948 resultados para treatment effect


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Anliegen dieser Dissertation ist die Untersuchung des Einflusses eines Lesestrategietrainings auf die Entwicklung des Leseverständnisses in den Klassen 2 und 4. In einer experimentellen Studie mit Prä-Post-Test-Design wurde die Wirksamkeit eines 25 Sitzungen umfassenden Trainings der Strategien Vorhersagen, kleinschrittiges Wiederholen und Zusammenfassen den Effekten einer lesefernen Kontrollbedingung gegenübergestellt. Die Lesestrategien wurden peergestützt vermittelt, d. h. in Dyaden aus einem leseschwächeren und einem lesestärkeren Kind. In drei Teilstudien wurden Fragestellungen zur differenzierten Analyse der Trainingswirksamkeit untersucht: (1) Wird die Trainingswirksamkeit durch die Effizienz der Worterkennungsprozesse beeinflusst?, (2) Kann die Entwicklung der Leseflüssigkeit durch das Lesestrategietraining gefördert werden? und (3) Können leseschwache Kinder von der Zusammenarbeit mit lesestärkeren Tutor(inn)en hinsichtlich der Verbesserung ihres Leseverständnisses profitieren?. Die Ergebnisse dieser Dissertation sprechen dafür, dass das eingesetzte peergestützte Lesestrategietraining das Leseverständnis und die Leseflüssigkeit von Zweit- und Viertklässler(inne)n unter bestimmten Voraussetzungen positiv beeinflussen konnte. Die Leseleistungen vor dem Training, die Effizienz der Worterkennungsprozesse und die Rolle im dyadischen Lernen erwiesen sich als relevante Einflussfaktoren für die Wirksamkeit des Strategietrainings. Zweitklässler(innen), die aufgrund guter Prä-Test Leseleistungen die Tutor(inn)enrolle erhielten, konnten ihr Leseverständnis gegenüber Kindern mit gleichen Leseleistungen in der Kontrollbedingung signifikant steigern. Leseschwache Zweitklässler(innen) hingegen schienen nur bei (relativ) effizienten Worterkennungsprozessen die Lesestrategien zur Steigerung ihres globalen Leseverständnisses nutzen zu können, wobei sie keinen Zugewinn aus der dyadischen Zusammenarbeit ziehen konnten. Bei ineffizienten Worterkennungsprozessen hatte das Strategietraining negative Auswirkungen auf das allgemeine Leseverständnis. Anders in Klasse 4: Kinder, die aufgrund unterdurchschnittlicher Leseleistungen im Prä-Test als Tutand(inn)en am Training teilnahmen, verbesserten ihr Leseverständnis und konnten dabei von der Zusammenarbeit mit lesestarken Tutor(inn)en profitieren. Für die Tutor(inn)en in Klasse 4 zeigte sich kein Effekt des Strategietrainings gegenüber der Kontrollgruppe. In beiden Klassenstufen stellte sich im Verlauf des Strategietrainings eine schnellere Entwicklung der Leseflüssigkeit der schwachen Leser(innen) ein. Zusammengefasst erzielte das Training die größten Effekte für gute Leser(innen) in Klasse 2 und schwache Leser(innen) in Klasse 4 – beide Gruppen konnten ihr Leseverständnis praktisch bedeutsam gegenüber Kindern mit gleichen Leseleistungen in der Kontrollbedingung steigern.

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This paper analyzes the measure of systemic importance ∆CoV aR proposed by Adrian and Brunnermeier (2009, 2010) within the context of a similar class of risk measures used in the risk management literature. In addition, we develop a series of testing procedures, based on ∆CoV aR, to identify and rank the systemically important institutions. We stress the importance of statistical testing in interpreting the measure of systemic importance. An empirical application illustrates the testing procedures, using equity data for three European banks.

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We carried out a randomized controlled trial in Bogotá, the recipient of Colombia´s highest number of internally displaced people (IDP), to assess whether the use of SMS to communicate eligibility to social benefits fosters the welfare of victimized internal refugees. Only a fraction of IDP are elegible to benefits. We inform eligibility via SMS to a random half of IDP-households who are, and estimate the Local Average Treatment Effect of the text message on the knowledge of the benefits available tothe displaced population. We show that while on the average treated households know their rights better than controls, a more disaggregate analysis suggest that there is variation of awareness across benefits. The intervention was overall successful in empowering IDP and the use of SMS should be widened as a social policy instrument. However our results suggest that text messages should be complemented with other communication strategies, yet to be evaluated.

