sven; Farrell, Geoffrey; Kowdley, Kris V.; Craxi, Antonio; Simon, Krzysztof; Fischer, Laurent; Melchor‐Khan, Liza; Vest, Jeffrey; Wiens, Brian L.; Vig, Pamela; Seyedkazemi, Star; Goodman, Zachary; Wong, Vincent Wai‐Sun; Loomba, Rohit; Tacke, Frank; Sanyal, Arun; Lefebvre, Eric

2018-01-01

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C—C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double‐blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1‐3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2‐point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of SH. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary endpoint of NAS improvement in the intent‐to‐treat population and resolution of SH was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144; 16% vs. 19%, P = 0.52 and 8% vs. 6%, P = 0.49, respectively). However, the fibrosis endpoint was met in significantly more subjects on CVC than placebo (20% vs. 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo. Conclusion: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of SH compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. (Hepatology 2018;67:1754‐1767). PMID:28833331

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE.

PubMed

Lassen, M R; Fisher, W; Mouret, P; Agnelli, G; George, D; Kakkar, A; Mismetti, P; Turpie, A G G

2012-05-01

Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles. © 2012 International Society on Thrombosis and Haemostasis.

Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation.

PubMed

Hoy, Sheridan M; Keating, Gillian M

2011-07-30

Dexmedetomidine (Precedex®), a pharmacologically active dextroisomer of medetomidine, is a selective α(2)-adrenergic receptor agonist. It is indicated in the US for the sedation of mechanically ventilated adult patients in an intensive care setting and in non-intubated adult patients prior to and/or during surgical and other procedures. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of dexmedetomidine in randomized, double-blind, placebo-controlled, multicentre studies in these indications. Post-surgical patients in an intensive care setting receiving dexmedetomidine required less rescue sedation with intravenous propofol or intravenous midazolam to achieve and/or maintain optimal sedation during the assisted ventilation period than placebo recipients, according to two randomized, double-blind, multinational studies. Moreover, significantly more dexmedetomidine than placebo recipients acquired and/or maintained optimal sedation without rescue sedation. Sedation with dexmedetomidine was also effective in terms of the total dose of morphine administered, with dexmedetomidine recipients requiring less morphine than placebo recipients; with regard to patient management, dexmedetomidine recipients were calmer and easier to arouse and manage than placebo recipients. Intravenous dexmedetomidine was effective as a primary sedative in two randomized, double-blind, placebo-controlled, multicentre studies in adult patients undergoing awake fibre-optic intubation or a variety of diagnostic or surgical procedures requiring monitored anaesthesia care. In one study, significantly fewer dexmedetomidine than placebo recipients required rescue sedation with intravenous midazolam to achieve and/or maintain optimal sedation; conversely, in another study, rescue sedation with intravenous midazolam was not required by significantly more dexmedetomidine than placebo recipients. Primary sedation with intravenous dexmedetomidine was also effective in terms of the secondary efficacy endpoints, including the mean total dose of midazolam and fentanyl administered and the percentage of patients requiring further sedation (in addition to dexmedetomidine or placebo and midazolam), with, for the most part, significant between-group differences observed in favour of dexmedetomidine over placebo. In general, no significant differences were observed between the dexmedetomidine and placebo treatment groups in the anaesthesiologists' assessment of ease of intubation, haemodynamic stability, patient cooperation and/or respiratory stability. Intravenous dexmedetomidine is generally well tolerated when utilized in mechanically ventilated patients in an intensive care setting and for procedural sedation in non-intubated patients. Dexmedetomidine is associated with a lower rate of postoperative delirium than midazolam or propofol; it is not associated with respiratory depression. While dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention. Thus, intravenous dexmedetomidine provides a further option as a short-term (<24 hours) primary sedative in mechanically ventilated adult patients in an intensive care setting and in non-intubated adult patients prior to and/or during surgical and other procedures.

Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

PubMed Central

French, JA; Baroldi, P; Brittain, ST; Johnson, JK

2014-01-01

Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediate-release OXC. PMID:24359313

U. S. Multinational Corporations and National Security Policy

DTIC Science & Technology

1975-08-01

tfol/o) action between them. A random .Ci • t° def^ne the areas of inter- Acers A ä^^^-ä z^r***- were no references to foreign or mil^Lf, as1...the rubber of Malaysia ,and the bauxite of Jamaica, Surinam and Australia. The essential characteristics of these natural resource regions have

Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION).

PubMed

Schernthaner, G; Durán-Garcia, S; Hanefeld, M; Langslet, G; Niskanen, L; Östgren, C J; Malvolti, E; Hardy, E

2015-07-01

To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control. In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed. Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p = 0.9415); however, a significant treatment-by-age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged <75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride. As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years. © 2015 John Wiley & Sons Ltd.

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.

PubMed

Aapro, Matti; Karthaus, Meinolf; Schwartzberg, Lee; Bondarenko, Igor; Sarosiek, Tomasz; Oprean, Cristina; Cardona-Huerta, Servando; Hansen, Vincent; Rossi, Giorgia; Rizzi, Giada; Borroni, Maria Elisa; Rugo, Hope

2017-04-01

Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK 1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT 3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

A three-country randomized controlled trial of a psychosocial intervention for caregivers combined with pharmacological treatment for patients with Alzheimer disease: effects on caregiver depression.

PubMed

Mittelman, Mary Sherman; Brodaty, Henry; Wallen, Aaron Seth; Burns, Alistair

2008-11-01

To evaluate the effectiveness of a combination of cholinesterase inhibitor therapy for patients with Alzheimer disease (AD) and psychosocial intervention, for their spouse caregivers compared with drug treatment alone in three countries simultaneously. Randomized controlled trial. Structured questionnaires were administered at baseline and at regular follow-up intervals for 24 months by independent raters blind to group assignment. Outpatient research clinics in New York City, U.S., Manchester, U.K. and Sydney, Australia. Volunteer sample of 158 spouse caregivers of community dwelling patients with AD. Five sessions of individual and family counseling within 3 months of enrollment and continuous availability of ad hoc telephone counseling were provided for half the caregivers. Donepezil was prescribed for all patients. Depressive symptoms of spouse caregivers measured at intake and follow-up assessments for 24 months using Beck Depression Inventory (revised). Depression scores of caregivers who received counseling decreased over time, whereas the depression scores for caregivers who did not receive counseling increased. The benefit of the psychosocial intervention was significant after controlling for site, gender and country was not accounted for by antidepressant use and increased over 2 years even though the individual and family counseling sessions occurred in the first 3 months. Effective counseling and support interventions can reduce symptoms of depression in caregivers when patients are taking donepezil. Harmonized multinational psychosocial interventions are feasible. Combined drug and supportive care approaches to the management of people with AD should be a priority.

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Measuring Organizational Learning Capability in Indian Managers and Establishing Firm Performance Linkage: An Empirical Analysis

ERIC Educational Resources Information Center

Bhatnagar, Jyotsna

2006-01-01

Purpose: The purpose of this research is to measure Organizational Learning Capability (OLC) perception in the managers of public, private and multinational organizations and establish the link between OLC and firm performance. Design/methodology/approach: The data were collected from a sample of 612 managers randomly drawn from Indian industry,…

Public Attitude toward Optician Education as Human Capital.

ERIC Educational Resources Information Center

Gerardi, Steven J.; Woods, Thomas A.; White, Debra R.; Hill, Roger S.

A study sought to identify what the public thinks about the appropriate level of education and training for opticians. A 10% random sample of 1,510 New York State customers (n=151) of a large multinational opticianry corporation was surveyed. Two categories of data were social background (combined annual family income, age, marital status, race,…

The need for randomization in animal trials: an overview of systematic reviews.

PubMed

Hirst, Jennifer A; Howick, Jeremy; Aronson, Jeffrey K; Roberts, Nia; Perera, Rafael; Koshiaris, Constantinos; Heneghan, Carl

2014-01-01

Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition. We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment. Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective. Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial.

PubMed

Morrow, David A; Scirica, Benjamin M; Fox, Keith A A; Berman, Gail; Strony, John; Veltri, Enrico; Bonaca, Marc P; Fish, Polly; McCabe, Carolyn H; Braunwald, Eugene

2009-09-01

Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.

Effects of Demographics on the Antihypertensive Efficacy of Triple Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide for Moderate to Severe Hypertension

PubMed Central

Calhoun, David A.; Lacourci00E8;re, Yves; Crikelair, Nora; Jia, Yan; Glazer, Robert D.

2014-01-01

Objective To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. Research design Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. Methods After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m2). Main outcome measures Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. Results Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (eg, Blacks, elderly). Conclusions Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. PMID:23721363

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

PubMed

Lyons, Owen D; Floras, John S; Logan, Alexander G; Beanlands, Robert; Cantolla, Joaquin Durán; Fitzpatrick, Michael; Fleetham, John; John Kimoff, R; Leung, Richard S T; Lorenzi Filho, Geraldo; Mayer, Pierre; Mielniczuk, Lisa; Morrison, Debra L; Ryan, Clodagh M; Series, Frederic; Tomlinson, George A; Woo, Anna; Arzt, Michael; Parthasarathy, Sairam; Redolfi, Stefania; Kasai, Takatoshi; Parati, Gianfranco; Delgado, Diego H; Bradley, T Douglas

2017-04-01

Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial.

PubMed

Feil, Katharina; Adrion, Christine; Teufel, Julian; Bösch, Sylvia; Claassen, Jens; Giordano, Ilaria; Hengel, Holger; Jacobi, Heike; Klockgether, Thomas; Klopstock, Thomas; Nachbauer, Wolfgang; Schöls, Ludger; Stendel, Claudia; Uslar, Ellen; van de Warrenburg, Bart; Berger, Ingrid; Naumann, Ivonne; Bayer, Otmar; Müller, Hans-Helge; Mansmann, Ulrich; Strupp, Michael

2017-01-10

Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new therapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on ataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to placebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA. An investigator-initiated, multicenter, European, randomized, double-blind, placebo-controlled, 2-treatment 2-period crossover phase III trial will be carried out. In total, 108 adult patients who meet the clinical criteria of CA of different etiologies (hereditary or non-hereditary, non-acquired) presenting with a SARA total score of at least 3 points will be randomly assigned in a 1:1 ratio to one of two different treatment sequences, either acetyl-DL-leucine (up to 5 g per day) followed by placebo or vice versa. Each sequence consists of two 6-week treatment periods, separated by a 4-week wash-out period. A follow-up examination is scheduled 4 weeks after the end of treatment. The primary efficacy outcome is the absolute change in the SARA total score. Secondary objectives are to demonstrate that acetyl-DL-leucine is effective in improving (1) motor function measured by the Spinocerebellar Ataxia Functional Index (SCAFI) and SARA subscore items and (2) QoL (EuroQoL 5 dimensions and 5 level version, EQ-5D-5 L), depression (Beck Depression Inventory, BDI-II) and fatigue (Fatigue Severity Score, FSS). Furthermore, the incidence of adverse events will be investigated. The results of this trial will inform whether symptomatic treatment with the modified amino-acid acetyl-DL-leucine is a worthy candidate for a new drug therapy to relieve ataxia symptoms and to improve patient care. If superiority of the experimental drug to placebo can be established it will also be re-purposing of an agent that has been previously used for the symptomatic treatment of dizziness. The trial was prospectively registered at www.clinicaltrialsregister.eu (EudraCT no. 2015-000460-34) and at https://www.germanctr.de (DRKS-ID: DRKS00009733 ).

A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

PubMed Central

2011-01-01

Background Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. Methods/Design A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. Discussion Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. Trial Registration Number ISRCTN45190901 PMID:21388549

A generic minimization random allocation and blinding system on web.

PubMed

Cai, Hongwei; Xia, Jielai; Xu, Dezhong; Gao, Donghuai; Yan, Yongping

2006-12-01

Minimization is a dynamic randomization method for clinical trials. Although recommended by many researchers, the utilization of minimization has been seldom reported in randomized trials mainly because of the controversy surrounding the validity of conventional analyses and its complexity in implementation. However, both the statistical and clinical validity of minimization were demonstrated in recent studies. Minimization random allocation system integrated with blinding function that could facilitate the implementation of this method in general clinical trials has not been reported. SYSTEM OVERVIEW: The system is a web-based random allocation system using Pocock and Simon minimization method. It also supports multiple treatment arms within a trial, multiple simultaneous trials, and blinding without further programming. This system was constructed with generic database schema design method, Pocock and Simon minimization method and blinding method. It was coded with Microsoft Visual Basic and Active Server Pages (ASP) programming languages. And all dataset were managed with a Microsoft SQL Server database. Some critical programming codes were also provided. SIMULATIONS AND RESULTS: Two clinical trials were simulated simultaneously to test the system's applicability. Not only balanced groups but also blinded allocation results were achieved in both trials. Practical considerations for minimization method, the benefits, general applicability and drawbacks of the technique implemented in this system are discussed. Promising features of the proposed system are also summarized.

Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON).

PubMed

de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv; Audhya, Paul; Bakris, George L; Chin, Melanie; Krauth, Melissa; Lambers Heerspink, Hiddo J; Meyer, Colin J; McMurray, John J; Parving, Hans-Henrik; Pergola, Pablo E; Remuzzi, Giuseppe; Toto, Robert D; Vaziri, Nosratola D; Wanner, Christoph; Warnock, David G; Wittes, Janet; Chertow, Glenn M

2013-01-01

Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD. Copyright © 2013 S. Karger AG, Basel.

Multiple Learning Tracks: For Training Multinational Managers

ERIC Educational Resources Information Center

Harvey, Michael G.; Kerin, Roger A.

1977-01-01

The problem of identifying and training college students to be effective multinational marketing managers is investigated in three parts: (1) Identification of multinational manager attributes, (2) selection of multinational managers, and (3) multiple "track" training programs. (TA)

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

Study Design Rigor in Animal-Experimental Research Published in Anesthesia Journals.

PubMed

Hoerauf, Janine M; Moss, Angela F; Fernandez-Bustamante, Ana; Bartels, Karsten

2018-01-01

Lack of reproducibility of preclinical studies has been identified as an impediment for translation of basic mechanistic research into effective clinical therapies. Indeed, the National Institutes of Health has revised its grant application process to require more rigorous study design, including sample size calculations, blinding procedures, and randomization steps. We hypothesized that the reporting of such metrics of study design rigor has increased over time for animal-experimental research published in anesthesia journals. PubMed was searched for animal-experimental studies published in 2005, 2010, and 2015 in primarily English-language anesthesia journals. A total of 1466 publications were graded on the performance of sample size estimation, randomization, and blinding. Cochran-Armitage test was used to assess linear trends over time for the primary outcome of whether or not a metric was reported. Interrater agreement for each of the 3 metrics (power, randomization, and blinding) was assessed using the weighted κ coefficient in a 10% random sample of articles rerated by a second investigator blinded to the ratings of the first investigator. A total of 1466 manuscripts were analyzed. Reporting for all 3 metrics of experimental design rigor increased over time (2005 to 2010 to 2015): for power analysis, from 5% (27/516), to 12% (59/485), to 17% (77/465); for randomization, from 41% (213/516), to 50% (243/485), to 54% (253/465); and for blinding, from 26% (135/516), to 38% (186/485), to 47% (217/465). The weighted κ coefficients and 98.3% confidence interval indicate almost perfect agreement between the 2 raters beyond that which occurs by chance alone (power, 0.93 [0.85, 1.0], randomization, 0.91 [0.85, 0.98], and blinding, 0.90 [0.84, 0.96]). Our hypothesis that reported metrics of rigor in animal-experimental studies in anesthesia journals have increased during the past decade was confirmed. More consistent reporting, or explicit justification for absence, of sample size calculations, blinding techniques, and randomization procedures could better enable readers to evaluate potential sources of bias in animal-experimental research manuscripts. Future studies should assess whether such steps lead to improved translation of animal-experimental anesthesia research into successful clinical trials.

Air Force Journal of Logistics. Volume 24, Number 3, Fall 2000

DTIC Science & Technology

2000-01-01

senior officers environment. 49 should hold key positions. The joint practice of assigning an In The Argument Culture, Deborah Tannen suggests Americans...Action Division, Directorate of Plans and Integration, Deputy 44. Deborah Tannen , The Argument Culture, New York: Random House, Chief of Staff for...staff.4 " Proportionate representation would Americans must find the opposing view. Tannen says Americans * establish multinationalism as the norm and

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Cultural Penetration in Latin America through Multinational Advertising Agencies.

ERIC Educational Resources Information Center

Del Toro, Wanda

Few studies have addressed the issue of cultural penetration of Latin American countries by multinational corporations (MNCs) and multinational advertising agencies (MAAs). Whether they are considered multinational or transnational, MAAs have expanded as a form of international communication in the global market, forming the backbone of MNCs.…

Trial of Naltrexone and Dextromethorphan for Gulf War Veterens’ Illness

DTIC Science & Technology

2016-03-01

held by the research pharmacist . Randomization was performed by drawing a card from a box that specified the order of administration. The study...study. The pills were administered in a randomized, double- blinded fashion. The code for the blinding was held by the research pharmacist

Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

USDA-ARS?s Scientific Manuscript database

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

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.

Lessons From LEADER - All-round Leadership.

PubMed

Kalra, Sanjay

2016-08-01

The large multinational, randomised, double-blind LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long Term Evaluation) trial recently reported the cardiovascular (CV) benefits achieved with liraglutide therapy in type 2 diabetes mellitus (T2DM). This editorial analyses the primary and secondary CV outcomes (CVO) results of the LEADER trial, and discusses the impact these will have on clinical practice of diabetes in specific, and medicine in general. It delves into the evolution of clinical and biochemical outcomes used in diabetes, and discusses the role of liraglutide in shaping future outcomes. The editorial describes the potential role of liraglutide in primary, secondary and tertiary prevention of CV disease (CVD), and suggests exaptation of this molecule for use in cardiology, nephrology and neurology.

Reiki therapy for postoperative oral pain in pediatric patients: pilot data from a double-blind, randomized clinical trial.

PubMed

Kundu, Anjana; Lin, Yuting; Oron, Assaf P; Doorenbos, Ardith Z

2014-02-01

To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

PubMed Central

Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

2014-01-01

Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

Validation of Placebo in a Manual Therapy Randomized Controlled Trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

2015-01-01

At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

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...

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…

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…

Marketing Norm Perception Among Medical Representatives in Indian Pharmaceutical Industry

PubMed Central

Nagashekhara, Molugulu; Agil, Syed Omar Syed; Ramasamy, Ravindran

2012-01-01

Study of marketing norm perception among medical representatives is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the perception of marketing norms among medical representatives. The research design is quantitative and cross sectional study with medical representatives as unit of analysis. Data is collected from medical representatives (n=300) using a simple random and cluster sampling using a structured questionnaire. Results indicate that there is no difference in the perception of marketing norms among male and female medical representatives. But there is a difference in opinion among domestic and multinational company’s medical representatives. Educational back ground of medical representatives also shows the difference in opinion among medical representatives. Degree holders and multinational company medical representatives have high perception of marketing norms compare to their counterparts. The researchers strongly believe that mandatory training on marketing norms is beneficial in decision making process during the dilemmas in the sales field. PMID:24826035

Fish Oil and Post-Operative Atrial Fibrillation – Results of the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

PubMed Central

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G.; Ferrazzi, Paolo; Gardner, Timothy J.; Latini, Roberto; Libby, Peter; Lombardi, Federico; O’Gara, Patrick T.; Page, Richard L.; Tavazzi, Luigi; Tognoni, Gianni

2013-01-01

Context Post-operative atrial fibrillation/flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and healthcare utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFA) reduce post-op AF, with mixed results. Objective To determine whether peri-operative n-3-PUFA supplementation reduces post-op AF. Design Randomized, double-blind, placebo-controlled, multinational, clinical trial. Patients A total of 1,516 patients scheduled for cardiac surgery across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Forty-eight percent of screened patients and 94% of eligible patients were enrolled. Intervention Patients were randomized to receive fish oil (1 g capsules containing ≥840 mg n-3-PUFA as ethyl esters) or placebo, with pre-operative loading of 10g over 3-5 days (or 8g over 2 days) followed post-operatively by 2g/d until hospital discharge or post-op day10, whichever first. Main Outcome Measures The primary endpoint was occurrence of post-op AF >30 sec. We also evaluated post-op AF lasting >1hr, resulting in symptoms, or treated with cardioversion; other secondary post-op AF endpoints; other tachyarrhythmias; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. All endpoints and analyses plans were prespecified. Results At enrollment, mean±SD age was 64±13 years, 72.2% were male, and 51.8% had planned valvular surgery. The primary endpoint occurred in 233 (30.7%) and 227 (30.0%) patients assigned to placebo and n-3-PUFA, respectively (OR=0.96, 95%CI=0.77-1.20; P=0.74). None of the secondary endpoints were significantly different, including post-op AF that was sustained, symptomatic, or treated (n=231 [30.5%] vs. n=224 [29.6%], P=0.70) or number of post-op AF episodes per patient (1 episode: n=220 [29.0%] vs. n=217 [28.6%]; 2 episodes: n=156 [20.6%] vs. n=157 [20.7%]; 3+ episodes: n=18 [2.4%] vs. n=21 [2.8%]; P=0.73). n-3-PUFA was generally well-tolerated, with no evidence for increased risk of bleeding or serious adverse events. Conclusions In this large multinational trial among patients undergoing cardiac surgery, peri-operative supplementation with n-3-PUFA, compared to placebo, did not reduce the risk of post-operative AF. PMID:23128104

Blinded interpretation of study results can feasibly and effectively diminish interpretation bias.

PubMed

Järvinen, Teppo L N; Sihvonen, Raine; Bhandari, Mohit; Sprague, Sheila; Malmivaara, Antti; Paavola, Mika; Schünemann, Holger J; Guyatt, Gordon H

2014-07-01

Controversial and misleading interpretation of data from randomized trials is common. How to avoid misleading interpretation has received little attention. Herein, we describe two applications of an approach that involves blinded interpretation of the results by study investigators. The approach involves developing two interpretations of the results on the basis of a blinded review of the primary outcome data (experimental treatment A compared with control treatment B). One interpretation assumes that A is the experimental intervention and another assumes that A is the control. After agreeing that there will be no further changes, the investigators record their decisions and sign the resulting document. The randomization code is then broken, the correct interpretation chosen, and the manuscript finalized. Review of the document by an external authority before finalization can provide another safeguard against interpretation bias. We found the blinded preparation of a summary of data interpretation described in this article practical, efficient, and useful. Blinded data interpretation may decrease the frequency of misleading data interpretation. Widespread adoption of blinded data interpretation would be greatly facilitated were it added to the minimum set of recommendations outlining proper conduct of randomized controlled trials (eg, the Consolidated Standards of Reporting Trials statement). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

2006-01-01

Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology

PubMed Central

Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Faragó, Geneviève; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

2011-01-01

Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [ per os] once daily for 5 days) vs amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use. PMID:21760724

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

PubMed

Beauvais, Francis

2013-04-01

The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used. Copyright © 2013. Published by Elsevier Ltd.

Sharing the Burden: How Effective is a Multinational Force in the Contemporary Operational Environment

DTIC Science & Technology

2007-06-01

multinational setting justifies a reassessment of the benefits and costs of multinational operations and that the solution may lie in a “modular...Nonetheless, Brown identifies benefits from multinational commitments, relevant to this study: legitimacy, burden sharing and access to the battlefield and...require more robust tools and would benefit if supplemented by alliance and cooperative partnerships. Nations “are increasingly disinclined to

Multinational Activities of Major U.S. Automotive Producers : Volume 1. Summary.

DOT National Transportation Integrated Search

1978-09-01

The multinational activities of General Motors, Ford, Chrysler, and American Motors are documented and analyzed. The study contains a compilation of data related to multinational operations; specifically it addresses research, development, engineerin...

Varenicline: a novel pharmacotherapy for smoking cessation.

PubMed

Jiménez-Ruiz, Carlos; Berlin, Ivan; Hering, Thomas

2009-07-09

Varenicline is an orally administered small molecule with partial agonist activity at the alpha4beta2 nicotinic acetylcholine receptor. Varenicline was approved by both the US FDA and the European Medicines Agency of the EU in 2006 as an aid to smoking cessation. Subsequently, varenicline has been approved in over 80 other countries. Varenicline is almost entirely absorbed following oral administration, and absorption is unaffected by food, smoking or the time of day. Varenicline undergoes only minimal metabolism and approximately 90% of the drug is excreted in the urine unchanged. Varenicline has a mean elimination half-life after repeated administration of approximately 24 hours in smokers. The area under the plasma concentration-time curve is increased in patients with moderate or severe renal failure. No clinically relevant varenicline-drug interactions have been identified. In two identical, randomized, double-blind, phase III clinical trials in healthy, motivated-to-quit, mainly Caucasian smokers aged 18-75 years in the US, 12 weeks of treatment with varenicline 1 mg twice daily was associated with significantly higher abstinence rates over weeks 9-12 than sustained-release bupropion 150 mg twice daily or placebo. In a separate phase III trial, an additional 12 weeks of treatment in smokers achieving abstinence in the first 12 weeks was associated with greater abstinence through to week 52 than placebo treatment. Varenicline treatment was also associated with significantly higher rates of abstinence than placebo treatment in randomized, double-blind, clinical trials in smokers in China, Japan, Korea, Singapore, Taiwan and Thailand. In a randomized, open-label, multi-national, phase III trial, varenicline treatment was associated with a significantly higher rate of abstinence than transdermal nicotine-replacement therapy. In these trials, varenicline treatment was associated with lower urge to smoke and satisfaction from smoking in relapsers than placebo or active comparators. In the two US phase III trials, 12 weeks of treatment with varenicline 1 mg twice daily had an acceptable safety and tolerability profile. Nausea and abnormal dreams were the most common adverse events that occurred in more varenicline than placebo recipients. The incidence and prevalence of nausea were greatest in weeks 1 and 2 of treatment, and declined thereafter. The prevalence of early adverse effects can be reduced by individual dose titration. Adverse events associated with varenicline therapy have been reported in post-marketing surveillance, including neuropsychiatric events such as depressed mood, agitation, changes in behaviour, suicidal ideation and suicide. Currently, it is unclear whether the association of varenicline therapy with these adverse events is causal, coincidental or related to smoking cessation. Given the greater efficacy of varenicline compared with other pharmacotherapies, and the high risk of morbidity and mortality associated with continued smoking, varenicline is a valuable pharmacological aid to smoking cessation.

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.

PubMed

Claeys, Carine; Drame, Mamadou; García-Sicilia, José; Zaman, Khalequ; Carmona, Alfonso; Tran, Phu My; Miranda, Mariano; Martinón-Torres, Federico; Thollot, Franck; Horn, Michael; Schwarz, Tino F; Behre, Ulrich; Merino, José M; Sadowska-Krawczenko, Iwona; Szymański, Henryk; Schu, Peter; Neumeier, Elisabeth; Li, Ping; Jain, Varsha K; Innis, Bruce L

2018-04-18

GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18-49 years; N = 120), children (3-17 years; N = 821), and infants (6-35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.

Does EEG-Neurofeedback Improve Neurocognitive Functioning in Children with Attention-Deficit/Hyperactivity Disorder? A Systematic Review and a Double-Blind Placebo-Controlled Study

ERIC Educational Resources Information Center

Vollebregt, Madelon A.; van Dongen-Boomsma, Martine; Buitelaar, Jan K.; Slaats-Willemse, Dorine

2014-01-01

Background: The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning…

Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

ERIC Educational Resources Information Center

Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

2007-01-01

Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

A Double-Blind Randomized Pilot Study Comparing Quetiapine and Divalproex for Adolescent Mania

ERIC Educational Resources Information Center

Delbello, Melissa P.; Kowatch, Robert A.; Adler, Caleb M.; Stanford, Kevin E.; Welge, Jeffrey A.; Barzman, Drew H.; Nelson, Erik; Strakowski, Stephen M.

2006-01-01

Objective: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. Method: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 [micro]g/mL) for 28 days for this double-blind study,…

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

PubMed

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

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.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

ERIC Educational Resources Information Center

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

A Randomized, Rater-Blinded, Parallel Trial of Intensive Speech Therapy in Sub-Acute Post-Stroke Aphasia: The SP-I-R-IT Study

ERIC Educational Resources Information Center

Martins, Isabel Pavao; Leal, Gabriela; Fonseca, Isabel; Farrajota, Luisa; Aguiar, Marta; Fonseca, Jose; Lauterbach, Martin; Goncalves, Luis; Cary, M. Carmo; Ferreira, Joaquim J.; Ferro, Jose M.

2013-01-01

Background: There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. Aims: A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT)…

A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

ERIC Educational Resources Information Center

Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

2012-01-01

Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Biederman, Joseph; Boellner, Samuel W.; Rugino, Thomas A.; Sangal, R. Bart; Earl, Craig Q.; Jiang, John G.; Swanson, James M.

2006-01-01

Objective: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). Method: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV…

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.

Auto-titrating continuous positive airway pressure treatment for obstructive sleep apnoea after acute quadriplegia (COSAQ): study protocol for a randomized controlled trial.

PubMed

Berlowitz, David J; Ayas, Najib; Barnes, Maree; Brown, Douglas J; Cistulli, Peter A; Geraghty, Tim; Graham, Alison; Lee, Bonsan Bonne; Morris, Meg; O'Donoghue, Fergal; Rochford, Peter D; Ross, Jack; Singhal, Balraj; Spong, Jo; Wadsworth, Brooke; Pierce, Robert J

2013-06-19

Quadriplegia is a severe, catastrophic injury that predominantly affects people early in life, resulting in lifelong physical disability. Obstructive sleep apnoea is a direct consequence of quadriplegia and is associated with neurocognitive deficits, sleepiness and reduced quality of life. The usual treatment for sleep apnoea is nasal continuous positive airway pressure (CPAP); however, this is poorly tolerated in quadriplegia. To encourage patients to use this therapy, we have to demonstrate that the benefits outweigh the inconvenience. We therefore propose a prospective, multinational randomized controlled trial of three months of CPAP for obstructive sleep apnoea after acute quadriplegia. Specialist spinal cord injury centres across Australia, New Zealand, the UK and Canada will recruit medically stable individuals who have sustained a (new) traumatic quadriplegia (complete or incomplete second cervical to first thoracic level lesions). Participants will be screened for obstructive sleep apnoea using full, portable sleep studies. Those with an apnoea hypopnoea index greater than 10 per hour will proceed to an initial three-night trial of CPAP. Those who can tolerate CPAP for at least 4 hours on at least one night of the initial trial will be randomized to either usual care or a 3-month period of auto-titrating CPAP. The primary hypothesis is that nocturnal CPAP will improve neuropsychological functioning more than usual care alone. The secondary hypothesis is that the magnitude of improvement of neuropsychological function will be predicted by the severity of baseline sleepiness measures, sleep fragmentation and sleep apnoea. Neuropsychological tests and full polysomnography will be performed at baseline and 3 months with interim measures of sleepiness and symptoms of autonomic dysfunction measured weekly. Spirometry will be performed monthly. Neuropsychological tests will be administered by blinded assessors. Recruitment commenced in July 2009. The results of this trial will demonstrate the effect of nocturnal CPAP treatment of obstructive sleep apnoea in acute quadriplegia. If CPAP can improve neurocognitive function after injury, it is likely that rehabilitation and subsequent community participation will be substantially improved for this group of predominantly young and severely physically disabled people. Australian New Zealand Clinical Trial Registry ACTRN12605000799651.

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

PubMed

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. ClinicalTrials.gov NCT01271933. A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial.

PubMed

Vranckx, Pascal; Lewalter, Thorsten; Valgimigli, Marco; Tijssen, Jan G; Reimitz, Paul-Egbert; Eckardt, Lars; Lanz, Hans-Joachim; Zierhut, Wolfgang; Smolnik, Rüdiger; Goette, Andreas

2018-02-01

The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored. The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis. The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design and rationale for the Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61 (CAMELLIA-TIMI 61) trial.

PubMed

Bohula, Erin A; Scirica, Benjamin M; Fanola, Christina; Inzucchi, Silvio E; Keech, Anthony; McGuire, Darren K; Smith, Steven R; Abrahamsen, Tim; Francis, Bruce H; Miao, Wenfeng; Perdomo, Carlos A; Satlin, Andrew; Wiviott, Stephen D; Sabatine, Marc S

2018-03-29

Lorcaserin, a selective serotonin 2C receptor agonist, is an effective pharmacologic weight-loss therapy that improves several cardiovascular risk factors. The long-term clinical cardiovascular and metabolic safety and efficacy in patients with elevated cardiovascular risk are unknown. CAMELLIA-TIMI 61 (NCT02019264) is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the safety and efficacy of lorcaserin with regard to major adverse cardiovascular events and progression to diabetes in overweight or obese patients at high cardiovascular risk. Overweight or obese patients either with established cardiovascular disease or with diabetes and at least 1 other cardiovascular risk factor were randomized in a 1:1 ratio to lorcaserin 10 mg twice daily or matching placebo. The primary safety objective is to assess for noninferiority of lorcaserin for the composite end point of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular event [MACE]) (with noninferiority defined as the upper bound of a 1-sided 97.5% CI excluding a hazard ratio of 1.4) compared with placebo assessed at an interim analysis with 460 adjudicated events. The efficacy objectives, assessed at study completion, will evaluate the superiority of lorcaserin for the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, or any coronary revascularization (MACE+) and the key secondary end point of conversion to diabetes. Recruitment began in January 2014 and was completed in November 2015 resulting in a total population of 12,000 patients. The trial is planned to continue until at least 1,401 adjudicated MACE+ events are accrued and the median treatment duration exceeds 2.5 years. CAMELLIA-TIMI 61 is investigating the safety and efficacy of lorcaserin for MACEs and conversion to diabetes in overweight or obese patients with established cardiovascular disease or multiple cardiovascular risk factors. Copyright © 2018. Published by Elsevier Inc.

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…

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

USDA-ARS?s Scientific Manuscript database

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

A Randomized Double-Blind Study of Atomoxetine versus Placebo for Attention-Deficit/Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Harfterkamp, Myriam; van de Loo-Neus, Gigi; Minderaa, Ruud B.; van der Gaag, Rutger-Jan; Escobar, Rodrigo; Schacht, Alexander; Pamulapati, Sireesha; Buitelaar, Jan K.; Hoekstra, Pieter J.

2012-01-01

Objective: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. Method: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or…

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

The Effects of Organization Design on Media Richness in Multinational Enterprises.

ERIC Educational Resources Information Center

Whitfield, J. Michael; And Others

1996-01-01

Examines effects of two organizational design parameters, divisionalization and centralization, on the media richness choices of Chief Executive Officers (CEOs) of multinational enterprises in obtaining information from foreign subsidiaries on strategic issues. Samples 86 US multinationals; finds formal divisional structure affects CEOs' use of…

Multinational Activities of Major U.S. Automotive Producers : Volume 3. Research, Development, and Engineering Abroad

DOT National Transportation Integrated Search

1978-09-01

This is Volume III of the report on the multinational activities of the four major U.S. automotive producers. The primary objective of Volume III is to evaluate the RD&E activities performed abroad by the U.S. automotive multinationals in order to de...

Consulting-Research Froblems with German and American Multinational Firms.

ERIC Educational Resources Information Center

Hildebrandt, Herbert W.

International researchers need to be aware of international problems and multinational managerial codes when they work with worldwide organizations. This paper develops the premise that consulting with German multinational companies is more complex than consulting with or researching for American firms. Discussion focuses on the following three…

More Than We Bargained For: The Impact of Consumer Culture in Southeast Asia.

ERIC Educational Resources Information Center

Frith, Katherine T.

Advertising by multinational corporations in Southeast Asia is generating a growing resistance to its perceived role in creating a "consumer culture" damaging to indigenous values systems. Critics of advertising in Southeast Asia argue that when multinational advertisers or their multinational advertising agencies move into this foreign…

Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia.

PubMed

Hajar, Saad; Al Hazmi, Ali; Wasli, Mustafa; Mousa, Ahmed; Rabiu, Mansour

2015-04-01

To determine the prevalence and causes of blindness and diabetic retinopathy (DR) in Jazan district, Southern Saudi Arabia. Using the standardized Rapid Assessment for Avoidable Blindness (RAAB) and DR cross-sectional methodology, 3800 subjects were randomly selected from the population of ≥50 years of age in Jazan, Saudi Arabia between November 2011 and January 2012. Participants underwent screening comprised of interview, random blood glucose test, and ophthalmic assessment including visual acuity (VA) and fundus examination. Among participants with VA less than 6/18 in either eye, the cause(s) of visual impairment was determined. Participants were classified as diabetic if they had previous diagnoses of diabetes, or random blood glucose more than 200 mg/dl. Diabetic participants were assessed for DR using dilated fundus examination. All data were recorded using the RAAB + DR standardized forms. The prevalence of bilateral blindness less than 3/60 was 3.3% (95% confidence interval [CI]: 2.74 - 3.90). Cataract was the leading cause of blindness (58.6%); followed by posterior segment diseases (20%), which included DR (7; 3.3%). The prevalence of diabetes mellitus (DM) was 22.4%, (95% CI: 21.09 - 23.79]), among them; 27.8% had DR. The prevalence of sight-threatening DR was 5.7%. The prevalence of DM and the corresponding proportion of DR in this region is lower than that reported in other regions of Saudi Arabia. However, the prevalence of blindness not related to DR is relatively higher than the other studies.

Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia

PubMed Central

Hajar, Saad; Hazmi, Ali Al; Wasli, Mustafa; Mousa, Ahmed; Rabiu, Mansour

2015-01-01

Objectives: To determine the prevalence and causes of blindness and diabetic retinopathy (DR) in Jazan district, Southern Saudi Arabia. Methods: Using the standardized Rapid Assessment for Avoidable Blindness (RAAB) and DR cross-sectional methodology, 3800 subjects were randomly selected from the population of ≥50 years of age in Jazan, Saudi Arabia between November 2011 and January 2012. Participants underwent screening comprised of interview, random blood glucose test, and ophthalmic assessment including visual acuity (VA) and fundus examination. Among participants with VA <6/18 in either eye, the cause(s) of visual impairment was determined. Participants were classified as diabetic if they had previous diagnoses of diabetes, or random blood glucose >200 mg/dl. Diabetic participants were assessed for DR using dilated fundus examination. All data were recorded using the RAAB + DR standardized forms. Results: The prevalence of bilateral blindness <3/60 was 3.3% (95% confidence interval [CI]: 2.74 - 3.90). Cataract was the leading cause of blindness (58.6%); followed by posterior segment diseases (20%), which included DR (7; 3.3%). The prevalence of diabetes mellitus (DM) was 22.4%, (95% CI: 21.09 - 23.79), among them; 27.8% had DR. The prevalence of sight-threatening DR was 5.7%. Conclusion: The prevalence of DM and the corresponding proportion of DR in this region is lower than that reported in other regions of Saudi Arabia. However, the prevalence of blindness not related to DR is relatively higher than the other studies. PMID:25828282

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

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.

The World Economy and Multinational Corporations: An Activity Program for Grades 9 through 12.

ERIC Educational Resources Information Center

Caterpillar Tractor Co., Peoria, IL.

This booklet for secondary students contains background information and activities about the multinational corporation (MNC). The major goal of the booklet is to impart an understanding of the economic concepts underlying the world economy and the activities of multinational business enterprises. The world economy, the exchange of goods and…

Evaluating the Investment Benefit of Multinational Enterprises' International Projects Based on Risk Adjustment: Evidence from China

ERIC Educational Resources Information Center

Chen, Chong

2016-01-01

This study examines the international risks faced by multinational enterprises to understand their impact on the evaluation of investment projects. Moreover, it establishes a 'three-dimensional' theoretical framework of risk identification to analyse the composition of international risk indicators of multinational enterprises based on the theory…

Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.

PubMed

Carbonell-Estrany, Xavier; Simões, Eric A F; Dagan, Ron; Hall, Caroline B; Harris, Brian; Hultquist, Micki; Connor, Edward M; Losonsky, Genevieve A

2010-01-01

Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged

On the topological structure of multinationals network

NASA Astrophysics Data System (ADS)

Joyez, Charlie

2017-05-01

This paper uses a weighted network analysis to examine the structure of multinationals' implantation countries network. Based on French firm-level dataset of multinational enterprises (MNEs) the network analysis provides information on each country position in the network and in internationalization strategies of French MNEs through connectivity preferences among the nodes. The paper also details network-wide features and their recent evolution toward a more decentralized structure. While much has been said on international trade network, this paper shows that multinational firms' studies would also benefit from network analysis, notably by investigating the sensitivity of the network construction to firm heterogeneity.

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. Methods/Design SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the ‘burden of hypoxia and hyperoxia’ expressed in ‘%hours’. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. Trial registration ClinicalTrial.gov, NCT01590316 PMID:23782447

Are Boys Discriminated in Swedish High Schools?

ERIC Educational Resources Information Center

Hinnerich, Bjorn Tyrefors; Hoglin, Erik; Johannesson, Magnus

2011-01-01

Girls typically have higher grades than boys in school and recent research suggests that part of this gender difference may be due to discrimination of boys in grading. We rigorously test this in a field experiment where a random sample of the same tests in the Swedish language is subject to blind and non-blind grading. The non-blind test score is…

Discrimination against Students with Foreign Backgrounds: Evidence from Grading in Swedish Public High Schools

ERIC Educational Resources Information Center

Hinnerich, Bjorn Tyrefors; Höglin, Erik; Johannesson, Magnus

2015-01-01

We rigorously test for discrimination against students with foreign backgrounds in high school grading in Sweden. We analyse a random sample of national tests in the Swedish language graded both non-blindly by the student's own teacher and blindly without any identifying information. The increase in the test score due to non-blind grading is…

Role of the multinational corporations in Nigeria's development

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

Okonkwo, P.A.

1978-01-01

A dominant characteristic of the decades immediately following World War II is the evolution of the multinational corporation. This evolution necessitated a change in the perspective of the international companies. The survival of the multinational corporations depended on its world profit perspective. Initially, the European countries provided the American multinational with world trade avenues while the European multinationals established subsidiaries in Africa. Recently, both the American and the European subsidiares have become interested in Nigeria because of its prospect as a potential market in Africa. The major objective of the research is to inquire about executive judgements and decision criteriamore » for marketing mix considerations and decisions. Also because of the uniqueness of Nigeria from the Western World in terms of its socio-cultural, legal, economic and political environments,executive decision criteria in the area of manufacturing was also investigated.« less

Maximum type I error rate inflation from sample size reassessment when investigators are blind to treatment labels.

PubMed

Żebrowska, Magdalena; Posch, Martin; Magirr, Dominic

2016-05-30

Consider a parallel group trial for the comparison of an experimental treatment to a control, where the second-stage sample size may depend on the blinded primary endpoint data as well as on additional blinded data from a secondary endpoint. For the setting of normally distributed endpoints, we demonstrate that this may lead to an inflation of the type I error rate if the null hypothesis holds for the primary but not the secondary endpoint. We derive upper bounds for the inflation of the type I error rate, both for trials that employ random allocation and for those that use block randomization. We illustrate the worst-case sample size reassessment rule in a case study. For both randomization strategies, the maximum type I error rate increases with the effect size in the secondary endpoint and the correlation between endpoints. The maximum inflation increases with smaller block sizes if information on the block size is used in the reassessment rule. Based on our findings, we do not question the well-established use of blinded sample size reassessment methods with nuisance parameter estimates computed from the blinded interim data of the primary endpoint. However, we demonstrate that the type I error rate control of these methods relies on the application of specific, binding, pre-planned and fully algorithmic sample size reassessment rules and does not extend to general or unplanned sample size adjustments based on blinded data. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Placebo Effects and the Common Cold: A Randomized Controlled Trial

PubMed Central

Barrett, Bruce; Brown, Roger; Rakel, Dave; Rabago, David; Marchand, Lucille; Scheder, Jo; Mundt, Marlon; Thomas, Gay; Barlow, Shari

2011-01-01

PURPOSE We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open-label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all. METHODS We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echinacea, and (4) those given open-label echinacea. Primary outcomes were illness duration and area-under-the-curve global severity. Secondary outcomes included neutrophil count and interleukin 8 levels from nasal wash at intake and 2 days later. RESULTS Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean illness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global severity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were −0.16 days (95% CI, −0.90 to 0.58 days) for illness duration and −22 severity points (95% CI, −70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, −0.28 to 1.12 days) and 22 severity points (95% CI, −19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group blinded to echinacea, and 70 pg/mL and 1 cell for the group with open-label echinacea, also not statistically significant. Among the 120 participants who at intake rated echinacea’s effectiveness as greater than 50 on a 100-point scale for which 100 is extremely effective, illness duration was 2.58 days shorter (95% CI, −4.47 to −0.68 days) in those blinded to placebo rather than no pill, and mean global severity score was 26% lower but not significantly different (−97.0, 95% CI, −249.8 to 55.8 points). In this subgroup, neither duration nor severity differed significantly between the group blinded to echinacea and the open-label echinacea group. CONCLUSIONS Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills. For the subgroup who believed in echinacea and received pills, illnesses were substantively shorter and less severe, regardless of whether the pills contained echinacea. These findings support the general idea that beliefs and feelings about treatments may be important and perhaps should be taken into consideration when making medical decisions. PMID:21747102

A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

PubMed

Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

2015-09-01

The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

Application status and its affecting factors of double standard for multinational corporations in Korea.

PubMed

Ki, Myung; Choi, Jaewook; Lee, Juneyoung; Park, Heechan; Yoon, Seokjoon; Kim, Namhoon; Heo, Jungyeon

2004-02-01

We intended to evaluate the double standard status and to identify factors of determining double standard criteria in multinational corporations of Korea, and specifically those in the occupational health and safety area. A postal questionnaire had been sent, between August 2002 and September 2002, to multinational corporations in Korea. A double standard company was defined as those who answered in more than one item as adopting a different standard among the five items regarding double standard identification. By comparing double standard companies with equivalent standard companies, determinants for double standards were then identified using logistic regression analysis. Of multinational corporations, 45.1% had adopted a double standard. Based on the question naire's scale level, the factor of 'characteristic and size of multinational corporation' was found to have the most potent impact on increasing double standard risk. On the variable level, factors of 'number of affiliated companies' and 'existence of an auditing system with the parent company' showed a strong negative impact on double standard risk. Our study suggests that a distinctive approach is needed to manage the occupational safety and health for multinational corporations. This approach should be focused on the specific level of a corporation, not on a country level.

Doing the Same with Less: A Randomized, Multinational, Open-Label, Adjudicator-Blinded Trial of an Algorithm vs. Standard of Care to Determine Treatment Duration for Staphylococcal Bacteremia

PubMed Central

Holland, Thomas L; Boucher, Helen W; Raad, Issam; Anderson, Deverick J; Cosgrove, Sara E; Aycock, Suzanne; Baddley, John W; Chow, Shein-Chung; Chu, Vivian H; Cook, Paul P; Corey, G Ralph; Daly, Jennifer S; Hachem, Ray Y; Chaftari, Anne-Marie; Horton, James M; Jenkins, Timothy C; Gu, Jiezhun; Levine, Donald P; Miro, Jose M; Riska, Paul; Rubin, Zachary A; Rupp, Mark E; Schrank, John; Sims, Matthew; Wray, Dannah; Zervos, Marcus J; Fowler, Vance

2017-01-01

Abstract Background The appropriate duration of antibiotics for staphylococcal bloodstream infection (BSI) is unknown. An algorithm to identify patients with staphylococcal BSI who can be safely treated with shorter courses of therapy would improve care and reduce total antibiotic use. Methods Adult patients with staphylococcal BSI were randomized to treatment based on algorithm-based therapy (ABT) or to standard of care (SOC). Co-primary outcomes were clinical success, as determined by a blinded Adjudication Committee, and serious adverse event (SAE) rates. The prespecified secondary outcome measure was antibiotic days by treatment group, among patients without complicated BSI. Prespecified durations of therapy in ABT were: S. aureus BSI (SAB): uncomplicated: 14 days; complicated: 4–6 weeks. Coagulase-negative staphylococci BSI (CoNSB): simple (1 positive blood culture) (0–3 days), uncomplicated (>1 positive blood culture) (5 days), complicated (7–28 days). Outcomes were compared using intention-to-treat principles. The target sample size was 500 patients, to ensure 90% power for establishing noninferiority within a margin of 15%. Results Between April 2011 and March 2017, 509 adults with suspected staphylococcal BSI at 16 sites in the US and Spain were randomized to ABT (N = 255) or SOC (N = 254). There were 116 patients with SAB (23%) and 385 (76%) with CoNSB (Figure 1). Overall success rate in the ABT group was 82.0% vs. 81.5% in the SOC group, difference 0.5%, 95% CI −5.2% to 6.1%. SAEs were reported in 32.9% of ABT vs. 28.3% of SOC patients (OR 1.2, 95% CI 0.9 to 1.8). Among evaluable patients without complicated BSI, mean duration of therapy was 4.4 days in the ABT group vs. 6.4 days in the SOC group (difference −2.0 days, 95% CI −3.3 to −-0.7, P = 0.003). Among patients with uncomplicated SAB, treatment durations were similar (15.3 days in ABT vs. 16.3 days in SOC, difference −1 day, 95% CI −3.89 to 1.91, P = 0.497), whereas for uncomplicated CoNSB, duration was shorter in the ABT group (5.3 days in ABT vs. 8.4 days in SOC, difference −3 days, 95% CI −4.87 to −1.34, P < 0.001). Conclusion The use of a treatment algorithm for staphylococcal BSI was associated with significant reductions in duration of antibiotic therapy in patients without complicated BSI, without significant differences in overall success or SAEs. Figure 1. Schematic of Study Design Disclosures V. Fowler Jr., NIH: Investigator, Contract HHSN272200900023C

Buffered Lidocaine With Sodium Bicarbonate did not Increase Inferior Alveolar Nerve Block Success Rate in Patients Having Symptomatic Irreversible Pulpitis.

PubMed

Parirokh, Masoud

2016-03-01

Effect of buffered 4% lidocaine on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind study. Schellenberg J, Drum M, Reader A, Nusstein J, Fowler S, Beck M. J Endod 2015;41(6):791-6. The study was supported by Meyers/Reader Graduate Endodontic Support Fund Double blinded randomized controlled trial. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Guided Imagery on Postoperative Outcomes in Patients Undergoing Same-Day Surgical Procedures: A Randomized, Single-Blind Study

DTIC Science & Technology

2010-06-01

2O0O;9Ot3):706-712. 20. Bertrand P, Maye J. A description of the indices of heart rate variabil- ity in orofacial pain paticnis. Bcihcsda, MD: National...neck proce- dures were randomly assigned into 2 groups for this single-blind investigation. Anxiety and baseline pain levels were documented...control group patients received no intervention. Data were collected on pain and nar- cotic consumption at 7- and 2-hour postoperative inter- vals. In

Local Nordic tobacco interests collaborated with multinational companies to maintain a united front and undermine tobacco control policies.

PubMed

Hiilamo, Heikki; Glantz, Stanton A

2013-03-01

To analyse how local tobacco companies in the Nordic countries, individually and through National Manufacturers' Associations, cooperated with British American Tobacco and Philip Morris in denying the health hazards of smoking and undermining tobacco control. Analysis of tobacco control policies in the Nordic countries and tobacco industry documents. Nordic countries were early adopters of tobacco control policies. The multinational tobacco companies recognised this fact and mobilised to oppose these policies, in part because of fear that they would set unfavourable precedents. Since at least 1972, the Nordic tobacco companies were well informed about and willing to participate in the multinational companies activities to obscure the health dangers of smoking and secondhand smoke and to oppose tobacco control policies. Cooperation between multinational companies, Nordic national manufacturer associations and local companies ensured a united front on smoking and health issues in the Nordic area that was consistent with the positions that the multinational companies were taking. This cooperation delayed smoke-free laws and undermined other tobacco control measures. Local tobacco companies worked with multinational companies to undermine tobacco control in distant and small Nordic markets because of concern that pioneering policies initiated in Nordic countries would spread to bigger market areas. Claims by the local Nordic companies that they were not actively involved with the multinationals are not supported by the facts. These results also demonstrate that the industry appreciates the global importance of both positive and negative public health precedents in tobacco control.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

The Army in Multinational Operations

DTIC Science & Technology

2010-05-01

multinational commanders may be faced with nations refusing to perform assigned tasks. The term “national red card” using a soccer simile has been coined...106. What is the multinational plan for recovery of critical aviation equipment, facilities, and resources? Constraints and Freedom of Action 5-107...quantity, and timeliness) suitable for likely combat search and rescue as well as recovery of encircled forces? Operations and Planning 20 May

Crosscultural Issues in the Process of Sending U.S. Employees of Multinational Corporations for Overseas Service: Theoretical Considerations with Practical Implications.

ERIC Educational Resources Information Center

Griffis, Betty Ann

Defining the multinational as a producing enterprise motivated by profit and owning or controlling facilities in more than one country, this paper analyzes the process employed by United States multinationals in sending parent country nationals abroad for service in a subsidiary. It first examines the process in its fullest form by citing…

The effectiveness of foot reflexology in inducing ovulation: a sham-controlled randomized trial.

PubMed

Holt, Jane; Lord, Jonathan; Acharya, Umesh; White, Adrian; O'Neill, Nyree; Shaw, Steve; Barton, Andy

2009-06-01

To determine whether foot reflexology, a complementary therapy, has an effect greater than sham reflexology on induction of ovulation. Sham-controlled randomized trial with patients and statistician blinded. Infertility clinic in Plymouth, United Kingdom. Forty-eight women attending the clinic with anovulation. Women were randomized to receive eight sessions of either genuine foot reflexology or sham reflexology with gentle massage over 10 weeks. The primary outcome was ovulation detected by serum progesterone level of >30 nmol/L during the study period. Twenty-six patients were randomized to genuine reflexology and 22 to sham (one randomized patient was withdrawn). Patients remained blinded throughout the trial. The rate of ovulation during true reflexology was 11 out of 26 (42%), and during sham reflexology it was 10 out of 22 (46%). Pregnancy rates were 4 out of 26 in the true group and 2 out of 22 in the control group. Because of recruitment difficulties, the required sample size of 104 women was not achieved. Patient blinding of reflexology studies is feasible. Although this study was too small to reach a definitive conclusion on the specific effect of foot reflexology, the results suggest that any effect on ovulation would not be clinically relevant. Sham reflexology may have a beneficial general effect, which this study was not designed to detect.

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.

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

PubMed

Hurtado, R; Celani, M; Geber, S

2016-10-01

To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. NCT01482416.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting.

PubMed

Bruynseels, Daniel; Solomon, Cristina; Hallam, Angela; Collins, Peter W; Collis, Rachel E; Hamlyn, Vincent; Hall, Judith E

2016-01-01

The gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. We have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. We feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

PubMed

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gaming Sea-based Multinational HA/DR Operations at PACOM Amphibious Leaders Symposium 2016

DTIC Science & Technology

2016-11-01

DISTRIBUTION STATEMENT A. Approved for public release: distribution unlimited. Gaming Sea-based Multinational HA/DR Operations...Marine Corps photo by Cpl. Wesley Timm. Approved by: November 2016 Dr. E.D. McGrady Director, Integration and Gaming Advanced Technology and...TYPE Final2 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Gaming Seabased Multinational HA/DR Operations at PACOM 5a. CONTRACT NUMBER N00014-16

Stilwell’s North Burma campaign: a case study in multinational mission command

DTIC Science & Technology

2017-05-25

history of providing multinational leadership , publications from the Army Press and Combat Studies Institute have not explored the use of the mission...the campaign. His leadership aided the US effort to reestablish its ground line of communication with its Chinese Nationalist allies. Stilwell’s...history of providing multinational leadership , publications from the Army Press and Combat Studies Institute have not explored the use of the mission

Local Nordic tobacco interests collaborated with multinational companies to maintain a united front and undermine tobacco control policies

PubMed Central

Hiilamo, Heikki; Glantz, Stanton A

2012-01-01

Objective To analyse how local tobacco companies in the Nordic countries, individually and through National Manufacturers’ Associations, cooperated with British American Tobacco and Philip Morris in denying the health hazards of smoking and undermining tobacco control. Methods Analysis of tobacco control policies in the Nordic countries and tobacco industry documents. Results Nordic countries were early adopters of tobacco control policies. The multinational tobacco companies recognised this fact and mobilised to oppose these policies, in part because of fear that they would set unfavourable precedents. Since at least 1972, the Nordic tobacco companies were well informed about and willing to participate in the multinational companies activities to obscure the health dangers of smoking and secondhand smoke and to oppose tobacco control policies. Cooperation between multinational companies, Nordic national manufacturer associations and local companies ensured a united front on smoking and health issues in the Nordic area that was consistent with the positions that the multinational companies were taking. This cooperation delayed smoke-free laws and undermined other tobacco control measures. Conclusions Local tobacco companies worked with multinational companies to undermine tobacco control in distant and small Nordic markets because of concern that pioneering policies initiated in Nordic countries would spread to bigger market areas. Claims by the local Nordic companies that they were not actively involved with the multinationals are not supported by the facts. These results also demonstrate that the industry appreciates the global importance of both positive and negative public health precedents in tobacco control. PMID:22199013

The risk of unblinding was infrequently and incompletely reported in 300 randomized clinical trial publications.

PubMed

Bello, Segun; Moustgaard, Helene; Hróbjartsson, Asbjørn

2014-10-01

To assess the proportion of clinical trials explicitly reporting the risk of unblinding, to evaluate the completeness of reporting on unblinding risk, and to describe the reported procedures involved in assessing unblinding. We sampled at random 300 blinded randomized clinical trials indexed in PubMed in 2010. Two authors read the trial publications and extracted data independently. Twenty-four trial publications, or 8% (95% confidence interval [CI], 5, 12%), explicitly reported the risk of unblinding, of which 16 publications, or 5% (95% CI, 3, 8%), reported compromised blinding; and 8 publications, or 3% (95% CI, 1, 5%), intact blinding. The reporting on risk of unblinding in the 24 trial publications was generally incomplete. The median proportion of assessments per trial affected by unblinding was 3% (range 1-30%). The most common mechanism for unblinding was perceptible physical properties of the treatments, for example, a difference in the taste and odor of a typhoid vaccine compared with its placebo. Published articles on randomized clinical trials infrequently reported risk of unblinding. This may reflect a tendency for avoiding reporting actual or suspected unblinding or a genuine low risk of unblinding. Copyright © 2014 Elsevier Inc. All rights reserved.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955–2013

PubMed Central

Armijo-Olivo, Susan; Cummings, Greta G.; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

Objectives To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. Methods We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Results Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955–2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. Conclusions The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed. PMID:29272315

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955-2013.

PubMed

Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955-2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed.

Coalition Logistics - The Multinational Force and Observers Model

DTIC Science & Technology

1986-05-19

MISSION The mission of the MFO, as specified by the protocol , is to supervise implemeutation of the peace treaty and to employ its best efforts to prevent ...result, a protocol was -- negotiated, calling for a multinational military force and civilian- ---- observer unit to serve in the Sinai--outside the...auspices of the United Nations.2 In this way, the protocol of 3 August 1981 created the Multinational Force and Observers and directed Lhat it be

Blind quantum computing with weak coherent pulses.

PubMed

Dunjko, Vedran; Kashefi, Elham; Leverrier, Anthony

2012-05-18

The universal blind quantum computation (UBQC) protocol [A. Broadbent, J. Fitzsimons, and E. Kashefi, in Proceedings of the 50th Annual IEEE Symposiumon Foundations of Computer Science (IEEE Computer Society, Los Alamitos, CA, USA, 2009), pp. 517-526.] allows a client to perform quantum computation on a remote server. In an ideal setting, perfect privacy is guaranteed if the client is capable of producing specific, randomly chosen single qubit states. While from a theoretical point of view, this may constitute the lowest possible quantum requirement, from a pragmatic point of view, generation of such states to be sent along long distances can never be achieved perfectly. We introduce the concept of ϵ blindness for UBQC, in analogy to the concept of ϵ security developed for other cryptographic protocols, allowing us to characterize the robustness and security properties of the protocol under possible imperfections. We also present a remote blind single qubit preparation protocol with weak coherent pulses for the client to prepare, in a delegated fashion, quantum states arbitrarily close to perfect random single qubit states. This allows us to efficiently achieve ϵ-blind UBQC for any ϵ>0, even if the channel between the client and the server is arbitrarily lossy.

Blind Quantum Computing with Weak Coherent Pulses

NASA Astrophysics Data System (ADS)

Dunjko, Vedran; Kashefi, Elham; Leverrier, Anthony

2012-05-01

The universal blind quantum computation (UBQC) protocol [A. Broadbent, J. Fitzsimons, and E. Kashefi, in Proceedings of the 50th Annual IEEE Symposiumon Foundations of Computer Science (IEEE Computer Society, Los Alamitos, CA, USA, 2009), pp. 517-526.] allows a client to perform quantum computation on a remote server. In an ideal setting, perfect privacy is guaranteed if the client is capable of producing specific, randomly chosen single qubit states. While from a theoretical point of view, this may constitute the lowest possible quantum requirement, from a pragmatic point of view, generation of such states to be sent along long distances can never be achieved perfectly. We introduce the concept of ɛ blindness for UBQC, in analogy to the concept of ɛ security developed for other cryptographic protocols, allowing us to characterize the robustness and security properties of the protocol under possible imperfections. We also present a remote blind single qubit preparation protocol with weak coherent pulses for the client to prepare, in a delegated fashion, quantum states arbitrarily close to perfect random single qubit states. This allows us to efficiently achieve ɛ-blind UBQC for any ɛ>0, even if the channel between the client and the server is arbitrarily lossy.

Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial.

PubMed

O'Donoghue, Michelle L; Braunwald, Eugene; White, Harvey D; Steen, Dylan P; Lukas, Mary Ann; Tarka, Elizabeth; Steg, P Gabriel; Hochman, Judith S; Bode, Christoph; Maggioni, Aldo P; Im, KyungAh; Shannon, Jennifer B; Davies, Richard Y; Murphy, Sabina A; Crugnale, Sharon E; Wiviott, Stephen D; Bonaca, Marc P; Watson, David F; Weaver, W Douglas; Serruys, Patrick W; Cannon, Christopher P; Steen, Dylan L

2014-09-10

Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme. To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event. SOLID-TIMI 52 was a multinational, double-blind, placebo-controlled trial that randomized 13,026 participants within 30 days of hospitalization with an ACS (non-ST-elevation or ST-elevation myocardial infarction [MI]) at 868 sites in 36 countries. Patients were randomized to either once-daily darapladib (160 mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. The primary end point (major coronary events) was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization for myocardial ischemia. Kaplan-Meier event rates are reported at 3 years. During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3% vs 15.6% at 3 years; hazard ratio [HR], 1.00 [95% CI, 0.91-1.09]; P = .93). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0% vs 15.0% at 3 years; HR, 0.99 [95% CI, 0.90-1.09]; P = .78). There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group [7.3% vs 7.1% at 3 years; HR, 0.94 [95% CI, 0.82-1.08]; P = .40). Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5% vs 2.5%) and also more likely to report diarrhea (10.6% vs 5.6%). In patients who experienced an ACS event, direct inhibition of Lp-PLA2 with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events. clinicaltrials.gov Identifier: NCT01000727.

Auto-titrating continuous positive airway pressure treatment for obstructive sleep apnoea after acute quadriplegia (COSAQ): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Quadriplegia is a severe, catastrophic injury that predominantly affects people early in life, resulting in lifelong physical disability. Obstructive sleep apnoea is a direct consequence of quadriplegia and is associated with neurocognitive deficits, sleepiness and reduced quality of life. The usual treatment for sleep apnoea is nasal continuous positive airway pressure (CPAP); however, this is poorly tolerated in quadriplegia. To encourage patients to use this therapy, we have to demonstrate that the benefits outweigh the inconvenience. We therefore propose a prospective, multinational randomized controlled trial of three months of CPAP for obstructive sleep apnoea after acute quadriplegia. Methods/design Specialist spinal cord injury centres across Australia, New Zealand, the UK and Canada will recruit medically stable individuals who have sustained a (new) traumatic quadriplegia (complete or incomplete second cervical to first thoracic level lesions). Participants will be screened for obstructive sleep apnoea using full, portable sleep studies. Those with an apnoea hypopnoea index greater than 10 per hour will proceed to an initial three-night trial of CPAP. Those who can tolerate CPAP for at least 4 hours on at least one night of the initial trial will be randomized to either usual care or a 3-month period of auto-titrating CPAP. The primary hypothesis is that nocturnal CPAP will improve neuropsychological functioning more than usual care alone. The secondary hypothesis is that the magnitude of improvement of neuropsychological function will be predicted by the severity of baseline sleepiness measures, sleep fragmentation and sleep apnoea. Neuropsychological tests and full polysomnography will be performed at baseline and 3 months with interim measures of sleepiness and symptoms of autonomic dysfunction measured weekly. Spirometry will be performed monthly. Neuropsychological tests will be administered by blinded assessors. Recruitment commenced in July 2009. Discussion The results of this trial will demonstrate the effect of nocturnal CPAP treatment of obstructive sleep apnoea in acute quadriplegia. If CPAP can improve neurocognitive function after injury, it is likely that rehabilitation and subsequent community participation will be substantially improved for this group of predominantly young and severely physically disabled people. Trial registration Australian New Zealand Clinical Trial Registry ACTRN12605000799651 PMID:23777510

A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

PubMed

Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

2016-01-01

A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

Laboratory animal research published in plastic surgery journals in 2014 has extensive waste: A systematic review.

PubMed

Freshwater, M Felix

2015-11-01

Laboratory animal research must be designed in a manner that minimizes bias if it is to yield valid and reproducible results. In 2009, a survey that examined 271 animal studies found that 87% did not use randomization and 86% did not use blinding. This has been called "research waste" because it wasted time and resources. This systematic review measured the quantity of research waste in plastic surgery journals in 2014. The PRISMA-P protocol was used. SCOPUS and PubMed searches were done for all animal studies published in 2014 in Aesthetic Plast Surg, Aesthet Surg J, Ann Plast Surg, JPRAS, J Plast Surg Hand Surg and Plast Reconstr Surg. These were supplemented by manual searches of the 2014 issues not indexed. Articles were analyzed for descriptions of randomization, randomization methodology, allocation concealment, and blinding of the primary outcome assessment. Corresponding authors who mentioned randomization without elaborating were emailed for details. 112 of 154 articles met the inclusion criteria. Only 24/112 (21.4%) had blinding of the primary outcome measure, 28/110 (25.5%) of articles that required randomization mentioned it. While 12/28 articles clearly described randomizing the intervention, only 4/28 described the method of randomization, and 2/28 mentioned allocation concealment. Only two authors responded and described the randomization methodology. The quality of plastic surgery laboratory animal research published in 2014 was poor. Use of the National Centre for the Replacement Refinement & Reduction of Animals in Research's "Animal Research: Reporting In Vivo Experiments" (ARRIVE) Guidelines by authors, and enforcement of them by editors and reviewers could improve research quality and reduce waste. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study.

PubMed

Adler, Lenard; Tanaka, Yoko; Williams, David; Trzepacz, Paula T; Goto, Taro; Allen, Albert J; Escobar, Rodrigo; Upadhyaya, Himanshu P

2014-08-01

We assessed the executive function in adults with attention-deficit/hyperactivity disorder (ADHD) during atomoxetine treatment in a randomized withdrawal trial. Responders (Conners' ADHD Rating Scale-Investigator Rated: Screening Version [adult prompts] ≥30% reduction from baseline and Clinical Global Impression Scale-ADHD Severity score ≤3) to open-label atomoxetine (40-100 mg/d, 12 weeks) entered a 37-week double-blind maintenance period. Patients who maintained response (double-blind atomoxetine for 12 weeks) were randomized 1:1 to atomoxetine (80-100 mg/d, n = 266) or placebo (n = 258) for 25 weeks (total duration, 1 year). Patients and investigators were blinded to response criteria and randomization timing. Change in executive function was assessed with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report and Informant T scores from the randomization to the last-observation-carried-forward postrandomization week 25 (after week 17). Of the enrolled patients (n = 2017; mean age, 33.2 years; male, 58.7%), 524 responders were randomized. During open-label atomoxetine, subscales and individual items on both BRIEF-A questionnaires showed significant improvement (P < 0.001). After randomization, the following T scores improved significantly (P ≤ 0.05) with patients in the atomoxetine group versus those in the placebo group: global executive composite, behavioral regulation, and metacognition indices; plan/organize, working memory, inhibit, task monitor and shift (both BRIEF-A questionnaires), emotional control and organization of materials (BRIEF-A Informant), and initiate (BRIEF-A Self-Report). Atomoxetine significantly improved the executive function compared with placebo, which was maintained for 25 weeks or more; the executive function of patients in the placebo group worsened but did not return to baseline levels after randomization.

The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Meidahl Petersen, Kasper; Eplov, Kasper; Kjær Nielsen, Torben; Jimenez-Solem, Espen; Petersen, Morten; Broedbaek, Kasper; Daugaard Popik, Sara; Kallehave Hansen, Lina; Enghusen Poulsen, Henrik; Trærup Andersen, Jon

2016-01-01

Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial.

PubMed

Huttner, Angela; Kowalczyk, Anna; Turjeman, Adi; Babich, Tanya; Brossier, Caroline; Eliakim-Raz, Noa; Kosiek, Katarzyna; Martinez de Tejada, Begoña; Roux, Xavier; Shiber, Shachaf; Theuretzbacher, Ursula; von Dach, Elodie; Yahav, Dafna; Leibovici, Leonard; Godycki-Cwirko, Maciek; Mouton, Johan W; Harbarth, Stephan

2018-05-01

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. ClinicalTrials.gov Identifier: NCT01966653.

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

PubMed Central

Kullberg, Bart Jan; Vasquez, José; Mootsikapun, Piroon; Nucci, Marcio; Paiva, José-Artur; Garbino, Jorge; Yan, Jean Li; Aram, Jalal; Capparella, Maria Rita; Conte, Umberto; Schlamm, Haran; Swanson, Robert; Herbrecht, Raoul

2017-01-01

Abstract Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non-albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5–10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%–80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population. PMID:28459966

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

PubMed

Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

2018-04-15

To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy

PubMed Central

Ogawa, Eiichi; Furusyo, Norihiro; Nguyen, Mindie H

2017-01-01

Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level <29 IU/mL at week 48. No amino-acid substitutions associated with viral breakthrough were detected by deep sequencing, and no resistance to TAF was found through week 96. In addition, no difference in the frequency of HBeAg or hepatitis B surface antigen loss was observed. However, TAF was associated with a significantly higher ALT normalization rate than was TDF, based on the American Association for the Study of Liver Diseases criteria (male: ALT ≤30 U/L and female: ALT ≤19 U/L). An analysis of renal safety showed that patients treated with TAF had a significantly lower decrease in the estimated glomerular filtration rate level than did patients treated with TDF. Similarly, the declines of hip and spine bone mineral density were significantly less in the TAF group. These trends of efficacy and renal/bone safety continued through week 96. Longer term follow-up and real-world data will be required to determine if the differences in viral/biochemical response and renal/bone safety seen with TAF in comparison with TDF are clinically relevant. PMID:29158666

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.

PubMed

Tricoci, Pierluigi; Huang, Zhen; Held, Claes; Moliterno, David J; Armstrong, Paul W; Van de Werf, Frans; White, Harvey D; Aylward, Philip E; Wallentin, Lars; Chen, Edmond; Lokhnygina, Yuliya; Pei, Jinglan; Leonardi, Sergio; Rorick, Tyrus L; Kilian, Ann M; Jennings, Lisa H K; Ambrosio, Giuseppe; Bode, Christoph; Cequier, Angel; Cornel, Jan H; Diaz, Rafael; Erkan, Aycan; Huber, Kurt; Hudson, Michael P; Jiang, Lixin; Jukema, J Wouter; Lewis, Basil S; Lincoff, A Michael; Montalescot, Gilles; Nicolau, José Carlos; Ogawa, Hisao; Pfisterer, Matthias; Prieto, Juan Carlos; Ruzyllo, Witold; Sinnaeve, Peter R; Storey, Robert F; Valgimigli, Marco; Whellan, David J; Widimsky, Petr; Strony, John; Harrington, Robert A; Mahaffey, Kenneth W

2012-01-05

Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Multinational corporations and culture in Liberia

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

Bonaparte, T.H.

1979-07-01

The proportion of multinational corporations (MCs) in a developing country (DC) has little to do with the degree of corruption of local culture that takes place. Rather, policy decisions taken by governments of DCs determine whether or not multinationals have a positive or negative impact, according to the author's research in Liberia among foreign managers, African supervisors, and Liberian workers. Even though Liberia has an open door policy toward MCs, very little violence has been done to Liberian culture. The reason is two-fold: 1) multinationals have maintained tight enclaves and have generally refused to integrate their values, managerial and otherwise,more » with those of the Liberian society; and 2) Liberian government officials have done little to generate Liberian interest in the business field or to force multinationals to play a more participative role in the society. The result has been growth without development, in the sense that the country's growth rate has increased over the years, but the Liberian people remain very much underdeveloped. A change of policy could bring about continued growth with development and without cultural disintegration.« less

Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double-blind, active-controlled, parallel group, multinational clinical trial.

PubMed

Ross, S A; Caballero, A E; Del Prato, S; Gallwitz, B; Lewis-D'Agostino, D; Bailes, Z; Thiemann, S; Patel, S; Woerle, H-J; von Eynatten, M

2015-02-01

To evaluate glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted. A total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5-12.0%, were randomized 1:1 to double-blind, free-combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per-protocol completers' cohort: n = 245). The mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by -2.8 ± 0.1% with linagliptin/metformin and -2.0 ± 0.1% with linagliptin; a treatment difference of -0.8% (95% confidence interval -1.1 to -0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent-to-treat principles: adjusted mean ± s.e. changes in HbA1c of -2.7 ± 0.1% and -1.8 ± 0.1%, respectively; treatment difference of -0.9% (95% CI -1.3 to -0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug-related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (-1.3 kg between-group difference; p =0.0033). Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non-insulin therapy. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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

Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

PubMed

Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

2015-02-01

Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P < .01) and manual dexterity assessed by the Box and Block test (P = .04) improved significantly more in the robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

Retention of blinding at follow-up in a randomized clinical study using a sham-control cervical manipulation procedure for neck pain: secondary analyses from a randomized clinical study.

PubMed

Vernon, Howard; Triano, John T; Soave, David; Dinulos, Maricelle; Ross, Kim; Tran, Steven

2013-10-01

Participants in clinical trials of spinal manipulation have not been rigorously blinded to group assignment. This study reports on secondary analyses of the retention of participant blinding beyond the immediate posttreatment time frame following a single-session, randomized clinical study. A novel control cervical manipulation procedure that has previously been shown to be therapeutically inert was contrasted with a typical manipulation procedure. A randomized clinical study of a single session of typical vs sham-control manipulation in patients with chronic neck pain was conducted. Findings of self-reported group registration at 24 to 48 hours posttreatment were computed. The Blinding Index (BI) of Bang et al was then applied to both the immediate and post-24- to 48-hour results. Twenty-four to 48 hours after treatment, 94% and 22% of participants in the typical and control groups, respectively, correctly identified their group assignment. When analyzed with the BI of Bang et al, the immediate posttreatment BI for the group receiving a typical manipulation was 0.22 (95% confidence interval [CI], -0.03 to 0.47); for the group receiving a control manipulation, it was 0.19 (95% CI, -0.06 to 0.43). The BI at post-24 hours was as follows: typical = 0.75 (95% CI, 0.59-0.91) and control = -0.34 (95% CI, -0.58 to -0.11). This study found that the novel sham-control cervical manipulation procedure may be effective in blinding sham group allocation up to 48 hours posttreatment. It appears that, at 48 hours posttreatment, the modified form of the typical cervical manipulation was not. The sham-control procedure appears to be a promising procedure for future clinical trials. © 2013. Published by National University of Health Sciences All rights reserved.

