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Treatment Differences (treatment + difference)
Kinds of Treatment Differences Selected AbstractsTHE COST OF MELANIZATION: BUTTERFLY WING COLORATION UNDERENVIRONMENTAL STRESSEVOLUTION, Issue 2 2004W. Talloen Abstract Evolutionary studies typically focus on adaptations to particular environmental conditions, thereby often ignoring the role of possible constraints. Here we focus on the case of variation in dorsal wing melanization in a satyrine butterfly Pararge aegeria. Because melanin is a complex polymer, its synthesis may be constrained if ambient conditions limit the resource budget. This hypothesis was tested by comparing melanization among butterflies that fed as larvae on host grasses experiencing different drought-stress treatments. Treatment differences were validated both at the level of the host plant (nitrogen, carbonate, and water content) and of the butterfly (life-history traits: survival, development time, and size at maturity). Melanization rate was measured as average gray value of the basal dorsal wing area. This area, close to the thorax, is known to be functionally significant for basking in order to thermoregulate. Individuals reared on drought-stressed host plants developed paler wings, and development of darker individuals was slower and less stable as estimated by their level of fluctuating asymmetry. These results provide evidence that melanin is indeed costly to synthesize, and that differences in environmental quality can induce phenotypic variation in wing melanization. Therefore, studies dealing with spatial and/or temporal patterns of variation in wing melanization should not focus on adaptive explanations alone, but rather on a cost-benefit balance under particular sets of environmental conditions. [source] Intercropping for the Improvement of Sorghum Yield, Soil Fertility and Striga Control in the Subsistence Agriculture Region of Tigray (Northern Ethiopia)JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 1 2005F. Reda Abstract Striga hermonthica is a major biotic constraint in the dry and less fertile areas of northern Ethiopia. Emphasis is being placed on improved cropping systems to address the interrelated problems of Striga and soil fertility decline. The potential benefits of intercropping were investigated at two sites representing different environments for crop yield improvement, soil fertility maintenance and Striga control. Ten food legume and oilseed crop species were compared in inter-row arrangement with sorghum under non-fertilized conditions. In most cases, there was no significant negative impact of intercropping on sorghum growth and development. Among the intercrops, two cowpea varieties , cv. TVU 1977 OD and cv. Blackeye bean , produced the highest supplemental yield of up to 329 and 623 kg ha,1 grain and 608 and 1173 kg ha,1 biomass at Adibakel and Sheraro respectively. Treatment differences on Striga infestation and measured soil fertility indicators were not significant. Nevertheless, valuable grain and biomass obtained from the legume intercrops, without seriously compromising sorghum yield, could offer multiple benefits as a source of protein, additional income, feeds for animals and manure in the subsistence agriculture regions of northern Ethiopia. [source] Development of methods to enhance extrinsic tooth discoloration for comparison of toothpastesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 20042. Two-product clinical study Abstract Background: Extrinsic staining of teeth is considered to be unsightly and a number of ,whitening' toothpastes have been formulated to inhibit or remove such tooth discoloration. The aim of this study was to compare the stain prevention of two toothpastes. Method: The study was a single-blind, randomised, placebo-controlled, crossover design, balanced for residual effects involving 24 healthy dentate volunteers. The treatments were as follows: (1) a whitening toothpaste product, (2) an experimental toothpaste formulation and (3) water. For each 4-day rinse period, subjects were rendered stain free on the teeth and tongue. Approximately on the hour from 09:00 to 16:00 hours, subjects rinsed with chlorhexidine mouth rinse for 1 min followed by warm black tea for 1 min. The treatment interventions were at 09:00 and 16:00 hours and before the chlorhexidine rinse. The toothpastes were rinsed as 3 g/10 ml water slurries and water as a 10 ml rinse each for 2 min. On day 5, subjects were scored for tooth and tongue stain intensity and area, and the product of these was calculated. The washout period was at least 9 days. Results: Treatment differences for the teeth were highly significant but not for the tongue. Paired contrasts for tooth stain intensity, area and product were mostly all significantly in favour of reduced staining by the experimental formulation compared with water and the whitening product. There were no significant differences between water and the whitening product. Conclusions: Using a forced dietary staining method, the data support a tooth stain-inhibitory/-removal action for the experimental formulation, but not the whitening product. [source] TRIZAL study: switching from successful HAART to TrizivirTM (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence resultsHIV MEDICINE, Issue 