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Silvicultural treatments have been shown to alter the composition of species assemblages in numerous taxa. However, the intensity and persistence of these effects have rarely been documented. We used a before-after, control-impact (BACI) paired design, i.e., five pairs of 25-ha study plots, 1-control and 1-treated plot, to quantify changes in the density of eight forest bird species in response to selection harvesting over six breeding seasons, one year pre- and five years postharvest. Focal species included mature forest associates, i.e., Northern Parula (Setophaga americana) and Black-throated Green Warbler (Setophaga virens), forest generalists, i.e., Yellow-bellied Sapsucker (Sphyrapicus varius) and Swainson’s Thrush (Catharus ustulatus), early-seral specialists, i.e., Mourning Warbler (Geothlypis philadelphia) and Chestnut-sided Warbler (Setophaga pensylvanica), species associated with shrubby forest gaps, i.e., Black-throated Blue Warbler (Setophaga caerulescens), and mid-seral species, i.e., American Redstart (Setophaga ruticilla). As predicted, we found a negative numerical response to the treatment in the Black-throated Green Warbler, no treatment effect in the Yellow-bellied Sapsucker, and a positive treatment effect in early-seral specialists. We only detected a year effect in the Northern Parula and the American Redstart. There was evidence for a positive treatment effect on the Swainson’s Thrush when the regeneration started to reach the pole stage, i.e., fifth year postharvest. These findings suggest that selection harvesting has the potential to maintain diverse avian assemblages while allowing sustainable management of timber supply, but future studies should determine whether mature-forest associates can sustain second- and third-entry selection harvest treatments.

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Background: Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. Results: Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. Conclusions: Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

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Pharmacogenetic trials investigate the effect of genotype on treatment response. When there are two or more treatment groups and two or more genetic groups, investigation of gene-treatment interactions is of key interest. However, calculation of the power to detect such interactions is complicated because this depends not only on the treatment effect size within each genetic group, but also on the number of genetic groups, the size of each genetic group, and the type of genetic effect that is both present and tested for. The scale chosen to measure the magnitude of an interaction can also be problematic, especially for the binary case. Elston et al. proposed a test for detecting the presence of gene-treatment interactions for binary responses, and gave appropriate power calculations. This paper shows how the same approach can also be used for normally distributed responses. We also propose a method for analysing and performing sample size calculations based on a generalized linear model (GLM) approach. The power of the Elston et al. and GLM approaches are compared for the binary and normal case using several illustrative examples. While more sensitive to errors in model specification than the Elston et al. approach, the GLM approach is much more flexible and in many cases more powerful. Copyright © 2005 John Wiley & Sons, Ltd.

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Sequential methods provide a formal framework by which clinical trial data can be monitored as they accumulate. The results from interim analyses can be used either to modify the design of the remainder of the trial or to stop the trial as soon as sufficient evidence of either the presence or absence of a treatment effect is available. The circumstances under which the trial will be stopped with a claim of superiority for the experimental treatment, must, however, be determined in advance so as to control the overall type I error rate. One approach to calculating the stopping rule is the group-sequential method. A relatively recent alternative to group-sequential approaches is the adaptive design method. This latter approach provides considerable flexibility in changes to the design of a clinical trial at an interim point. However, a criticism is that the method by which evidence from different parts of the trial is combined means that a final comparison of treatments is not based on a sufficient statistic for the treatment difference, suggesting that the method may lack power. The aim of this paper is to compare two adaptive design approaches with the group-sequential approach. We first compare the form of the stopping boundaries obtained using the different methods. We then focus on a comparison of the power of the different trials when they are designed so as to be as similar as possible. We conclude that all methods acceptably control type I error rate and power when the sample size is modified based on a variance estimate, provided no interim analysis is so small that the asymptotic properties of the test statistic no longer hold. In the latter case, the group-sequential approach is to be preferred. Provided that asymptotic assumptions hold, the adaptive design approaches control the type I error rate even if the sample size is adjusted on the basis of an estimate of the treatment effect, showing that the adaptive designs allow more modifications than the group-sequential method.