32 CFR 268.9 - Discussion of terms.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., excepting branches or agencies thereof located in the United States. (3) Any branch, subsidiary, or allied... organization of a multinational or regional character with headquarters abroad. (6) Any official multinational...

Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

PubMed Central

Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

2010-01-01

Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. Conclusion The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID:27186096

Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome.

PubMed

Fukuda, Sanae; Nojima, Junzo; Kajimoto, Osami; Yamaguti, Kouzi; Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

2016-07-08

The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study. Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation. Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study. The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms. © 2016 BioFactors, 42(4):431-440, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.

PubMed

Ashida, Ryo; Okamura, Yukiyasu; Wakabayashi-Nakao, Kanako; Mizuno, Takashi; Aoki, Shuichi; Uesaka, Katsuhiko

2018-06-08

To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD. © 2018 S. Karger AG, Basel.

Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers in late-postmenopausal women with osteopenia: a multinational, 24-month, randomized, double-blind, placebo-controlled, parallel-group, phase III trial.

PubMed

Välimäki, Matti J; Farrerons-Minguella, Jordi; Halse, Johan; Kröger, Heikki; Maroni, Marilyn; Mulder, Henk; Muñoz-Torres, Manuel; Sääf, Maria; Snorre Øfjord, Erik

2007-09-01

Randomized clinical trials have shown that risedronate reduces the risk for both ver- tebral and nonvertebral fractures in postmenopausal women with osteoporosis (bone mineral density [BMD] T-score, <-2.5). If left untreated, osteopenia (T-score, between -1 and -2.5) may progress to osteo- porosis. Risedronate sodium, a pyridinyl bisphospho- nate, is an antiresorptive drug approved by the US Food and Drug Administration for the prevention and treatment of osteoporosis in postmenopausal women. Although the effects of risedronate in preventing frac- tures has been established, its effects in maintaining or increasing BMD in osteopenia have not. In this clinical trial, the efficacy and tol- erability of risedronate in improving and maintaining BMD levels in late-postmenopausal women with os- teopenia were assessed. This 24-month, randomized, double- blind, placebo-controlled, parallel-group, Phase III trial was conducted at 14 study centers across Finland, The Netherlands, Norway, Spain, and Sweden. Late- postmenopausal (> or =5 years from menopause) women with lumbar spine (LS) BMD T-score between -1 and -2.5 and the presence of > or =1 additional risk factor for osteo- porosis or proximal femur (Fern) BMD T-score < or = -1 were randomized to receive risedronate 5 mg (n = 114) or placebo (n = 57) PO QD for 24 months. The primary efficacy end point was the percentage change from baseline in LS BMD at study end point (24 months or last observation carried forward). Secondary efficacy end points were the percentage changes from base- line in total proximal Fern BMD and 2 bone turnover markers-urinary type I collagen cross-linked N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBAP)-at 12 months and study end point. Tolerability was assessed using reported adverse events (AEs), laboratory analysis, and physical exami- nation including vital-sign measurements. A total of 171 women were included (mean [SD] age, 65.9 [6.8] years; mean [SD] LS BMD T-score,-1.82 [0.42]; risedronate group, 114 patients; placebo group, 57). At study end point, LS BMD had significantly increased from baseline in the risedronate group (P < 0.05) but remained unchanged in the placebo group (mean [SE] %Delta, +4.49% [0.38%] and +0.05% [0.54%], respectively; P < 0.001). Between- treatment differences in mean (SE) percentage changes from baseline in LS BMD and Fem BMD were signif- icant at 12 months and study end point (LS BMD, both P < 0.001; Fem BMD, P = 0.002 and P < 0.001, respectively). At 12 months and study end point, ris- edronate use was associated with significantly reduced concentrations of uNTx and sBAP compared with placebo (both, P < 0.001). Risedronate treatment was well tolerated with regard to gastrointestinal AEs; the most frequent AEs in the risedronate group were hy- pertension (n = 13), constipation (n = 8), and hyper- cholesterolemia (n = 8). In these late-postmenopausal women with LS osteopenia and > or=1 additional risk factor or hip osteopenia, 24-month treatment with risedronate 5 mg/d was associated with the prevention of bone loss at the spine and hip (based on significant increases in BMD in the LS and total proximal Fem) and reduced bone resorption (based on significantly reduced concen- trations of uNTx and sBAP) and was well tolerated.

Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product.

PubMed

Chowdary, P; Kearney, S; Regnault, A; Hoxer, C S; Yee, D L

2016-07-01

Health-related quality of life (HRQoL) of individuals with haemophilia has greatly improved with the use of factor replacement and routine prophylaxis. To explore the HRQoL of individuals with haemophilia B treated with nonacog beta pegol, an extended half-life recombinant factor IX, in a single-blind, randomized multinational phase III pivotal trial (paradigm(™) 2) and its open-label extension (paradigm(™) 4). In the pivotal trial, adolescents and adults with haemophilia B were allocated to 28-week on-demand treatment or randomized to 52 weeks of prophylaxis with 10 or 40 IU kg(-1) nonacog beta pegol administered every seven days. In the extension trial, patients could continue on the same treatment or switch to the alternate dosing regimen at any time. HRQoL was assessed with the HAEMO-QOL/HAEM-A-QOL age-specific questionnaires and the EQ-5D. In the pivotal trial, adults receiving 40 IU kg(-1) prophylaxis reported significant improvements in the 'HAEM-A-QOL Total' score (-6.4 ± 8.5, P = 0.017) and in 'Sport' (-15.3 ± 8.5, P = 0.020), 'Feeling' (-15.2 ± 18.3, P = 0.010) and 'Partnership' (-9.6 ± 15.5, P = 0.046) domain scores; no significant improvements were seen in the other arms. At the pivotal trial end, fewer patients reported problems in the EQ-5D 'Mobility' and 'Pain/Discomfort' dimensions, in particular those receiving prophylaxis. In the extension trial, adult patients switching from 10 to 40 IU kg(-1) prophylaxis showed significant improvements in 'HAEM-A-QOL Total' score (-12.5 ± 8.7, P = 0.016) and 'Physical health' domain (-23.1 ± 14.4, P = 0.016). Prophylactic treatment with nonacog beta pegol 40 IU kg(-1) once weekly leads to HRQoL benefits in individuals with haemophilia B; this might be related to fewer bleeding episodes and higher FIX activity levels. © 2016 John Wiley & Sons Ltd.

Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial.

PubMed

Boccia, Ralph; Grunberg, Steven; Franco-Gonzales, Edwin; Rubenstein, Edward; Voisin, Daniel

2013-05-01

Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation. In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h). Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation). Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.

Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

2017-01-01

Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

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.

Publication bias in animal research presented at the 2008 Society of Critical Care Medicine Conference.

PubMed

Conradi, Una; Joffe, Ari R

2017-07-07

To determine a direct measure of publication bias by determining subsequent full-paper publication (P) of studies reported in animal research abstracts presented at an international conference (A). We selected 100 random (using a random-number generator) A from the 2008 Society of Critical Care Medicine Conference. Using a data collection form and study manual, we recorded methodology and result variables from A. We searched PubMed and EMBASE to June 2015, and DOAJ and Google Scholar to May 2017 to screen for subsequent P. Methodology and result variables were recorded from P to determine changes in reporting from A. Predictors of P were examined using Fisher's Exact Test. 62% (95% CI 52-71%) of studies described in A were subsequently P after a median 19 [IQR 9-33.3] months from conference presentation. Reporting of studies in A was of low quality: randomized 27% (the method of randomization and allocation concealment not described), blinded 0%, sample-size calculation stated 0%, specifying the primary outcome 26%, numbers given with denominators 6%, and stating number of animals used 47%. Only being an orally presented (vs. poster presented) A (14/16 vs. 48/84, p = 0.025) predicted P. Reporting of studies in P was of poor quality: randomized 39% (the method of randomization and allocation concealment not described), likely blinded 6%, primary outcome specified 5%, sample size calculation stated 0%, numbers given with denominators 34%, and number of animals used stated 56%. Changes in reporting from A to P occurred: from non-randomized to randomized 19%, from non-blinded to blinded 6%, from negative to positive outcomes 8%, from having to not having a stated primary outcome 16%, and from non-statistically to statistically significant findings 37%. Post-hoc, using publication data, P was predicted by having positive outcomes (published 62/62, unpublished 33/38; p = 0.003), or statistically significant results (published 58/62, unpublished 20/38; p < 0.001). Only 62% (95% CI 52-71%) of animal research A are subsequently P; this was predicted by oral presentation of the A, finally having positive outcomes, and finally having statistically significant results. Publication bias is prevalent in critical care animal research.

Contact force sensing for ablation of persistent atrial fibrillation: A randomized, multicenter trial.

PubMed

Conti, Sergio; Weerasooriya, Rukshen; Novak, Paul; Champagne, Jean; Lim, Hong Euy; Macle, Laurent; Khaykin, Yaariv; Pantano, Alfredo; Verma, Atul

2018-02-01

Impact of contact force sensing (CFS) on ablation of persistent atrial fibrillation (PeAF) is unknown. The purpose of the TOUCH AF (Therapeutic Outcomes Using Contact force Handling during Ablation of Persistent Atrial Fibrillation) randomized trial was to compare CFS-guided ablation to a CFS-blinded strategy. Patients (n = 128) undergoing first-time ablation for persistent AF were randomized to a CFS-guided vs CFS-blinded strategy. In the CFS-guided procedure, operators visualized real-time force data. In the blinded procedure, force data were hidden. Wide antral pulmonary vein isolation plus a roof line were performed. Patients were followed at 3, 6, 9, and 12 months with clinical visit, ECG, and 48-hour Holter monitoring. The primary endpoint was cumulative radiofrequency (RF) time for all procedures. Atrial arrhythmia >30 seconds after 3 months was a recurrence. PeAF was continuous for 26 weeks (interquartile range [IQR] 13-52), and left atrial size was 45 ± 5 mm. Force in the CFS-blinded and CFS-guided arms was 12 g [IQR 6-20] and 14 g [IQR 9-20] (P = .10), respectively. Total RF time did not differ between CFS-guided and CFS-blinded groups (49 ± 14 min vs 50 ± 20 min, respectively; P = .70). Single procedure freedom from atrial arrhythmia was 60% in the CFS-guided arm and 63% in the CFS-blinded arm off drugs. Lesions with gaps were associated with significantly less force (11.4 g [IQR 6-19] vs 13.2 g [IQR 8-20], respectively; P = .0007) and less force-time integral (174 gs [IQR 91-330] vs 210 gs [IQR 113-388], respectively; P <.001). CFS-guided ablation resulted in no difference to RF time or 12-month outcome. Lower force/force-time integral was associated with significantly more gaps. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

“Does Organizational Culture Influence the Ethical Behavior in the Pharmaceutical Industry?”

PubMed Central

Nagashekhara, Molugulu; Agil, Syed Omar Syed

2011-01-01

Study of ethical behavior among medical representatives in the profession is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the influence of organizational culture on ethical behavior of medical representatives. Medical representatives working for both domestic and multinational companies constitutes the sample (n=300). Data is collected using a simple random and cluster sampling through a structured questionnaire. The research design is hypothesis testing. It is a cross-sectional and correlational study, conducted under non-contrived settings. Chi-square tests were shows that there is an association between the organizational culture and ethical behavior of medical representatives. In addition, the strength of the association is measured which report to Cramer’s V of 63.1% and Phi Value of 2.749. Results indicate that multinational company medical reps are more ethical compared to domestic company medical representatives vast difference in both variance and in t test results. Through better organizational culture, pharmaceutical companies can create the most desirable behavior among their employees. Authors conclude that apart from organizational culture, the study of additional organizational, individual and external factors are imperative for better understanding of ethical behavior of medical representatives in the pharmaceutical industry in India. PMID:24826027

"Does organizational culture influence the ethical behavior in the pharmaceutical industry?".

PubMed

Nagashekhara, Molugulu; Agil, Syed Omar Syed

2011-12-01

Study of ethical behavior among medical representatives in the profession is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the influence of organizational culture on ethical behavior of medical representatives. Medical representatives working for both domestic and multinational companies constitutes the sample (n=300). Data is collected using a simple random and cluster sampling through a structured questionnaire. The research design is hypothesis testing. It is a cross-sectional and correlational study, conducted under non-contrived settings. Chi-square tests were shows that there is an association between the organizational culture and ethical behavior of medical representatives. In addition, the strength of the association is measured which report to Cramer's V of 63.1% and Phi Value of 2.749. Results indicate that multinational company medical reps are more ethical compared to domestic company medical representatives vast difference in both variance and in t test results. Through better organizational culture, pharmaceutical companies can create the most desirable behavior among their employees. Authors conclude that apart from organizational culture, the study of additional organizational, individual and external factors are imperative for better understanding of ethical behavior of medical representatives in the pharmaceutical industry in India.

The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies.

PubMed

Hadji, Peyman; Asmar, Lina; van Nes, Johanna G H; Menschik, Thomas; Hasenburg, Annette; Kuck, Joachim; Nortier, Johan W R; van de Velde, Cornelis J H; Jones, Stephen E; Ziller, May

2011-06-01

We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen.

Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory.

PubMed

Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen; Haahr, Mette T; Altman, Douglas G; Gøtzsche, Peter C

2009-09-01

To compare the reporting on blinding in protocols and articles describing randomized controlled trials. We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.

Optical image encryption by random shifting in fractional Fourier domains

NASA Astrophysics Data System (ADS)

Hennelly, B.; Sheridan, J. T.

2003-02-01

A number of methods have recently been proposed in the literature for the encryption of two-dimensional information by use of optical systems based on the fractional Fourier transform. Typically, these methods require random phase screen keys for decrypting the data, which must be stored at the receiver and must be carefully aligned with the received encrypted data. A new technique based on a random shifting, or jigsaw, algorithm is proposed. This method does not require the use of phase keys. The image is encrypted by juxtaposition of sections of the image in fractional Fourier domains. The new method has been compared with existing methods and shows comparable or superior robustness to blind decryption. Optical implementation is discussed, and the sensitivity of the various encryption keys to blind decryption is examined.

MTOR-driven quasi-programmed aging as a disposable soma theory: blind watchmaker vs. intelligent designer.

PubMed

Blagosklonny, Mikhail V

2013-06-15

If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. "Quasi-programmed" by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it.

The case for a multinational Mars Surveyor Program

NASA Astrophysics Data System (ADS)

Rea, D. G.; Carr, M. H.; Craig, M. K.

1989-10-01

A coordinated multinational Mars Surveyor Program involving a series of robotic missions is proposed in order to select worthwhile human landing sites for discoveries, for safe operations, and for testing and proving technologies for making human flight to Mars possible. Some characteristics motivating exploration of the planet are briefly discussed, including the possibility of life, geological features, and meteorological conditions. The necessity for preliminary exploration of Mars by robots prior to human exploration is discussed, and the rationale behind a multinational approach for a Mars Surveyor Program is presented.

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder.

PubMed

Colonna, Lucien; Andersen, Henning Friis; Reines, Elin Heldbo

2005-10-01

A randomized, double-blind, 24-week-fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was safety was conducted in primary care patients with moderate to severe major depressive disorder (MDD). This was a randomized, double-blind, 24-week fixeddose study. Patients were randomly assigned to treatment with escitalopram 10 mg/day (n = 175) or citalopram 20 mg/day (n = 182). Clinical response was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity (CGI-S) scale. The prospectively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment, using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously. Based on the primary parameter, escitalopram was at least as efficacious as citalopram. Based on the prospectively defined secondary parameter, mean change from baseline in the CGI-S score, escitalopram was statistically significantly superior to citalopram at Week 24. The importance of long-term treatment could be demonstrated, in that more than half (55% and 51%) of the patients who had not responded by Week 8 achieved remission by Week 24. Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment, and the overall adverse event profiles for the two drugs were similar. For the intent-to-treat population, there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group, particularly after Week 8. Patients with MDD responded well to long-term treatment with either escitalopram or citalopram. This study demonstrated the importance of extending treatment of depression beyond 8 weeks.

Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.

PubMed

Mulligan, Kathleen; Zackin, Robert; Clark, Rebecca A; Alston-Smith, Beverly; Liu, Tun; Sattler, Fred R; Delvers, Thomas B; Currier, Judith S

2005-03-14

Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.

Risk factors of severity of abuse against older women in the home setting: A multinational European study.

PubMed

Donder, Liesbeth De; Lang, Gert; Ferreira-Alves, José; Penhale, Bridget; Tamutiene, Ilona; Luoma, Minna-Liisa

2016-01-01

This article examines the ecological risk factors of abuse against older women. Data from 2,880 older women were randomly collected in five European countries (Austria, Belgium, Finland, Lithuania, and Portugal) using a standardized questionnaire. Results indicate that overall 30.1 % older women had at least one experience of abuse in the past year. The findings demonstrate that a single emphasis on personal risk factors (e.g., health, coping) is important but too simple: Abuse is multifaceted and is embedded in environmental (e.g., loneliness, household income) as well as macrocultural contexts (e.g., old age dependency ratio).

Leadership styles of nurse managers in a multinational environment.

PubMed

Suliman, Wafika A

2009-01-01

This is a descriptive study conducted at a multinational working environment, where 1500 nurses representing 52 nationalities are employed. The study aimed at exploring the predominant leadership style of nurse managers through self-evaluation and staff nurses' evaluation and the impact of working in a multinational environment on their intention to stay or quit. The value lies in its focus on leadership styles in an environment where national diversity among managers, staff, and patients is very challenging. The study included 31 nurse managers and 118 staff nurses using Bass and Avolio's (1995) Multifactor Leadership Questionnaire. The results showed that nurse managers and staff nurses reported transformational leadership as predominant with significant difference in favor of nurse managers. Participants' nationality and intention to stay or quit affected their perception of transformational leadership as a predominant style. The implications highlight the need for senior nursing management to set effective retention strategies for transformational nurse managers who work at multinational environments.

Multinationals' Political Activities on Climate Change

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

Kolk, A.; Pinkse, J.

2007-06-15

This article explores the international dimensions of multinationals' corporate political activities, focusing on an international issue - climate change - being implemented differently in a range of countries. Analyzing data from Financial Times Global 500 firms, it examines the influence on types and process of multinationals' political strategies, reckoning with institutional contexts and issue saliency. Findings show that the type of political activities can be characterized as an information strategy to influence policy makers toward market-based solutions, not so much withholding action on emission reduction. Moreover, multinationals pursue self-regulation, targeting a broad range of political actors. The process of politicalmore » strategy is mostly one of collective action. International differences particularly surface in the type of political actors aimed at, with U.S. and Australian firms focusing more on non-government actors (voluntary programs) than European and Japanese firms. Influencing home-country (not host-country) governments is the main component of international political strategy on climate change.« less

Blind Students' Learning of Probability through the Use of a Tactile Model

ERIC Educational Resources Information Center

Vita, Aida Carvalho; Kataoka, Verônica Yumi

2014-01-01

The objective of this paper is to discuss how blind students learn basic concepts of probability using the tactile model proposed by Vita (2012). Among the activities were part of the teaching sequence "Jefferson's Random Walk", in which students built a tree diagram (using plastic trays, foam cards, and toys), and pictograms in 3D…

Effects of Weighted Vests on Classroom Behavior for Children with Autism and Cognitive Impairments

ERIC Educational Resources Information Center

Hodgetts, Sandra; Magill-Evans, Joyce; Misiaszek, John

2011-01-01

This randomized controlled single-case study investigated the effects of weighted vests for 10 children with autism in a classroom setting. Blinded observers rated targeted behaviors through video taken during structured table-top activities typically part of the classroom routine. Blinded teachers rated each child's behavior with the Conners'…

Business Communication Consulting and Research in Multinational Companies.

ERIC Educational Resources Information Center

Hildebrandt, Herbert W.

1978-01-01

Describes three issues involved in communication research and consulting for multinational companies, particularly those in Germany: qualifications for doing international consulting and research, problems of American scholar-researchers in those firms, and suggestions for dealing with those issues. (JMF)

Culture and International Management: A Review.

ERIC Educational Resources Information Center

Miroshnik, Victoria

2002-01-01

A literature review explored the effectiveness of cross-cultural managements of multinational companies. The effect of national culture on organizational culture was analyzed and ways in which multinational companies can adopt the national differences were suggested. (Contains 42 references.) (JOW)

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

PubMed

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

NASA Astrophysics Data System (ADS)

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

The administration to Indonesians of monosodium L-glutamate in Indonesian foods: an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study.

PubMed

Prawirohardjono, W; Dwiprahasto, I; Astuti, I; Hadiwandowo, S; Kristin, E; Muhammad, M; Kelly, M F

2000-04-01

Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

A randomized double-blind trial of two low dose combined oral contraceptives.

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

A Prospective, Randomized, Double-Blind Comparison of 2% Mepivacaine With 1 : 20,000 Levonordefrin Versus 2% Lidocaine With 1 : 100,000 Epinephrine for Maxillary Infiltrations

PubMed Central

Lawaty, Ingrid; Drum, Melissa; Reader, Al; Nusstein, John

2010-01-01

The purpose of this prospective, randomized, double-blind crossover study was to compare the anesthetic efficacy of 2% mepivacaine with 1 : 20,000 levonordefrin versus 2% lidocaine with 1 : 100,000 epinephrine in maxillary central incisors and first molars. Sixty subjects randomly received, in a double-blind manner, maxillary central incisor and first molar infiltrations of 1.8 mL of 2% mepivacaine with 1 : 20,000 levonordefrin and 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine at 2 separate appointments spaced at least 1 week apart. The teeth were electric pulp tested in 2-minute cycles for a total of 60 minutes. Anesthetic success (obtaining 2 consecutive 80 readings with the electric pulp tester within 10 minutes) was not significantly different between 2% mepivacaine with 1 : 20,000 levonordefrin and 2% lidocaine with 1 : 100,000 epinephrine for the central incisor and first molar. However, neither anesthetic agent provided an hour of pulpal anesthesia. PMID:21174567

Oxandrolone augmentation of resistance training in older women: a randomized trial

USDA-ARS?s Scientific Manuscript database

INTRODUCTION: Sarcopenia is disproportionately present in older women with disability, and optimum treatment is not clear. We conducted a double-blind, randomized, placebo-controlled trial to determine whether oxandrolone administration in elderly women improves body composition or physical function...

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis

PubMed Central

Rosenbaum, J. T.; Landewé, R.; Marzo‐Ortega, H.; Sieper, J.; van der Heijde, D.; Davies, O.; Bartz, H.; Hoepken, B.; Nurminen, T.; Deodhar, A.

2016-01-01

Objective Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID‐axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. Methods The RAPID‐axSpA (NCT01087762) trial is double‐blind and placebo‐controlled to week 24, dose‐blind to week 48, and open‐label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose‐blind phase were re‐randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient‐years. Results At baseline, 38 of 218 CZP‐randomized patients (17.4%) and 31 of 107 placebo‐randomized patients (29.0%) had past uveitis history. During the 24‐week double‐blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6–8.8] per 100 patient‐years) than in placebo (10.3 [95% CI 2.8–26.3] per 100 patient‐years). All cases observed during the 24‐week double‐blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5–50.1] per 100 patient‐years) than placebo (38.5 [95% CI 10.5–98.5] per 100 patient‐years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2–7.4] per 100 patient‐years) and were similar between AS (4.4 [95% CI 2.3–7.7] per 100 patient‐years) and nr‐axial SpA (5.6 [95% CI 2.9–9.8] per 100 patient‐years). Conclusion The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti–tumor necrosis factor antibodies. PMID:26815944

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis.

PubMed

Rudwaleit, M; Rosenbaum, J T; Landewé, R; Marzo-Ortega, H; Sieper, J; van der Heijde, D; Davies, O; Bartz, H; Hoepken, B; Nurminen, T; Deodhar, A

2016-06-01

Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years). The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies. © 2016, American College of Rheumatology.

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Gathier, C S; van den Bergh, W M; Slooter, A J C

2014-04-01

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Five Themes Impacting Collaboration in a Joint Interagency Multinational Public Operational Context (Les cinq Facteurs Influencant la Collaboration en Contexte Operationnel Interarmees, Interorganisationnel, Multinational et Public)

DTIC Science & Technology

2011-03-01

cited by the Director of Land Concepts and Designs as an important enabler for the Army of Tomorrow operating concept of adaptive dispersed operations...2010). La partie 1.3 porte sur l’influence du pouvoir sur la collaboration. Étant donné l’ampleur des FC comparativement à celle de la plupart des...Multinational Public (JIMP) operating environment, the capacity to be "JIMP-capable" is now cited by the Director of Land Concepts and Designs as an important

CRM System Implementation in a Multinational Enterprise

NASA Astrophysics Data System (ADS)

Mishra, Alok; Mishra, Deepti

The concept of customer relationship management (CRM) resonates with managers in today's competitive economy. As more and more organizations realize the significance of becoming customer-centric in today's competitive era, they embrace CRM as a core business strategy. CRM an integration of information technology and relationship marketing provides the infrastructure that facilitates long-term relationship building with customers at an enterprise-wide level. Successful CRM implementation is a complex, expensive and rarely technical projects. This paper presents the successful implementation of CRM in a multinational organization. This study will facilitate in understanding transition, constraints and implementation of CRM in multinational enterprises.

Economic Evaluation alongside Multinational Studies: A Systematic Review of Empirical Studies

PubMed Central

Oppong, Raymond; Jowett, Sue; Roberts, Tracy E.

2015-01-01

Purpose of the study This study seeks to explore methods for conducting economic evaluations alongside multinational trials by conducting a systematic review of the methods used in practice and the challenges that are typically faced by the researchers who conducted the economic evaluations. Methods A review was conducted for the period 2002 to 2012, with potentially relevant articles identified by searching the Medline, Embase and NHS EED databases. Studies were included if they were full economic evaluations conducted alongside a multinational trial. Results A total of 44 studies out of a possible 2667 met the inclusion criteria. Methods used for the analyses varied between studies, indicating a lack of consensus on how economic evaluation alongside multinational studies should be carried out. The most common challenge appeared to be related to addressing differences between countries, which potentially hinders the generalisability and transferability of results. Other challenges reported included inadequate sample sizes and choosing cost-effectiveness thresholds. Conclusions It is recommended that additional guidelines be developed to aid researchers in this area and that these be based on an understanding of the challenges associated with multinational trials and the strengths and limitations of alternative approaches. Guidelines should focus on ensuring that results will aid decision makers in their individual countries. PMID:26121465

Prevalence and Causes of Visual Impairment and Blindness among Cocoa Farmers in Ghana.

PubMed

Boadi-Kusi, Samuel Bert; Hansraj, Rekha; Mashige, Khathutshelo Percy; Osafo-Kwaako, Alfred; Ilechie, Alex Azuka; Abokyi, Samuel

2017-02-01

To determine the prevalence and causes of visual impairment and blindness among cocoa farmers in Ghana in order to formulate early intervention strategies. A cross-sectional study using multistage random sampling from four cocoa growing districts in Ghana was conducted from November 2013 to April 2014. A total of 512 cocoa farmers aged 40 years and older were interviewed and examined. The brief interview questionnaire was administered to elicit information on the demographics and socioeconomic details of participants. The examination included assessment of visual acuity (VA), retinoscopy, subjective refraction, direct ophthalmoscopy, slit-lamp biomicroscopy and intraocular pressure (IOP). For quality assurance, a random sample of cocoa farmers were selected and re-examined independently. Moderate to severe visual impairment (VA <6/18 to 3/60 in the better-seeing eye) was present in 89 participants (17.4%) and 27 (5.3%) were blind (presenting VA <3/60 in the better eye) defined using presenting VA. The main causes of visual impairment were cataract (45, 38.8%), uncorrected refractive error (42, 36.2%), posterior segment disorders (15, 12.9%), and corneal opacity (11, 9.5%). The prevalence of visual impairment and blindness among cocoa farmers in Ghana is relatively high. The major causes of visual impairment and blindness are largely preventable or treatable, indicating the need for early eye care service interventions.

Blind or ultrasound-guided corticosteroid injections and short-term response in subacromial impingement syndrome: a randomized, double-blind, prospective study.

PubMed

Dogu, Beril; Yucel, Serap Dalgic; Sag, Sinem Yamac; Bankaoglu, Mujdat; Kuran, Banu

2012-08-01

The aim of this study was to compare the accuracy of blind vs. ultrasonography-guided corticosteroid injections in subacromial impingement syndrome and determine the correlation between accuracy of the injection location and clinical outcome. Forty-six patients with subacromial impingement syndrome were randomized for ultrasonography-guided (group 1, n = 23) and blind corticosteroid injections (group 2, n = 23). Magnetic resonance imaging analysis was performed immediately after the injection. Changes in shoulder range of motion, pain, and shoulder function were recorded. All patients were assessed before the injection and 6 wks after the injection. Accurate injections were performed in 15 (65%) group 1 patients and in 16 (70%) group 2 patients. There was no statistically significant difference in the injection location accuracy between the two groups (P > 0.05). At the end of the sixth week, regardless of whether the injected mixture was found in the subacromial region or not, all of the patients showed improvements in all of the parameters evaluated (P < 0.05). Blind injections performed in the subacromial region by experienced individuals were reliably accurate and could therefore be given in daily routines. Corticosteroid injections in the subacromial region were very effective in improving the pain and functional status of patients with subacromial impingement syndrome during the short-term follow-up.

Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

ERIC Educational Resources Information Center

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. Method: 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…

Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

2007-01-01

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

Utility and Cost-Effectiveness of Motivational Messaging to Increase Survey Response in Physicians: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Chan, Randolph C. H.; Mak, Winnie W. S.; Pang, Ingrid H. Y.; Wong, Samuel Y. S.; Tang, Wai Kwong; Lau, Joseph T. F.; Woo, Jean; Lee, Diana T. F.; Cheung, Fanny M.

2018-01-01

The present study examined whether, when, and how motivational messaging can boost the response rate of postal surveys for physicians based on Higgin's regulatory focus theory, accounting for its cost-effectiveness. A three-arm, blinded, randomized controlled design was used. A total of 3,270 doctors were randomly selected from the registration…

Multinational Quality Assurance

ERIC Educational Resources Information Center

Kinser, Kevin

2011-01-01

Multinational colleges and universities pose numerous challenges to the traditional models of quality assurance that are designed to validate domestic higher education. When institutions cross international borders, at least two quality assurance protocols are involved. To guard against fraud and abuse, quality assurance in the host country is…

Communication Effectiveness in Multinational Organizations: Developing Universal Intercultural Skills.

ERIC Educational Resources Information Center

Baird, John W.; Stull, James B.

The increase in size and number of multinational corporations requires programs for training their personnel in intercultural communication emphasizing development of skills necessary for cultural adaptation and a "universal" perspective. Currently, intercultural training is either nonexistent or emphasizes mastery of language with…

Multinational Activities of Major U.S. Automotive Producers : Volume 2. Data on Foreign Facilities and Operations.

DOT National Transportation Integrated Search

1978-09-01

The objective of Volume II is to present data gathered from several sources, public and private, on three aspects of multinational involvement for General Motors Corporation, Ford Motor Company, Chrysler Corporation, and American Motors Corporation. ...

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies.

PubMed

Sorensen, Jens Benn; Skovsgaard, Torben; Bork, Ellen; Damstrup, Lars; Ingeberg, Sten

2008-04-01

The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. Patients with previously untreated GI cancer receiving bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC-grading) and duration of OM. Among 225 patients randomized, 206 answered the questionnaire (70, 64, and 63 patients in Arms A, B, and C, respectively) and were well balanced with respect to diagnoses, stage, age, sex, smoking habits, and performance status. Mucositis grade 3-4 occurred more frequently in Arm B (33%) than in A (13%, P< .01) and C (11%, P< .005). Duration was significantly longer in B than in both A (P= .035) and C (P= .003). The frequency and duration of OM are significantly improved by prophylactic chlorhexidine and by cryotherapy. The latter is easy and inexpensive but has limited use, as it is drug- and schedule-dependent. The current study is the first double-blind randomized evaluation of prophylactic chlorhexidine in a large adult patient population with solid tumors receiving highly OM-inducing chemotherapy. A role for chlorhexidine in the prevention of OM is suggested, which should be evaluated further.

Comparison of Arthroscopically Guided Suprascapular Nerve Block and Blinded Axillary Nerve Block vs. Blinded Suprascapular Nerve Block in Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

PubMed

Ko, Sang Hun; Cho, Sung Do; Lee, Chae Chil; Choi, Jang Kyu; Kim, Han Wook; Park, Seon Jae; Bae, Mun Hee; Cha, Jae Ryong

2017-09-01

The purpose of this study was to compare the results of arthroscopically guided suprascapular nerve block (SSNB) and blinded axillary nerve block with those of blinded SSNB in terms of postoperative pain and satisfaction within the first 48 hours after arthroscopic rotator cuff repair. Forty patients who underwent arthroscopic rotator cuff repair for medium-sized full thickness rotator cuff tears were included in this study. Among them, 20 patients were randomly assigned to group 1 and preemptively underwent blinded SSNB and axillary nerve block of 10 mL 0.25% ropivacaine and received arthroscopically guided SSNB with 10 mL of 0.25% ropivacaine. The other 20 patients were assigned to group 2 and received blinded SSNB with 10 mL of 0.25% ropivacaine. Visual analog scale (VAS) score for pain and patient satisfaction score were assessed 4, 8, 12, 24, 36, and 48 hours postoperatively. The mean VAS score for pain was significantly lower 4, 8, 12, 24, 36, and 48 hours postoperatively in group 1 (group 1 vs. group 2; 5.2 vs. 7.4, 4.1 vs. 6.1, 3.0 vs. 5.1, 2.1 vs. 4.2, 0.9 vs. 3.9, and 1.3 vs. 3.3, respectively). The mean patient satisfaction score was significantly higher at postoperative 4, 8, 12, 24, 36, and 48 hours in group 1 (group 1 vs. group 2; 6.7 vs. 3.9, 7.4 vs. 5.1, 8.8 vs. 5.9, 9.2 vs. 6.7, 9.5 vs. 6.9, and 9.0 vs. 7.2, respectively). Arthroscopically guided SSNB and blinded axillary nerve block in arthroscopic rotator cuff repair for medium-sized rotator cuff tears provided more improvement in VAS for pain and greater patient satisfaction in the first 48 postoperative hours than blinded SSNB.

A true blind for subjects who receive spinal manipulation therapy.

PubMed

Kawchuk, Gregory N; Haugen, Rick; Fritz, Julie

2009-02-01

To determine if short-duration anesthesia (propofol and remifentanil) can blind subjects to the provision or withholding of spinal manipulative therapy (SMT). Placebo control. Day-procedure ward, University of Alberta Hospital. Human subjects with uncomplicated low back pain (LBP) (n=6). In each subject, propofol and remifentanil were administered intravenously. Once unconsciousness was achieved (3-5min), subjects were placed in a lateral recumbent position and then randomized to either a control group (n=3) or an experimental group (with SMT, n=3); subjects received a single SMT to the lumbar spine. Subjects were given a standardized auditory and visual cue and then allowed to recover from anesthesia in a supine position (3-5min). Before anesthesia and 30 minutes after recovery, a blinded evaluator asked each subject to quantify their LBP by using an 11-point scale. This same evaluator then assessed the ability of each subject to recall specific memories while under presumed anesthesia including events related to treatment and specific auditory and visual cues. In either the experimental or control group, subjects could not recall any event while under anesthesia. Some SMT subjects reported pain reduction greater than the minimally important clinical difference and greater than control subjects. No adverse events were reported. Short-duration, low-risk general anesthesia can create effective blinding of subjects to the provision or withholding of SMT. An anesthetic blind for SMT subjects solves many, if not all, problems associated with prior SMT blinding strategies. Although further studies are needed to refine this technique, the potential now exists to conduct the first placebo-controlled randomized controlled trial to assess SMT efficacy.

Prevalence of visual impairment and blindness in Upper Egypt: a gender-based perspective.

PubMed

Mousa, Ahmed; Courtright, Paul; Kazanjian, Arminee; Bassett, Ken

2014-06-01

To estimate the prevalence, causes of and risk factors for vision loss in Upper Egypt. In this cross-sectional study, four villages in Upper Egypt were randomly selected; within these four villages, households were randomly selected and within the selected households all residents aged ≥ 40 years were enumerated and enrolled. Door-to-door eye examinations of household members were conducted. Data on relevant demographic and socioeconomic characteristics were collected. The prevalence and causes of vision loss and associated risk factors were assessed. Sex differences in prevalence and determinants were also evaluated. The prevalence of best eye presenting visual impairment, severe visual impairment, and blindness were 23.9%, 6.4%, and 9.3% respectively. The prevalence of blindness among women significantly exceeded that among men (11.8% vs. 5.4%, respectively, p = 0.021). The prevalence of cataract was 22.9% (higher in women, 26.5% than men 17.2%, p = 0.018). The prevalence of trachomatous trichiasis was 9.7% (higher among women, 12.5%, than men, 5.4%, p = 0.012). The principal causes of blindness were cataract (60%), uncorrected refractive errors (16%) and corneal opacities (12%). Age, sex, family size, illiteracy, unemployment, water source and sanitation methods and living conditions were the major risk factors for vision loss. The prevalence of visual impairment remains high in Egypt, particularly among women. Risk factors for blindness may differ between men and women. There is a need for qualitative investigations to better understand the causes behind the excess in prevalence of blindness among women.