2 2003C Katlama Objective To assess the antiviral efficacy, safety, and adherence in subjects who switched to TrizivirÔ following long-term HIV-1 RNA suppression. Study design A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening. Methods Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with TrizivirÔ administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of , 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment. Results At week 48, the proportion of treatment failures in TrizivirÔ arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the TrizivirÔ arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the TrizivirÔ arm (P < 0.001 and P = 0.006, respectively). Conclusion Switching to TrizivirÔ offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy. [source] Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease,INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2001D. Wilkinson Abstract Objectives To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD). Background Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. Method A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36,mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS). Results Patients treated with galantamine 24,mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p,=,0.01) and 4.2 points on per protocol analysis ( p,=,0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p,<,0.05) and CGIC (36-mg/day dose, p,<,0.05). Galantamine was well tolerated at the lower doses of 18 and 24,mg/day where it produced mild, transient effects typical of cholinomimetic agents. Conclusion This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease. Copyright © 2001 John Wiley & Sons, Ltd. [source] Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2009Jacques P Brown Abstract Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score , ,2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p , 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. [source] A pilot study using nabilone for symptomatic treatment in Huntington's disease,MOVEMENT DISORDERS, Issue 15 2009Adrienne Curtis BSC Abstract Pilot study of nabilone in Huntington's disease (HD). Double-blind, placebo-controlled, cross-over study of nabilone versus placebo. Primary outcome, Unified Huntington's Disease Rating Scale (UHDRS) total motor score. Secondary measures: UHDRS subsections for chorea, cognition and behavior, and neuropsychiatric inventory (NPI). 44 randomized patients received either nabilone (1 or 2 mg) followed by placebo (n = 22), or placebo followed by nabilone (n = 22). Recruiting was straightforward. Nabilone safe and well tolerated, no psychotic episodes. Assessment of either dose of nabilone versus placebo showed a treatment difference of 0.86 (95% CI: ,1.8 to 3.52) for total motor score; 1.68 (95% CI: 0.44 to 2.92) for chorea; 3.57 (95% CI: ,3.41 to 10.55) for UHDRS cognition; 4.01 (95% CI: ,0.11 to 8.13) for UHDRS behavior, and 6.43 (95% CI: 0.2 to 12.66) for the NPI. Larger longer RCT of nabilone in HD is feasible and warranted. © 2009 Movement Disorder Society [source] An optimal adaptive design to address local regulations in global clinical trials,PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 3 2010Xiaolong Luo Abstract After multi-regional clinical trials (MRCTs) have demonstrated overall significant effects, evaluation for a region-specific effect is often important. Recent guidance (see, e.g. 1) from regulatory authorities regarding evaluation for possible country-specific effects has led to research on statistical designs that incorporate such evaluations in MRCTs. These statistical designs are intended to use the MRCTs to address the requirements for global registration of a medicinal product. Adding a regional requirement could change the probability for declaring positive effect for the region when there is indeed no treatment difference as well as when there is in fact a true difference within the region. In this paper, we first quantify those probability structures based on the guidance issued by the Ministry of Health, Labour and Welfare (MHLW) of Japan. An adaptive design is proposed to consider those probabilities and to optimize the efficiency for regional objectives. This two-stage approach incorporates comprehensive global objectives into an integrated study design and may mitigate the need for a separate local bridging study. A procedure is used to optimize region-specific enrollment based on an objective function. The overall sample size requirement is assessed. We will use simulation analyses to illustrate the performance of the proposed study design. Copyright © 2010 John Wiley & Sons, Ltd. [source] Randomized controlled trial of intraputamenal glial cell line,derived neurotrophic factor infusion in Parkinson diseaseANNALS OF NEUROLOGY, Issue 3 2006Anthony E. Lang MD Objective Glial cell line,derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15,g/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F-dopa uptake. Results At 6 months, mean percentage changes in "off" UPDRS motor score were ,10.0% and ,4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, ,23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). Interpretation Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome. Ann Neurol 2006 [source] The efficacy and safety of