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Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

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This paper considers methods for testing for superiority or non-inferiority in active-control trials with binary data, when the relative treatment effect is expressed as an odds ratio. Three asymptotic tests for the log-odds ratio based on the unconditional binary likelihood are presented, namely the likelihood ratio, Wald and score tests. All three tests can be implemented straightforwardly in standard statistical software packages, as can the corresponding confidence intervals. Simulations indicate that the three alternatives are similar in terms of the Type I error, with values close to the nominal level. However, when the non-inferiority margin becomes large, the score test slightly exceeds the nominal level. In general, the highest power is obtained from the score test, although all three tests are similar and the observed differences in power are not of practical importance. Copyright (C) 2007 John Wiley & Sons, Ltd.

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We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

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Vitamin E absorption requires the presence of fat; however, limited information exists on the influence of fat quantity on optimal absorption. In the present study we compared the absorption of stable-isotope-labelled vitamin E following meals of varying fat content and source. In a randomised four-way cross-over study, eight healthy individuals consumed a capsule containing 150 mg H-2-labelled RRR-alpha-tocopheryl acetate with a test meal of toast with butter (17.5 g fat), cereal with full-fat milk (17.5 g fat), cereal with semi-skimmed milk (2.7 g fat) and water (0g fat). Blood was taken at 0, 0.5, 1, 1.5, 2, 3, 6 and 9 h following ingestion, chylomicrons were isolated, and H-2-labelled alpha-tocopherol was analysed in the chylomicron and plasma samples. There was a significant time (P<0.001) and treatment effect (P<0.001) in H-2-labelled alpha-tocopherol concentration in both chylomicrons and plasma between the test meals. H-2-labelled alpha-tocopherol concentration was significantly greater with the higher-fat toast and butter meal compared with the low-fat cereal meal or water (P< 0.001), and a trend towards greater concentration compared with the high-fat cereal meal (P= 0.065). There was significantly greater H-2-labelled α-tocopherol concentration with the high-fat cereal meal compared with the low-fat cereal meal (P< 0.05). The H-2-labelled alpha-tocopherol concentration following either the low-fat cereal meal or water was low. These results demonstrate that both the amount of fat and the food matrix influence vitamin E absorption. These factors should be considered by consumers and for future vitamin E intervention studies.

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The average UK adult consumes less than three portions of fruit and vegetables daily, despite evidence to suggest that consuming five portions daily could help prevent chronic diseases. It is recommended that fruit juice should only count as one of these portions, as juicing removes fibre and releases sugars. However, fruit juices contain beneficial compounds such as vitamin C and flavonoids and could be a useful source of dietary phytochemicals. Two randomised controlled cross-over intervention studies investigating the effects of chronic and acute consumption of commercially-available fruit- and vegetable-puree-based drinks (FVPD) on bioavailability, antioxidant status and CVD risk factors are described. Blood and urine samples were collected during both studies and vascular tone was measured using laser Doppler imaging. In the chronic intervention study FVPD consumption was found to significantly increase dietary carotenoids (P = 0.001) and vitamin C (P = 0.003). Plasma carotenoids were increased (P = 0.001), but the increase in plasma vitamin C was not significant. There were no significant effects on oxidative stress, antioxidant status and other CVD risk factors. In the acute intervention study FVPD were found to increase total plasma nitrate and nitrite (P = 0.001) and plasma vitamin C (P = 0.002). There was no effect on plasma lipids or uric acid, but there was a lower glucose and insulin peak concentration after consumption of the FVPD compared with the sugar-matched control. There was a trend towards increased vasodilation following both chronic and acute FVPD consumption. All volunteers were retrospectively genotyped for the eNOS G298T polymorphism and the effect of genotype on the measurements is discussed. Overall, there was a non-significant trend towards increased endothelium-dependent vasodilation following both acute and chronic FVPD consumption. However, there was a significant time x treatment effect (P < 0.05) of acute FVPD consumption in individuals with the GG variant of the eNOS gene.