Rapid assessment of avoidable blindness and diabetic retinopathy in Republic of Moldova.

PubMed

Zatic, Tatiana; Bendelic, Eugen; Paduca, Ala; Rabiu, Mansour; Corduneanu, Angela; Garaba, Angela; Novac, Victoria; Curca, Cristina; Sorbala, Inga; Chiaburu, Andrei; Verega, Florentina; Andronic, Victoria; Guzun, Irina; Căpăţină, Olga; Zamă-Mardari, Iulea

2015-06-01

To evaluate the prevalence and causes of blindness and visual impairment, the prevalence of diabetes mellitus and diabetic retinopathy among people aged ≥50 years in the Republic of Moldova using Rapid Assessment of Avoidable Blindness plus Diabetic Retinopathy ('RAAB+DR') techniques. 111 communities of people aged ≥50 years were randomly selected. In addition to standard RAAB procedures in all people with diabetes (previous history of the disease or with a random blood glucose level >11.1 mm/L (200 mg/dL)), a dilated fundus examination was performed to assess the presence and the degree of diabetic retinopathy using the Scottish DR grading system. 3877 (98%) people out of the 3885 eligible people were examined. The prevalence of blindness was 1.4% (95% CI 1.0% to 1.8%). The major causes of blindness and severe visual impairment were untreated cataract (58.2%), glaucoma (10.9%), and other posterior segment causes (10.9%). The estimated prevalence of diabetes was 11.4%. Among all people with diabetes, 55.9% had some form of retinopathy, and sight threatening diabetic retinopathy affected 14.6%. The RAAB+DR survey in the Republic of Moldova established that untreated cataract is the major cause of avoidable blindness in rural areas. This needs to be tackled by expanding the geographical coverage of cataract surgical services. 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.

Assessment of Visual Status of the Aeta, a Hunter-Gatherer Population of the Philippines (An AOS Thesis)

PubMed Central

Allingham, R. Rand

2008-01-01

Purpose A screening study was performed to assess levels of visual impairment and blindness among a representative sample of older members of the Aeta, an indigenous hunter-gatherer population living on the island of Luzon in the Philippines. Methods Unrelated older Aeta couples were randomly invited to participate in a visual screening study. All consented individuals had ocular history, medical history, complete ophthalmic examination, height, weight, and blood pressure taken. Results A total of 225 individuals were screened from 4 villages. Visual acuity, both uncorrected and pinhole corrected, was significantly worse among older vs younger age-groups for women, men, and when combined (P < .001). Visual impairment was present in 48% of uncorrected and 43% of pinhole corrected eyes in the oldest age-group. Six percent of the screened population was bilaterally blind. The major causes of blindness were readily treatable. The most common etiologies as a proportion of blind eyes were cataract (66%), refractive error (20%), and trauma (7%). No cases of primary open-angle, primary angle-closure, or exfoliation glaucoma were observed in this population. Discussion Visual impairment and blindness were common in the Aeta population. Primary forms of glaucoma, a major cause of blindness found in most population-based studies, were not observed. The absence of primary glaucoma in this population may reflect random sampling error. However, based on similar findings in the Australian Aborigine, this raises the possibility that these two similar populations may share genetic and/or environmental factors that are protective for glaucoma.. PMID:19277240

Small Nations in Multinational Operations and Armenian Perspectives

DTIC Science & Technology

2014-12-12

National Security Powers: Are the Checks in Balance?” In U.S. Army War College Guide to National Security Issues, Volume II: National Security Policy and...SMALL NATIONS IN MULTINATIONAL OPERATIONS AND ARMENIAN PERSPECTIVES A thesis presented to the Faculty of the U.S. Army

Multinationals, state-owned corporations, and the transformation of imperialism: a Brazilian case study

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

Evans, P.

1977-10-01

The Brazilian petrochemical industry is used as a case study in cooperation of state-owned and multinational corporations in bringing capitalism into the Third World. The petrochemical industry was chosen because it entails enormous transfers of capital investment and technology and the development of internal industrialization. Active participation by the host state, while it modifies the capitalization process, also is seen to provide a mutually beneficial partnership. A chronological account is given of the process by which Brazil evolved a system for encouraging multinationals to bring basic industries while participating directly in production. Multinationals have found that state-owned corporations do notmore » destroy capitalism, while the state-owned corporations have adapted to a profit orientation. A new ruling class has emerged in the process to provide technical and managerial skills. A disappointing social record developed at the same time and indicates the capitalization process was not able to provide the expected social benefits. (DCK)« less

Breast-feeding: the role of multinational corporations in Latin America.

PubMed

Bader, M B

1976-01-01

The decline in birthrates in the developed countries of the world has forced multinational corporations engaged in the production of infant formula to seek out new markets in the developing countries, where burgeoning population rates potentially guarantee the long-term profitability of these corporations. This development, ostensibly benign and nutritionally advantageous to infants in developing countries, has serious public health consequences, due to the high relative cost of purchased formula and the paucity of hygienic facilities essential to the sterile preparation of bottle formula. This paper delineates in detail economic and contraceptive advantages of breast-feeding, and examines the role of health personnel and multinational advertising techniques which have catalyzed the decline in breast-feeding. In addition, the paper focuses on the question of cultural imperialism and current efforts to regulate the multinational firms through both United Nations groups and stock-holders' suits. Finally, some suggestions are made concerning ameliorative public policy approaches to the breast-feeding controversy.

Corneal wound healing after superficial foreign body injury: vitamin A and dexpanthenol versus a calf blood extract. A randomized double-blind study.

PubMed

Egger, S F; Huber-Spitzy, V; Alzner, E; Scholda, C; Vecsei, V P

1999-01-01

A prospective randomized double-blind clinical study was performed to investigate corneal wound healing after treatment either with an eye gel containing calf blood extract or an eye ointment containing vitamin A and dexpanthenol. A total of 54 outpatients were included in this study, all treated for corneal foreign body injury. The size of the corneal lesions was measured by planimetry on days 0, 1, and on the following days until complete epithelial healing occurred. Results showed the calf blood extract eye gel to be statistically more effective in promoting corneal wound healing, especially in patients with wound areas larger than 6 mm(2).

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial.

PubMed

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-04-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information.

Using Internet Resources in Teaching Financial Reporting and Analysis of Multinational Enterprises.

ERIC Educational Resources Information Center

Agami, Abdel M.

2003-01-01

Provides some sources of corporate financial information on the Internet and illustrates how to use these resources in teaching international business and, more specifically, financial reporting and analysis of multinational enterprises. Points out some of the advantages and limitations of these resources. (EV)

Current Status of Diversity Initiatives in Selected Multinational Corporations.

ERIC Educational Resources Information Center

Wentling, Rose Mary; Palma-Rivas, Nilda

2000-01-01

Interviews with eight diversity managers in multinational corporations revealed a variety of domestic and international diversity initiatives, especially in leadership and management. Formal and informal methods were used to plan them. Business unit managers were responsible for implementation. Evaluation was difficult and time consuming. (SK)

Intercultural Communication Problems in Japanese Multinationals.

ERIC Educational Resources Information Center

Nishiyama, Kazuo

Many large Japanese-owned multinational corporations have established successful subsidiaries in the United States, but distinct ethnic and cultural differences have caused communication problems between Japanese managers and American laborers and business people. Many top executives of the Japanese subsidiaries are sent to the United States on a…

Koinonia: The Requirements and Vision for an Unclassified Information-Sharing System

DTIC Science & Technology

2013-06-01

of an effort to share information with multinational partners in Multinational Planning Augmentation Team (MPAT) ( Tempest Express Fact Sheet 2011... Tempest fact sheet. Global Security.org. May 7, 2011. Accessed May 3, 2013. http://www.globalsecurity.org/military/ops/ tempest -express.htm U.S

The Gluten-Free, Casein-Free Diet in Autism: Results of a Preliminary Double Blind Clinical Trial

ERIC Educational Resources Information Center

Elder, Jennifer Harrison; Shankar, Meena; Shuster, Jonathan; Theriaque, Douglas; Burns, Sylvia; Sherrill, Lindsay

2006-01-01

This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12…

A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

ERIC Educational Resources Information Center

Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

2011-01-01

Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

Adjunctive use of a facial moisturizer SPF 30 containing ceramide precursor improves tolerability of topical tretinoin 0.05%: a randomized, investigator-blinded, split-face study.

PubMed

Schorr, Ethlynn S; Sidou, Farzi; Kerrouche, Nabil

2012-09-01

To assess the benefit of adjunctive use of a SPF 30 moisturizing lotion in reducing local side effects associated with atopical tretinoin cream. This was a randomized, investigator/evaluator-blinded, split-face comparison in subjects with healthy skin. Subjects applied tretinoin cream 0.05% once daily to the whole face and Cetaphil 174; Dermacontrol Moisturizer (CDM) once daily to one side of the face based on randomization. Tolerability, perference and skin hydration were evaluated at each week, and a cosmetic acceptability questionnaire regarding CDM was completed at the end of the study. The majority (about 83% to 86%) of subjects experienced skin irritations on both sides of their face, though predominantly mild for the CDM + tretinoin treated side. Tolerability preferences favored the CDM+tretinoin sides. Adjunctive use of CDM with a topical tretinoin cream improves tolerance of the treatment.

Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

ERIC Educational Resources Information Center

Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

2009-01-01

A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

Computerized Training of Working Memory in Children with ADHD-A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Klingberg, Torkel; Fernell, Elisabeth; Olesen, Pernille J.; Johnson, Mats; Gustafsson, Per; Dahlstrom, Kerstin; Gillberg, Christopher G.; Forssberg, Hans; Westerberg, Helena

2005-01-01

Objective: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic…

Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI 5b. GRANT...forthcoming, The current study addresses this need through a double blind, placebo- controlled , randomized clinical trial (RCT) of a group

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 double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

PubMed

Whitley, Julie Anne; Rich, Bonnie L

2008-12-01

To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Patients' perspectives in the management of psoriasis: the Italian results of the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey.

PubMed

Gisondi, Paolo; Girolomoni, Giampiero

2017-08-01

The perspective of patients with psoriasis about medical care treatment goals and strategies is receiving increasing attention. Here, we performed a country-based analysis of the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, in order to provide specific information on patients' perspective of treatment of psoriasis in Italy. This was a systematic household telephone survey recruiting subjects by random digit dialing. Household members ≥18 years were included if they had ever been diagnosed with psoriasis. About 12,785 households were screened in Italy. 132 patients were ineligible for the analysis, including patients with psoriatic arthritis. 359 patients were surveyed. About half of the patients had very mild disease with less than 1 palm skin involvement, and 38% had 1-10 palm skin disease. It is noteworthy that 48% of patients with widespread disease were not taking any medication. Patients indicated the relief of symptoms, including itching (54.9%), as the main goal for their current therapy, whereas 14.2% reported no specific expectation from their medication. Overall, 70% of patients declared to be satisfied by their therapy, in terms of primary goal reached. Our findings suggest that most psoriasis patients have mild/moderate disease in Italy, and that a portion of patients with severe disease does not receive an adequate treatment.

Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study.

PubMed

van Nes, J G H; Fontein, D B Y; Hille, E T M; Voskuil, D W; van Leeuwen, F E; de Haes, J C J M; Putter, H; Seynaeve, C; Nortier, J W R; van de Velde, C J H

2012-07-01

Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch postmenopausal early breast cancer patients were randomized between 5 years of exemestane, or tamoxifen (2.5-3 years) followed by exemestane (2.5-2 years). 742 patients were invited to participate in the QoL side study and complete questionnaires at 1 (T1) and 2 (T2) years after start of endocrine treatment. Questionnaires comprised the EORTC QLQ-C30 and BR23 questionnaires, supplemented with FACT-ES questions. 543 patients completed questionnaires at T1 and 454 patients (84%) at T2. Overall QoL and most functioning scales improved over time. The only clinically relevant and statistically significant difference between treatment types concerned insomnia; exemestane-treated patients reported more insomnia than tamoxifen-treated patients. Discrepancy was observed between QoL issue scores reported by the patients and adverse events reported by physicians. Certain QoL issues are treatment- and/or time-specific and deserve attention by health care providers. There is a need for careful inquiry into QoL issues by those prescribing endocrine treatment to optimize QoL and treatment adherence.

Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.

PubMed

Mohammadi, Mohammad-Reza; Kazemi, Mohammad-Reza; Zia, Ebtehal; Rezazadeh, Shams-Ali; Tabrizi, Mina; Akhondzadeh, Shahin

2010-11-01

The aim of the present study was to further evaluate, under double blind and controlled conditions, the efficacy of amantadine for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents as compared to methylphenidate. This was a 6-week randomized clinical trial. Forty patients (28 boys and 12 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive the treatment using capsule of amantadine at a dose of 100-150 mg/day depending on weight (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate at a dose of 20-30 mg/day for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.02; p = 0.86 and df = 1; F = 0.01; p = 0.89, respectively). Side effects of decreased appetite and restlessness were observed more frequently in the methylphenidate group. The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD. Nevertheless, the present results do not constitute proof of efficacy. Copyright © 2010 John Wiley & Sons, Ltd.

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.

Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Blay, Jean-Yves; Pápai, Zsuzsanna; Tolcher, Anthony W; Italiano, Antoine; Cupissol, Didier; López-Pousa, Antonio; Chawla, Sant P; Bompas, Emmanuelle; Babovic, Nada; Penel, Nicolas; Isambert, Nicolas; Staddon, Arthur P; Saâda-Bouzid, Esma; Santoro, Armando; Franke, Fabio A; Cohen, Patrick; Le-Guennec, Solenn; Demetri, George D

2015-05-01

Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9-33·2) in the placebo group and 30·5 months (20·7-37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45-2·69] vs 1·41 [1·38-1·58] months; hazard ratio 0·76 [95% CI 0·59-0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study.

PubMed

Conaghan, Philip G; Hunter, David J; Cohen, Stanley B; Kraus, Virginia B; Berenbaum, Francis; Lieberman, Jay R; Jones, Deryk G; Spitzer, Andrew I; Jevsevar, David S; Katz, Nathaniel P; Burgess, Diane J; Lufkin, Joelle; Johnson, James R; Bodick, Neil

2018-04-18

Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point). Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study.

PubMed

Park, Won; Yoo, Dae Hyun; Jaworski, Janusz; Brzezicki, Jan; Gnylorybov, Andriy; Kadinov, Vladimir; Sariego, Irmgadt Goecke; Abud-Mendoza, Carlos; Escalante, William Jose Otero; Kang, Seong Wook; Andersone, Daina; Blanco, Francisco; Hong, Seung Suh; Lee, Sun Hee; Braun, Jürgen

2016-01-20

CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs). This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed. Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions. CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed. ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.

Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

PubMed

Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Blumberg, Joëlle; Ruszniewski, Philippe

2014-07-17

Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

Staffing UK University Campuses Overseas: Lessons from MNE Practice

ERIC Educational Resources Information Center

Salt, John; Wood, Peter

2014-01-01

This article suggests that as their internal labor markets become more multinational in scope, UK universities may acquire similar staffing characteristics to commercial multinational enterprises (MNEs). Comparing evidence from four UK universities with several surveys of MNEs it concludes that, although there are broad similarities in the…

Multinational Activities of Major U.S. Automotive Producers : Volume 5. Diffusion of Production and Sales Operations Abroad.

DOT National Transportation Integrated Search

1978-09-01

This is Volume V on the multi-national activities of the major U.S. automotive producers. The purpose of this Volume is to evaluate the foreign manufacturing and sales activities of the General Motors Corporation, Ford Motor Company, and Chrysler Cor...

The Role of Language in National and Multinational Enterprises in Taiwan.

ERIC Educational Resources Information Center

Du-Babcock, Bertha; Babcock, Richard D.

Communication patterns and language use in four national and multinational companies operating in Taiwan illustrate the potential for communication problems when more than one language is in use. The companies include Texas Instruments, Kaohsiung Monomer Company, Ltd., Bank of America, and Cheng-Yia International Corporation. In the four…

Evaluating Organizational Change at a Multinational Transportation Corporation: Method and Reflections

ERIC Educational Resources Information Center

Plakhotnik, Maria S.

2016-01-01

The purpose of this perspective on practice is to share my experience conducting an organizational change evaluation using qualitative methodology at a multinational transportation company Global Logistics. I provide a detailed description of the three phase approach to data analysis and my reflections on the process.

An Assessment of E-Training Effectiveness in Multinational Companies in Malaysia

ERIC Educational Resources Information Center

Ramayah, Thurasamy; Ahmad, Noor Hazlina; Hong, Tan Say

2012-01-01

E-training has developed into a revolutionary way of learning in Malaysian organizations due to rapid growth in information technology infrastructure. The present study endeavors to determine the critical factors that influence e-training effectiveness in multinational companies (MNCs) in Malaysia. By integrating Technology Acceptance Model (TAM),…

The Role of Culture on Knowledge Transfer: The Case of the Multinational Corporation

ERIC Educational Resources Information Center

Lucas, Leyland M.

2006-01-01

Purpose: This paper aims to look at the issue of culture's role in knowledge transfer within multinational corporations (MNCs). Studies of MNCs have hinted at the importance of culture to the performance of subsidiaries. Using Hofstede's cultural dimensions of power distance, individualism/collectivism, uncertainty avoidance, and…

GLOBAL CHANGE RESEARCH NEWS #10: MULTIAGENCY, MULTINATIONAL GLOBAL CHANGE RESEARCH EFFORT IN THE UPPER SAN PEDRO BASIN

EPA Science Inventory

This edition reports on a multiagency, multinational global-change research effort that seeks to evaluate the consequences of natural and human-induced changes in semi-arid environments. The Semi-Arid Land-Surface-Atmosphere Program ("SALSA") is focused on the environmentally sen...

Standardized Evaluation for Multi-National Development Programs.

ERIC Educational Resources Information Center

Farrell, W. Timothy

This paper takes the position that standardized evaluation formats and procedures for multi-national development programs are not only desirable but possible in diverse settings. The key is the localization of standard systems, which involves not only the technical manipulation of items and scales, but also the contextual interpretation of…

Multinational Corporate Penetration, Industrialism, Region, and Social Security Expenditures: A Cross-National Analysis.

ERIC Educational Resources Information Center

Clark, Roger; Filinson, Rachel

1991-01-01

Examined determinants of spending on social security programs, using data from 75 nations representative of core, semiperipheral, and peripheral nations. Industrialization variables had strong effects in models involving all nations, as did multinational corporate penetration in extraction, particularly when region was controlled; such penetration…

A Content Analysis of Multinationals' Web Communication Strategies: Cross-Cultural Research Framework and Pre-Testing.

ERIC Educational Resources Information Center

Okazaki, Shintaro; Alonso Rivas, Javier

2002-01-01

Discussion of research methodology for evaluating the degree of standardization in multinational corporations' online communication strategies across differing cultures focuses on a research framework for cross-cultural comparison of corporate Web pages, applying traditional advertising content study techniques. Describes pre-tests that examined…

Multinational Scanning: A Study of the Information Sources Utilized by Headquarters Executives in Multinational Companies

ERIC Educational Resources Information Center

Keegan, Warren J.

1974-01-01

Findings reveal the great importance of human sources of information and sources outside the organization. Divisional boundaries, functional specialization, and level were all found to act as significant barriers to information flows, and thus as limitations to organizational effectiveness. (Author/WM)

The Management of Training in Multinational Corporations: Comparative Case Studies.

ERIC Educational Resources Information Center

Noble, Charles

1997-01-01

Case studies of British and Australian multinational corporations in the food and drink industry investigated how training and development are managed. Competency-based education and industry boards are important elements in both countries. Lack of a training culture in the industry and little innovation in training were observed. (SK)

A Comparative Perspective of Intercultural Sensitivity between College Students and Multinational Employees in China

ERIC Educational Resources Information Center

Peng, Shi-Yong

2006-01-01

Using the Intercultural Sensitivity Scale formulated by G. M. Chen and Starosta, the intercultural sensitivity of English major students, non-English major students, and multinational employees in China were investigated. In this study, intercultural sensitivity was defined as consisting of interaction engagement, interaction confidence, respect…

Managing Human Resources in a Multinational Context

ERIC Educational Resources Information Center

Sumetzberger, Walter

2005-01-01

Purpose: To develop more sensitivity for different patterns of human resource management in multinational companies. Design/methodology/approach: Systemic approach; the concepts and models are based on the evaluation of consulting projects in the field of human resource management. Findings: A concept of four typical varieties of human resource…

Intraorganizational Career Advancement and Voluntary Turnover in a Multinational Bank in Taiwan

ERIC Educational Resources Information Center

Zhao, Wei; Zhou, Xueguang

2008-01-01

Purpose: This study aims to investigate how various aspects of intraorganizational career advancement--current career attainments, recent pace of upward mobility, and future prospect of career advancement--affect voluntary turnover, drawing empirical evidence from a multinational corporation (MNC) in Taiwan's cultural and labor market environment.…

The Role of Thoracic Medial Branch Blocks in Managing Chronic Mid and Upper Back Pain: A Randomized, Double-Blind, Active-Control Trial with a 2-Year Followup

PubMed Central

Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J. E.; Cash, Kimberly A.; Pampati, Vidyasagar; Fellows, Bert

2012-01-01

Study Design. A randomized, double-blind, active-control trial. Objective. To determine the clinical effectiveness of therapeutic thoracic facet joint nerve blocks with or without steroids in managing chronic mid back and upper back pain. Summary of Background Data. The prevalence of thoracic facet joint pain has been established as 34% to 42%. Multiple therapeutic techniques utilized in managing chronic thoracic pain of facet joint origin include medial branch blocks, radiofrequency neurotomy, and intraarticular injections. Methods. This randomized double-blind active controlled trial was performed in 100 patients with 50 patients in each group who received medial branch blocks with local anesthetic alone or local anesthetic and steroids. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant improvement with significant pain relief and functional status improvement of 50% or more were observed in 80% of the patients in Group I and 84% of the patients in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of thoracic facets with or without steroids may provide a management option for chronic function-limiting thoracic pain of facet joint origin. PMID:22851967

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.

Topical Botulinum Toxin Type A Liposomal Cream for Primary Axillary Hyperhidrosis: A Double-Blind, Randomized, Split-Site, Vehicle-Controlled Study.

PubMed

Lueangarun, Suparuj; Sermsilp, Chairat; Tempark, Therdpong

2018-04-13

Despite its effectiveness in treating primary axillary hyperhidrosis (PAH), topical botulinum toxin type A (BTX-A) is highly resistant to transdermal absorption. Topical BTX-A liposomal cream is recommended as a novel, noninvasive modality to enhance skin penetration. To evaluate the efficacy and safety of topical BTX-A liposomal cream in comparison with liposomal vehicle cream alone in the treatment of PAH. A prospective, randomized, double-blinded, split-site study was conducted in 20 subjects, aged 18 to 50 years, all of whom had symmetrical axillary sweating with Hyperhidrosis Disease Severity Scale scores between 2 to 4. All subjects were double-blinded to treatment regimens and randomly given 2 bottles, one containing topical BTX-A liposomal cream and one containing the vehicle cream without BTX-A, to be applied consistently to the same axilla nightly for 7 consecutive days. Clinical improvement and adverse reactions were evaluated at every follow-up visit. Axillary skin treated with topical BTX-A demonstrated superior sweat reduction and patient satisfaction to vehicle cream-treated axillary skin, with clinical and statistical significance, at baseline, weeks 2, 4, 6, and 8 of follow-up, without adverse effects. Topical BTX-A liposomal cream pharmaceutically enhances drug delivery, is painless, cost-effective, and overall an innovative treatment of PAH.

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.

Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

PubMed

Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

2015-01-01

Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

PubMed

Mohammadi, Mohammad-Reza; Hafezi, Poopak; Galeiha, Ali; Hajiaghaee, Reza; Akhondzadeh, Shahin

2012-01-01

A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of buspirone was less effective than methylphenidate in the treatment of ADHD.

Real versus sham proximal biofield therapy in the treatment of warts of the hands and feet in adults: study protocol for a randomized controlled trial (MAGNETIK study).

PubMed

Gaillard, Cathy; Allain, Laure; Legros, Hélène; Brucato, Sylvie; Desgue, Yohann; Rouillon, Christophe; Peyro-Saint-Paul, Laure; Dompmartin, Anne

2017-06-07

Despite the lack of scientific studies on biofield therapies, they are widely acclaimed by patients. The mechanisms of action are not explained by current allopathic medical approaches. Warts are common and contagious viral lesions that may be refractory to standard dermatologic treatments such as cryotherapy, laser therapy, and keratolytic ointments. Biofield therapies are efficient in various pathologies. Their ability to treat warts has never been demonstrated in a scientific study with a robust methodology. Patients with refractory warts often place their trust in these alternative therapies because of the poor results obtained from traditional medicine. We propose a prospective, randomized, single-blind, assessor-blind trial to evaluate the efficacy of treatment of warts by biofield therapy. Subjects with warts on their feet or hands will be randomized into two groups: real biofield therapy versus sham therapy. The diagnosis will be made at the time of inclusion, and follow-up will take place in week 3. Comparison of pictures of the warts at baseline and after 3 weeks will be used as the primary outcome measure. The hypothesis is that the extent of the disappearance of the original wart in the group treated by real biofield therapy will be 70% and that it will be 30% in the group treated by sham therapy. Using 90% power and an alpha risk of 5%, 31 subjects are required in each group for a two-tailed proportion comparison test. To our knowledge, this is the first study to evaluate the efficacy of biofield therapy on warts. Therefore, the aim of this study is to extend knowledge of biofield therapy to another area of medicine such as dermatology and to propose complementary or alternative practices to improve patient well-being. The main strength of the study is that it is a randomized, single-blind, assessor-blind, placebo-controlled study. ClinicalTrials.gov identifier: NCT02773719 . Registered on 22 April 2016.

Effect of study design on the reported effect of cardiac resynchronization therapy (CRT) on quantitative physiological measures: stratified meta-analysis in narrow-QRS heart failure and implications for planning future studies.

PubMed

Jabbour, Richard J; Shun-Shin, Matthew J; Finegold, Judith A; Afzal Sohaib, S M; Cook, Christopher; Nijjer, Sukhjinder S; Whinnett, Zachary I; Manisty, Charlotte H; Brugada, Josep; Francis, Darrel P

2015-01-06

Biventricular pacing (CRT) shows clear benefits in heart failure with wide QRS, but results in narrow QRS have appeared conflicting. We tested the hypothesis that study design might have influenced findings. We identified all reports of CRT-P/D therapy in subjects with narrow QRS reporting effects on continuous physiological variables. Twelve studies (2074 patients) met these criteria. Studies were stratified by presence of bias-resistance steps: the presence of a randomized control arm over a single arm, and blinded outcome measurement. Change in each endpoint was quantified using a standardized effect size (Cohen's d). We conducted separate meta-analyses for each variable in turn, stratified by trial quality. In non-randomized, non-blinded studies, the majority of variables (10 of 12, 83%) showed significant improvement, ranging from a standardized mean effect size of +1.57 (95%CI +0.43 to +2.7) for ejection fraction to +2.87 (+1.78 to +3.95) for NYHA class. In the randomized, non-blinded study, only 3 out of 6 variables (50%) showed improvement. For the randomized blinded studies, 0 out of 9 variables (0%) showed benefit, ranging from -0.04 (-0.31 to +0.22) for ejection fraction to -0.1 (-0.73 to +0.53) for 6-minute walk test. Differences in degrees of resistance to bias, rather than choice of endpoint, explain the variation between studies of CRT in narrow-QRS heart failure addressing physiological variables. When bias-resistance features are implemented, it becomes clear that these patients do not improve in any tested physiological variable. Guidance from studies without careful planning to resist bias may be far less useful than commonly perceived. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Wissel, Jörg; Ganapathy, Vaidyanathan; Ward, Anthony B; Borg, Jörgen; Ertzgaard, Per; Herrmann, Christoph; Haggstrom, Anders; Sakel, Mohamed; Ma, Julia; Dimitrova, Rozalina; Fulford-Smith, Antony; Gillard, Patrick

2016-07-01

Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P < 0.05). Higher proportions of patients in the pain subgroup achieved ≥30% and ≥50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P < 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion.

PubMed

Martin, Seth S; Feldman, David I; Blumenthal, Roger S; Jones, Steven R; Post, Wendy S; McKibben, Rebeccah A; Michos, Erin D; Ndumele, Chiadi E; Ratchford, Elizabeth V; Coresh, Josef; Blaha, Michael J

2015-11-09

We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real-time activity data and 16 personal factors with a 10 000 steps/day goal. Forty-eight outpatients (46% women, 21% nonwhite) enrolled with a mean±SD age of 58±8 years, body mass index of 31±6 kg/m(2), and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], -580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). An automated tracking-texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Quality of life and visual function in Nigeria: findings from the National Survey of Blindness and Visual Impairment.

PubMed

Tran, Hang My; Mahdi, Abdull M; Sivasubramaniam, Selvaraj; Gudlavalleti, Murthy V S; Gilbert, Clare E; Shah, Shaheen P; Ezelum, C C; Abubakar, Tafida; Bankole, Olufunmilayo O

2011-12-01

To assess associations of visual function (VF) and quality of life (QOL) by visual acuity (VA), causes of blindness and types of cataract procedures in Nigeria. Multi-stage stratified cluster random sampling was used to identify a nationally representative sample of persons aged ≥ 40 years. VF/QOL questionnaires were administered to participants with VA <6/60 in one or both eyes and/or Mehra-Minassian cataract grade 2B or 3 in one or both eyes and a random sample of those with bilateral VA ≥ 6/12. VF/QOL questionnaires were administered to 2076 participants. Spearman's rank correlation showed a strong correlation between decreasing VA and VF/QOL scores (p<0.0001) with greatest impact on social (p<0.0001) and mobility-related activities (p<0.0001). People who were blind due to glaucoma had lower VF and QOL scores than those who were blind due to cataract. Mean VF and QOL scores were lower after couching compared with conventional cataract surgery (mean VF score=51.0 vs 63.0 and mean QOL score=71.3 vs 79.3). Finally, VF and QOL scores were lower among populations with specific characteristics. Populations with the following characteristics should be targeted to improve VF and QOL: people who are blind, older people, women, manual labourers, people living in rural areas, those living in the northern geopolitical zones, those practising Islamic and Traditionalism faith, those not currently married and those who have undergone couching.

Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

PubMed Central

Thase, Michael E.

2010-01-01

Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

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.

Front blind spot crashes in Hong Kong.

PubMed

Cheng, Yuk Ki; Wong, Koon Hung; Tao, Chi Hang; Tam, Cheok Ning; Tam, Yiu Yan; Tsang, Cheuk Nam

2016-09-01

In 2012-2014, our laboratory had investigated a total of 9 suspected front blind spot crashes, in which the medium and heavy goods vehicles pulled away from rest and rolled over the pedestrians, who were crossing immediately in front of the vehicles. The drivers alleged that they did not see any pedestrians through the windscreens or the front blind spot mirrors. Forensic assessment of the goods vehicles revealed the existence of front blind spot zones in 3 out of these 9 accident vehicles, which were attributed to the poor mirror adjustments or even the absence of a front blind spot mirror altogether. In view of this, a small survey was devised involving 20 randomly selected volunteers and their goods vehicles and 5 out of these vehicles had blind spots at the front. Additionally, a short questionnaire was conducted on these 20 professional lorry drivers and it was shown that most of them were not aware of the hazards of blind spots immediately in front of their vehicles, and many did not use the front blind spot mirrors properly. A simple procedure for quick measurements of the coverage of front blind spot mirrors using a coloured plastic mat with dimensional grids was also introduced and described in this paper. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea. Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume. Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls. Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo. PMID:23431314

Chorionic gonadotropin in weight control. A double-blind crossover study.

PubMed

Young, R L; Fuchs, R J; Woltjen, M J

1976-11-29

Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Using English as the Common Corporate Language in a German Multinational

ERIC Educational Resources Information Center

Swift, Jonathan S.; Wallace, James

2011-01-01

Purpose: This study aims to examine a German multinational that uses English as the common corporate language (CCL) for internal communications with its international subsidiaries/agencies. It examines use of English within the workplace, and problems/opportunities it presents to those who use it. Design/methodology: The questionnaire was piloted…

Assessment of a Multinational Online Faculty Development Program on Online Teaching: Reflections of Candidate E-Tutors

ERIC Educational Resources Information Center

Adnan, Muge; Kalelioglu, Filiz; Gulbahar, Yasemin

2017-01-01

Teaching online requires different skills, roles and competencies for online instructors compared to teaching in traditional learning environments. Universities should offer ongoing support in various forms to help academic staff through their online journey. This paper provides insights into a multinational faculty development program for…

Developing Managerial Talent: Exploring the Link between Management Talent and Perceived Performance in Multinational Corporations (MNCs)

ERIC Educational Resources Information Center

Sheehan, Maura

2012-01-01

Purpose: To examine the association between talent management (TM) and perceived subsidiary performance. Focus is given to the development of one key talent group--line managers--in subsidiaries of multinational corporations (MNCs). Specifically, the paper examines: whether there is a positive relationship between Management Development (MD) and…

Measuring the Value of Succession Planning and Management: A Qualitative Study of Multinational Companies

ERIC Educational Resources Information Center

Kim, Yeonsoo

2010-01-01

This article proposes a model for planning and operating an effective succession planning and management (SP&M) program and measuring its value. The nature of the research is exploratory, following a qualitative approach using in-depth interviews. Representatives of multinational companies interviewed for this study revealed that succession…

The Status of International Business Communication Training in the 100 Largest Multinational United States Corporations.

ERIC Educational Resources Information Center

Zimpfer, Forest; Underwood, Robert

The 100 largest multinational U.S. corporations were surveyed concerning business communication training provided for personnel assigned to overseas posts. The survey requested information on the existence and content of such formal training programs and the qualifications of their training directors. Results drawn from the 43 usable responses…

Pre-Interaction Management in Multinational Companies in Central Europe

ERIC Educational Resources Information Center

Nekvapil, Jiri; Sherman, Tamah

2009-01-01

This article is devoted to the linguistic, communicative and sociocultural situation in branches of multinational companies located in the Czech Republic and Hungary. There are typically several languages used in these branches. In addition to the local languages, there are the languages of the parent companies--most commonly English or German,…

Confucius Institutes: Distributed Leadership and Knowledge Sharing in a Worldwide Network

ERIC Educational Resources Information Center

Li, Hsi Chang; Mirmirani, Sam; Ilacqua, Joseph A.

2009-01-01

Purpose: The purpose of this paper is to focus on Confucius Institutes and assess the applicability of theories of leadership and knowledge sharing to multinational organizations and worldwide networks. Growth of multinational trade and decrease in international tension have facilitated the globalization of both profit-seeking and non-profit…

Knowledge Sharing in an American Multinational Company Based in Malaysia

ERIC Educational Resources Information Center

Ling, Chen Wai; Sandhu, Manjit S.; Jain, Kamal Kishore

2009-01-01

Purpose: This paper seeks to examine the views of executives working in an American based multinational company (MNC) about knowledge sharing, barriers to knowledge sharing, and strategies to promote knowledge sharing. Design/methodology/approach: This study was carried out in phases. In the first phase, a topology of organizational mechanisms for…

National Bibliography in a Multi-National State as Accomplished in the USSR.

ERIC Educational Resources Information Center

Vesirova, L. A.

Soviet national bibliographies register all types of publications printed in the Soviet Union regardless of the language in which they were published. These bibliographies are known as state bibliographies. This report dwells on the characteristics of the organization of a state bibliographic system in a multi-national socialistic state. The…

Safety and Health in Multinational Enterprises: What Have We Learnt?

ERIC Educational Resources Information Center

Romero, Ana Teresa

1993-01-01

Analyzes the practices of multinationals in the sphere of occupational safety and health and poses the question of safety and health and industrial risks in terms of environmental problems. Indicates that the future of safety and health may hinge on the adaptation and implementation of recommendations of International Labour Organisation members.…

Developing Collaboratively an International School Special Needs Plan for Multicultural, Multilingual, and Multinational Secondary Students.

ERIC Educational Resources Information Center

Jonietz, Patricia L.

The International School of Brussels (Belgium) developed a program of Curriculum-Based Assessment (CBA) to increase support for "at risk" multicultural, multilingual, and multinational students. The at-risk population included three groups: those who passed standardized English as a Foreign Language tests but were not literate enough for…

Attention Training in Individuals with Generalized Social Phobia: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Amir, Nader; Beard, Courtney; Taylor, Charles T.; Klumpp, Heide; Elias, Jason; Burns, Michelle; Chen, Xi

2009-01-01

The authors conducted a randomized, double-blind placebo-controlled trial to examine the efficacy of an attention training procedure in reducing symptoms of social anxiety in 44 individuals diagnosed with generalized social phobia (GSP). Attention training comprised a probe detection task in which pictures of faces with either a threatening or…

Telephone-Based Coping Skills Training for Patients Awaiting Lung Transplantation

ERIC Educational Resources Information Center

Blumenthal, James A.; Babyak, Michael A.; Keefe, Francis J.; Davis, R. Duane; LaCaille, Rick A.; Carney, Robert M.; Freedland, Kenneth E.; Trulock, Elbert; Palmer, Scott M.

