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Design Study (design + study)
Selected AbstractsLaryngeal Preservation With Supracricoid Partial Laryngectomy Results in Improved Quality of Life When Compared With Total Laryngectomy,THE LARYNGOSCOPE, Issue 2 2001Gregory S. Weinstein MD Abstract Objectives/Hypotheses Study 1: To assess the oncologic outcome following supracricoid partial laryngectomy (SCPL). Study 2: To compare the quality of life (QOL) following SCPL to total laryngectomy (TL) with tracheoesophageal puncture (TEP). Study 3: To analyze whole organ TL sections to determine the percentage of lesions amenable to SCPL. Study Design Study 1: A retrospective review of patients who underwent SCPL. Study 2: A non-randomized, prospective study using QOL instruments to compare patients who underwent either SCPL or TL. Study 3: A retrospective histopathologic study of TL specimens assessed for the possibility of performing an SCPL. Methods Study 1: Twenty-five patients with carcinoma of the larynx underwent SCPL between June 1992 and June 1999. Various rates of oncologic outcome were calculated. Study 2: Thirty-one patients participated in the QOL assessment. This included the SF-36 general health status measure, the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, and the University of Michigan Voice-Related Quality of Life (VRQOL) instrument. Study 3: Ninety surgical specimens were obtained and studied from the total laryngectomy cases in the Tucker Collection. Multiple sites were evaluated for the presence of carcinoma. A computer program was written to classify whether the patient was amenable to SCPL. Results Study 1: The overall local control rate was 96% (24/25). The local control rate following SCPL with cricohyoidoepiglottopexy (CHEP) was 95% (20/21). The local control rate following SCPL with cricohyoidopexy (CHP) was 100% (4/4). Study 2: The SCPL had significantly higher domain scores than TL and TEP in the following categories for the SF-36: physical function, physical limitations, general health, vitality, social functioning, emotional limitations, and physical health summary. The significantly higher domains for the SCPL when compared with the TL and TEP for the HNQOL were eating and pain. Finally, when voice-related QOL was assessed with the V-RQOL, the domains of physical functioning and the total score were significantly better with SCPL when compared with TL and TEP. Study 3: Forty of 90 (44%) laryngeal whole organ specimens were determined to be resectable by SCPL. In 16 (18%) specimens, the patients could have undergone SCPL with CHEP and in 24 (27%) specimens the patients could have undergone SCPL with CHP. Among the 40 (44%) specimens determined to be able to have undergone SCPL, 19 were glottic (1 T1, 15 T2, 3 T3) and 21 were supraglottic (9 T2, 12 T3). Conclusions 1) A review of the literature and an analysis of the data in this study indicate that excellent local control may be expected following SCPL. 2) The QOL following SCPL, as measured by three validated QOL instruments, is superior to TL with TEP. 3) A histologic assessment of whole organ sections of TL specimens indicates that many patients who have been subjected to TL may have been candidates for SCPL. 4) If the indications and contraindications are rigorously adhered to, SCPLs are reasonable alternatives to TL in selected cases. [source] Effects of back care education in elementary schoolchildrenACTA PAEDIATRICA, Issue 8 2000G Cardon The purpose of this study was to investigate the effects of a back care education programme, consisting of six sessions of 1 h each, in fourth- and fifth-grade elementary schoolchildren. Testing consisted of a practical performance and a back care knowledge test. Forty-two subjects and 36 controls performed a pre-test and were tested within 1 wk after the programme. To monitor effects and follow-up effects on a larger sample, 82 different pupils were tested within 1 wk after the programme and 116 other children 3 mo after. Both larger samples were compared with one group of 129 controls. Interrater reliability for the test items of the practical assessment was high; intraclass correlation coefficients varied from 0.785 to 0.980. In the pre/post design study, interaction between time and condition was significant for the sum score of the practical assessment and for the knowledge test (p < 0.001), with higher scores for the intervention group (15% improvement for the knowledge test score, 31.6% for the practical sum score). Significantly higher sum scores for the knowledge test and for all practical assessment items were found in the intervention groups, tested within 1 wk and 3 mo after the programme, in comparison with the control group (p <0.001). Conclusion: The effectiveness of a primary educational prevention programme on back care principles was demonstrated in this study. Effectiveness, long-term outcomes and behavioural changes need further evaluation to optimize back care prevention programmes for elementary schoolchildren. [source] Acute cognitive effects of donepezil in young, healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009Ana LC Zaninotto Abstract Objective The acute nootropic potential of donepezil in young healthy volunteers has not been adequately investigated mainly because in previous studies: (1) effects were assessed before peak-plasma concentration (Tmax) was reached; (2) only a few cognitive processes were assessed. Here we investigated a myriad of cognitive effects of augmentation of acetylcholine using an acute dose of donepezil in healthy adults at theoretical Tmax. Methods This was a double-blind, placebo controlled, parallel group design study of cognitive effects of acute oral donepezil (5,mg). Subjects were tested twice after donepezil ingestion: 90,min (time that coincides with previous testing in the literature) and 210,min. (theoretical Tmax). The test battery