abatacept in patients with non,life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 10 2010J. T. Merrill Objective To evaluate abatacept therapy in patients with non,life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis. Methods In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (,10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper. Results A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference ,3.5 [95% CI ,15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period). Conclusion Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non,life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment. [source] Testing Homogeneity of Two Zero-inflated Poisson PopulationsBIOMETRICAL JOURNAL, Issue 1 2009Siu Keung Tse Abstract The problem of testing treatment difference in the occurrence of a safety parameter in a randomized parallel-group comparative clinical trial under the assumption that the number of occurrence follows a zero-inflated Poisson (ZIP) distribution is considered. Likelihood ratio tests (LRT) for homogeneity of two ZIP populations are derived under the hypotheses that (i) there is no difference in inflation parameters, (ii) there is no difference in non-zero means; and (iii) there is no difference in both inflation parameters and non-zero means. Approximate formulas for sample size calculation are also obtained for achieving a desired power for detecting a clinically meaningful difference under the corresponding alternative hypotheses. An example concerning the assessment of the gastrointestinal (GI) safety in terms of the number of erosion counts of a newly developed compound for the treatment of osteoarthritis and rheumatoid arthritis is given for illustration purpose (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Establishing Efficacy of a New Experimental Treatment in the ,Gold Standard' DesignBIOMETRICAL JOURNAL, Issue 6 2005Dieter Hauschke Abstract Provided that there are no ethical concerns, the comparison of an active drug with placebo in a randomized two-arm clinical trial provides the most convincing way to demonstrate the efficacy of a new experimental treatment. However, in a placebo-controlled clinical trial it is not sufficient to demonstrate merely a statistically significant treatment difference. Regulatory authorities strongly recommend to assess additionally whether the observed treatment difference is also of clinical relevance. The inherent issue is the necessity of the a priori definition of what constitutes a clinically relevant difference in efficacy. This problem can be solved in a three-arm study by including an active control group. We address the necessary conditions in the gold standard design which allow the claim of efficacy for the new treatment with particular focus on assay sensitivity. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] DWEPP: a dynamic soil erosion model based on WEPP source termsEARTH SURFACE PROCESSES AND LANDFORMS, Issue 7 2007N. S. Bulygina Abstract A new rangeland overland-flow erosion model was developed based on Water Erosion Prediction Project (WEPP) sediment source and sink terms. Total sediment yield was estimated for rainfall simulation plots from the WEPP field experiments as well as for a small watershed without a well developed channel network. Both WEPP and DWEPP gave a similar level of prediction accuracy for total event soil losses measured from both rainfall simulation and small watershed experiments. Predictions for plot and hillslope scale erosion simulations were in the range of expected natural variability. Sediment yield dynamics were plotted and compared with experimental results for plots and hillslope, and the results were satisfactory. Effects of cover and canopy on the predicted sediment yields were well represented by the model. DWEPP provides a new tool for assessing erosion rates and dynamics, has physically based erosion mechanics descriptions, is sensitive to treatment differences on the experimental plots and has a well developed parameter database inherited from WEPP. Copyright © 2006 John Wiley & Sons, Ltd. [source] Ethnic differences in drinking outcomes following a brief alcohol intervention in the trauma care settingADDICTION, Issue 1 2010Craig A. Field ABSTRACT Background Evidence suggests that brief interventions in the trauma care setting reduce drinking, subsequent injury and driving under the influence (DUI) arrest. However, evidence on the effectiveness of these interventions in ethnic minority groups is lacking. The current study evaluates the efficacy of brief intervention among whites, blacks and Hispanics in the United States. Methods We conducted a two-group parallel randomized trial comparing brief motivational intervention (BMI) and treatment as usual with assessment (TAU+) to evaluate treatment differences in drinking patterns by ethnicity. Patients were recruited from a level 1 urban trauma center over a 2-year period. The study included 1493 trauma patients, including 668 whites, 288 blacks and 537 Hispanics. Hierarchical linear modeling was used to evaluate ethnic differences in drinking outcomes including volume per week, maximum amount consumed in 1 day, percentage days abstinent and percentage days heavy drinking at 6- and 12-month follow-up. Analyses controlled for age, gender, employment