2006-01-01

Impaired quality of life is associated with increased mortality in patients with advanced lung disease. Using a randomized controlled trial with allocation concealment and blinded outcome assessment at 2 tertiary care teaching hospitals, the authors randomly assigned 328 patients with end-stage lung disease awaiting lung transplantation to 12…

A Proposed Multisite Double-Blind Randomized Clinical Trial of Neurofeedback for ADHD: Need, Rationale, and Strategy

ERIC Educational Resources Information Center

Kerson, Cynthia

2013-01-01

Objective: Additional treatments with persisting benefit are needed for ADHD. Because ADHD often shows excessive theta electroencephalogram (EEG) power, low beta, and excessive theta-beta ratio (TBR), a promising treatment is neurofeedback (NF) downtraining TBR. Although several nonblind randomized clinical trials (RCTs) show a medium-large…

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

Native whey induces higher and faster leucinemia than other whey protein supplements and milk: A randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Resistance exercise and protein intake are both strong stimuli for muscle protein synthesis. The potential for a protein to acutely increase muscle protein synthesis seems partly dependent on absorption kinetics and the amino acid composition. The aim of this double-blinded randomized cross-over stu...

Training Anxious Children to Disengage Attention from Threat: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Bar-Haim, Yair; Morag, Inbar; Glickman, Shlomit

2011-01-01

Background: Threat-related attention biases have been implicated in the etiology and maintenance of anxiety disorders. As a result, attention bias modification (ABM) protocols have been employed as treatments for anxious adults. However, they have yet to emerge for children. A randomized, double-blind placebo-controlled trial was conducted to…

A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

2010-01-01

Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

Intervention for Verb Argument Structure in Children with Persistent SLI: A Randomized Control Trial

ERIC Educational Resources Information Center

Ebbels, Susan H.; van der Lely, Heather K. J.; Dockrell, Julie E.

2007-01-01

Purpose: The authors aimed to establish whether 2 theoretically motivated interventions could improve use of verb argument structure in pupils with persistent specific language impairment (SLI). Method: Twenty-seven pupils with SLI (ages 11;0-16;1) participated in this randomized controlled trial with "blind" assessment. Participants were randomly…

The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

EPA Science Inventory

Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

Interpretation Training in Individuals with Generalized Social Anxiety Disorder: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Amir, Nader; Taylor, Charles T.

2012-01-01

Objective: To examine the efficacy of a multisession computerized interpretation modification program (IMP) in the treatment of generalized social anxiety disorder (GSAD). Method: The sample comprised 49 individuals meeting diagnostic criteria for GSAD who were enrolled in a randomized, double-blind placebo-controlled trial comparing IMP (n = 23)…

“A question of balance”: addressing the public health impacts of multinational enterprises in the OECD Guidelines for Multinational Enterprises

PubMed Central

Yang, Joshua S.; McDaniel, Patricia A.; Malone, Ruth E.

2012-01-01

Background The global community is beginning to address non-communicable diseases, but how to increase the accountability of multinational enterprises (MNEs) for the health impacts of their products and practices remains unclear. We examine the Organization for Economic Cooperation and Development’s (OECD) efforts to do so through voluntary MNE guidelines. Methods We developed a historical case study of how the OECD Guidelines for Multinational Enterprises were developed and revised from 1973–2000 through an analysis of publicly available archived OECD and tobacco industry documents. Results The first edition of the Guidelines was a purely economic instrument. Outside pressures and a desire to ward off more stringent regulatory efforts resulted in the addition over time of guidelines related to the environment, consumer interests, sustainable development, and human rights. Conclusion Despite their voluntary nature, the Guidelines can play a role in efforts to help balance the interests of MNEs and public health by providing a starting point for efforts to create binding provisions addressing MNEs’ contributions to disease burden or disease reduction. PMID:23046298

Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

PubMed

Garg, Satish K; Admane, Karim; Freemantle, Nick; Odawara, Masato; Pan, Chang-Yu; Misra, Anoop; Jarek-Martynowa, Iwona R; Abbas-Raza, Syed; Mirasol, Roberto C; Perfetti, Riccardo

2015-02-01

Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

PubMed

Balagopal, Ashwin; Asmuth, David M; Yang, Wei-Teng; Campbell, Thomas B; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R; Lalloo, Umesh G; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B; Semba, Richard D; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2015-10-01

Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

Pre-cART Elevation of CRP and CD4+ T-cell Immune Activation Associated with HIV Clinical Progression in a Multinational Case-Cohort Study

PubMed Central

Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

2015-01-01

Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART. PMID:26017661

Renal and Metabolic Toxicities Following Initiation of HIV-1 Treatment Regimen in a Diverse, Multinational Setting: A Focused Safety Analysis of ACTG PEARLS (A5175)

PubMed Central

Romo, F. Touzard; Smeaton, L.M.; Campbell, T.B.; Riviere, C.; Mngqibisa, R.; Nyirenda, M.; Supparatpinyo, K.; Kumarasamy, N.; Hakim, J.G.; Flanigan, T.P.

2015-01-01

Background Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings. Methods This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups. Results Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1–13.1), history of diabetes (OR, 10.7; 95% CI, 2.1–55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7–5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001). Conclusions TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study. PMID:25433664

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

PubMed Central

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.

2015-01-01

Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136. PMID:25681380

Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

PubMed

Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

2014-02-01

Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

Prevalence of blindness and diabetic retinopathy in northern Jordan.

PubMed

Rabiu, Mansur M; Al Bdour, Muawyah D; Abu Ameerh, Mohammed A; Jadoon, Muhammed Z

2015-01-01

To estimate the prevalence of blindness, visual impairment, diabetes, and diabetic retinopathy in north Jordan (Irbid) using the rapid assessment of avoidable blindness and diabetic retinopathy methodology. A multistage cluster random sampling technique was used to select participants for this survey. A total of 108 clusters were selected using probability proportional to size method while subjects within the clusters were selected using compact segment method. Survey teams moved from house to house in selected segments examining residents 50 years and older until 35 participants were recruited. All eligible people underwent a standardized examination protocol, which included ophthalmic examination and random blood sugar test using digital glucometers (Accu-Chek) in their homes. Diabetic retinopathy among diabetic patients was assessed through dilated fundus examination. A total of 3638 out of the 3780 eligible participants were examined. Age- and sex-adjusted prevalence of blindness, severe visual impairment, and visual impairment with available correction were 1.33% (95% confidence interval [CI] 0.87-1.73), 1.82% (95% CI 1.35-2.25), and 9.49% (95% CI 8.26-10.74), respectively, all higher in women. Untreated cataract and diabetic retinopathy were the major causes of blindness, accounting for 46.7% and 33.2% of total blindness cases, respectively. Glaucoma was the third major cause, accounting for 8.9% of cases. The prevalence of diabetes mellitus was 28.6% (95% CI 26.9-30.3) among the study population and higher in women. The prevalence of any retinopathy among diabetic patients was 48.4%. Cataract and diabetic retinopathy are the 2 major causes of blindness and visual impairment in northern Jordan. For both conditions, women are primarily affected, suggesting possible limitations to access to services. A diabetic retinopathy screening program needs to proactively create sex-sensitive awareness and provide easily accessible screening services with prompt treatment.

Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Solomon, James A; Tyring, Stephen; Staedtler, Gerald; Sand, Meike; Nkulikiyinka, Richard; Shakery, Kaweh

2016-09-01

Papulopustular rosacea (PPR) is characterized by centrofacial papules and pustules commonly associated with erythema. To compare investigator-reported efficacy outcomes for azelaic acid (AzA) foam 15% versus vehicle foam in PPR, a randomized, vehicle-controlled, double-blind phase 3 clinical trial was conducted at 48 US sites. Participants received AzA foam or vehicle foam for 12 weeks. Secondary efficacy outcomes included change in inflammatory lesion count (ILC), therapeutic response rate according to investigator global assessment (IGA), and change in erythema rating. This study was comprised of 961 participants with PPR. The results support the therapeutic superiority of AzA foam over vehicle foam.

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial

PubMed Central

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-01-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information. PMID:11934908

Multinational medical support to operations: challenges, benefits and recommendations for the future.

PubMed

Cordell, R F

2012-03-01

This paper considers the strategic aspects of medical support to military operations as delivered through multi-national collaboration. The military medical services are in essence a people organisation; the purpose of the organisation is primarily to support the people engaged in military operations, and also the people providing healthcare to them. Increasingly, supporting the latter also includes preparation for the ethical dilemmas that they will face. Providing health advice and healthcare on operations is now usually undertaken on a multinational basis, in order to generate sufficient medical capacity to meet the requirement with assets of the appropriate (and NATO mandated) capability. This will be an enduring feature, particularly in light of increasing costs of providing high quality healthcare and the operational and logistic challenges of delivering this capability in adverse environments, and in the context of medical personnel being a limited resource. The key to overcoming the challenges, often the result of the "people issues" such as cultural differences, is to recognise the value that the inherent diversity of multinational healthcare provision brings. The benefit is realised through sharing best practice, and the lessons from challenges met, as well as through burden sharing, and to understand that challenges are most commonly the result of misunderstandings, such as those inherent in language differences. The advice for those bringing a multinational team together includes considering the implications of culture (noting differences in national and military perspectives, and in medical processes such as clinical governance), to ensure effective communication, and to utilise feedback to confirm understanding. It is important not to prejudge or denigrate others. Share information and knowledge, provide positive reinforcement when things go well, and recognise that there will inevitably be challenges and use these as an opportunity to learn. Above all, the personal touch builds a culture within the multinational team that transcends national culture; celebrating success breeds success and thus optimal outcome for patients.

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups?

PubMed Central

2014-01-01

Background Studies suggest that expectations powerfully shape clinical outcomes. For subjective outcomes in adequately blinded trials, health improvements are substantial and largely explained by non-specific factors. The objective of this study was to investigate if unblinding in randomized controlled trials (RCTs) is associated with enhanced placebo effects for intervention groups and nocebo effects for placebo groups. For these effects, a secondary objective was to explore potential moderating factors. Methods We included RCTs that investigated the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for male erectile dysfunction by comparing one PDE-5 inhibitor to placebo. In addition, to be included studies must have reported scores for change from baseline, or baseline and final International Index of Erectile Functioning-Erectile Functioning domain score (IIEF-EF), and be published in either English, French, Dutch, or German. We searched for both published and unpublished relevant trials using PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials, a clinical trials register (clinicaltrials.gov) and the Food and Drug Administration clinical reviews through March 2012. We evaluated the blinding status of trials with the Cochrane Risk of Bias Tool, using the domains of allocation sequence concealment, blinding of participants, healthcare providers and outcome assessors. Across these four domains, studies that scored low risk of bias were judged to be adequately blinded and studies that scored unclear or high risk of bias were judged to be inadequately blinded. Results We included 110 studies (205 journal publications and 2 unpublished sources) that involved 23,877 participants; 93 (85%), 51 (46%), 93 (85%) and 93 (85%) studies were assessed with an unclear risk of bias for allocation concealment, blinding of participant, blinding of caregiver and blinding of outcome assessor, respectively. None of the studies reported testing of blinding. None of the 205 journal publications provided sufficient details to assess allocation concealment, blinding of participants, caregivers and outcome assessors. After contacting authors for additional information, we judged five studies to be adequately (n = 1,202) and 16 to be inadequately (n = 3,006) blinded. The IIEF-EF score for placebo groups in adequately blinded trials versus inadequately blinded trials was 1.92 points (95% CI, 0.64 to 3.20) versus 1.56 (95% CI, 0.93 to 2.20), respectively. The IIEF-EF score for intervention groups in adequately blinded trials versus inadequately blinded trials was 9.40 (95% CI, 6.96 to 11.83) versus 8.33 (95% CI, 7.29 to 9.37), respectively. In a secondary analysis, prior experience with the drug affected the scores; in placebo groups with participants naïve to the intervention the score was 2.89 (95% CI, 2.33 to 3.45) versus -0.11 (95% CI, -2.06 to 1.84) with participants having prior experience. In the intervention groups, these scores were 7.99 (95% CI, 6.85 to 9.14) versus 8.33 (95% CI, 7.51 to 9.16), respectively. Unblinding lowered placebo scores (creating a nocebo effect) by 19% (0.33 points; 95% CI, -0.96 to 1.62). Unblinding lowered intervention scores by 11% (1.0; 95% CI, -1.35 to 3.47). The results provided no conclusive evidence for nocebo or enhanced placebo effects. Patients taking a PDE-5 inhibitor for the first time experience a larger placebo effect that accounts for 35% of the total effect. Conclusions Given the overall poor reporting of blinding in clinical trial reports and the small number of trials that could be rated as adequately or inadequately blinded, we could not draw any robust conclusions about the existence or absence of nocebo and enhanced placebo effects. A large placebo effect was found for patients taking PDE-5 inhibitors for the first time. It was not clear if previous exposure to the drug impacted trial blinding. We found clear evidence that studies assessing a subjective continuous outcome fail to report on measures taken to secure double blinding. Although we observed a trend for the presence of a nocebo effect, there was insufficient evidence to quantify its impact on expectations. RCTs with patients with no prior experience with PDE-5 inhibitors reported larger placebo effects and possibly these studies were better blinded. Future research should further investigate the factors that contribute to blinding and their impact on health outcomes in randomized trials of subjectively assessed conditions. This research is part of a PhD project and has no external funding. The authors have no competing interests to declare. PMID:24555576

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

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.

Caffeine's Influence on Nicotine's Effects in Nonsmokers

PubMed Central

Blank, Melissa D.; Kleykamp, Bethea A.; Jennings, Janine M.; Eissenberg, Thomas

2011-01-01

Objective To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions In nonsmokers, nicotine effects are not influenced by moderate caffeine doses. PMID:17555378

Melatonin improves sleep in children with epilepsy: randomized, double-blind cross-over study

PubMed Central

Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

2015-01-01

Objective Insomnia, especially maintenance insomnia is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, cross-over study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods Eleven pre-pubertal, developmentally normal children aged 6–11 years with epilepsy were randomized by software algorithm to receive placebo or 9 mg sustained release melatonin for 4 weeks, followed by a 1-week washout and 4-week crossover condition. The pharmacy performed blinding; patients, parents and study staff other than a statistician were blinded. Primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. Secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on EEG and reaction time measures on psychomotor vigilance task. Statistical tests appropriate for cross-over designs were used for analysis. Results Data were analyzed from ten subjects who completed the study. Melatonin decreased sleep latency (Mean difference (MD): 11.4 min, p= 0.02) and WASO (MD 22 min, p=0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, Slow-wave sleep duration and REM latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. Conclusion Sustained-release melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed but the study was too small to allow any conclusions to be drawn in this regard. PMID:25862116

The Norwegian Cervical Arthroplasty Trial (NORCAT): 2-year clinical outcome after single-level cervical arthroplasty versus fusion-a prospective, single-blinded, randomized, controlled multicenter study.

PubMed

Sundseth, Jarle; Fredriksli, Oddrun Anita; Kolstad, Frode; Johnsen, Lars Gunnar; Pripp, Are Hugo; Andresen, Hege; Myrseth, Erling; Müller, Kay; Nygaard, Øystein P; Zwart, John-Anker

2017-04-01

Standard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion, but the use of arthroplasty, designed to preserve motion, has increased, and most studies report clinical outcome in its favor. Few of these trials, however, blinded the patients. We, therefore, conducted the Norwegian Cervical Arthroplasty Trial, and present 2-year clinical outcome after arthroplasty or fusion. This multicenter trial included 136 patients with single-level cervical disc disease. The patients were randomized to arthroplasty or fusion, and blinded to the treatment modality. The surgical team was blinded to randomization until nerve root decompression was completed. Primary outcome was the self-rated Neck Disability Index. Secondary outcomes were the numeric rating scale for pain and quality of life questionnaires Short Form-36 and EuroQol-5Dimension-3 Level. There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion (P < 0.001), and no observed significant between-group differences at any follow-up times. However, linear mixed model analyses, correcting for baseline values, dropouts and missing data, revealed a difference in Neck Disability Index (P = 0.049), and arm pain (P = 0.027) in favor of fusion at 2 years. The duration of surgery was longer (P < 0.001), and the frequency of reoperations higher (P = 0.029) with arthroplasty. The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up. However, the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty. http://www.clinicaltrials.gov NCT 00735176.19.

Progress and problems for randomized clinical trials: from streptomycin to the era of megatrials.

PubMed

Hilbrich, Lutz; Sleight, Peter

2006-09-01

Randomized clinical trials (RCTs) are the definitive contributors to evidence-based medicine. RCTs assessing serious outcomes in cardiovascular disease have grown, with 'megatrials' becoming more common with the realization that wrong conclusions resulted from random error in inadequately sized trials. Simple design and a heterogeneous patient population were early features, but multinational trials have increased in scientific, logistical, bureaucratic, regulatory, and legal complexity. These studies now exceed the financial means of academia or medical charities. Governments have left the bill with the pharmaceutical industry, encouraging a symbiosis with academics, who contribute medical and scientific expertise, and access to patients. Industry provides pharmacological, pharmaceutical, technical and regulatory know-how, good clinical practice expertise, and legal assistance during the trial. Study supervision is then in the hands of an independent steering committee and associated subcommittees, until appropriate dissemination of results. Prospectively defined interaction with the sponsor facilitates unbiased design and conduct, but arrangements need careful implementation to avoid conflicts of interest. The patient is protected by a strong data safety monitoring board that is wholly independent. Megatrials are under threat from over-regulation, increasing costs, and difficulties in execution. These issues merit urgent public and political education and debate.

Fear of blindness and perceptions about blind people. The Andhra Pradesh Eye Disease Study.

PubMed

Giridhar, Pyda; Dandona, Rakhi; Prasad, Mudigonda N; Kovai, Vilas; Dandona, Lalit

2002-09-01

This study assessed the fear of being affected by illness and disability including blindness, and perceptions of the population towards blind people in the Indian state of Andhra Pradesh. A total of 11,786 subjects of all ages were sampled from 94 clusters in one urban and three rural study areas of Andhra Pradesh using stratified, random, cluster, systematic sampling to represent the population of this state. A total of 10,293 subjects of all ages underwent a detailed interview and dilated ocular evaluation. Subjects > 15 years of age (7,432) were interviewed regarding fear of illness/disability and their perceptions of blind people. The fear of blindness was assessed in comparison to cancer, severe mental illness, heart attack, losing limbs, deafness, inability to speak, and paralysis. A majority of the study population feared all the illnesses and disabilities assessed. The prevalence of fear of blindness was 90.9% (95% confidence interval 89.1-92.8%) and 92.1% (95% confidence interval 90.6-93.6%) in urban and rural study areas respectively. With multiple logistic regression the fear of blindness was significantly higher for those with any level of education and for those living in the rural study areas. The proportion of those having positive feelings towards blind people was higher in the urban study area. A high prevalence of blindness, 1.84%, has been reported in this population previously. These data suggest that this population feared blindness, and yet there is a high rate of blindness. This reflects the need for increasing awareness about blindness in this population through eye health promotion strategies in order to reduce blindness, and awareness regarding the availability of rehabilitation services.

A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

2009-01-01

A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

Effect of chiropractic manipulation on vertical jump height in young female athletes with talocrural joint dysfunction: a single-blind randomized clinical pilot trial.

PubMed

Hedlund, Sofia; Nilsson, Hans; Lenz, Markus; Sundberg, Tobias

2014-02-01

The main objective of this pilot study was to explore the effect of chiropractic high-velocity, low-amplitude (HVLA) manipulation on vertical jump height in young female athletes with talocrural joint dysfunction. This was a randomized assessor-blind clinical pilot trial. Twenty-two female handball players with talocrural joint dysfunction were randomized to receive either HVLA manipulation (n = 11) or sham treatment (n = 11) once a week during a 3-week period. The main outcome was change in vertical jump height from baseline to follow-up within and between groups after 3 weeks. Nineteen athletes completed the study. After 3 weeks, the group receiving HVLA manipulation (n = 11) had a statistically significant mean (SD) improvement in vertical jump height of 1.07 (1.23) cm (P = .017). The sham treatment group (n = 8) improved their vertical jump height by 0.59 (2.03) cm (P = .436). The between groups' change was 0.47 cm (95% confidence interval, -1.31 to 2.26; P = .571) in favor of the group receiving HVLA manipulation. Blinding and sham procedures were feasible, and there were no reported adverse events. The results of this pilot study show that a larger-scale study is feasible. Preliminary results suggest that chiropractic HVLA manipulation may increase vertical jump height in young female athletes with talocrural joint dysfunction. However, the clinical result in favor of HVLA manipulation compared with sham treatment needs statistical confirmation in a larger randomized clinical trial. Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial.

PubMed

Eckstein, Hans-Henning; Ringleb, Peter; Allenberg, Jens-Rainer; Berger, Jürgen; Fraedrich, Gustav; Hacke, Werner; Hennerici, Michael; Stingele, Robert; Fiehler, Jens; Zeumer, Hermann; Jansen, Olav

2008-10-01

The SPACE trial is a multinational, prospective, randomised study to test the hypothesis that carotid artery stenting is not inferior to carotid endarterectomy for treating patients with severe symptomatic carotid artery stenosis. We did not prove non-inferiority of carotid artery stenting compared with carotid endarterectomy for the 30-day complication rate, and we now report the results at 2 years. Between March, 2001, and February, 2006, patients with symptomatic, severe (>or=70%) carotid artery stenosis were recruited to this non-inferiority trial and randomly assigned with a block randomisation design to have carotid artery angioplasty with stenting or carotid artery endarterectomy. 2-year endpoints include several clinical endpoints and the incidence of recurrent carotid stenosis of at least 70%. Clinical and vascular follow-up was done by a certified neurologist. Analyses were by intention to treat and per protocol. This trial is registered with ISRCTN, number 57874028.12. 1 214 patients were randomly assigned (613 were randomly assigned to carotid angioplasty with stenting and 601 were randomly assigned to carotid endarterectomy). In both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischaemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9.5%vs 8.8%; hazard ratio (HR) 1.10, 95%CI 0.75 to 1.61; log-rank p=0.62; per protocol 9.4%vs 7.8%; HR 1.23, 95%CI 0.82 to 1.83; log-rank p=0.31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10.7% versus 4.6% (p=0.0009) and 11.1% versus 4.6% (p=0.0007), respectively. Only two incidences of recurrent stenoses after carotid artery stenting led to neurological symptoms. After 2 years' follow-up, the rate of recurrent ipsilateral ischaemic strokes reported in the SPACE trial is similar for both treatment groups. The incidence of recurrent carotid stenosis at 2 years, as defined by ultrasound, is significantly higher after carotid artery stenting. However, it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria.

Continuous Linguistic Rhetorical Education as a Means of Optimizing Language Policy in Russian Multinational Regions

ERIC Educational Resources Information Center

Vorozhbitova, Alexandra A.; Konovalova, Galina M.; Ogneva, Tatiana N.; Chekulaeva, Natalia Y.

2017-01-01

Drawing on the function of Russian as a state language the paper proposes a concept of continuous linguistic rhetorical (LR) education perceived as a means of optimizing language policy in Russian multinational regions. LR education as an innovative pedagogical system shapes a learner's readiness for self-projection as a strong linguistic…

Human Resource Development Practices, Managers and Multinational Enterprises in Australia: Thinking Globally, Acting Locally

ERIC Educational Resources Information Center

Sablok, Gitika; Stanton, Pauline; Bartram, Timothy; Burgess, John; Boyle, Brendan

2017-01-01

Purpose: The purpose of this paper is to examine the HRD practices of multinational enterprises (MNEs) operating in Australia to understand the value that MNEs place on investment in their human capital, particularly managerial talent. Design/methodology/approach: Drawing on a representative sample of 211 MNEs operating in Australia, this paper…

The Multilingual Reality of the Multinational Workplace: Language Policy and Language Use

ERIC Educational Resources Information Center

Angouri, Jo

2013-01-01

In the multinational corporation (MNC) context the crossing of linguistic boundaries and the fast-paced change of linguistic ecologies due to market trends and new business activities is the rule rather than the exception. Accordingly, the aim of this paper is to discuss language policy and language practice in one consortium of three…

Army Engineers in a Joint and Multinational Environment

DTIC Science & Technology

2008-05-22

operatio 0 in a maneuver battalion in national ns. The battalion also lacked...construction management section (CMS) to fulfill these requirements and provide operatio mission guidance for the multinational units. The CMS, led by a lieuten...also deleting from the inventory the engineer group headquarters, relying 115 Andrew Feickert, “U.S. Army’s Modular Redesign: Issues for Congress

The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends

ERIC Educational Resources Information Center

Schendel, Diana E.; Bresnahan, Michaeline; Carter, Kim W.; Francis, Richard W.; Gissler, Mika; Grønborg, Therese K.; Gross, Raz; Gunnes, Nina; Hornig, Mady; Hultman, Christina M.; Langridge, Amanda; Lauritsen, Marlene B.; Leonard, Helen; Parner, Erik T.; Reichenberg, Abraham; Sandin, Sven; Sourander, Andre; Stoltenberg, Camilla; Suominen, Auli; Surén, Pål; Susser, Ezra

2013-01-01

The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in…

Critical Success Factors: How One Multinational Company Develops Global E-Learning

ERIC Educational Resources Information Center

Nathan, Edward Pavel

2011-01-01

This research study examined how a multinational company determined what the critical success factors (CSFs) were for developing global e-learning. The study analyzed how these CSFs were grouped together to make their management more efficient. There were 21 participants in the study who were key stakeholders from the United States, Europe, Latin…

"Hej Seppo, Could You Pls Comment on This!"--Internal Email Communication in Lingua Franca English in a Multinational Company

ERIC Educational Resources Information Center

Kankaanranta, Anne

2006-01-01

Recent turbulence in the corporate world resulting from cross-border mergers and acquisitions and advances in communication technology has meant major changes for internal communication in multinational companies. For example, in Finnish-Swedish mergers the common corporate language is increasingly English even though Swedish has traditionally…

Critical Success Factors: How One Multinational Company Develops Global E-Learning

ERIC Educational Resources Information Center

Nathan, Edward Pavel

2009-01-01

This research study examined how a multinational company determined what the critical success factors (CSFs) were for developing global e-learning. The study analyzed how these CSFs were grouped together in order to make their management more efficient. There were 21 participants in the study who were key stakeholders and came from one of four…

A Survey of Current and Future Perceived Multi-National Corporation Manufacturing Training Needs in Tianjin, (T.E.D.A.) China.

ERIC Educational Resources Information Center

Hickey, Will

2001-01-01

Describes a study that surveyed current and perceived future employer-provided training practices among multinational corporations manufacturing companies in the Tianjin Economic Development Area (T.E.D.A.) of China. Highlights include labor market; human resources management in China; workforce productivity; and return on investment. (Author/LRW)

Cross-Cultural Adjustment Process of Expatriate Families in a Multinational Organization: A Family System Theory Perspective

ERIC Educational Resources Information Center

Rosenbusch, Katherine

2010-01-01

The purpose of this survey based study was to examine whether the characteristics (i.e., flexibility and cohesion) of expatriate families in a multinational corporation as measured by the Family Adaptability and Cohesion Evaluation Scale can predict cross-cultural adjustment of the expatriate (individual level of analysis) and his/her family…

Evaluating Knowledge, Attitudinal, and Behavioral Change Effects from a Multinational HIV/AIDS Education Program for Youth

ERIC Educational Resources Information Center

Hardre, Patricia L.; Garcia, Fe; Apamo, Peter; Mutheu, Lucy; Ndege, Monica; Bois, Iderle

2010-01-01

This project tracked the mid-term evaluation processes, practices, and products of a multinational program to reduce at-risk behaviors for HIV/AIDS among children in Kenya, Tanzania, and Haiti. It focused on participant and community perceptions; program effectiveness in promoting abstinence and monogamy decisions; and factors supporting ongoing…

Medical Therapy for Benign Prostatic Hyperplasia: New Terminology, New Concepts, Better Choices

PubMed Central

Kaplan, Steven A

2006-01-01

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an “enlarged prostate”; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted. PMID:16985556

Prevalence and causes of corneal blindness.

PubMed

Wang, Haijing; Zhang, Yaoguang; Li, Zhijian; Wang, Tiebin; Liu, Ping

2014-04-01

The study aimed to assess the prevalence and causes of corneal blindness in a rural northern Chinese population. Cross-sectional study. The cluster random sampling method was used to select the sample. This population-based study included 11 787 participants of all ages in rural Heilongjiang Province, China. These participants underwent a detailed interview and eye examination that included the measurement of visual acuity, slit-lamp biomicroscopy and direct ophthalmoscopy. An eye was considered to have corneal blindness if the visual acuity was <9/18 because of corneal diseases. The main outcome measure was prevalence rates of corneal blindness and low vision. Among the 10 384 people enrolled in the study, the prevalence of corneal blindness is 0.3% (95% confidence interval 0.2-0.4%). The leading cause was keratitis in childhood (40.0%), followed by ocular trauma (33.3%) and keratitis in adulthood (20.0%). Age and illiteracy were found to be associated with an increased prevalence of corneal blindness. Blindness because of corneal diseases in rural areas of Northern China is a significant public health problem that needs to be given more attention. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Cost-effectiveness analysis of antimuscarinics in the treatment of patients with overactive bladder in Spain: A decision-tree model

PubMed Central

2011-01-01

Background Fesoterodine, a new once daily antimuscarinic, has proven to be an effective, safe, and well-tolerated treatment in patients with overactive bladder (OAB). To date, no analysis has evaluated the economic costs and benefits associated with fesoterodine, compared to antimuscarinics in Spain. The purpose of this analysis was to assess the economic value of OAB treatment with fesoterodine relative to extended release tolterodine and solifenacin, from the societal perspective. Methods The economic model was based on data from two 12-week, randomized, double-blind, and multicenter trials comparing fesoterodine and tolterodine extended released (ER). Treatment response rates for solifenacin were extracted from the published literature. Discontinuation and efficacy were based on the results of a 12-week multinational randomized clinical trial extrapolated to 52 weeks. Changes in health related quality of life were assessed with the King's Health Questionnaire, which was transformed into preference-based utility values. Medical costs included (expressed in € 2010) were antimuscarinics, physician visits, laboratory tests, incontinence pads and the costs of OAB-related comorbidities, fractures, skin infections, urinary tract infections, depression, and nursing home admissions associated with incontinence. Time lost from work was also considered. Univariate sensitivity analyses were also performed. Results At week 12, continents accounted for 50.6%, 40.6% and 47.2% of patients in the fesoterodine, tolterodine, and solifenacin groups, respectively. By week 52, the projected proportions of patients remaining on therapy were 33.1%, 26.5% and 30.8%, respectively. The projected quality- adjusted life years (QALY) gain (compared to baseline) over the 52-week simulation period were 0.01014, 0.00846 and 0.00957, respectively. The overall treatment cost was estimated at €1,937, €2,089 and €1,960 for fesoterodine, tolterodine and solifenacin, respectively. Therefore, treatment with fesoterodine resulted in similar overall costs and greater QALY gain than treatment with either tolterodine or solifenacin. Sensitivity analysis showed that these results were robust to all changes performed. Conclusions The results of this economic analysis suggest that fesoterodine is a cost-effective alternative to tolterodine and solifenacin for the treatment of patients with OAB in Spain. Fesoterodine provides additional health benefits while maintain a similar level of costs being a cost-effective treatment strategy from a societal perspective. PMID:21599928

Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial.

PubMed

Castellsagué, Xavier; Paavonen, Jorma; Jaisamrarn, Unnop; Wheeler, Cosette M; Skinner, S Rachel; Lehtinen, Matti; Naud, Paulo; Chow, Song-Nan; Del Rosario-Raymundo, Maria Rowena; Teixeira, Julio C; Palmroth, Johanna; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Garland, Suzanne M; Szarewski, Anne; Poppe, Willy A J; Romanowski, Barbara; Schwarz, Tino F; Tjalma, Wiebren A A; Bosch, F Xavier; Bozonnat, Marie-Cecile; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

2014-10-30

More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer. The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models. A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development. More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation. clinicaltrials.gov: NCT00122681 .

Supersampling multiframe blind deconvolution resolution enhancement of adaptive-optics-compensated imagery of LEO satellites

NASA Astrophysics Data System (ADS)

Gerwe, David R.; Lee, David J.; Barchers, Jeffrey D.

2000-10-01

A post-processing methodology for reconstructing undersampled image sequences with randomly varying blur is described which can provide image enhancement beyond the sampling resolution of the sensor. This method is demonstrated on simulated imagery and on adaptive optics compensated imagery taken by the Starfire Optical Range 3.5 meter telescope that has been artificially undersampled. Also shown are the results of multiframe blind deconvolution of some of the highest quality optical imagery of low earth orbit satellites collected with a ground based telescope to date. The algorithm used is a generalization of multiframe blind deconvolution techniques which includes a representation of spatial sampling by the focal plane array elements in the forward stochastic model of the imaging system. This generalization enables the random shifts and shape of the adaptive compensated PSF to be used to partially eliminate the aliasing effects associated with sub- Nyquist sampling of the image by the focal plane array. The method could be used to reduce resolution loss which occurs when imaging in wide FOV modes.

Supersampling multiframe blind deconvolution resolution enhancement of adaptive optics compensated imagery of low earth orbit satellites

NASA Astrophysics Data System (ADS)

Gerwe, David R.; Lee, David J.; Barchers, Jeffrey D.

2002-09-01

We describe a postprocessing methodology for reconstructing undersampled image sequences with randomly varying blur that can provide image enhancement beyond the sampling resolution of the sensor. This method is demonstrated on simulated imagery and on adaptive-optics-(AO)-compensated imagery taken by the Starfire Optical Range 3.5-m telescope that has been artificially undersampled. Also shown are the results of multiframe blind deconvolution of some of the highest quality optical imagery of low earth orbit satellites collected with a ground-based telescope to date. The algorithm used is a generalization of multiframe blind deconvolution techniques that include a representation of spatial sampling by the focal plane array elements based on a forward stochastic model. This generalization enables the random shifts and shape of the AO- compensated point spread function (PSF) to be used to partially eliminate the aliasing effects associated with sub-Nyquist sampling of the image by the focal plane array. The method could be used to reduce resolution loss that occurs when imaging in wide- field-of-view (FOV) modes.

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

PubMed

Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial.

PubMed

Alumkal, Joshi J; Chowdhury, Simon; Loriot, Yohann; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Carles, Joan; Flaig, Thomas W; Dorff, Tanya B; Phung, De; Forer, David; Noonberg, Sarah B; Mansbach, Hank; Beer, Tomasz M; Higano, Celestia S

2017-10-01

The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial.

PubMed

Höglinger, Günter U; Huppertz, Hans-Jürgen; Wagenpfeil, Stefan; Andrés, María V; Belloch, Vincente; León, Teresa; Del Ser, Teodoro

2014-04-01

It is believed that glycogen synthase kinase-3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase-3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double-blind, placebo-controlled trial in patients with mild-to-moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52-week MRI. Automated, observer-independent, atlas-based, and mask-based volumetry was done on high-resolution, T1-weighted, three-dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: -1.3% ± 1.4% vs. -3.1% ± 2.3%, respectively), cerebrum (-1.3% ± 1.5% vs. -3.2% ± 2.1%, respectively), parietal lobe (-1.6% ± 1.9% vs. -4.1% ± 3.0%, respectively), and occipital lobe (-0.3% ± 1.8% vs. -2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society.

Virtual Reality Job Interview Training in Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Smith, Matthew J.; Ginger, Emily J.; Wright, Katherine; Wright, Michael A.; Taylor, Julie Lounds; Humm, Laura Boteler; Olsen, Dale E.; Bell, Morris D.; Fleming, Michael F.

2014-01-01

The feasibility and efficacy of virtual reality job interview training (VR-JIT) was assessed in a single-blinded randomized controlled trial. Adults with autism spectrum disorder were randomized to VR-JIT (n = 16) or treatment-as-usual (TAU) (n = 10) groups. VR-JIT consisted of simulated job interviews with a virtual character and didactic…

Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

2014-01-01

The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. A 2-year randomized, placebo-controlled, double-blind, clinical trial invo...

The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

2015-01-01

Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

Vestibular Stimulation for ADHD: Randomized Controlled Trial of Comprehensive Motion Apparatus

ERIC Educational Resources Information Center

Clark, David L.; Arnold, L. Eugene; Crowl, Lindsay; Bozzolo, Hernan; Peruggia, Mario; Ramadan, Yaser; Bornstein, Robert; Hollway, Jill A.; Thompson, Susan; Malone, Krista; Hall, Kristy L.; Shelton, Sara B.; Bozzolo, Dawn R.; Cook, Amy

2008-01-01

Objective: This research evaluates effects of vestibular stimulation by Comprehensive Motion Apparatus (CMA) in ADHD. Method: Children ages 6 to 12 (48 boys, 5 girls) with ADHD were randomized to thrice-weekly 30-min treatments for 12 weeks with CMA, stimulating otoliths and semicircular canals, or a single-blind control of equal duration and…

Working Memory Training in Young Children with ADHD: A Randomized Placebo-Controlled Trial

ERIC Educational Resources Information Center

Dongen-Boomsma, Martine; Vollebregt, Madelon A.; Buitelaar, Jan K.; Slaats-Willemse, Dorine

2014-01-01

Background: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the efficacy of Cogmed Working Memory Training…

The Effect of Food Stamp Nutrition Education on the Food Insecurity of Low-Income Women Participants

ERIC Educational Resources Information Center

Eicher-Miller, Heather A.; Mason, April C.; Abbott, Angela R.; McCabe, George P.; Boushey, Carol J.