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Background & aims The consumption of long chain n − 3 polyunsaturated fatty acids (LC n − 3 PUFA) is known to be cardio-protective. Data on the influence of LC n − 3 PUFA on arterial stiffness in the postprandial state is limited. The aim of this study was to investigate the acute effects of a LC n − 3 PUFA-rich meal on measures of arterial stiffness. Methods Twenty-five healthy subjects (12 men, 13 women) received a control and a LC n − 3 PUFA-rich meal on two occasions in a random order. Arterial stiffness was measured at baseline, 30, 60, 90, 120, 180 and 240 min after meal consumption by pulse wave analysis and digital volume pulse to derive an augmentation index and a stiffness index respectively. Blood samples were taken for measurement of lipids, glucose and insulin. Results Consumption of the LC n − 3 PUFA-rich meal had an attenuating effect on augmentation index (P = 0.02) and stiffness index (P = 0.03) compared with the control meal. A significant treatment effect (P = 0.036) was seen for plasma non-esterified fatty acids concentrations. Conclusions These data indicate that acute LC n − 3 PUFA-rich meal consumption can improve postprandial arterial stiffness. This has important implications for the beneficial properties of LC n − 3 PUFA and cardiovascular risk reduction.

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Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behaviour therapy in addition to standard care for patients with psychosis and a co-morbid substance use problem. Design Two-centre, open, rater-blind randomised controlled trial Setting UK Secondary Care Participants 327 patients with clinical diagnoses of schizophrenia, schizophreniform or schizoaffective disorder and DSM-IV diagnoses of drug and/or alcohol dependence or abuse Interventions Participants were randomly allocated to integrated motivational interviewing and cognitive behaviour therapy or standard care. Therapy has two phases. Phase one – “motivation building” – concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two –“Action” – supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year. Main outcomes The primary outcome was death from any cause or admission to hospital in the 12 months after therapy. Secondary outcomes were frequency and amount of substance use (Timeline Followback), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, global assessment of functioning and deliberate self harm, at 12 and 24 months, with additional Timeline Followback assessments at 6 and 18 months. Analysis was by intention-to-treat with robust treatment effect estimates. Results 327 participants were randomised. 326 (99.7%) were assessed on the primary outcome, 246 (75.2%) on main secondary outcomes at 24 months. Regarding the primary outcome, there was no beneficial treatment effect on hospital admissions/ death during follow-up, with 20.2% (33/163) of controls and 23.3% (38/163) of the therapy group deceased or admitted (adjusted odds-ratio 1.16; P= 0.579; 95% confidence interval 0.68 to 1.99). For secondary outcomes there was no treatment effect on frequency of substance use or perceived negative consequences, but a statistically significant effect of therapy on amount used per substance-using day (adjusted odds-ratios: (a) for main substance 1.50; P=0.016; 1.08 to 2.09, (b) all substances 1.48; P=0.017; 1.07 to 2.05). There was a statistically significant treatment effect on readiness to change use at 12 months (adjusted odds-ratio 2.05; P=0.004; 1.26 to 3.31), not maintained at 24 months. There were no treatment effects on assessed clinical outcomes. Conclusions Integrated motivational interviewing and cognitive behaviour therapy for people with psychosis and substance misuse does not improve outcome in terms of hospitalisation, symptom outcomes or functioning. It does result in a reduction in amount of substance use which is maintained over the year’s follow up. Trial registration Current Controlled Trials: ISRCTN14404480

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The fermentability of rice bran (RB), alone or in combination with one of two probiotics, by canine faecal microbiota was evaluated in stirred, pH-controlled, anaerobic batch cultures. RB enhanced the levels of bacteria detected by probes Bif164 (bifidobacteria) and Lab158 (lactic acid bacteria); however, addition of the probiotics did not have a significant effect on the predominant microbial counts compared with RB alone. RB sustained levels of Bifidobacterium longum 05 throughout the fermentation; in contrast, Lactobacillus acidophilus 14 150B levels decreased significantly after 5-h fermentation. RB fermentation induced changes in the short-chain fatty acid (SCFA) profile. However, RB combined with probiotics did not alter the SCFA levels compared with RB alone. Denaturing gradient gel electrophoresis analysis of samples obtained at 24 h showed a treatment effect with RB, which was not observed in the RB plus probiotic systems. Overall, the negative controls displayed lower species richness than the treatment systems and their banding profiles were distinct. This study illustrates the ability of a common ingredient found in pet food to modulate the canine faecal microbiota and highlights that RB may be an economical alternative to prebiotics for use in dog food.