status, marital status, prior alcohol treatment, type of injury and injury severity. Special emphasis was given to potential ethnic differences by testing the interaction between ethnicity and BMI. Results At 6- and 12-month follow-up, BMI significantly reduced maximum amount consumed in 1 day (P < 0.001; P < 0.001, respectively) and percentage days heavy drinking (P < 0.05; P < 0.05, respectively) among Hispanics. Hispanics in the BMI group also reduced average volume per week at 12-month follow-up (,2 = 6.8, df = 1, P < 0.01). In addition, Hispanics in TAU+ reduced maximum amount consumed at 6- and 12-month follow-up (P < 0.001; P < 0.001) and volume per week at 12-month follow-up (P < 0.001). Whites and blacks in both BMI and TAU+ reduced volume per week and percentage days heavy drinking at 12-month follow-up (P < 0.001; P < 0.01, respectively) and decreased maximum amount at 6- (P < 0.001) and 12-month follow-up (P < 0.001). All three ethnic groups In both BMI and TAU+ reduced volume per week at 6-month follow-up (P < 0.001) and percentage days abstinent at 6- (P < 0.001) and 12-month follow-up (P < 0.001). Conclusions All three ethnic groups evidenced reductions in drinking at 6- and 12-month follow-up independent of treatment assignment. Among Hispanics, BMI reduced alcohol intake significantly as measured by average volume per week, percentage days heavy drinking and maximum amount consumed in 1 day. [source] Are differences in guidelines for the treatment of nicotine dependence and non-nicotine dependence justified?ADDICTION, Issue 12 2009John R. Hughes ABSTRACT Despite the many similarities between nicotine dependence and other drug dependences, national guidelines for their treatment differ in several respects. The recent national guideline for the treatment of nicotine dependence has (i) less emphasis on detailed assessment; (ii) less emphasis on treatment of psychiatric comorbidity; (iii) less acceptance of reduction of use as an initial treatment goal; (iv) greater emphasis on pharmacological interventions; and (v) less emphasis on psychosocial treatment than national guidelines for non-nicotine dependences. These treatment differences may occur because (i) nicotine does not cause behavioral intoxication; (ii) psychiatric comorbidity is less problematic with nicotine dependence; (iii) psychosocial problems are less severe with nicotine dependence; and (iv) available pharmacotherapies for nicotine dependence are safer, more numerous and more easily available. However, it is unclear whether these treatment differences are, in fact, justifiable because of the scarcity of empirical tests. We suggest several possible empirical tests. [source] The effects of chronic nitrogen fertilization on alpine tundra soil microbial communities: implications for carbon and nitrogen cyclingENVIRONMENTAL MICROBIOLOGY, Issue 11 2008Diana R. Nemergut Summary Many studies have shown that changes in nitrogen (N) availability affect primary productivity in a variety of terrestrial systems, but less is known about the effects of the changing N cycle on soil organic matter (SOM) decomposition. We used a variety of techniques to examine the effects of chronic N amendments on SOM chemistry and microbial community structure and function in an alpine tundra soil. We collected surface soil (0,5 cm) samples from five control and five long-term N-amended plots established and maintained at the Niwot Ridge Long-term Ecological Research (LTER) site. Samples were bulked by treatment and all analyses were conducted on composite samples. The fungal community shifted in response to N amendments, with a decrease in the relative abundance of basidiomycetes. Bacterial community composition also shifted in the fertilized soil, with increases in the relative abundance of sequences related to the Bacteroidetes and Gemmatimonadetes, and decreases in the relative abundance of the Verrucomicrobia. We did not uncover any bacterial sequences that were closely related to known nitrifiers in either soil, but sequences related to archaeal nitrifiers were found in control soils. The ratio of fungi to bacteria did not change in the N-amended soils, but the ratio of archaea to bacteria dropped from 20% to less than 1% in the N-amended plots. Comparisons of aliphatic and aromatic carbon compounds, two broad categories of soil carbon compounds, revealed no between treatment differences. However, G-lignins were found in higher relative abundance in the fertilized soils, while proteins were detected in lower relative abundance. Finally, the activities of two soil enzymes involved in N cycling changed in response to chronic N amendments. These results suggest that chronic N fertilization induces significant shifts in soil carbon dynamics that correspond to shifts in microbial community structure and function. [source] Oral vitamin E supplementation on oxidative stress, vitamin and antioxidant status in intensely exercised horsesEQUINE VETERINARY JOURNAL, Issue S36 2006C. A. WILLIAMS Summary Reasons for performing study: Vitamin E is the most commonly supplemented antioxidant in horses; however, previous research is not conclusive as to the recommended level for exercising horses. Objective: To evaluate the effects of 3 levels of vitamin E supplementation on oxidative stress and vitamin/antioxidant