2009-01-01

Objective: To determine the effect of Food Stamp Nutrition Education (FSNE) in Indiana on participants' food insecurity and food insufficiency. Design: A single-blind randomized design. A randomized experimental group completed 5 FSNE lessons as an intervention between a pre- and posttest, whereas a control group completed a pre- and posttest…

Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

USDA-ARS?s Scientific Manuscript database

Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

A Randomized Controlled Trial of Trauma-Focused Cognitive Behavioral Therapy for Sexually Exploited, War-Affected Congolese Girls

ERIC Educational Resources Information Center

O'Callaghan, Paul; McMullen, John; Shannon, Ciaran; Rafferty, Harry; Black, Alastair

2013-01-01

Objective: To assess the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) delivered by nonclinical facilitators in reducing posttraumatic stress, depression, and anxiety and conduct problems and increasing prosocial behavior in a group of war-affected, sexually exploited girls in a single-blind, parallel-design, randomized,…

Survey of blindness and low vision in Egbedore, South-Western Nigeria.

PubMed

Kolawole, O U; Ashaye, A O; Adeoti, C O; Mahmoud, A O

2010-01-01

Developing efficient and cost-effective eye care programmes for communities in Nigeria has been hampered by inadequate and inaccurate data on blindness and low vision. To determine the prevalence and causes of blindness and low vision among adults 50 years and older in South-Western Nigeria in order to develop viable eye care programme for the community. Twenty clusters of 60 subjects of age 50 years and older were selected by systematic random cluster sampling. Information was collected and ocular examinations were conducted on each consenting subject. Data were recorded in specially designed questionnaire and analysed using descriptive statistical methods. Out of the 1200 subjects enrolled for the study, 1183(98.6%) were interviewed and examined. Seventy five (6.3%)) of the 1183 subjects were bilaterally blind and 223(18.9%) had bilateral low vision according to WHO definition of blindness and low vision. Blindness was about 1.6 times commoner in men than women. Cataract, glaucoma and posterior segment disorders were major causes of bilateral blindness. Bilateral low vision was mainly due to cataract, refractive errors and posterior segment disorders. The prevalence of blindness and low vision in this study population was high. The main causes are avoidable. Elimination of avoidable blindness and low vision calls for attention and commitment from government and eye care workers in South Western Nigeria.

Blind Bayesian restoration of adaptive optics telescope images using generalized Gaussian Markov random field models

NASA Astrophysics Data System (ADS)

Jeffs, Brian D.; Christou, Julian C.

1998-09-01

This paper addresses post processing for resolution enhancement of sequences of short exposure adaptive optics (AO) images of space objects. The unknown residual blur is removed using Bayesian maximum a posteriori blind image restoration techniques. In the problem formulation, both the true image and the unknown blur psf's are represented by the flexible generalized Gaussian Markov random field (GGMRF) model. The GGMRF probability density function provides a natural mechanism for expressing available prior information about the image and blur. Incorporating such prior knowledge in the deconvolution optimization is crucial for the success of blind restoration algorithms. For example, space objects often contain sharp edge boundaries and geometric structures, while the residual blur psf in the corresponding partially corrected AO image is spectrally band limited, and exhibits while the residual blur psf in the corresponding partially corrected AO image is spectrally band limited, and exhibits smoothed, random , texture-like features on a peaked central core. By properly choosing parameters, GGMRF models can accurately represent both the blur psf and the object, and serve to regularize the deconvolution problem. These two GGMRF models also serve as discriminator functions to separate blur and object in the solution. Algorithm performance is demonstrated with examples from synthetic AO images. Results indicate significant resolution enhancement when applied to partially corrected AO images. An efficient computational algorithm is described.

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

PubMed

Nutman, J; Brooks, L J; Deakins, K M; Baldesare, K K; Witte, M K; Reed, M D

1994-10-01

To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. Prospective, double-blind, randomized study. Pediatric intensive care unit in a university teaching hospital. Twenty-eight patients with stridor during the immediate postextubation period. After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

2 L PEG plus ascorbic acid versus 4 L PEG plus simethicon for colonoscopy preparation: a randomized single-blind clinical trial.

PubMed

Gentile, Maurizio; De Rosa, Michele; Cestaro, Giovanni; Forestieri, Pietro

2013-06-01

The 2 L polyethylene glycol (PEG) lavage solution has been proved to be similarly safe and effective as 4 L PEG formulations, in spite of the reduced volume. To compare low-volume PEG-based solution combined with ascorbic acid with high-volume PEG-based solution combined with simethicon in terms of efficacy and patient tolerability. This was a single-blind prospective randomized trial. Patients were randomized to receive either 2 L PEG plus ascorbic acid (PEG+Asc) or 4 L PEG plus simethicon (PEG+Sim). The primary endpoint was overall colon cleansing evaluation, assessed by blinded investigators using Aronchick score. Secondary end points included patient compliance and tolerability and adverse events. Sixty patients received PEG+Asc and 60 received PEG+Sim. Overall bowel cleansing score was considered adequate in 81.67% of the PEG+Asc and 80% of the PEG+Sim groups, respectively. Excellent and good ratings were recorded in 11.6% and 38.3% receiving PEG+Asc as compared with 26.6% and 23.3% of patients receiving PEG+Sim. Patient tolerability and safety were similar with both the preparations. According to our data, low-volume PEG+Asc has comparable efficacy, safety, and tolerability as high-volume PEG+Sim; therefore, it can be considered as a good alternative solution for bowel preparation. More improvements are necessary to achieve the target of a perfect preparation.

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

Randomized, Double-Blinded, Phase 2 Trial of WR 279,396 (Paromomycin and Gentamicin) for Cutaneous Leishmaniasis in Panama

PubMed Central

Sosa, Néstor; Capitán, Zeuz; Nieto, Javier; Nieto, Melissa; Calzada, José; Paz, Hector; Spadafora, Carmenza; Kreishman-Deitrick, Mara; Kopydlowski, Karen; Ullman, Diane; McCarthy, William F.; Ransom, Janet; Berman, Jonathan; Scott, Charles; Grogl, Max

2013-01-01

In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after 6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for Paromomycin Alone (P = 0.099). When all treated lesions were included, the final cure rate for WR 279,398-treated patients was again 87%, but the final cure rate for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both creams were well tolerated with mild application site reactions being the most frequent adverse event. The increased final cure rate in the WR 279,396 group in this small Phase 2 study suggests that the combination product may provide greater clinical benefit than paromomycin monotherapy against L. panamensis cutaneous leishmaniasis. PMID:23857024

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.

The Effects of the Bali Yoga Program for Breast Cancer Patients on Chemotherapy-Induced Nausea and Vomiting: Results of a Partially Randomized and Blinded Controlled Trial.

PubMed

Anestin, Annélie S; Dupuis, Gilles; Lanctôt, Dominique; Bali, Madan

2017-10-01

Complementary and alternative medicine has been shown to be beneficial in reducing chemotherapy-induced nausea and vomiting. However, conclusive results are lacking in order to confirm its usefulness. The purpose of this study was to determine whether a standardized yoga intervention could reduce these adverse symptoms. This was a partially randomized and blinded controlled trial comparing a standardized yoga intervention with standard care. Eligible patients were adults diagnosed with stages I to III breast cancer receiving chemotherapy. Patients randomized to the experimental group participated in an 8-week yoga program. There was no significant difference between the experimental and control groups on chemotherapy-induced nausea and vomiting after 8 weeks. Results suggest the yoga program is not beneficial in managing these adverse symptoms. However, considering preliminary evidence suggesting yoga's beneficial impact in cancer symptom management, methodological limitations should be explored and additional studies should be conducted.

Efficacy of Intravenous Acetaminophen in Periimplantation Pain of Cardiac Electronic Devices: A Randomized Double-Blinded Study.

PubMed

Mollazadeh, Reza; Eftekhari, Mohammad Reza; Eslami, Masoud

2017-06-01

Although intravenous acetaminophen has been administered to reduce postoperative pain, it has not been used during cardiac implantable electronic devices (CIEDs) implantation. This was a randomized double-blinded interventional study. Thirty-two patients who were referred for new CIED implantation during July 2012 until April 2013 randomly received placebo or 1 g of intravenous acetaminophen. All patients were treated with local anesthesia. Pain score during incision, pocket creation, and in the recovery room, and the patients' need for analgesics during the 6 hours after the procedure were recorded in both groups. Seventeen and 15 patients received acetaminophen and placebo, respectively. Pain scores in patients treated with acetaminophen were significantly lower (4.4 vs 2.9, P = .004), and they received less analgesics (17% vs 60%, P = .014). Intravenous administration of acetaminophen is effective for pain relief in patients undergoing CIED implantation and decreases the need for postoperative analgesics. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

PubMed Central

2012-01-01

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making. PMID:23151403

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Multinational corporations and health care in the United States and Latin America: strategies, actions, and effects.

PubMed

Jasso-Aguilar, Rebeca; Waitzkin, Howard; Landwehr, Angela

2004-01-01

In this article we analyze the corporate dominance of health care in the United States and the dynamics that have motivated the international expansion of multinational health care corporations, especially to Latin America. We identify the strategies, actions, and effects of multinational corporations in health care delivery and public health policies. Our methods have included systematic bibliographical research and in-depth interviews in the United States, Mexico, and Brazil. Influenced by public policy makers in the United States, such organizations as the World Bank, International Monetary Fund, and World Trade Organization have advocated policies that encourage reduction and privatization of health care and public health services previously provided in the public sector. Multinational managed care organizations have entered managed care markets in several Latin American countries at the same time as they were withdrawing from managed care activities in Medicaid and Medicare within the United States. Corporate strategies have culminated in a marked expansion of corporations' access to social security and related public sector funds for the support of privatized health services. International financial institutions and multinational corporations have influenced reforms that, while favorable to corporate interests, have worsened access to needed services and have strained the remaining public sector institutions. A theoretical approach to these problems emphasizes the falling rate of profit as an economic motivation of corporate actions, silent reform, and the subordination of polity to economy. Praxis to address these problems involves opposition to policies that enhance corporate interests while reducing public sector services, as well as alternative models that emphasize a strengthened public sector

Multinational Corporations and Health Care in the United States and Latin America: Strategies, Actions, and Effects*

PubMed Central

JASSO-AGUILAR, REBECA; WAITZKIN, HOWARD; LANDWEHR, ANGELA

2010-01-01

In this article we analyze the corporate dominance of health care in the United States and the dynamics that have motivated the international expansion of multinational health care corporations, especially to Latin America. We identify the strategies, actions, and effects of multinational corporations in health care delivery and public health policies. Our methods have included systematic bibliographical research and in-depth interviews in the United States, Mexico, and Brazil. Influenced by public policy makers in the United States, such organizations as the World Bank, International Monetary Fund, and World Trade Organization have advocated policies that encourage reduction and privatization of health care and public health services previously provided in the public sector. Multinational managed care organizations have entered managed care markets in several Latin American countries at the same time as they were withdrawing from managed care activities in Medicaid and Medicare within the United States. Corporate strategies have culminated in a marked expansion of corporations’ access to social security and related public sector funds for the support of privatized health services. International financial institutions and multinational corporations have influenced reforms that, while favorable to corporate interests, have worsened access to needed services and have strained the remaining public sector institutions. A theoretical approach to these problems emphasizes the falling rate of profit as an economic motivation of corporate actions, silent reform, and the subordination of polity to economy. Praxis to address these problems involves opposition to policies that enhance corporate interests while reducing public sector services, as well as alternative models that emphasize a strengthened public sector. PMID:15779471

Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report.

PubMed

Sperber, A D; Gwee, K A; Hungin, A P; Corazziari, E; Fukudo, S; Gerson, C; Ghoshal, U C; Kang, J-Y; Levy, R L; Schmulson, M; Dumitrascu, D; Gerson, M-J; Chen, M; Myung, S-J; Quigley, E M M; Whorwell, P J; Zarzar, K; Whitehead, W E

2014-11-01

Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting. © 2014 John Wiley & Sons Ltd.

D-camphor-crataegus berry extract combination increases blood pressure and cognitive functioning in the elderly - a randomized, placebo controlled double blind study.

PubMed

Werner, Natalie S; Duschek, Stefan; Schandry, Rainer

2009-12-01

The present study investigated whether the D-camphor-crataegus berry extract combination Korodin elevates blood pressure and enhances cognitive performance in the elderly population. Eighty women aged between 50 and 80 years were examined based on a randomized, placebo controlled double blind design. Blood pressure was measured sphygmomanometrically and through continuous noninvasive recording. Cognitive performance was assessed by means of two tests measuring general information processing capacity and visuomotor speed. The administration of the drug led to a short term increase in blood pressure as well as in cognitive performance as compared to placebo. Potential physiological mechanisms of action mediating this effect, including hemodynamic alterations, sympathetic stimulation as well as improvement of cerebral metabolism are discussed.

Theater Logistics Management: A Case for a Joint Distribution Solution

DTIC Science & Technology

2008-03-15

Multinational (JIIM) operations necessitate creating joint-multinational-based distribution management centers which effectively manage materiel...in the world. However, as the operation continued, the inherent weakness of the intra-theater logistical distribution management link became clear...compounded the distribution management problem. The common thread between each of the noted GAO failures is the lack of a defined joint, theater

Multinational Corporations and British Labour: A Review of Attitudes and Responses.

ERIC Educational Resources Information Center

Gennard, John

Multinational corporations operating in Great Britain, specifically American industry, are arousing fears on the part of British labor, which can be grouped into these categories: (1) a threat to the job security of union members, (2) a change in the balance of power at the collective bargaining table in favor of the employers, (3) a clash of…

The P15--A Multinational Assessment Battery for Collecting Data on Health Indicators Relevant to Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Perry, J.; Linehan, C.; Kerr, M.; Salvador-Carulla, L.; Zeilinger, E.; Weber, G.; Walsh, P.; Van Schrojenstein Lantman-De-Valk, H.; Haveman, M.; Azema, B.; Buono, S.; Cara, A. C.; Germanavicius, A.; Van Hove, G.; Maatta, T.; Berger, D. M.; Tossebro, J.

2010-01-01

Background: Health disparities between adults with intellectual disabilities (ID) and the general population have been well documented but, to date, no dedicated assessment battery for measuring health disparity has been available. This paper reports on the development and testing of a multinational assessment battery for collecting data on a…

Learning Experiences of Nurses as Part of a European Union Project on Complementary Therapies: A Multinational Qualitative Study.

PubMed

Boz, İlkay; Özer, Zeynep; Teskereci, Gamze; Kavradim, Selma Turan

The objectives of this study were to investigate learning experiences of the nurses who participated in transnational and multinational occupational training. A qualitative descriptive methodology was used. Data are clustered into 3 categories "occupational training," "complementary care," and "intercultural interaction." This research has revealed many insights into the transnational training of nurses.

Factors in the Effective Transfer of Knowledge from Multinational Enterprises to Their Foreign Subsidiaries: A Mozambican Case Study

ERIC Educational Resources Information Center

Duarte Moleiro Martins, José

2016-01-01

The purpose of this article is to better understand the role of internal stakeholders in subsidiaries of multinational companies (MNCs) in order to offer potential insights into the cross-border transfer of knowledge from those companies' headquarters to their subsidiaries. The focus is upon subsidiaries in developing countries, here Mozambique.…

The Invisible Blockade and the Covert War: U.S. Relations with Chile, 1970-1973

DTIC Science & Technology

1979-06-01

U.S.- owned multinational corporations , pursued a course of action, publicly, economically and covertly, bent on discrediting, disrupting and dislodging...government, in concert with U.S.- .owned multinational corporations , pursued a course of action, publicly, economically and covertly, bent on...513 E. CONCLUSION -------------------------------------- 64 IV. COVERT GOVERNMENTAL AND CORPORATE PRESSURES-------- 67 A. ATTEMPTS TO KEEP

Multinational corporations, the politics of the world economy, and their effects on women's health in the developing world: a review.

PubMed

Hippert, Christine

2002-12-01

Presently, globalization and the world economy maintain power relations that hamper the economic integrity and the political autonomy of the developing world. My paper addresses specific economic conditions that perpetuate poverty and poor health. I examine multinational corporations and their effects on women's health, particularly in Mexico and parts of Asia. The advent of multinational corporate business in Mexico, Malaysia, Philippines, India, and Indonesia has led to increased poverty and human rights abuses. Women bear the brunt of this because of specific international economic arrangements and their low social status, both locally and globally. As a result, their physical, mental, and emotional health is suffering. Solutions to these health problems have been proposed on multiple levels: international top-down approaches (i.e., employing international protectionist regulatory standards, exposing multinationals who infringe on their workers' human rights), as well as local grassroots organizational campaigns (i.e., conducting informational human rights workshops for factory workers). Ultimately, the answers lie in holding corporations accountable to their laborers while developing countries maintain their comparative advantage; this is the only way women's health will improve and the developing world can entice corporate investment.

International taxation of multinational enterprises in developed countries

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

Adams, J.D.R.; Whalley, J.

1977-01-01

The authors, specialists in law and economics, respectively, adopt an interdisciplinary approach to the international taxation of multinational corporations in developed countries, with particular emphasis on the EEC and the United States, integrating both legal and economic aspects of the subject. Since the international nature of the activities of multinational companies brings them within the scope of the domestic tax provisions of different countries, the authors outline the principles behind the domestic tax treatment of companies, and then assess the economic impact of this treatment. They subsequently examine the international taxation of multinationals, paying special attention to the OECD modelmore » treaty which seeks to remove the problem of international double taxation; reactions of governments to each other's fiscal policies are also examined, with special attention being paid to tax havens. Finally, they look at the EEC proposals for the harmonization of corporate tax systems within the Community and postulate how these proposals would operate if put into effect. There are numerous examples throughout the book of international taxation at work, and these together with the clear text provide a readily comprehensible account of a subject that can seem highly complicated to the uninitiated.« less

Exploring the Measurement Properties of the eHealth Literacy Scale (eHEALS) Among Baby Boomers: A Multinational Test of Measurement Invariance.

PubMed

Sudbury-Riley, Lynn; FitzPatrick, Mary; Schulz, Peter J

2017-02-27

The eHealth Literacy Scale (eHEALS) is one of only a few available measurement scales to assess eHealth literacy. Perhaps due to the relative paucity of such measures and the rising importance of eHealth literacy, the eHEALS is increasingly a choice for inclusion in a range of studies across different groups, cultures, and nations. However, despite its growing popularity, questions have been raised over its theoretical foundations, and the factorial validity and multigroup measurement properties of the scale are yet to be investigated fully. The objective of our study was to examine the factorial validity and measurement invariance of the eHEALS among baby boomers (born between 1946 and 1964) in the United States, United Kingdom, and New Zealand who had used the Internet to search for health information in the last 6 months. Online questionnaires collected data from a random sample of baby boomers from the 3 countries of interest. The theoretical underpinning to eHEALS comprises social cognitive theory and self-efficacy theory. Close scrutiny of eHEALS with analysis of these theories suggests a 3-factor structure to be worth investigating, which has never before been explored. Structural equation modeling tested a 3-factor structure based on the theoretical underpinning to eHEALS and investigated multinational measurement invariance of the eHEALS. We collected responses (N=996) to the questionnaires using random samples from the 3 countries. Results suggest that the eHEALS comprises a 3-factor structure with a measurement model that falls within all relevant fit indices (root mean square error of approximation, RMSEA=.041, comparative fit index, CFI=.986). Additionally, the scale demonstrates metric invariance (RMSEA=.040, CFI=.984, ΔCFI=.002) and even scalar invariance (RMSEA=.042, CFI=.978, ΔCFI=.008). To our knowledge, this is the first study to demonstrate multigroup factorial equivalence of the eHEALS, and did so based on data from 3 diverse nations and random samples drawn from an increasingly important cohort. The results give increased confidence to researchers using the scale in a range of eHealth assessment applications from primary care to health promotions. ©Lynn Sudbury-Riley, Mary FitzPatrick, Peter J Schulz. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.02.2017.

Exploring the Measurement Properties of the eHealth Literacy Scale (eHEALS) Among Baby Boomers: A Multinational Test of Measurement Invariance

PubMed Central

2017-01-01

Background The eHealth Literacy Scale (eHEALS) is one of only a few available measurement scales to assess eHealth literacy. Perhaps due to the relative paucity of such measures and the rising importance of eHealth literacy, the eHEALS is increasingly a choice for inclusion in a range of studies across different groups, cultures, and nations. However, despite its growing popularity, questions have been raised over its theoretical foundations, and the factorial validity and multigroup measurement properties of the scale are yet to be investigated fully. Objective The objective of our study was to examine the factorial validity and measurement invariance of the eHEALS among baby boomers (born between 1946 and 1964) in the United States, United Kingdom, and New Zealand who had used the Internet to search for health information in the last 6 months. Methods Online questionnaires collected data from a random sample of baby boomers from the 3 countries of interest. The theoretical underpinning to eHEALS comprises social cognitive theory and self-efficacy theory. Close scrutiny of eHEALS with analysis of these theories suggests a 3-factor structure to be worth investigating, which has never before been explored. Structural equation modeling tested a 3-factor structure based on the theoretical underpinning to eHEALS and investigated multinational measurement invariance of the eHEALS. Results We collected responses (N=996) to the questionnaires using random samples from the 3 countries. Results suggest that the eHEALS comprises a 3-factor structure with a measurement model that falls within all relevant fit indices (root mean square error of approximation, RMSEA=.041, comparative fit index, CFI=.986). Additionally, the scale demonstrates metric invariance (RMSEA=.040, CFI=.984, ΔCFI=.002) and even scalar invariance (RMSEA=.042, CFI=.978, ΔCFI=.008). Conclusions To our knowledge, this is the first study to demonstrate multigroup factorial equivalence of the eHEALS, and did so based on data from 3 diverse nations and random samples drawn from an increasingly important cohort. The results give increased confidence to researchers using the scale in a range of eHealth assessment applications from primary care to health promotions. PMID:28242590

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Assuaging Nuclear Energy Risks: The Angarsk International Uranium Enrichment Center

NASA Astrophysics Data System (ADS)

Myers, Astasia

2011-06-01

The recent nuclear renaissance has motivated many countries, especially developing nations, to plan and build nuclear power reactors. However, domestic low enriched uranium demands may trigger nations to construct indigenous enrichment facilities, which could be redirected to fabricate high enriched uranium for nuclear weapons. The potential advantages of establishing multinational uranium enrichment sites are numerous including increased low enrichment uranium access with decreased nuclear proliferation risks. While multinational nuclear initiatives have been discussed, Russia is the first nation to actualize this concept with their Angarsk International Uranium Enrichment Center (IUEC). This paper provides an overview of the historical and modern context of the multinational nuclear fuel cycle as well as the evolution of Russia's IUEC, which exemplifies how international fuel cycle cooperation is an alternative to domestic facilities.

Reducing Proliferation Rick Through Multinational Fuel Cycle Facilities

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

Amanda Rynes

2010-11-01

With the prospect of rapid expansion of the nuclear energy industry and the ongoing concern over weapons proliferation, there is a growing need for a viable alternative to traditional nation-based fuel production facilities. While some in the international community remain apprehensive, the advantages of multinational fuel cycle facilities are becoming increasingly apparent, with states on both sides of the supply chain able to garner the security and financial benefits of such facilities. Proliferation risk is minimized by eliminating the need of states to establish indigenous fuel production capabilities and the concept's structure provides an additional internationally monitored barrier against themore » misuse or diversion of nuclear materials. This article gives a brief description of the arguments for and against the implementation of a complete multinational fuel cycle.« less

[Problems of study designs with randomization, blinding and placebos].

PubMed

Heusser, P

1999-04-01

As randomised double-blind trials are not rarely demanded as a prerequisite for the scientific acceptance of complementary medicine, the author has analysed the soundness of this demand on the basis of the international literature. As a result there appeared a number of methodological, practical and ethical problems which question the theoretically deduced primal value of this study design relative to the needs of medical practice and of health insurance issues. The experimental instruments of randomisation, blinding and placebo deliberately exclude essential therapeutic factors which are integral elements of complementary medical concepts; therefore, it is suggested to supplement quantitatively and collectively oriented experimental research by non-experimental procedures, which adequately reflect the context- and practice-related individual reality.

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…

Restorations in abrasion/erosion cervical lesions: 8-year results of a triple blind randomized controlled trial.

PubMed

Dall'Orologio, Giovanni Dondi; Lorenzi, Roberta

2014-10-01

An equivalence randomized controlled trial within the subject was organized to evaluate the clinical long-term success of a new 2-step etch & rinse adhesive and a new nano-filled ormocer. 50 subjects, 21 males and 29 females aged between 21 and 65, were randomized to receive 150 restorations, 100 with the new restorative material, 50 with the composite as control, placed in non-carious cervical lesions with the same bonding system. The main outcome measure was the cause of failure at 8 years. Randomization was number table-generated, with allocation concealment by opaque sequentially numbered sealed and stapled envelopes. Subjects, examiner, and analyst were blinded to group assignment. Two interim analyses were performed. Data were analyzed by ANOVA and Cox test (P < 0.05). After 8 years, 40 subjects and 120 teeth were included in the analysis of the primary outcome. There were eight failures in the experimental group and four failures in the control group. The cumulative loss rate was 7% for both restorative materials, with the annual failure lower than 1%, without any statistically significant difference. There were two key elements of failure: the presence of sclerotic dentin and the relationship between lesion and gingival margin.

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.

Fixed, low radiant exposure vs. incremental radiant exposure approach for diode laser hair reduction: a randomized, split axilla, comparative single-blinded trial.

PubMed

Pavlović, M D; Adamič, M; Nenadić, D

2015-12-01

Diode lasers are the most commonly used treatment modalities for unwanted hair reduction. Only a few controlled clinical trials but not a single randomized controlled trial (RCT) compared the impact of various laser parameters, especially radiant exposure, onto efficacy, tolerability and safety of laser hair reduction. To compare the safety, tolerability and mid-term efficacy of fixed, low and incremental radiant exposures of diode lasers (800 nm) for axillary hair removal, we conducted an intrapatient, left-to-right, patient- and assessor-blinded and controlled trial. Diode laser (800 nm) treatments were evaluated in 39 study participants (skin type II-III) with unwanted axillary hairs. Randomization and allocation to split axilla treatments were carried out by a web-based randomization tool. Six treatments were performed at 4- to 6-week intervals with study subjects blinded to the type of treatment. Final assessment of hair reduction was conducted 6 months after the last treatment by means of blinded 4-point clinical scale using photographs. The primary endpoint was reduction in hair growth, and secondary endpoints were patient-rated tolerability and satisfaction with the treatment, treatment-related pain and adverse effects. Excellent reduction in axillary hairs (≥ 76%) at 6-month follow-up visit after receiving fixed, low and incremental radiant exposure diode laser treatments was obtained in 59% and 67% of study participants respectively (Z value: 1.342, P = 0.180). Patients reported lower visual analogue scale (VAS) pain score on the fixed (4.26) than on the incremental radiant exposure side (5.64) (P < 0.0003). The only side-effect was mild and transient erythema. Subjects better tolerated the fixed, low radiant exposure protocol (P = 0.03). The majority of the study participants were satisfied with both treatments. Both low and incremental radiant exposures produced similar hair reduction and high and comparable patient satisfaction. However, low radiant exposure diode laser treatments were less painful and better tolerated. © 2015 European Academy of Dermatology and Venereology.

Blinded randomized controlled study of a web-based otoscopy simulator in undergraduate medical education.

PubMed

Stepniak, Camilla; Wickens, Brandon; Husein, Murad; Paradis, Josee; Ladak, Hanif M; Fung, Kevin; Agrawal, Sumit K

2017-06-01

OtoTrain is a Web-based otoscopy simulator that has previously been shown to have face and content validity. The objective of this study was to evaluate the effectiveness of this Web-based otoscopy simulator in teaching diagnostic otoscopy to novice learners STUDY DESIGN: Prospective, blinded randomized control trial. Second-year medical students were invited to participate in the study. A pretest consisted of a series of otoscopy videos followed by an open-answer format assessment pertaining to the characteristics and diagnosis of each video. Participants were then randomly divided into a control group and a simulator group. Following the pretest, both groups attended standard otology lectures, but the simulator group was additionally given unlimited access to OtoTrain for 1 week. A post-test was completed using a separate set of otoscopy videos. Tests were graded based on a comprehensive marking scheme. The pretest and post-test were anonymized, and the three evaluators were blinded to student allotment. A total of 41 medical students were enrolled in the study and randomized to the control group (n = 20) and the simulator group (n = 21). There was no significant difference between the two groups on their pretest scores. With the standard otology lectures, the control group had a 31% improvement in their post-test score (mean ± standard error of the mean, 30.4 ± 1.5) compared with their pretest score (23.3 ± 1.8) (P < .001). The simulator group had the addition of OtoTrain to the otology lectures, and their score improved by 71% on their post-test (37.8 ± 1.6) compared to their pretest (22.1 ± 1.9) (P < .001). Comparing the post-test results, the simulator group had a 24% higher score than the control group (P < .002). Inter-rater reliability between the blinded evaluators was excellent (r = 0.953, P < .001). The use of OtoTrain increased the diagnostic otoscopic performance in novice learners. OtoTrain may be an effective teaching adjunct for undergraduate medical students. 1b. Laryngoscope, 127:1306-1311, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Immediate effects of blood donation on physical and cognitive performance-A randomized controlled double-blinded trial.

PubMed

Eliassen, Håkon S; Hervig, Tor; Backlund, Sebastian; Sivertsen, Joar; Iversen, Vegard Vereide; Kristoffersen, Morten; Wengaard, Eivind; Gramstad, Arne; Fosse, Theodor; Bjerkvig, Christopher K; Apelseth, Torunn; Doughty, Heidi; Strandenes, Geir

2018-06-01

The success of implementing damage control resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation; however, none have investigated the effects of blood donation on cognitive performance. We describe a prospective double-blinded, randomized, controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (baseline day), immediately after donation (Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank, where eligibility requirements were met on the testing days, and providing informed consent. Participants were randomized to either the experimental (n = 26) or control group (n = 31). Control group participants underwent a 'mock donation" in which a phlebotomy needle was placed but blood was not withdrawn. In the experimental group, mean ± SEM VO2max declined 6% from 41.35 ± 1.7 mLO2/(min·kg) at baseline to 39.0 ± 1.6 mLO2/(min·kg) on Day 0 and increased to 40.51 ± 1.5 mLO2/(min·kg) on Day 7. Comparable values in the control group were 42.1 ± 1.8 mLO2/(min·kg) at baseline, 41.6 ± 1.8 mLO2/(min·kg)) on Day 1 (1% decline from baseline), and 41.8 ± 1.8 mLO2/(min·kg) on Day 7.Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences (p > 0.05). Our main findings are that executive cognitive and physical performances were well maintained after whole blood donation in healthy blood donors. The findings inform postdonation guidance on when donors may be required to return to duty. Randomized, controlled, double-blinded prospective trial study, level 1.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

PubMed Central

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

The Mission Partner Environment: Challenges To Multinational Information Sharing

DTIC Science & Technology

2016-02-15

Harvey , Royal Air Force 15 February 2016 DISTRIBUTION A. Approved for public release: distribution unlimited. ii Disclaimer The views expressed...troops, with non-U.S. commanders in charge of vast areas of inhospitable geography . The enormous size and scope of this mission created incredibly...between people and organizations separated by wide geography is the requirement for a persistent and durable means for multinational communication and

How China Could Affect the Future of U.S. Defense Corporations

DTIC Science & Technology

2010-12-01

of Jonathan Galloway , who addressees among many things, the global implications of DMNCs by differentiating the driving mechanisms for these... Galloway , “The Military-Industrial Linkages of U.S.-Based Multinational Corporations,” International Studies Quarterly 16, no. 4, Multinational...individual percentages.56 Galloway states “it stands to reason that their managements will be interested in preserving the dynamic equilibrium between

Implications for the U.S. of Anglo-French Defense Cooperation

DTIC Science & Technology

2012-04-30

multinational European military development projects are viewed with scepticism in the UK, the Anglo- French arrangement could strengthen the prospects...multinational European military development projects are viewed with scepticism in the UK, the Anglo- French arrangement could strengthen the prospects for...programme. The UK also dropped out of the Horizon Common New Generation Frigate project , which included France and Italy (Antill, 2011). Continued

The Promotion of Bottle Feeding by Multinational Corporations: How Advertising and the Health Professions Have Contributed. Cornell International Nutritioon Monograph Series, Number 2 (1975).

ERIC Educational Resources Information Center

Greiner, Ted; Latham, Michael C., Ed.

This report investigates the ways bottle feeding of infants is promoted by multinational corporations. Data were obtained from the following: (1) a survey of available infant food advertising in newspapers and magazines from developing countries; (2) a study of some interrelationships between the health professions and infant food companies,…

Whole body vibration exercise for chronic low back pain: study protocol for a single-blind randomized controlled trial.

PubMed

Wang, Xue-Qiang; Pi, Yan-Lin; Chen, Pei-Jie; Chen, Bin-Lin; Liang, Lei-Chao; Li, Xin; Wang, Xiao; Zhang, Juan

2014-04-02

Low back pain affects approximately 80% of people at some stage in their lives. Exercise therapy is the most widely used nonsurgical intervention for low back pain in practice guidelines. Whole body vibration exercise is becoming increasingly popular for relieving musculoskeletal pain and improving health-related quality of life. However, the efficacy of whole body vibration exercise for low back pain is not without dispute. This study aims to estimate the effect of whole body vibration exercise for chronic low back pain. We will conduct a prospective, single-blind, randomized controlled trial of 120 patients with chronic low back pain. Patients will be randomly assigned into an intervention group and a control group. The intervention group will participate in whole body vibration exercise twice a week for 3 months. The control group will receive general exercise twice a week for 3 months. Primary outcome measures will be the visual analog scale for pain, the Oswestry Disability Index and adverse events. The secondary outcome measures will include muscle strength and endurance of spine, trunk proprioception, transversus abdominis activation capacity, and quality of life. We will conduct intention-to-treat analysis if any participants withdraw from the trial. Important features of this study include the randomization procedures, single-blind, large sample size, and a standardized protocol for whole body vibration in chronic low back pain. This study aims to determine whether whole body vibration exercise produces more beneficial effects than general exercise for chronic low back pain. Therefore, our results will be useful for patients with chronic low back pain as well as for medical staff and health-care decision makers. Chinese Clinical Trial Registry: ChiCTR-TRC-13003708.

Pentoxifylline for the treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized double-blind, placebo-controlled studies.

PubMed

Zeng, Tao; Zhang, Cui-Li; Zhao, Xiu-Lan; Xie, Ke-Qin

2014-06-01

Pentoxifylline has been used to treat nonalcoholic fatty liver diseases (NAFLDs) due to its anti-tumor necrosis factor-α effects. We conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials to investigate the effect of pentoxifylline on the biochemical and histological parameters of NAFLD patients. A comprehensive literature search was conducted in the database including PubMed, Embase, ISI web of knowledge, the Cochrane Library, and Google Scholar to identify randomized, double-blind, placebo-controlled clinical trials about the effects of pentoxifylline on NAFLD. The pooled weighted mean difference (WMD) with 95% confidence interval (CI) was calculated to compare the effects of pentoxifylline and placebo. Five well-designed studies were retrieved. Pooled results showed that pentoxifylline significantly reduced the serum alanine transaminase activity (WMD=-27.97; 95% CI: -42.59, -13.34) and aspartate transaminase activity (WMD=-13.97; 95% CI: -23.31, -4.63) in NAFLD patients compared with placebo. In addition, pentoxifylline significantly improved steatosis (WMD=-0.68; 95% CI: -1.01, -0.34), lobular inflammation (WMD=-0.49; 95% CI: -0.86, -0.12), and fibrosis (WMD=-0.60; 95% CI: -0.99, -0.21). Furthermore, pentoxifylline also led to significant reduction in BMI (WMD=-0.51; 95% CI: -0.96, -0.06) and fasting glucose (WMD=-8.97; 95% CI: -14.52, -3.42), but did not significantly affect the serum tumor necrosis factor α and adiponectin levels when compared with placebo. Pentoxifylline could reduce the aminotransferase activities and improve the histological parameters in NAFLD patients. Large well-designed, randomized, placebo-controlled studies are needed to confirm these results.

Short-term and practice effects of metronome pacing in Parkinson's disease patients with gait freezing while in the 'on' state: randomized single blind evaluation.

PubMed

Cubo, Esther; Leurgans, Sue; Goetz, Christopher G

2004-12-01

In a randomized single blind parallel study, we tested the efficacy of an auditory metronome on walking speed and freezing in Parkinson's disease (PD) patients with freezing gait impairment during their 'on' function. No pharmacological treatment is effective in managing 'on' freezing in PD. Like visual cues that can help overcome freezing, rhythmic auditory pacing may provide cues that help normalize walking pace and overcome freezing. Non-demented PD patients with freezing during their 'on' state walked under two conditions, in randomized order: unassisted walking and walking with the use of an audiocassette with a metronome recording. The walking trials were randomized and gait variables were rated from videotapes by a blinded evaluator. Outcome measures were total walking time (total trial time-total freezing time), which was considered the time over a course of specified length, freezing time, average freeze duration and number of freezes. All outcomes were averaged across trials for each person and then compared across conditions using Signed Rank tests. Twelve non-demented PD patients with a mean age of 65.8 +/- 11.2 years, and mean PD duration of 12.4 +/- 7.3 years were included. The use of the metronome slowed ambulation and increased the total walking time (P < 0.0005) only during the first visit, without affecting any freezing variable. In the nine patients who took the metronome recording home and used it daily for 1 week while walking, freezing remained unimproved. Though advocated in prior publications as a walking aid for PD patients, auditory metronome pacing slows walking and is not a beneficial intervention for freezing during their 'on' periods.

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.

Validity and reliability of global operative assessment of laparoscopic skills (GOALS) in novice trainees performing a laparoscopic cholecystectomy.

PubMed

Kramp, Kelvin H; van Det, Marc J; Hoff, Christiaan; Lamme, Bas; Veeger, Nic J G M; Pierie, Jean-Pierre E N

2015-01-01

Global Operative Assessment of Laparoscopic Skills (GOALS) assessment has been designed to evaluate skills in laparoscopic surgery. A longitudinal blinded study of randomized video fragments was conducted to estimate the validity and reliability of GOALS in novice trainees. In total, 10 trainees each performed 6 consecutive laparoscopic cholecystectomies. Sixty procedures were recorded on video. Video fragments of (1) opening of the peritoneum; (2) dissection of Calot's triangle and achievement of critical view of safety; and (3) dissection of the gallbladder from the liver bed were blinded, randomized, and rated by 2 consultant surgeons using GOALS. Also, a grade was given for overall competence. The correlation of GOALS with live observation Objective Structured Assessment of Technical Skills (OSATS) scores was calculated. Construct validity was estimated using the Friedman 2-way analysis of variance by ranks and the Wilcoxon signed-rank test. The interrater reliability was calculated using the absolute and consistency agreement 2-way random-effects model intraclass correlation coefficient. A high correlation was found between mean GOALS score (r = 0.879, p = 0.021) and mean OSATS score. The GOALS score increased significantly across the 6 procedures (p = 0.002). The trainees performed significantly better on their sixth when compared with their first cholecystectomy (p = 0.004). The consistency agreement interrater reliability was 0.37 for the mean GOALS score (p = 0.002) and 0.55 for overall competence (p < 0.001) of the 3 video fragments. The validity observed in this randomized blinded longitudinal study supports the existing evidence that GOALS is a valid tool for assessment of novice trainees. A relatively low reliability was found in this study. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Does addition of 'mud-pack and hot pool treatment' to patient education make a difference in fibromyalgia patients? A randomized controlled single blind study.

PubMed

Bağdatlı, Ali Osman; Donmez, Arif; Eröksüz, Rıza; Bahadır, Güler; Turan, Mustafa; Erdoğan, Nergis

2015-12-01

The aim of this randomized controlled single-blind study is to explore whether addition of mud-pack and hot pool treatments to patient education make a significant difference in short and mild term outcomes of the patients with fibromyalgia. Seventy women with fibromyalgia syndrome were randomly assigned to either balneotherapy with mud-pack and hot pool treatments (35) or control (35) groups. After randomization, five patients from balneotherapy group and five patients from control group were dropped out from the study with different excuses. All patients had 6-h patient education programme about fibromyalgia syndrome and were given a home exercise programme. The patients in balneotherapy group had heated pool treatment at 38 °C for 20 min a day, and mud-pack treatment afterwards on back region at 45 °C. Balneotherapy was applied on weekdays for 2 weeks. All patients continued to take their medical treatment. An investigator who was blinded to the intervention assessed all the patients before and after the treatment, at the first and the third months of follow-up. Outcome measures were FIQ, BDI and both patient's and physician's global assessments. Balneotherapy group was significantly better than control group at after the treatment and at the end of the first month follow-up assessments in terms of patient's and physician's global assessment, total FIQ score, and pain intensity, fatigue, non-refreshed awaking, stiffness, anxiety and depression subscales of FIQ. No significant difference was found between the groups in terms of BDI scores. It is concluded that patient education combined with 2 weeks balneotherapy application has more beneficial effects in patients with fibromyalgia syndrome as compared to patient education alone.

Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for a Randomized, Double-Blind, Placebo- Controlled Trial.

PubMed

Mao, Jun J; Li, Qing S; Soeller, Irene; Rockwell, Kenneth; Xie, Sharon X; Amsterdam, Jay D

2014-11-01

Anxiety symptoms are among the most common reasons for consumers to use Complementary and Alternative Medicine (CAM) therapy. Although many botanicals have been proposed as putative remedies for anxiety symptoms, there has been a paucity of controlled trials of these remedies. A preliminary study of the anxiolytic effect of Chamomile ( Matricaria recutita ) in humans suggests that chamomile may have anxiolytic and antidepressant activity. We now seek to conduct a 5-year randomized, double-blind, placebo-substitution study to examine the short and long-term safety and efficacy of chamomile extract in Generalized Anxiety Disorder (GAD). 180 subjects with moderate to severe GAD will receive initial open-label pharmaceutical-grade chamomile extract 500-1,500 mg daily for 8 weeks. Responders to treatment who remain well for an additional 4 weeks of consolidation therapy, will be randomized to double-blind continuation therapy with either chamomile extract 500-1,500 mg daily or placebo for an additional 26 weeks. The primary outcome will be the time to relapse during study continuation therapy in each treatment condition. Secondary outcomes will include the proportion of subjects in each treatment condition who relapse, as well as the proportion of subjects with treatment-emergent adverse events. Quality of life ratings will also be compared between treatment conditions during short and long-term therapy. Many individuals with mental disorders decline conventional therapy and seek CAM therapies for their symptoms. Thus, the identification of effective CAM therapy is of relevance to reducing the burden of mental illness. This study builds upon our prior findings of significant superiority of chamomile versus placebo in reducing GAD symptoms. We now extend these preliminary findings by conducting a randomized long-term safety and efficacy study of chamomile in GAD.

Wrist-ankle acupuncture (WAA) for primary dysmenorrhea (PD) of young females: study protocol for a randomized controlled trial.

PubMed

Chen, Yingfan; Tian, Sinan; Tian, Jing; Shu, Shi

2017-08-22

Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).

Cap Assisted Upper Endoscopy for Examination of the Major Duodenal Papilla: A Randomized, Blinded, Controlled Crossover Study (CAPPA Study).

PubMed

Abdelhafez, Mohamed; Phillip, Veit; Hapfelmeier, Alexander; Elnegouly, Mayada; Poszler, Alexander; Strobel, Kilian; Born, Peter; Dollhopf, Markus; Kassem, Abdel Meguid; Calavrezos, Lenika; Klare, Peter; Schlag, Christoph; Bajbouj, Monther; Schmid, Roland M; von Delius, Stefan

2017-05-01

Examination of major duodenal papilla (MDP) by standard forward-viewing esophagogastroduodenoscopy (S-EGD) is limited. Cap assisted esophagogastroduodenoscopy (CA-EGD) utilizes a cap fitted to the tip of the endoscope that can depress the mucosal folds and thus might improve visualization of MDP. The aim of this study was to compare CA-EGD to S-EGD for complete examination of the MDP. Prospective, randomized, blinded, controlled crossover study. Subjects scheduled for elective EGD were randomized to undergo S-EGD (group A) or CA-EGD (group B) before undergoing a second examination by the alternate method. Images of the MDP were evaluated by three blinded multicenter-experts. Our primary outcome measure was complete examination of the papilla. Secondary outcome measures were duration and overall diagnostic yield. A total of 101 patients were randomized and completed the study. Complete examination of MDP was achieved in 98 patients using CA-EGD compared to 24 patients using S-EGD (97 vs. 24%, P<0.001). Median duration from intubation of the esophagus until localization of the MDP was shorter with CA-EGD (46. vs. 96 s., P<0.001). In group A, 11 extra lesions and 12 additional incidental findings were detected by secondary CA-EGD, whereas neither were detected by secondary S-EGD in group B (22 vs. 0% and 24 vs. 0%, P<0.001 and P<0.001). CA-EGD enabled complete examination of MDP in almost all cases compared to a low success rate of S-EGD. CA-EGD detected a significant amount of lesions and incidental findings when added to S-EGD. CA-EGD is a safe and effective method for examination of MDP.

Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Fleischhacker, W Wolfgang; Hobart, Mary; Ouyang, John; Forbes, Andy; Pfister, Stephanie; McQuade, Robert D; Carson, William H; Sanchez, Raymond; Nyilas, Margareta; Weiller, Emmanuelle

2017-01-01

Brexpiprazole has previously demonstrated efficacy in acute schizophrenia trials. The objective of this trial was to assess the efficacy, safety, and tolerability of maintenance treatment with brexpiprazole in adults with schizophrenia. Patients with an acute exacerbation of psychotic symptoms were converted to brexpiprazole (1-4mg/d) over 1 to 4 weeks and entered a single-blind stabilization phase. Those patients who met stability criteria for 12 weeks were randomized 1:1 to double-blind maintenance treatment with either brexpiprazole (at their stabilization dose) or placebo for up to 52 weeks. The primary efficacy endpoint was the time from randomization to impending relapse. Safety and tolerability were also assessed. A total of 524 patients were enrolled, 202 of whom were stabilized on brexpiprazole and randomized to brexpiprazole (n=97) or placebo (n=105). Efficacy was demonstrated at a prespecified interim analysis (conducted after 45 events), and so the trial was terminated early. The final analysis showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo (P<.0001, log-rank test). The hazard ratio for the final analysis was 0.292 (95% confidence interval: 0.156, 0.548); mean dose at last visit, 3.6mg. The proportion of patients meeting the criteria for impending relapse was 13.5% with brexpiprazole and 38.5% with placebo (P<.0001). During the maintenance phase, the incidence of adverse events was comparable to placebo. or patients with schizophrenia already stabilized on brexpiprazole, maintenance treatment with brexpiprazole was efficacious, with a favorable safety profile. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study.

PubMed

Pakseresht, Siroos; Boostani, Hatam; Sayyah, Mehdi

2011-10-11

Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition. Many herbs with psychotropic effects exist which can have fewer side effects compared to more conventional medications. Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in the world with an effect on GABA. This plant is reported to be safe on humans. Our objective in this study was to compare the efficacy of the extract of Valeriana Officinalis L. with placebo in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty-one adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (765 mg/day) or placebo (30 mg/day) for 8 weeks. The results showed significant difference between the extract and placebo in the end of treatment (P=0.000). Somnolence was the only significant difference between the two groups in terms of observed side effects (P=0.02). The results suggest that Valeriana Officinalis L. has some antiobsessive and compulsive effects. However, further studies are needed to confirm these findings. Psychiatrists often find that many patients cannot tolerate the side effects of psychiatry medicine Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in world with effect on GABA.The results showed significant difference between the extract and placebo in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness.

PubMed

Cohen, Steven P; Peterlin, B Lee; Fulton, Larry; Neely, Edward T; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C; Jacobs, Michael B; Plunkett, Anthony R; Verdun, Aubrey J; Stojanovic, Milan P; Hanling, Steven; Constantinescu, Octav; White, Ronald L; McLean, Brian C; Pasquina, Paul F; Zhao, Zirong

2015-12-01

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline -2.743 ± 2.487 vs -1.377 ± 1.970; P < 0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline -1.925 ± 3.204 vs -0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline -2.738 ± 2.753 vs -1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures.

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness

PubMed Central

Cohen, Steven P.; Peterlin, B. Lee; Fulton, Larry; Neely, Edward T.; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C.; Jacobs, Michael B.; Plunkett, Anthony R.; Verdun, Aubrey J.; Stojanovic, Milan P.; Hanling, Steven; Constantinescu, Octav; White, Ronald L.; McLean, Brian C.; Pasquina, Paul F.; Zhao, Zirong

2015-01-01

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline −2.743 ± 2.487 vs −1.377 ± 1.970; P <0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline−1.925 ± 3.204 vs−0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline −2.738 ± 2.753 vs −1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures. PMID:26447705

Effectiveness and Cost-Effectiveness of Different Weekly Frequencies of Pilates for Chronic Low Back Pain: Randomized Controlled Trial.

PubMed

Miyamoto, Gisela Cristiane; Moura, Katherinne Ferro; Franco, Yuri Rafael dos Santos; Oliveira, Naiane Teixeira Bastos de; Amaral, Diego Diulgeroglo Vicco; Branco, Amanda Nery Castelo; Silva, Maria Liliane da; Lin, Christine; Cabral, Cristina Maria Nunes

2016-03-01

The Pilates method has been recommended to patients with low back pain, but the evidence on effectiveness is inconclusive. In addition, there is still no evidence for the cost-effectiveness of this method or for the ideal number of sessions to achieve the highest effectiveness. The aim of this study will be to investigate the effectiveness and cost-effectiveness of the Pilates method with different weekly frequencies in the treatment of patients with nonspecific low back pain. This is a randomized controlled trial with blinded assessor. This study will be conducted at a physical therapy clinic in São Paulo, Brazil. Two hundred ninety-six patients with nonspecific low back pain between the ages of 18 and 80 years will be assessed and randomly allocated to 4 groups (n=74 patients per group). All groups will receive an educational booklet. The booklet group will not receive additional exercises. Pilates group 1 will follow a Pilates-based program once a week, Pilates group 2 will follow the same program twice a week, and Pilates group 3 will follow the same program 3 times a week. The intervention will last 6 weeks. A blinded assessor will evaluate pain, quality-adjusted life-years, general and specific disability, kinesiophobia, pain catastrophizing, and global perceived effect 6 weeks, 6 months, and 12 months after randomization. Therapists and patients will not be blinded. This will be the first study to investigate different weekly frequencies of treatment sessions for nonspecific low back pain. The results of this study will contribute to a better definition of treatment programs for this population. © 2016 American Physical Therapy Association.

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 Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study.

PubMed

Jin, Cai De; Kim, Moo Hyun; Bang, Junghee; Serebruany, Victor

The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017. © 2017 S. Karger AG, Basel.

Does addition of `mud-pack and hot pool treatment' to patient education make a difference in fibromyalgia patients? A randomized controlled single blind study

NASA Astrophysics Data System (ADS)

Bağdatlı, Ali Osman; Donmez, Arif; Eröksüz, Rıza; Bahadır, Güler; Turan, Mustafa; Erdoğan, Nergis

2015-12-01

The aim of this randomized controlled single-blind study is to explore whether addition of mud-pack and hot pool treatments to patient education make a significant difference in short and mild term outcomes of the patients with fibromyalgia. Seventy women with fibromyalgia syndrome were randomly assigned to either balneotherapy with mud-pack and hot pool treatments (35) or control (35) groups. After randomization, five patients from balneotherapy group and five patients from control group were dropped out from the study with different excuses. All patients had 6-h patient education programme about fibromyalgia syndrome and were given a home exercise programme. The patients in balneotherapy group had heated pool treatment at 38 °C for 20 min a day, and mud-pack treatment afterwards on back region at 45 °C. Balneotherapy was applied on weekdays for 2 weeks. All patients continued to take their medical treatment. An investigator who was blinded to the intervention assessed all the patients before and after the treatment, at the first and the third months of follow-up. Outcome measures were FIQ, BDI and both patient's and physician's global assessments. Balneotherapy group was significantly better than control group at after the treatment and at the end of the first month follow-up assessments in terms of patient's and physician's global assessment, total FIQ score, and pain intensity, fatigue, non-refreshed awaking, stiffness, anxiety and depression subscales of FIQ. No significant difference was found between the groups in terms of BDI scores. It is concluded that patient education combined with 2 weeks balneotherapy application has more beneficial effects in patients with fibromyalgia syndrome as compared to patient education alone.

Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial.

PubMed

Harada, Tasuku; Kosaka, Saori; Elliesen, Joerg; Yasuda, Masanobu; Ito, Makoto; Momoeda, Mikio

2017-11-01

To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (Flexible MIB ) compared with placebo to treat endometriosis-associated pelvic pain (EAPP). A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm. Thirty-two centers. A total of 312 patients with endometriosis. Patients were randomized to Flexible MIB , placebo, or dienogest. The Flexible MIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to Flexible MIB . Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm. Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase. Compared with placebo, Flexible MIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). Flexible MIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas. Flexible MIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis. NCT01697111. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

DTIC Science & Technology

2014-10-01

o Aude Henin, Ph.D. (MGH PI) o Dina Hirshfeld- Becker , Ph.D. (independent evaluator at MGH) o Angela Utschig, Ph.D. (study therapist at MGH) o...intranasal oxytocin or placebo. Participants and evaluators will be blind to treatment condition. In year 1 of the study, we set up the study framework...experimental treatment, and OT before 12 sessions of CBT treatment. Volunteers (patients) and evaluators will be blind to condition assignment

Methodological reporting of randomized trials in five leading Chinese nursing journals.

PubMed

Shi, Chunhu; Tian, Jinhui; Ren, Dan; Wei, Hongli; Zhang, Lihuan; Wang, Quan; Yang, Kehu

2014-01-01

Randomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field. In June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0. In total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34 ± 0.97 (Mean ± SD). No RCT reported descriptions and changes in "trial design," changes in "outcomes" and "implementation," or descriptions of the similarity of interventions for "blinding." Poor reporting was found in detailing the "settings of participants" (13.1%), "type of randomization sequence generation" (1.8%), calculation methods of "sample size" (0.4%), explanation of any interim analyses and stopping guidelines for "sample size" (0.3%), "allocation concealment mechanism" (0.3%), additional analyses in "statistical methods" (2.1%), and targeted subjects and methods of "blinding" (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of "participants," "interventions," and definitions of the "outcomes" and "statistical methods." The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score. The completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods.

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

PubMed

Dalai, Shebani Sethi; Adler, Sarah; Najarian, Thomas; Safer, Debra Lynn

2018-01-01

Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of topical ropivacaine with and without ketamine on post-surgical pain in children undergoing tonsillectomy: a randomized controlled double-blind study.

PubMed

Hong, Boohwi; Lim, Chae Seong; Kim, Yoon-Hee; Lee, Jung Un; Kim, Yong Min; Jung, Choonho; Jo, Yumin

2017-08-01

Tonsillectomy in pediatric patients may cause severe postoperative pain. Topical local anesthetics are an easy and safe way to control post-tonsillectomy pain, but there is no benefit during the early postoperative stage. Topical ketamine shows a good effect on early stage postoperative pain. We compared the effect of topical ropivacaine with and without ketamine on post-tonsillectomy pain. Patients aged 3-7 years undergoing tonsillectomy were selected to participate in the study. Our study was performed in a randomized, placebo-controlled, double-blind manner. Patients were randomly assigned to one of two groups using computer-generated random numbers. The researchers who assessed the pain score, the caregivers, and the patient were blinded to group assignment. One group received topical ropivacaine with saline (RS group) and the other group received topical ropivacaine with 20 mg ketamine (RK group) on the tonsillar bed. Pain scores using the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) at 15 min and 30 min, and at 1, 2, 4, 8, 16 and 24 h were recorded. Rescue analgesic requirement and complications were also recorded. A total of 66 patients were randomly assigned to the RS group (n = 33) and the RK group (n = 33). The mCHEOPS scores were significantly lower in the RK group at 15 min (P = 0.046). The mCHEOPS scores of the two groups decreased with time, but there was no intergroup interaction. The RS group received more analgesics until 1 h after surgery and the RK group received more analgesics during 1-24 h after surgery. There were no differences in adverse outcomes. Topical ropivacaine with ketamine can reduce immediate postoperative pain and analgesic requirement better than ropivacaine alone.

A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.

PubMed

Blume-Peytavi, Ulrike; Hillmann, Kathrin; Dietz, Ekkehart; Canfield, Douglas; Garcia Bartels, Natalie

2011-12-01

Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects. We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics. After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS. Because of differences in the formulations tested, study participants were not blinded to treatment. Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

PubMed

Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

2017-09-01

A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression.

PubMed

Krogh, Jesper; Petersen, Lone; Timmermann, Michael; Saltin, Bengt; Nordentoft, Merete

2007-01-01

In western countries, the yearly incidence of depression is estimated to be 3-5% and the lifetime prevalence is 17%. In patient populations with chronic diseases the point prevalence may be 20%. Depression is associated with increased risk for various conditions such as osteoporoses, cardiovascular diseases, and dementia. WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability. In 2000 the cost of depression in the US was estimated to 83 billion dollars. A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms. However, a meta-analysis from 2001 stated: "The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow-up." The major objective for this randomized trial is to compare the effect of non-aerobic, aerobic, and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale (HAM-D(17)) as primary outcome. The secondary outcome is the effect of the intervention on working status (i.e., lost days from work, employed/unemployed) and the tertiary outcomes consist of biological responses. The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through general practitioners and psychiatrist and randomized to three different interventions: 1) non-aerobic, -- progressive resistance training, 2) aerobic training, -- cardio respiratory fitness, and 3) relaxation training with minimal impact on strength or cardio respiratory fitness. Training for all three groups takes place twice a week for 4 months. Evaluation of patients' symptoms takes place four and 12 months after inclusion. The trial is designed to include 45 patients in each group. Statistical analysis will be done as intention to treat (all randomized patients). Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008-2009.

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.

Is magnetotherapy applied to bilateral hips effective in ankylosing spondylitis patients? A randomized, double-blind, controlled study.

PubMed

Turan, Yasemin; Bayraktar, Kevser; Kahvecioglu, Fatih; Tastaban, Engin; Aydin, Elif; Kurt Omurlu, Imran; Berkit, Isil Karatas

2014-03-01

This double-blind, randomized controlled study was conducted with the aim to investigate the effect of magnetic field therapy applied to the hip region on clinical and functional status in ankylosing spondylitis (AS) patients. Patients with AS (n = 66) who were diagnosed according to modified New York criteria were enrolled in this study. Patients were randomly divided in two groups. Participants were randomly assigned to receive magnetic field therapy (2 Hz) (n = 35), or placebo magnetic field therapy (n = 31) each hip region for 20 min. Patients in each group were given heat pack and short-wave treatments applied to bilateral hip regions. Both groups had articular range of motion and stretching exercises and strengthening exercises for surrounding muscles for the hip region as well as breathing and postural exercises by the same physical therapist. These treatment protocols were continued for a total of 15 sessions (1 session per day), and patients were examined by the same physician at months 1, 3 and 6. Visual analogue scale (VAS) pain, VAS fatigue, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrologic Index (BASMI), DFI, Harris hip assessment index and Ankylosing Spondylitis Quality of Life scale (ASQOL) were obtained at the beginning of therapy and at month 1, month 3 and month 6 for each patient. There were no significant differences between groups in the VAS pain, VAS fatigue, morning stiffness, BASDAI, BASFI, BASMI, DFI, Harris hip assessment index and ASQoL at baseline, month 1, month 3 or month 6 (p > 0.05). Further randomized, double-blind controlled studies are needed in order to establish the evidence level for the efficacy of modalities with known analgesic and anti-inflammatory action such as magnetotherapy, particularly in rheumatic disorders associated with chronic pain.

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

The end of corporate imperialism.

PubMed

Prahalad, C K; Lieberthal, Kenneth

2003-08-01

As they search for growth, multinational corporations will have no choice but to compete in the big emerging markets of China, India, Indonesia, and Brazil. But while it is still common to question how such corporations will change life in those markets, Western executives would be smart to turn the question around and ask how multinationals themselves will be transformed by these markets. To be successful, MNCs will have to rethink every element of their business models, the authors assert in this seminal HBR article from 1998. During the first wave of market entry in the 1980s, multinationals operated with what might be termed an imperialist mind-set, assuming that the emerging markets would merely be new markets for their old products. But this mind-set limited their success: What is truly big and emerging in countries like China and India is a new consumer base comprising hundreds of millions of people. To tap into this huge opportunity, MNCs need to ask themselves five basic questions: Who is in the emerging middle class in these countries? How do the distribution networks operate? What mix of local and global leadership do you need to foster business opportunities? Should you adopt a consistent strategy for all of your business units within one country? Should you take on local partners? The transformation that multinational corporations must undergo is not cosmetic--simply developing greater sensitivity to local cultures will not do the trick, the authors say. To compete in the big emerging markets, multinationals must reconfigure their resources, rethink their cost structures, redesign their product development processes, and challenge their assumptions about who their top-level managers should be.

The prevalence and causes of blindness in the Sultanate of Oman: the Oman Eye Study (OES)

PubMed Central

Khandekar, R; Mohammed, A J; Negrel, A D; Al Riyami, A

2002-01-01

Aims: To estimate the magnitude and the causes of blindness through a community based nationwide survey in Oman. This was conducted in 1996–7. Methods: A stratified cluster random sampling procedure was used to select 12 400 people. The WHO/PBD standardised survey methodology was used, with suitable adaptation. The major causes of blindness were identified among those found blind. Results: A total of 11 417 people were examined (response rate 91.8%) The prevalence of blindness in the Omani population was estimated to be 1.1% (95% CI 0.9 to 1.3), blindness being defined according to the WHO Tenth Revision of the International Classification of Diseases. Prevalence of blindness was clearly related to increasing age, with estimates of 0.08% for the 0–14 age group, 0.1% for the 15–39 age group, 2.3% for the 40–59 age group, and 16.8% for the group aged 60 +. There was a statistically significant difference between the prevalence in females (1.4%) and males (0.8%). The northern and central regions had a higher prevalence of blindness (1.3% to 3%). The major causes of blindness were unoperated cataract (30.5%), trachomatous corneal opacities (23.7%), and glaucoma (11.5%) Conclusions: Despite an active eye healthcare programme, blindness due to cataract and trachoma remains a public health problem of great concern in several regions of the sultanate. These results highlight the need, when planning effective intervention strategies, to target the eye healthcare programme to the ageing population, with special emphasis on women. PMID:12185115

Do TETRA (Airwave) base station signals have a short-term impact on health and well-being? A randomized double-blind provocation study.

PubMed

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-06-01

"Airwave" is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported "electrosensitivity" and of participants who served as controls. Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

PubMed

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Do TETRA (Airwave) Base Station Signals Have a Short-Term Impact on Health and Well-Being? A Randomized Double-Blind Provocation Study

PubMed Central

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-01-01

Background “Airwave” is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. Objectives We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported “electrosensitivity” and of participants who served as controls. Methods Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. Results We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Conclusions Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself. PMID:20075020

Change blindness in pigeons (Columba livia): the effects of change salience and timing

PubMed Central

Herbranson, Walter T.

2015-01-01

Change blindness is a well-established phenomenon in humans, in which plainly visible changes in the environment go unnoticed. Recently a parallel change blindness phenomenon has been demonstrated in pigeons. The reported experiment follows up on this finding by investigating whether change salience affects change blindness in pigeons the same way it affects change blindness in humans. Birds viewed alternating displays of randomly generated lines back-projected onto three response keys, with one or more line features on a single key differing between consecutive displays. Change salience was manipulated by varying the number of line features that changed on the critical response key. Results indicated that change blindness is reduced if a change is made more salient, and this matches previous human results. Furthermore, accuracy patterns indicate that pigeons’ effective search area expanded over the course of a trial to encompass a larger portion of the stimulus environment. Thus, the data indicate two important aspects of temporal cognition. First, the timing of a change has a profound influence on whether or not that change will be perceived. Second, pigeons appear to engage in a serial search for changes, in which additional time is required to search additional locations. PMID:26284021

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12 PMID:28445471

The International Collaboration for Autism Registry Epidemiology (iCARE): multinational registry-based investigations of autism risk factors and trends.

PubMed

Schendel, Diana E; Bresnahan, Michaeline; Carter, Kim W; Francis, Richard W; Gissler, Mika; Grønborg, Therese K; Gross, Raz; Gunnes, Nina; Hornig, Mady; Hultman, Christina M; Langridge, Amanda; Lauritsen, Marlene B; Leonard, Helen; Parner, Erik T; Reichenberg, Abraham; Sandin, Sven; Sourander, Andre; Stoltenberg, Camilla; Suominen, Auli; Surén, Pål; Susser, Ezra

2013-11-01

The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in multinational collaboration concerning data access security, confidentiality and management. Data are obtained by integrating existing national or state-wide, population-based, individual-level data systems and undergo rigorous harmonization and quality control processes. Analyses are performed using database federation via a computational infrastructure with a secure, web-based, interface. iCARE provides a unique, unprecedented resource in autism research that will significantly enhance the ability to detect environmental and genetic contributions to the causes and life course of autism.

Mapping R&D within Multinational Networks: Evidence from the Electronics Industry

NASA Astrophysics Data System (ADS)

Urze, Paula; Manatos, Maria João

Based on the final results of the R&D.COM - Local R&D COMpetencies within Global Value Chains project, this paper aims at mapping the trajectories of delocalised R&D units within a multinational’s global strategy and designing the knowledge flows within the global value chain. This analysis was performed using typologies proposed in the theoretical framework, which help us to have an overview of the network. The methodology is grounded on one extended case study that involves a local R&D unit (Portugal), a foreign R&D unit (Netherlands) and the headquarters (Norway) - developed on a multinational from the electronics industry. This case is an example of a multinational company where R&D is developed mainly in the headquarters but it is also delocalised to some subsidiaries with a certain level of autonomy.

Nivolumab-Based Treatments for Advanced Melanoma

Cancer.gov

A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

Prevalence of blindness and cataract surgical coverage in Narayani Zone, Nepal: a rapid assessment of avoidable blindness (RAAB) study.

PubMed

Pradhan, Sangita; Deshmukh, Avnish; Giri Shrestha, Puspa; Basnet, Prajwal; Kandel, Ram Prasad; Lewallen, Susan; Sapkota, Yuddha Dhoj; Bassett, Ken; Yin, Vivian T

2018-03-01

The 1981 Nepal Blindness Survey first identified the Narayani Zone as one of the regions with the highest prevalence of blindness in the country. Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found it to have the country's highest blindness prevalence. This study examines the impact on blind avoidable and treatable eye conditions in this region after significant increase in eye care services in the past decade. The rapid assessment of avoidable blindness (RAAB) methodology was used with mobile data collection using the mRAAB smartphone app. Data analysis was done using the standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants aged 50 years or older were randomly sampled proportional to population size. Of the 5000 participants surveyed, 4771 (95.4%) were examined. The age-adjusted and sex-adjusted prevalence of bilateral blindness, severe visual impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to 1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%), respectively. Cataract remains the primary cause of blindness and SVI despite cataract surgery coverage (CSC) of 91.5% for VA<3/60. Women still account for two-thirds of blindness. The prevalence of blindness in people over the age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with the national average; however, significant gender inequity persists. CSC has improved but continues to favour men. © 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.

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

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

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.

Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study.

PubMed

Asgary, S; Naderi, G H; Sadeghi, M; Kelishadi, R; Amiri, M

2004-01-01

The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C. curvisepala Lind. or placebo three times daily for more than 4 months. Blood pressure (BP) was measured each month. Statistical analysis was carried out using Student's t-test. The results obtained showed a significant decrease in both systolic and diastolic BP after 3 months (p < 0.05). C. curvisepala has a time-dependent antihypertensive effect.

Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Fullmer, Spencer; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2014-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of the administration of the combination acetaminophen/hydrocodone on the anesthetic success of mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. One hundred emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, identical capsules of either a combination dose of 1000 mg acetaminophen/10 mg hydrocodone or placebo 60 minutes before the administration of a conventional inferior alveolar nerve (IAN) block. Endodontic access was begun 15 minutes after completion of the block, and all patients used for data analysis had profound lip numbness. Success was defined as no or mild pain (visual analog scale recordings) on pulpal access or instrumentation. The success rate for the IAN block was 32% for the combination dose of 1000 mg acetaminophen/10 hydrocodone and 28% for the placebo dose, with no statistically significant difference between the 2 groups (P = .662). A combination dose of 1000 mg acetaminophen/10 mg hydrocodone given 60 minutes before the administration of the IAN block did not result in a statistically significant increase in anesthetic success for mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Electroacupuncture versus sham electroacupuncture for urinary retention in poststroke patients: study protocol for a multicenter, randomized controlled trial.

PubMed

Shin, Seungwon; Lee, Jiwon; Yoo, Junghee; Lim, Sung Min; Lee, Euiju

2016-04-12

This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control. A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles. The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors. This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015.

Obsessive-compulsive symptoms in a randomized, double-blind study with olanzapine or risperidone in young patients with early psychosis.

PubMed

van Nimwegen, Lonneke; de Haan, Lieuwe; van Beveren, Nico; Laan, Winfried; van den Brink, Wim; Linszen, Don

2008-04-01

The prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia is relatively high. Antipsychotics have been found to influence OCS. To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis. One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder were randomized in a double-blind design to groups of 6 weeks' treatment with olanzapine (n = 59) or risperidone (n = 63), with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks. Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group (N = 122: -2.2 vs -0.3, z = -2.651, P < 0.01), in patients with baseline Y-BOCS total score greater than 0 (n = 58: -5.1 vs -0.4, z = -2.717, P < 0.01), and in patients with baseline Y-BOCS total score greater than 10 (n = 29: -7.1 vs -0.6, z = -2.138, P = 0.032). In this randomized, 6-week, double-blind trial, we found a significant and clinically relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone.

Does EEG-neurofeedback improve neurocognitive functioning in children with attention-deficit/hyperactivity disorder? A systematic review and a double-blind placebo-controlled study.

PubMed

Vollebregt, Madelon A; van Dongen-Boomsma, Martine; Buitelaar, Jan K; Slaats-Willemse, Dorine

2014-05-01

The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning in children with ADHD, and a systematic review on this topic was performed. Forty-one children (8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly allocated to EEG-neurofeedback or placebo-neurofeedback treatment for 30 sessions, twice a week. Children were stratified by age, electrophysiological state of arousal, and medication use. Neurocognitive tests of attention, executive functioning, working memory, and time processing were administered before and after treatment. Researchers, teachers, children and their parents, with the exception of the neurofeedback-therapist, were all blind to treatment assignment. Outcome measures were the changes in neurocognitive performance before and after treatment. www.clinicaltrials.gov: NCT00723684. No significant treatment effect on any of the neurocognitive variables was found. A systematic review of the current literature also did not find any systematic beneficial effect of EEG-neurofeedback on neurocognitive functioning. Overall, the existing literature and this study fail to support any benefit of neurofeedback on neurocognitive functioning in ADHD, possibly due to small sample sizes and other study limitations. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

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

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.

Improving temporal bone dissection using self-directed virtual reality simulation: results of a randomized blinded control trial.

PubMed

Zhao, Yi Chen; Kennedy, Gregor; Yukawa, Kumiko; Pyman, Brian; O'Leary, Stephen

2011-03-01

A significant benefit of virtual reality (VR) simulation is the ability to provide self-direct learning for trainees. This study aims to determine whether there are any differences in performance of cadaver temporal bone dissections between novices who received traditional teaching methods and those who received unsupervised self-directed learning in a VR temporal bone simulator. Randomized blinded control trial. Royal Victorian Eye and Ear Hospital. Twenty novice trainees. After receiving an hour lecture, participants were randomized into 2 groups to receive an additional 2 hours of training via traditional teaching methods or self-directed learning using a VR simulator with automated guidance. The simulation environment presented participants with structured training tasks, which were accompanied by real-time computer-generated feedback as well as real operative videos and photos. After the training, trainees were asked to perform a cortical mastoidectomy on a cadaveric temporal bone. The dissection was videotaped and assessed by 3 otologists blinded to participants' teaching group. The overall performance scores of the simulator-based training group were significantly higher than those of the traditional training group (67% vs 29%; P < .001), with an intraclass correlation coefficient of 0.93, indicating excellent interrater reliability. Using other assessments of performance, such as injury size, the VR simulator-based training group also performed better than the traditional group. This study indicates that self-directed learning on VR simulators can be used to improve performance on cadaver dissection in novice trainees compared with traditional teaching methods alone.

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.

Risk of bias reporting in the recent animal focal cerebral ischaemia literature.

PubMed

Bahor, Zsanett; Liao, Jing; Macleod, Malcolm R; Bannach-Brown, Alexandra; McCann, Sarah K; Wever, Kimberley E; Thomas, James; Ottavi, Thomas; Howells, David W; Rice, Andrew; Ananiadou, Sophia; Sena, Emily

2017-10-15

Findings from in vivo research may be less reliable where studies do not report measures to reduce risks of bias. The experimental stroke community has been at the forefront of implementing changes to improve reporting, but it is not known whether these efforts are associated with continuous improvements. Our aims here were firstly to validate an automated tool to assess risks of bias in published works, and secondly to assess the reporting of measures taken to reduce the risk of bias within recent literature for two experimental models of stroke. We developed and used text analytic approaches to automatically ascertain reporting of measures to reduce risk of bias from full-text articles describing animal experiments inducing middle cerebral artery occlusion (MCAO) or modelling lacunar stroke. Compared with previous assessments, there were improvements in the reporting of measures taken to reduce risks of bias in the MCAO literature but not in the lacunar stroke literature. Accuracy of automated annotation of risk of bias in the MCAO literature was 86% (randomization), 94% (blinding) and 100% (sample size calculation); and in the lacunar stroke literature accuracy was 67% (randomization), 91% (blinding) and 96% (sample size calculation). There remains substantial opportunity for improvement in the reporting of animal research modelling stroke, particularly in the lacunar stroke literature. Further, automated tools perform sufficiently well to identify whether studies report blinded assessment of outcome, but improvements are required in the tools to ascertain whether randomization and a sample size calculation were reported. © 2017 The Author(s).

Decisive Action Training Environment at the Joint Multinational Readiness Center, Volume 3: Multinational Interoperability

DTIC Science & Technology

2016-09-01

training in the decisive action training environment, with rotations routinely featuring several thousand participants from many nations and operating in...teams work with exercise participants before they arrive at the training center. The goal is to ensure all formations understand — and are able to...capabilities, location, and extensive experience working with NATO and partner countries, the JMTC is uniquely positioned to implement NATO training

Competence and Human Resource Development in Multinational Companies in Three European Union Member States: A Comparative Analysis between Austria, the Netherlands and the United Kingdom. CEDEFOP Panorama Series.