status in intensely exercised horses to determine the optimal level of vitamin E supplementation. Methods: Twelve unfit Standardbreds were divided into 3 groups, supplemented orally with 0 (CON), 5000 (MOD), or 10,000 (HI) iu/day of DL-,-tocopheryl acetate. The 3 times 3 Latin square design consisted of three 4 week supplementation periods with 4 week wash out periods between. After each period, horses underwent a treadmill interval exercise test. Blood samples were collected and heart rate (HR) measured before, during and after exercise. Data were analysed using ANOVA with repeated measures in SAS. Results: The CON group had lower HR throughout the test compared to the MOD and HI groups (P<0.05). There was an increase in plasma retinol (RET), ,-carotene (BC), red blood cell total glutathione and glutathione peroxidase with exercise (P<0.05), but all groups returned to baseline after 24 h. Plasma ,-tocopherol (TOC) increased from baseline with exercise (P<0.0001) in all groups; treatment differences were observed at 24 h (P<0.05). The HI and CON groups had lower BC compared to the MOD group (P = 0.05). Conclusions: Horses supplemented with vitamin E, at nearly 10-times the 1989 NRC recommended level, did not experience lower oxidative stress compared to control horses. Additionally, lower plasma BC levels observed in the HI group, which may indicate that vitamin E has an inhibitory effect on BC metabolism. Potential relevance: Supplementation above control levels is not more beneficial to oxidative stress and antioxidant status in intensely exercising horses; indeed, levels 10 times in excess may be detrimental to BC and should be avoided. [source] The response of manured forage maize to starter phosphorus fertilizer on chalkland soils in southern EnglandGRASS & FORAGE SCIENCE, Issue 2 2000Withers The impact of various starter phosphorus (P) fertilizers on the growth, nutrient uptake and dry-matter (DM) yield of forage maize (Zea mais) continuously cropped on the same area and receiving annual, pre-sowing, broadcast dressings of liquid and semi-solid dairy manures was investigated in two replicated plot experiments and in whole-field comparisons in the UK. In Experiment 1 on a shallow calcareous soil (27 mg l,1 Olsen-extractable P) in 1996, placement of starter P fertilizer (17 or 32 kg ha,1) did not benefit crop growth or significantly (P > 0·05) increase DM yield at harvest. However, in Experiment 2 on a deeper non-calcareous soil (41 mg l,1 Olsen-extractable P) in 1997, placement of starter P fertilizer (19 or 41 kg P ha,1), either applied alone or in combination with starter N fertilizer (10 or 25 kg N ha,1), significantly increased early crop growth (P < 0·01) and DM yield at harvest by 1·3 t ha,1 (P < 0·05) compared with a control without starter N or P fertilizer. Placement of starter N fertilizer alone did not benefit early crop growth, but gave similar yields as P, or N and P, fertilizer treatments at harvest. Large treatment differences in N and P uptake by mid-August had disappeared by harvest. In field comparisons over the 4-year period 1994,97, the addition of starter P fertilizer increased field cumulative surplus P by over 70%, but without significantly (P > 0·05) increasing DM yield, or nutrient (N and P) uptake, compared with fields that did not receive starter P fertilizer. The results emphasized the extremely low efficiency with which starter P fertilizers are utilized by forage maize and the need to budget manure and fertilizer P inputs more precisely in order to avoid excessive soil P accumulation and the consequent increased risk of P transfer to water causing eutrophication. [source] Acute cholecystokinin effects on event-related potentials in healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2002Verner J. Knott Abstract This study investigated the effects of a continuous slow infusion of cholecystokinin tetrapeptide (CCK-4), a neuropeptide with panicogenic properties, on brain event-related potentials (ERPs) in healthy adults. Twenty-four volunteers, 15 females and 9 males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. ERPs, elicited within a standard auditory odd-ball paradigm requiring the counting of rare (20%) occurring ,deviant' tones interspersed among more frequent (80%) occurring ,standard' tones, were assessed once before infusion, and at 10,min and 40,min after the onset of infusion. Compared with the placebo, CCK-4 delayed the latencies of N100 and P200 components elicited by ,deviant' stimuli. No significant treatment differences were observed with respect to N200, P300b, mood or adverse symptoms. These preliminary findings suggest that CCK-4 may interfere with information processing relating to the selection of significant stimuli and as such, may be of relevance to mechanisms underlying panic disorder. Copyright © 2002 John Wiley & Sons, Ltd. [source] Assessment of visibility of facial wrinkle reduction by various types of observersINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2004J. H. D. M. Westerink The prime objective of many facial wrinkle-reduction treatments is to achieve visible improvement. The visibility of before/after treatment differences is therefore often part of the efficacy assessment. This paper investigates whether the background knowledge of the people acting as