ERIC Educational Resources Information Center

Markowitsch, Jorg; Kollinger, Iris; Warmerdam, John; Moerel, Hans; Konrad, John; Burell, Catherine; Guile, David

A comparative analysis of human resources development and management in the subsidiaries of three multinational companies (Xerox, Glaxo Wellcome, and AXA Nordstern Colonia) was conducted in these three European Union (EU) member states: Austria, the United Kingdom, and the Netherlands. Case studies were used, focusing on competence needs and…

Multinational Experiment 7. Protecting Access to Space: Presentation to Senior Leaders

DTIC Science & Technology

2013-07-08

Multinational Experiment 7: Outcome 3: Space Access Briefing to SLS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...operations Consequence management Ship status during search & rescue Tele-medicine Broadband internet TV signal distribution Satellite radio Rural...military-usage • Significant economic & societal consequences Access to space at risk • Current approach unsustainable • Broad range of threats

National Security Implications of Transnational Economic Activity

DTIC Science & Technology

1993-04-01

ABSTRACT SECURITY CLASSIFICATION rUNCLASSIFIED/UNLIMITED El SAME AS RPT. O DTIC USERS Unclassified 22a. NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE...Activity This paper discusses the impact of regional trading arrangements (RTA’s), multinational corporations (MNC’s), and transnational financial activity...multinational corporation investment and taxation. o The U.S. must strengthen its national economy in order to be a world class player in transnational

A randomized, 14-day, double-blind study evaluating conversion from hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 μg/h or 20 μg/h in patients with osteoarthritis pain.

PubMed

Ripa, Steven R; McCarberg, Bill H; Munera, Catherine; Wen, Warren; Landau, Craig J

2012-06-01

The objective of this study was to evaluate continued pain control and tolerability of converting patients from Vicodin (hydrocodone/acetaminophen; HCD/APAP) to the buprenorphine transdermal system (BTDS). Adult patients with pain from osteoarthritis receiving a stable dosage of HCD/APAP (i.e., 15 - 30 mg hydrocodone/day) were switched to an equivalent or near-equivalent dosage of open-label Vicodin for 7 days. Patients maintaining acceptable analgesia were stratified based on their Vicodin dosage and randomized to receive either titratable BTDS 10 μg/h or fixed-dose BTDS 20 μg/h. The primary efficacy variable was completion of the 14-day double-blind phase. Tolerability was assessed. A total of 84.3% of patients met the primary end point, completion of the 14-day double-blind phase (167/198 patients, 95% CI 79.3 - 89.4). Adverse events were consistent with those associated with the use of opioid analgesics and transdermal patches. There was a similar analgesic and tolerability profile when patients treated with Vicodin for osteoarthritis pain were switched to 7-day BTDS treatment.

Efficacy of kinesio taping on isokinetic quadriceps torque in knee osteoarthritis: a double blinded randomized controlled study.

PubMed

Anandkumar, Sudarshan; Sudarshan, Shobhalakshmi; Nagpal, Pratima

2014-08-01

Double blind pre-test post-test control group design. To compare the isokinetic quadriceps torque, standardized stair-climbing task (SSCT) and pain during SSCT between subjects diagnosed with knee osteoarthritis pre and post kinesio tape (KT) application with and without tension. Strength of the quadriceps and torque producing capability is frequently found to be compromised in knee osteoarthritis. The efficacy of KT in improving isokinetic quadriceps torque in knee osteoarthritis is unknown, forming the basis for this study. Forty subjects were randomly allocated to either the experimental (therapeutic KT with tension) or control group (sham KT without tension) with the allocation being concealed. Pre and post test measurements of isokinetic quadriceps torque, SSCT and pain during SSCT were carried out by a blinded assessor. A large effect size with significant improvements in the peak quadriceps torque (concentric and eccentric at angular velocities of 90° per second and 120° per second), SSCT and pain were obtained in the experimental group when compared to the control group. Application of therapeutic KT is effective in improving isokinetic quadriceps torque, SSCT and reducing pain in knee osteoarthritis.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

The PEDALS Stationary Cycling Intervention and Health-Related Quality of Life in Children with Cerebral Palsy: A Randomized Controlled Trial

ERIC Educational Resources Information Center

DeMuth, Sharon K.; Knutson, Loretta M.; Fowler, Eileen G.

2012-01-01

Aim: The aim of this study was to assess health-related quality of life (HRQOL) following a stationary cycling intervention in children with cerebral palsy (CP). Method: This was a phase I multisite randomized controlled trial with single blinding. HRQOL was evaluated using the Pediatric Quality of Life Inventory SF15 (PedsQL; children) and…

Effects of a Web-Based Decision Aid Regarding Diagnostic Self-Testing. A Single-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Ickenroth, Martine H. P.; Grispen, J. E. J.; de Vries, N. K.; Dinant, G. J.; Ronda, G.; van der Weijden, T.

2016-01-01

Currently, there are many diagnostic self-tests on body materials available to consumers. The aim of this study was to assess the effect of an online decision aid on diagnostic self-testing for cholesterol and diabetes on knowledge among consumers with an intention to take these tests. A randomized controlled trial was designed. A total of 1259…

Buspirone versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial

ERIC Educational Resources Information Center

Davari-Ashtiani, Rozita; Shahrbabaki, Mahin Eslami; Razjouyan, Katayoon; Amini, Homayoun; Mazhabdar, Homa

2010-01-01

The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate…

Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial.

PubMed

Isacsson, Göran; Nohlert, Eva; Fransson, Anette M C; Bornefalk-Hermansson, Anna; Wiman Eriksson, Eva; Ortlieb, Eva; Trepp, Livia; Avdelius, Anna; Sturebrand, Magnus; Fodor, Clara; List, Thomas; Schumann, Mohamad; Tegelberg, Åke

2018-05-16

The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA. To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective. In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy. Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively). The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive. In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude. Registered with ClinicalTrials.gov (#NCT02148510).

Which is your choice for prolonging the analgesic duration of single-shot interscalene brachial blocks for arthroscopic shoulder surgery? intravenous dexamethasone 5 mg vs. perineural dexamethasone 5 mg randomized, controlled, clinical trial.

PubMed

Chun, Eun Hee; Kim, Youn Jin; Woo, Jae Hee

2016-06-01

The aim of this study was to compare the effect of intravenous (I.V.) dexamethasone with that of perineural dexamethasone on the prolongation of analgesic duration of single-shot interscalene brachial plexus blocks (SISB) in patients undergoing arthroscopic shoulder surgery. We performed a prospective, randomized, double-blind, placebo-controlled study. Patients undergoing elective arthroscopic shoulder surgery with ultrasound-guided SISB were enrolled and randomized into 2 groups. A total volume of 12 mL of the study drug was prepared with a final concentration of 0.5% ropivacaine. In the I.V. group, patients received SISB using ropivacaine 5 mg mL with normal saline (control) with dexamethasone 5 mg I.V. injection. In the perineural group, patients received SISB using ropivacaine 5 mg mL with dexamethasone 5 mg, with normal saline 1 mL I.V. injection. The primary outcome was the time to the first analgesic request, defined as the time between the end of the operation and the first request of analgesics by the patient. The secondary outcomes included patient satisfaction scores, side effects, and neurological symptoms. Patients were randomly assigned to 1 of the 2 groups using a computer-generated randomization table. An anesthesiologist blinded to the group assignments prepared the solutions for injection. The patients and the investigator participating in the study were also blinded to the group assignments. One hundred patients were randomized. Data were analyzed for 99 patients. One case in the I.V. group was converted to open surgery and was therefore not included in the study. Perineural dexamethasone significantly prolonged analgesic duration (median, standard error: 1080 minutes, 117.5 minutes) compared with I.V. dexamethasone (810 minutes, 48.1 minutes) (P = 0.02). There were no significant differences in side effects, neurological symptoms, or changes in blood glucose values between the 2 groups. Our results show that perineural dexamethasone 5 mg is more effective than I.V. dexamethasone 5 mg with regard to analgesic duration of SISB for arthroscopic shoulder surgery.

The effects of blinding on the outcomes of psychotherapy and pharmacotherapy for adult depression: A meta-analysis.

PubMed

Cuijpers, P; Karyotaki, E; Andersson, G; Li, J; Mergl, R; Hegerl, U

2015-09-01

Randomized trials with antidepressants are often run under double blind placebo-controlled conditions, whereas those with psychotherapies are mostly unblinded. This can introduce bias in favor of psychotherapy when the treatments are directly compared. In this meta-analysis, we examine this potential source of bias. We searched Pubmed, PsycInfo, Embase and the Cochrane database (1966 to January 2014) by combining terms indicative of psychological treatment and depression, and limited to randomized trials. We included 35 trials (with 3721 patients) in which psychotherapy and pharmacotherapy for adult depression were directly compared with each other. We calculated effect sizes for each study indicating the difference between psychotherapy and pharmacotherapy at post-test. Then, we examined the difference between studies with a placebo condition and those without in moderator analyses. We did not find a significant difference between the studies with and those without a placebo condition. The studies in which a placebo condition was included indicated no significant difference between psychotherapy and pharmacotherapy (g=-0.07; NNT=25). Studies in which no placebo condition was included (and patients and clinicians in both conditions were not blinded), resulted in a small, but significant difference between psychotherapy and pharmacotherapy in favor of pharmacotherapy (g=-0.13; NNT=14). Studies comparing psychotherapy and pharmacotherapy in which both groups of patients (and therapists) are not blinded (no placebo condition is included) result in a very small, but significantly higher effect for pharmacotherapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Randomized, blinded, placebo- and positive-controlled crossover study to determine the effect of multiple doses of apixaban on the QTc interval.

PubMed

Frost, Charles; Nepal, Sunil; Byon, Wonkyung; Moore, Kenneth; Reeves, Richard A; Boyd, Rebecca; LaCreta, Frank

2015-05-01

Apixaban is an oral, direct factor Xa inhibitor indicated for the prevention and treatment of thromboembolic disease. This randomized, blinded, 4-way crossover study investigated the potential effect of apixaban on the QTc interval. Forty healthy subjects (39 completers) each received 3 days of the following treatments: blinded apixaban 10 mg once daily (QD), 50 mg QD (supratherapeutic), matched apixaban placebo QD, and a single dose of open-label moxifloxacin 400 mg on Day 3, preceded by 2 days of placebo QD. Triplicate electrocardiograms obtained over 24 hours on Days -1 (baseline) and 3 were read by a blinded third party. The mean placebo-adjusted, time-matched, Fridericia-corrected change from baseline QTc (ΔΔQTcF) for apixaban and moxifloxacin was estimated at each time point. The maximum ΔΔQTcF was 1.51 milliseconds (one-sided upper 95% confidence interval [CI] 3.71 milliseconds) after apixaban 50 mg QD, 1.36 milliseconds (one-sided upper 95%CI 3.54 milliseconds) after apixaban 10 mg QD, and 10.21 milliseconds (lower 95%CI 8.07 milliseconds) after moxifloxacin. Concentration-response analysis suggested no evidence of a positive relationship between apixaban concentration and ΔQTcF. Apixaban doses up to 50 mg QD for 3 days were well tolerated and did not prolong the QTc interval in healthy subjects. © 2015, The American College of Clinical Pharmacology.

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

PubMed

Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0.23 (SA5; 95% CI, 0.19-0.30), and 0.23 (SA6; 95% CI, 0.19-0.30) (P < .001 for all). Correlations of rPFS and OS in enzalutamide-treated patients were 0.89 (95% CI, 0.86-0.92) by Spearman ρ and 0.72 (95% CI, 0.68-0.77) by Kendall τ. Sensitivity analyses in PREVAIL demonstrated the robustness of the PCWG2 rPFS definition using additional measures of progression. There was concordance between central and investigator review and a positive correlation between rPFS and OS among enzalutamide-treated patients. clinicaltrials.gov Identifier: NCT01212991.

Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

PubMed

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G; Ferrazzi, Paolo; Gardner, Timothy J; Latini, Roberto; Libby, Peter; Lombardi, Federico; O'Gara, Patrick T; Page, Richard L; Tavazzi, Luigi; Tognoni, Gianni

2012-11-21

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.

Comparing the effectiveness of ultrasound-guided versus blind steroid injection in the treatment of severe carpal tunnel syndrome

PubMed

Karaahmet, Özgür Zeliha; Gürçay, Eda; Kara, Murat; Serçe, Azize; Kıraç Ünal, Zeynep; Çakcı, Aytül

2017-12-19

Background/aim: This study aimed to compare the effectiveness of ultrasound (US)-guided injection versus blind injection of corticosteroids in the treatment of carpal tunnel syndrome (CTS). Materials and methods: This prospective, randomized clinical trial included patients with severe CTS based on clinical and electrophysiological criteria. The patients were evaluated for clinical and electrophysiological parameters at baseline and 4 weeks after treatment. Symptom severity and hand function were assessed by the Boston questionnaire. The patients underwent blind injection or US-guided injection. Results: When compared with baseline, both groups showed significant improvement in Boston questionnaire scores and all electrophysiological parameters. Significant differences were observed between the groups for clinical parameters (Boston Symptom Severity Scale: P = 0.007; Functional Status Scale: P < 0.001) in favor of the US-guided group. Conclusion: This study demonstrated that both US-guided and blind injections were effective in reducing symptoms and improving hand function. US-guided injections may yield more effective clinical results in the short-term than blind injections in the treatment of patients with severe CTS.

Effectiveness of energy conservation management on fatigue and participation in multiple sclerosis: A randomized controlled trial.

PubMed

Blikman, Lyan Jm; van Meeteren, Jetty; Twisk, Jos Wr; de Laat, Fred Aj; de Groot, Vincent; Beckerman, Heleen; Stam, Henk J; Bussmann, Johannes Bj

2017-10-01

Fatigue is a frequently reported and disabling symptom in multiple sclerosis (MS). To investigate the effectiveness of an individual energy conservation management (ECM) intervention on fatigue and participation in persons with primary MS-related fatigue. A total of 86 severely fatigued and ambulatory adults with a definite diagnosis of MS were randomized in a single-blind, two-parallel-arm randomized clinical trial to the ECM group or the information-only control group in outpatient rehabilitation departments. Blinded assessments were carried out at baseline and at 8, 16, 26 and 52 weeks after randomization. Primary outcomes were fatigue (fatigue subscale of Checklist Individual Strength - CIS20r) and participation (Impact on Participation and Autonomy scale - IPA). Modified intention-to-treat analysis was based on 76 randomized patients (ECM, n = 36; MS nurse, n=40). No significant ECM effects were found for fatigue (overall difference CIS20r between the groups = -0.81; 95% confidence interval (CI), -3.71 to 2.11) or for four out of five IPA domains. An overall unfavourable effect was found in the ECM group for the IPA domain social relations (difference between the groups = 0.19; 95% CI, 0.03 to 0.35). The individual ECM format used in this study did not reduce MS-related fatigue and restrictions in participation more than an information-only control condition.

Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.

PubMed

Syed, Yahiya Y; McKeage, Kate; Scott, Lesley J

2014-04-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex®] is an oromucosal spray formulation that contains principally THC and CBD at an approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants. The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2), and thus, may modulate the effects of excitatory (glutamate) and inhibitory (gamma-aminobutyric acid) neurotransmitters. THC/CBD is approved in a number of countries, including Germany and the UK, as an add-on treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In the largest multinational clinical trial that evaluated the approved THC/CBD regimen in this population, 12 weeks' double-blind treatment with THC/CBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks' single-blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale. A significantly greater proportion of THC/CBD than placebo recipients achieved a ≥ 30% reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THC/CBD has been also shown in at least one everyday clinical practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials. Dizziness and fatigue were reported most frequently during the first 4 weeks of treatment and resolved within a few days even with continued treatment. Thus, add-on THC/CBD is a useful symptomatic treatment option for its approved indication.

Efficacy and complications associated with a modified inferior alveolar nerve block technique. A randomized, triple-blind clinical trial.

PubMed

Montserrat-Bosch, Marta; Figueiredo, Rui; Nogueira-Magalhães, Pedro; Arnabat-Dominguez, Josep; Valmaseda-Castellón, Eduard; Gay-Escoda, Cosme

2014-07-01

To compare the efficacy and complication rates of two different techniques for inferior alveolar nerve blocks (IANB). A randomized, triple-blind clinical trial comprising 109 patients who required lower third molar removal was performed. In the control group, all patients received an IANB using the conventional Halsted technique, whereas in the experimental group, a modified technique using a more inferior injection point was performed. A total of 100 patients were randomized. The modified technique group showed a significantly higher onset time in the lower lip and chin area, and was frequently associated to a lingual electric discharge sensation. Three failures were recorded, 2 of them in the experimental group. No relevant local or systemic complications were registered. Both IANB techniques used in this trial are suitable for lower third molar removal. However, performing an inferior alveolar nerve block in a more inferior position (modified technique) extends the onset time, does not seem to reduce the risk of intravascular injections and might increase the risk of lingual nerve injuries.

Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Valadares, Fabiana; Garbi Novaes, Maria Rita Carvalho; Cañete, Roberto

2013-01-01

Breast cancer (BC) represents the highest incidence of malignancy in women throughout the world. Medicinal fungi can stimulate the body, reduce side-effects associated with chemotherapy and improve the quality of life in patients with cancer. To evaluate the effects of dietary supplementation of Agaricus sylvaticus on clinical and nutritional parameters in BC patients undergoing chemotherapy. A randomized, placebo-controlled, double-blind, clinical trial was carried out at the Oncology Clinic, Hospital of the Federal District-Brazil from September 2007 to July 2009. Forty six patients with BC, Stage II and III, were randomly assigned to receive either nutritional supplement with A. sylvaticus (2.1 g/day) or placebo. Patients were evaluated during treatment period. Patient supplemented with A. sylvaticus improved in clinical parameters and gastrointestinal functions. Poor appetite decreased by 20% with no changes in bowel functions (92.8%), nausea and vomiting (80%). Dietary supplementation with A. sylvaticus improved nutritional status and reduced abnormal bowel functions, nausea, vomiting, and anorexia in patients with BC receiving chemotherapy.

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).

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

[Computer-assisted education in problem-solving in neurology; a randomized educational study].

PubMed

Weverling, G J; Stam, J; ten Cate, T J; van Crevel, H

1996-02-24

To determine the effect of computer-based medical teaching (CBMT) as a supplementary method to teach clinical problem-solving during the clerkship in neurology. Randomized controlled blinded study. Academic Medical Centre, Amsterdam, the Netherlands. 103 Students were assigned at random to a group with access to CBMT and a control group. CBMT consisted of 20 computer-simulated patients with neurological diseases, and was permanently available during five weeks to students in the CBMT group. The ability to recognize and solve neurological problems was assessed with two free-response tests, scored by two blinded observers. The CBMT students scored significantly better on the test related to the CBMT cases (mean score 7.5 on a zero to 10 point scale; control group 6.2; p < 0.001). There was no significant difference on the control test not related to the problems practised with CBMT. CBMT can be an effective method for teaching clinical problem-solving, when used as a supplementary teaching facility during a clinical clerkship. The increased ability to solve problems learned by CBMT had no demonstrable effect on the performance with other neurological problems.

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

PubMed

Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

2015-03-01

Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.

A randomized, double-blind, safety and tolerability study to assess the ophthalmic and renal effects of tafenoquine 200 mg weekly versus placebo for 6 months in healthy volunteers.

PubMed

Leary, Kevin J; Riel, Michael A; Roy, Michael J; Cantilena, Louis R; Bi, Daoqin; Brater, D Craig; van de Pol, Corina; Pruett, Khadeeja; Kerr, Caron; Veazey, James M; Beboso, Ronnie; Ohrt, Colin

2009-08-01

A randomized, double-blind, placebo-controlled study was conducted to assess the effect of tafenoquine, 200 mg weekly for 6 months on ophthalmic and renal safety. This trial was carried out after observations in previous clinical trials that tafenoquine may be associated with the development of corneal deposits and elevations in serum creatinine. In 120 healthy volunteers who received tafenoquine or placebo in a 2:1 randomization, there was no effect on night vision or other ophthalmic indices measured. Persons taking tafenoquine also showed no difference in mean change in glomerular filtration rate (GFR, mL/s/1.73 m(2)) after 6 months of dosing, with a treatment difference of -0.061 (95% confidence interval, -0.168, 0.045), and non-inferiority margin of -0.247 mL/s/1.73 m(2). Tafenoquine was well tolerated over the course of the study. The results of this study showed no clinically significant effects of tafenoquine on ophthalmic or renal function, and support its continued development as an antimalarial drug.

Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

PubMed

Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

2015-03-01

In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Olive Oil, Sunflower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study).

PubMed

Cooke, Alison; Cork, Michael J; Victor, Suresh; Campbell, Malcolm; Danby, Simon; Chittock, John; Lavender, Tina

2016-03-01

Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. One-hundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans-epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79-100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin.

Safety and Efficacy of Rice Bran Supercritical CO2 Extract for Hair Growth in Androgenic Alopecia: A 16-Week Double-Blind Randomized Controlled Trial.

PubMed

Choi, Jae-Suk; Park, Jae Beom; Moon, Woi-Sook; Moon, Jin-Nam; Son, Sang Wook; Kim, Mi-Ryung

2015-01-01

We conducted a 16-week double-blind randomized controlled single-center trial to evaluate the safety and efficacy of dermal rice bran supercritical CO2 extract (RB-SCE) in the treatment of androgenic alopecia. Fifty alopecia patients were randomly assigned to the experimental and placebo groups. The experimental group received a dermal application of 0.5% RB-SCE (8 mL/d) to the head skin for 16 weeks while the control group received a dermal application of placebo. Changes in hair count, diameter, and density were evaluated with a Folliscope(®). Patient satisfaction was evaluated via questionnaire and clinical photographs were rated by dermatologists. The results showed that RB-SCE significantly increased hair density and hair diameter in male subjects. Patient satisfaction and the evaluation of photographs by dermatologists also confirmed the effectiveness of RB-SCE in the treatment of alopecia. No adverse reactions related to RB-SCE were reported. Therefore, RB-SCE shows promise for use in functional cosmetics and pharmaceuticals.

Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

PubMed

Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

2013-02-27

This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

Double-blind, Randomized, 8-week Placebo-controlled followed by a 16-week open label extension study, with the LPA1 receptor antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis.

PubMed

Allanore, Yannick; Distler, Oliver; Jagerschmidt, Alexandre; Illiano, Stephane; Ledein, Laetitia; Boitier, Eric; Agueusop, Inoncent; Denton, Christopher P; Khanna, Dinesh

2018-05-06

Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15. The primary endpoint was safety during the double-blind phase of the trial. Exploratory endpoints included the identification of a LPA-induced gene signature in patients 'skin. 17 of 32 subjects were randomized to placebo and 15 to SAR100842; 30 patients participated in the extension study. The most frequent adverse events reported for SAR100842 during the blinded phase were headache, diarrhea, nausea and fall and the safety profile was acceptable during the extension part. At Week 8, mean reduction in mRSS was numerically greater in the SAR100842 compared to placebo (mean change [SD]: -3.57 [4.18] versus -2.76 [4.85]; difference [95% CI]: -1.2 [-4.37 to 2.02], p=0.46). A greater reduction of LPA related genes was observed in skin of SAR100842 group at Week 8, indicating LPA 1 target engagement. SAR100842, a selective orally available LPA 1 receptor antagonist, was well tolerated in patients with dcSSc. MRSS improved during the study although not reaching significance, and additional gene signature analysis suggested target engagement. These results need to be confirmed in a larger controlled trial. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer.

PubMed

Govindan, Ramaswamy; Szczesna, Aleksandra; Ahn, Myung-Ju; Schneider, Claus-Peter; Gonzalez Mella, Pablo Fernando; Barlesi, Fabrice; Han, Baohui; Ganea, Doina Elena; Von Pawel, Joachim; Vladimirov, Vladimir; Fadeeva, Natalia; Lee, Ki Hyeong; Kurata, Takayasu; Zhang, Li; Tamura, Tomohide; Postmus, Pieter E; Jassem, Jacek; O'Byrne, Kenneth; Kopit, Justin; Li, Mingshun; Tschaika, Marina; Reck, Martin

2017-10-20

Purpose Patients with squamous non-small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were randomly assigned (1:1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population.

A Paired, Double-Blind, Randomized Comparison of a Moisturizing Durable Barrier Cream to 10% Glycerine Cream in the Prophylactic Management of Postmastectomy Irradiation Skin Care: Trans Tasman Radiation Oncology Group (TROG) 04.01

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

Graham, Peter H., E-mail: peter.graham@sesiahs.health.nsw.gov.au; Plant, Natalie; Graham, Jennifer L.

2013-05-01

Purpose: A previous, unblinded study demonstrated that an alcohol-free barrier film containing an acrylate terpolymer (ATP) was effective in reducing skin reactions compared with a 10% glycerine cream (sorbolene). The different appearances of these products precluded a blinded comparison. To test the acrylate terpolymer principle in a double-blinded manner required the use of an alternative cream formulation, a moisturizing durable barrier cream (MDBC); the study was conducted by the Trans Tasman Radiation Oncology Group (TROG) as protocol 04.01. Methods and Materials: A total of 333 patients were randomized; 1 patient was ineligible and 14 patients withdrew or had less thanmore » 7 weeks' observations, leaving 318 for analysis. The chest wall was divided into medial and lateral compartments, and patients were randomized to have MDBC applied daily to the medial or lateral compartment and sorbolene to the other compartment. Weekly observations, photographs, and symptom scores (pain and pruritus) were collected to week 12 or resolution of skin reactions if earlier. Skin dose was confirmed by centrally calibrated thermoluminescent dosimeters. Results: Rates of medial and lateral compartment Common Toxicity Criteria (CTC), version 3, greater than or equal to grade 3 skin reactions were 23% and 41%, but rates by skin care product were identical at 32%. There was no significant difference between MDBC and sorbolene in the primary endpoint of peak skin reactions or secondary endpoints of area-under-the-curve skin reaction scores. Conclusions: The MDBC did not reduce the peak skin reaction compared to sorbolene. It is possible that this is related to the difference in the formulation of the cream compared with the film formulation. Skin dosimetry verification and double blinding are essential for radiation skin care comparative studies.« less

NBI‐98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double‐blind, placebo‐controlled study

PubMed Central

Jimenez, Roland; Hauser, Robert A.; Factor, Stewart A.; Burke, Joshua; Mandri, Daniel; Castro‐Gayol, Julio C.

2015-01-01

ABSTRACT Background Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI‐98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6‐week, double‐blind, placebo‐controlled, dose‐titration study evaluating the safety, tolerability, and efficacy of NBI‐98854 for the treatment of tardive dyskinesia. Methods Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI‐98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change—Tardive Dyskinesia score assessed by the blinded investigator. Results Two hundred five potential subjects were screened, and 102 were randomized; 76% of NBI‐98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI‐98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change—Tardive Dyskinesia (p < 0.0001). Treatment‐emergent adverse event rates were 49% in the NBI‐98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted. Conclusion NBI‐98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI‐98854 now underway. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:26346941

NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study.

PubMed

O'Brien, Christopher F; Jimenez, Roland; Hauser, Robert A; Factor, Stewart A; Burke, Joshua; Mandri, Daniel; Castro-Gayol, Julio C

2015-10-01

Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia. Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change-Tardive Dyskinesia score assessed by the blinded investigator. Two hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change-Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted. NBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Asia Pacific Economic Cooperation (APEC) and the 2008 Meetings in Lima, Peru

DTIC Science & Technology

2009-03-31

major retailers and multinational corporations who source products from manufacturers and sourcing companies around the world. In turn, these companies...on orders from U.S., European, or Japanese retailers or brand name distributors to initiate the multinational manufacturing of the consumer products...describes a “patchwork of bilateral hub-and-spoke FTAs in a noodle bowl.” According to some experts, the growth of bilateral trade agreements (BTAs

The Military Dimension of the Niger Delta Crisis: Increasing the Effectiveness of Security Forces Through Information Operations

DTIC Science & Technology

2010-06-11

Torulagha makes strong accusations against the oil companies who he says barely conduct any environmental assessment before engaging in exploratory...residents widely regard the GoN as ―having collaborated with the multinational oil firms to alter the social and environmental stability of the area ...residents demanded resource control in the face of environmental degradation by multinational oil companies; and complaints of government marginalization

Multinational Limited Objective Experiment II (MN LOE II)

DTIC Science & Technology

2003-06-01

multinational ONA development to the international players for the first time. Vignette 4 promoted the systems-of-systems approach , the need to...as a result of ongoing famines and economic chaos. The new nation adopted the South Korean form of government and economic system. Concern of a...negative impact on the economy of the south , as they combined with the north, was well founded. Without a Korean “Marshall Plan” instituted by the

A European perspective--the European clinical research infrastructures network.

PubMed

Demotes-Mainard, J; Kubiak, C

2011-11-01

Evaluating research outcomes requires multinational cooperation in clinical research for optimization of treatment strategies and comparative effectiveness research, leading to evidence-based practice and healthcare cost containment. The European Clinical Research Infrastructures Network (ECRIN) is a distributed ESFRI (European Strategy Forum on Research Infrastructures) roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific potential. Servicing multinational trials started during its preparatory phase, and ECRIN will now apply for an ERIC (European Research Infrastructures Consortium) status by 2011. By creating a single area for clinical research in Europe, this achievement will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of the research and education capacity, tackling the major societal challenges starting with the area of healthy ageing, and removing barriers to bring ideas to the market.

Multinational corporate penetration, industrialism, region, and social security expenditures: a cross-national analysis.

PubMed

Clark, R; Filinson, R

1991-01-01

This study examines the determinants of spending on social security programs. We draw predictions from industrialism and dependency theories for the explanation of social security programs. The explanations are tested with data on seventy-five nations, representative of core, semipheripheral and peripheral nations. Industrialization variables such as the percentage of older adults and economic productivity have strong effects in models involving all nations, as does multinational corporate (MNC) penetration in extraction, particularly when region is controlled; such penetration is negatively associated with spending on social security. We then look at industrialism and dependency effects for peripheral and non-core nations alone. The effects of all industrialization variables, except economic productivity, appear insignificant for peripheral nations, while the effects of region and multinational corporate penetration in extractive and agricultural industries appears significant. Models involving all non-core nations (peripheral and semi-peripheral) look more like models for all nations than for peripheral nations alone.

Lost in Translation? Challenges and Opportunities for Raising Health and Safety Awareness among a Multinational Workforce in the United Arab Emirates

PubMed Central

Cooling, Robert Fletcher; Aw, Tar-Ching

2012-01-01

The United Arab Emirates (UAE) has experienced tremendous economic and industrial growth in the petroleum, airline, maritime and construction sectors, especially since the discovery of oil reserves. Mass recruitment of low skilled or unskilled laborers from less-developed countries has been utilized to satisfy the manpower demands of these fast paced industrial developments. Such workforce recruitment has created an unusual populace demographic, with the total UAE population estimated at 8.3 million, composed of 950,000 Emiratis, with the remainder being multinational expatriate workers, with varying educational qualifications, work experience, religious beliefs, cultural practices, and native languages. These unique characteristics pose a challenge for health and safety professionals tasked with ensuring the UAE workforce adheres to specific occupational health and safety procedures. The paper discusses two case studies that employ a novel multimedia approach to raising health and safety awareness among a multinational workforce. PMID:23251846

[Survey on avoidable blindness and visual impairment in Panama].

PubMed

López, Maritza; Brea, Ileana; Yee, Rita; Yi, Rodolfo; Carles, Víctor; Broce, Alberto; Limburg, Hans; Silva, Juan Carlos

2014-12-01

Determine prevalence of blindness and visual impairment in adults aged ≥ 50 years in Panama, identify their main causes, and characterize eye health services. Cross-sectional population study using standard Rapid Assessment of Avoidable Blindness methodology. Fifty people aged ≥ 50 years were selected from each of 84 clusters chosen through representative random sampling of the entire country. Visual acuity was assessed using a Snellen chart; lens and posterior pole status were assessed by direct ophthalmoscopy. Cataract surgery coverage was calculated and its quality assessed, along with causes of visual acuity < 20/60 and barriers to access to surgical treatment. A total of 4 125 people were examined (98.2% of the calculated sample). Age- and sex-adjusted prevalence of blindness was 3.0% (95% CI: 2.3-3.6). The main cause of blindness was cataract (66.4%), followed by glaucoma (10.2%). Cataract (69.2%) was the main cause of severe visual impairment and uncorrected refractive errors were the main cause of moderate visual impairment (60.7%). Surgical cataract coverage in individuals was 76.3%. Of all eyes operated for cataract, 58.0% achieved visual acuity ≤ 20/60 with available correction. Prevalence of blindness in Panama is in line with average prevalence found in other countries of the Region. This problem can be reduced, since 76.2% of cases of blindness and 85.0% of cases of severe visual impairment result from avoidable causes.

A Randomized Controlled Trial Comparing Botulinum Toxin A Dosage in the Upper Extremity of Children with Spasticity

ERIC Educational Resources Information Center

Kawamura, Anne; Campbell, Kent; Lam-Damji, Sophie; Fehlings, Darcy

2007-01-01

This study compared the effects of low and high doses of botulinum toxin A (BTX-A) to improve upper extremity function. Thirty-nine children (22 males, 17 females) with a mean age of 6 years 2 months (SD 2y 9mo) diagnosed with spastic hemiplegia or triplegia were enrolled into this double-blind, randomized controlled trial. The high-dose group…

Clinical Evaluation of Acupuncture as Treatment for Complications of Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor-Blind Trial.

PubMed

Liao, Hsien-Yin; Ho, Wen-Chao; Chen, Chun-Chung; Lin, Jaung-Geng; Chang, Chia-Chi; Chen, Liang-Yu; Lee, De-Chih; Lee, Yu-Chen

2017-01-01

Background and Purpose . The effect of acupuncture as treatment for poststroke complications is questionable. We performed a randomized, sham-controlled double-blind study to investigate it. Methods . Patients with first-time acute stroke were randomized to receive 24 sessions of either real or sham acupuncture during an eight-week period. The primary outcome measure was change in National Institute of Health Stroke Scale (NIHSS) score. Secondary outcome measures included changes in Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Hamilton Depression Rating Scale (HAM-D), and Visual Analogue Scale (VAS) for pain scores. Results . Of the 52 patients who were randomized to receive acupuncture ( n = 28) or placebo ( n = 24), 10 patients in the acupuncture group and 9 patients in the placebo group failed to complete the treatment. In total, 18 patients in the acupuncture group and 15 patients in the control group completed the treatment course. Reduction in pain was significantly greater in the acupuncture group than in the control group ( p value = 0.04). There were no significant differences in the other measures between the two groups. Conclusions . Acupuncture provided more effective poststroke pain relief than sham acupuncture treatment. However, acupuncture had no better effect on neurological, functional, and psychological improvement.

Clinical study on the therapeutic role of midodrine in non azotemic cirrhotic patients with tense ascites: a double-blind, placebo-controlled, randomized trial.

PubMed

Ali, Ahmed; Farid, Samar; Amin, Mona; Kassem, Mohamed; Al-Garem, Nouman

2014-10-01

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension. Midodrine has demonstrated usefulness in hepatorenal syndrome. The objective of the present work was to study the role of midodrine in patients with non-azotemic cirrhosis with tense ascites. This prospective randomized double blind placebo-controlled study was conducted on 67 non azotemic inpatients with liver cirrhosis and tense ascites (52 men and 15 women; age range, 45-72). One patient declined to participate in the study, 33 patients were randomly assigned to take midodrine hydrochloride, and 33 patients were randomly assigned to take placebo. Out of 67 enrolled patients, 60 patients (30: in midodrine group; 30: in placebo group) completed the study and 6 patients lost to follow up. Patients were assessed for patients’ characteristics, history of tapping their ascetic fluid, laboratory values, and Doppler parameters before and after the study. Average 24-h urine volume was assessed before and after the start of the study. significant reduction in body weight and abdominal girth was observed after 2 weeks of midodrine therapy. Midodrine appeared to be effective in lowering body weights and abdominal girths of non azotemic cirrhotic patients with tense ascites.

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

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

Specialized stroke rehabilitation services in seven countries: Preliminary results from nine rehabilitation centers.

PubMed

Langhammer, Birgitta; Becker, Frank; Sunnerhagen, Katharina S; Zhang, Tong; Du, Xiaoxia; Bushnik, Tamara; Panchenko, Maria; Keren, Ofer; Banura, Samir; Elessi, Khamis; Luzon, Fuad; Lundgren-Nilsson, Åsa; Li, Xie; Sällström, Susanne; Stanghelle, Johan Kvalvik

2015-12-01

There is a lack of defined levels of rehabilitation, indicating possibly random content and access to specialized services. The aim of the study was to perform a multinational descriptive study of specialized rehabilitation in persons with stroke, to elucidate what the different centers define as prerequisites for specialized rehabilitation, and to analyze whether these descriptions map to currently applied standards or constructs of specialized rehabilitation. A secondary aim was to look for similarities and differences between therapies and services for persons with stroke in the sub-acute stage in the different institutions. Descriptive data of the collaborating centers regarding structure and processes of services were recorded and compared with the British Society of Rehabilitation Medicine and Specialized Services National Definitions sets. Comparisons of the definitions showed that all centers admitted severely disabled persons with stroke, in need of complex rehabilitation, and provided high levels of physical services, with specialized equipment and facilities. However, funding, size, university affiliation, quality accreditation, staffing levels, specialist training, cognitive and vocational services, coordination of the professional teams, admission procedures, time and type of therapies, estimated length of stay, and follow-up procedures differed between the centers. This multinational study of specialized stroke rehabilitation centers shows that a universal definition of specialized rehabilitation is possible, even in quite different countries and settings, in terms of general principles. There were however differences in structures and procedures, which may influence patients' outcomes, indicating a need for refinement of the definitions to be globally applicable. © 2015 World Stroke Organization.

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.

PubMed

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E; Wallis, Carol L; Tripathy, Srikanth; Morgado, Mariza G; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G; Lama, Javier R; Rassool, Mohammed; Santos, Breno R; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B; Eshleman, Susan H

2015-05-15

Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98). In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. NCT00084136. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tolerance of beta blocked hypertensives during orthostatic and altitude stress.

DOT National Transportation Integrated Search

1992-04-01

To evaluate the effects of orthostatic, altitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive males are females qualifyin...