observers in such assessments has an impact on the results, e.g., the subjects themselves are familiar with their faces, skin professionals have much experience in judging skin quality, and thus both might be more sensitive to small changes. In a clinical study, 44 female subjects were regularly treated during a period of 12 weeks with one of three wrinkle-reduction treatments: K, L and M (placebo). Photographs were taken before treatment and after 6 and 12 weeks. Three different types of observers judged the photographs: ,Observer type I: Twenty-four lay observers were given the 0- and 6-week and the 0- and 12-week pairs of photographs of all subjects to indicate the one with the least wrinkles in a two-alternative forced-choice procedure; ,Observer type II: The subjects themselves were given the 0- and 6-week and the 0- and 12-week pairs of their own photographs (eight replications) to indicate the photograph with the least wrinkles (two-alternative forced-choice); ,Observer type III: A trained panel of skin professionals (n = 3) each gave a 9-point Fitzpatrick wrinkle-severity score for all individual 0- and 12-week photographs. It was found that the lay observers perceived the same differences as the subjects themselves: significant improvements after 12 weeks for treatment K (P < 0.0005 and P = 0.005, respectively). No visible effects were seen for treatments L and M, but, most importantly, a significant difference between treatments K and M (placebo) (P = 0.015 and P = 0.01 for independent observers and the subjects themselves, respectively). The trained panel also identified this difference between K and M (P = 0.013) in favor of K, but here it was due to a significant deterioration over time of the ,placebo-treated' wrinkles (M, P = 0.03). Thus, in conclusion, no indications were found that extra knowledge , in the form of familiarity with the own face or in the form of professional training , results in the identification of more treatments that show significantly visible wrinkle reduction. [source] Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2004Peter Paul De Deyn Abstract Objectives Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings. Methods Patients (n,=,652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5,mg/day). Results Mean age was 76.6±10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items,primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5,mg olanzapine group (,6.2,±,4.9) was significantly greater than with placebo (,5.0,±,6.1, p,=,0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz,2.5 olanzapine group (2.8,±,1.4, p,=,0.030) relative to placebo (3.2,±,1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol. Conclusions While 1.0,mg olanzapine did not show significant differences from placebo, the 2.5,mg dose was a reasonable starting dose. Olanzapine at 7.5,mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated. Copyright © 2004 John Wiley & Sons, Ltd. [source] Yield, Boll Distribution and Fibre Quality of Hybrid Cotton (Gossypium hirsutum L.) as influenced by Organic and Modern Methods of CultivationJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 4 2006D. Blaise Abstract India is the largest cotton-growing country (8.9 million hectares) in the world and most of the area is rain-dependent. Large amount of pesticides are used for the control of sucking pests and lepidopterans. Increasing demand for clean organic fibre has led to an interest in organic cotton. However, information on the effects of organic cultivation on fibre quality is limited. Seed cotton yield and fibre quality (length, strength, micronaire and uniformity) were determined for an organic and modern method of cultivation during 3 years (2002,2003 to 2004,2005) of a 11-year (1994,1995 to 2004,2005) study. Vertical and horizontal distribution of bolls on a cotton plant was also determined in 2003,2004 and 2004,2005. At the end of year 11, soil samples were collected and analysed for soil organic carbon content, water-stable aggregates (%), and mean weight diameter. Averaged over 3 years, an additional 94 kg seed cotton ha,1 was produced in the organic over the modern method of cultivation and the difference was significant. The year × treatment interaction was significant. Seed cotton yield in the organic plots was significantly greater than the modern method of cultivation plots in 2003,2004 because of a well-distributed normal rainfall and low pest incidence. The main stem nodes 13,22 accounted for the largest numbers of bolls present on the plant. Plants of the organic plots had significantly (37,71 %) more bolls on nodes 13,27 than those for the plants of the modern method of cultivation. Lateral distribution of bolls on a sympodial (fruiting) branch, was noticed up to fruiting point 11. However, treatment differences were not significant. With regard to fibre quality (length, strength, fineness and uniformity), differences between years were significant. Inferior quality fibre was produced in 2004,2005 because of delayed planting and early cessation of rain. On average, cotton grown under organic conditions compared with the modern method of cultivation had significantly better fibre length (25.1 vs. 24.0 mm) and strength (18.8 vs. 17.9 g tex,1). Soil samples of the organic plots had significantly greater C content, water-stable aggregates and mean weight diameter than the modern method of cultivation plots. Differences were restricted to the top layers (0,0.1 and 0.1,0.2 m). Yield benefits of growing cotton in an organic system over the modern method of cultivation are expected to be greater in years receiving normal rainfall and having low pest incidence. [source] Relay Cropping of Sorghum and Legume Shrubs for Crop Yield Improvement and Striga Control in the Subsistence Agriculture Region of Tigray (Northern Ethiopia)JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 1 2005F. Reda Abstract Striga hermonthica is a major constraint in the subsistence agriculture regions of northern Ethiopia. Low soil fertility and overall environmental degradation has contributed to the build up of the parasitic weed infestation. Improved cropping systems have to be introduced to address the interrelated problems of Striga and soil fertility decline. Thus, relay cropping of sorghum with legume shrubs was investigated at two locations representing different environments. Results showed that the output of the improved cropping system was dependent on ecological endowments. Relay cropping led to significant improvement in yield at Sheraro, at the site with relatively better weather and soil conditions. The legume shrubs resulted in significantly lower sorghum yield in a dryland location (Adibakel). Overall Striga infestation declined over the 3-year period; however, treatment differences were not apparent. Among the two legume shrubs, Sesbania sesban was better adapted to the dryland areas. Relay cropping could provide a viable option for farmers in both types of environments that are characterized by accelerated decline in natural resource base. However, it could mean compromising the yield of non-fertilized sorghum in the interest of long-term benefits of low incidence of Striga and more rewarding crop enterprise in dry areas. [source] Effects of three PTSD treatments on anger and guilt: Exposure therapy, eye movement desensitization and reprocessing, and relaxation training,JOURNAL OF TRAUMATIC STRESS, Issue 1 2006Jennifer A. Stapleton This study sought to investigate the efficacy of prolonged exposure, eye movement desensitization and reprocessing, and relaxation training on trait anger and guilt and on trauma-related anger and guilt within the context of posttraumatic stress disorder (PTSD) treatment. Fifteen PTSD patients completed each treatment and were assessed at posttreatment and at 3-month follow-up. All three treatments were associated with significant reductions in all measures of anger and guilt, with gains maintained at follow-up. There were no significant treatment differences in efficacy or in the proportion of patients who worsened on anger or guilt measures over the course of treatment. Between-treatment effect sizes were generally very small. Results suggest that all three treatments are associated with reductions in anger and guilt, even for patients who initially have high levels of these emotions. However, these PTSD therapies may not be sufficient for treating anger and guilt; additional interventions may be required. [source] Rotigotine improves restless legs syndrome: A 6-month randomized, double-blind, placebo-controlled trial in the United States,,§MOVEMENT DISORDERS, Issue 11 2010Wayne A. Hening MD Abstract This randomized, double-blinded, placebo-controlled trial (NCT00135993) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome (RLS) over a 6-month maintenance period. A total of 505 eligible participants with moderate to severe RLS (IRLS sum score , 15) were randomly assigned to five groups to receive either placebo or rotigotine (0.5, 1, 2, or 3 mg/24 hr) delivered by once-daily transdermal patch (fixed-dose regimen). The two co-primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions (CGI-1) score. On both primary measures, 2 and 3 mg/24 hr rotigotine was superior to placebo (P < 0.001). Adjusted treatment differences to placebo for the IRLS sum score were ,4.5 (95% CI: ,6.9, ,2.2) for 2 mg/24 hr rotigotine, ,5.2 (95% CI: ,7.5, ,2.9) for 3 mg/24 hr rotigotine, and for CGI item 1 ,0.65 (95% CI: ,1.0, ,0.3) and ,0.9 (95% CI: ,1.3, ,0.5) for the 2 and 3 mg/24 hr doses, respectively. Skin reactions (27%) and known dopaminergic side effects such as nausea (18.1%) and headache (11.6%) were mostly mild or moderate in rotigotine subjects. Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms. Treatment efficacy was maintained throughout the 6-month double-blind period. © 2010 Movement Disorder Society [source] Nonparametric confidence intervals for Tmax in sequence-stratified crossover studiesPHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 1 2008Susan A. Willavize Abstract Tmax is the time associated with the maximum serum or plasma drug concentration achieved following a dose. While Tmax is continuous in theory, it is usually discrete in practice because it is equated to a nominal sampling time in the noncompartmental pharmacokinetics approach. For a 2-treatment crossover design, a Hodges,Lehmann method exists for a confidence interval on treatment differences. For appropriately designed crossover studies with more than two treatments, a new median-scaling method is proposed to obtain estimates and confidence intervals for treatment effects. A simulation study was done comparing this new method with two previously described rank-based nonparametric methods, a stratified ranks method and a signed ranks method due to Ohrvik. The Normal theory, a nonparametric confidence interval approach without adjustment for periods, and a nonparametric bootstrap method were also compared. Results show that less dense sampling and period effects cause increases in confidence interval length. The Normal theory method can be liberal (i.e. less than nominal coverage) if there is a true treatment effect. The nonparametric methods tend to be conservative with regard to coverage probability and among them the median-scaling method is least conservative and has shortest confidence intervals. The stratified ranks method was the most conservative and had very long confidence intervals. The bootstrap method was generally less conservative than the median-scaling method, but it tended to have longer confidence intervals. Overall, the median-scaling method had the best combination of coverage and confidence interval length. All methods performed adequately with respect to bias. Copyright © 2007 John Wiley & Sons, Ltd. [source] Developing tools for the safety specification in risk management plans: lessons learned from a pilot project,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2008Andrew J. P. Cooper BSc Abstract Purpose Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use. Methods Archive data from a successful MAA were utilised. Methods were assessed for demonstrating the extent of clinical safety experience, evaluating the sensitivity of the clinical trial data to detect treatment differences and identifying safety signals from adverse event and laboratory data to define the extent of safety knowledge with the drug. Results The extent of clinical safety experience was demonstrated by plots of patient exposure over time. Adverse event data were presented using dot plots, which display the percentages of patients with the events of interest, the odds ratio, and 95% confidence interval. Power and confidence interval plots were utilised for evaluating the sensitivity of the clinical database to detect treatment differences. Box and whisker plots were used to display laboratory data. Conclusions This project enabled us to identify new evidence-based methods for presenting and evaluating clinical safety data. These methods represent an advance in the way safety data from clinical trials can be analysed and presented. This project emphasises the importance of early and comprehensive planning of the safety package, including evaluation of the use of epidemiology data. Copyright © 2008 John Wiley & Sons, Ltd. [source] The role of low soil temperature in the inhibition of growth and PSII function during dark chilling in soybean genotypes of contrasting tolerancePHYSIOLOGIA PLANTARUM, Issue 1 2007Abram J. Strauss Dark chilling affects growth and yield of warm-climate crops such as soybean [Glycine max (L.) Merr.]. Several studies have investigated chilling-stress effects on photosynthesis and other aspects of metabolism, but none have compared effects of whole-plant chilling (WPC; shoots and roots) with that of aboveground chilling in legumes. This is important because low root temperatures might induce additional constraints, such as inhibition of N2 fixation, thereby aggravating chilling-stress symptoms. Effects of dark chilling on PSII, shoot growth, leaf ureide content and photosynthetic capacity were studied in two soybean genotypes, Highveld Top (chilling tolerant) and PAN809 (chilling sensitive), in experiments comparing effects of WPC with that of shoot chilling (SC). Both treatments inhibited shoot growth in PAN809 but not Highveld Top. Also, WPC in PAN809 caused a decrease in leaf ureide content followed by severe chlorosis and alterations in O-J-I-P fluorescence-rise kinetics, distinct from SC. A noteworthy difference was the appearance of a ,K peak in the O-J-I-P fluorescence rise in response to WPC. These genotypic and treatment differences also reflected in the degree of inhibition of CO2 assimilation rates. The appearance of a ,K peak, coupled with growth inhibition, reduced ureide content, chlorosis and lower CO2 assimilation rates, provides mechanistic information about how WPC might have aggravated chilling-stress symptoms in PAN809. We introduce a model explaining how chilling soil temperatures might trigger N-limitation in sensitive genotypes and how characteristic changes in O-J-I-P fluorescence-rise kinetics are linked to changes in carbon and nitrogen metabolism. [source] Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthmaRESPIROLOGY, Issue 3 2003Carolyn RUTHERFORD Objective: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. Methodology: HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000,2000 µg/day (n = 67) compared with remaining on BDP/BUD ,1750 µg/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of ,0.5 was considered to be clinically meaningful. Results: There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Conclusion: Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL. [source] Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Martin M. Miner MD ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source] | |||||||||||||||||||||||||||||||