included tasks that tap cognitive domains that are sensitive to acetylcholine manipulations. Results At both testing times donepezil improved long-term recall of prose, objects recall, recall of spatial locations, and integration of objects with their locations, some effects having been related to self-reported mood enhancement. However, improvement of performance in the central executive measure (backward digit span) occurred only at Tmax. Conclusion Positive cognitive effects of acute donepezil can be observed in various cognitive domains including mood, but its full nootropic potential is more clearly found close to theoretical peak-plasma concentration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effects of lorazepam on visual perceptual abilitiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2008S. Pompéia Abstract Objective To evaluate the effects of an acute dose of the benzodiazepine (BZ) lorazepam in young healthy volunteers on five distinguishable visual perception abilities determined by previous factor-analytic studies. Methods This was a double-blind, cross-over design study of acute oral doses of lorazepam (2,mg) and placebo in young healthy volunteers. We focused on a set of paper-and-pencil tests of visual perceptual abilities that load on five correlated but distinguishable factors (Spatial Visualization, Spatial Relations, Perceptual Speed, Closure Speed, and Closure Flexibility). Some other tests (DSST, immediate and delayed recall of prose; measures of subjective mood alterations) were used to control for the classic BZ-induced effects. Results Lorazepam impaired performance in the DSST and delayed recall of prose, increased subjective sedation and impaired tasks of all abilities except Spatial Visualization and Closure Speed. Only impairment in Perceptual Speed (Identical Pictures task) and delayed recall of prose were not explained by sedation. Conclusion Acute administration of lorazepam, in a dose that impaired episodic memory, selectively affected different visual perceptual abilities before and after controlling for sedation. Central executive demands and sedation did not account for results, so impairment in the Identical Pictures task may be attributed to lorazepam's visual processing alterations. Copyright © 2008 John Wiley & Sons, Ltd. [source] Study of a longitudinal flux permanent magnet linear generator for wave energy convertersINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 14 2006O. Danielsson Abstract A directly coupled linear permanent magnet generator of longitudinal flux-type is investigated. The generator will be used for power take-off in a wave energy converter. A combined field- and circuit model, solved by a time stepping finite element technique, is used to model and analyse the electromagnetic behaviour of the machine. A large number of simulations form the basis of a design study where the influence of armature current level, number of cables per slot, and pole width is investigated with respect to efficiency, generator size, and the load angle. A case study is performed for a chosen generator design. The electromagnetic behaviour is examined both for nominal load and for overloads. The generator has a nominal output power of 10 kW for a constant piston speed of 0.7 ms,1. The electromagnetic efficiency at nominal load is 86.0%, the load angle 6.6°, and the power fluctuation 1.3%. At 300% overload the load angle barely exceeds 12° and the cable temperature is below 25°C provided that the stator back is thermally connected to the sea water. The numerical calculations have been verified for small speeds by experiments. Copyright © 2006 John Wiley & Sons, Ltd. [source] Does integrated trauma-informed substance abuse treatment increase treatment retention?JOURNAL OF COMMUNITY PSYCHOLOGY, Issue 7 2007Hortensia Amaro This article presents findings from a quasi-experimental, nonrandomized group design study that explored whether trauma-enhanced substance abuse treatment results in longer residential treatment stays and improved outcomes compared with treatment-as-usual. We used a subsample (N = 461) of participants in the Women, Co-Occurring Disorders and Violence Study, which was sponsored by the Substance Abuse and Mental Health Services Administration. The intervention group was 31% less likely to discontinue treatment within 4 months. Baseline mental health and trauma symptoms and alcohol and drug severity scores predicted neither overall length of time in treatment nor differences in retention between intervention and comparison groups. Substance abuse and mental health symptoms improved with increased duration of treatment, particularly for women with more severe baseline symptoms. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 845,862, 2007. [source] Comprehensive process design study for layered-NOX -control in a tangentially coal fired boilerAICHE JOURNAL, Issue 3 2010Wei Zhou Abstract As emissions regulations for coal-fired power plants become stricter worldwide, layering combustion modification and post-combustion NOX control technologies can be an attractive option for efficient and cost-effective NOX control in comparison to selective catalytic reduction (SCR) technology. The layered control technology approach designed in this article consists of separate overfire air (SOFA), reburn, and selective noncatalytic reduction (SNCR). The combined system can achieve up to 75% NOX reduction. The work presented in this article successfully applied this technology to NRG Somerset Unit 6, a 120-MW tangential coal-fired utility boiler, to reduce NOX emissions to 0.11 lb/MMBtu (130 mg/Nm3), well under the US EPA SIP Call target of 0.15 lb/MMBtu. The article reviews an integrated design study for the layered system at Somerset and evaluates the performance of different layered-NOX -control scenarios including standalone SNCR (baseline), separated overfire air (SOFA) with SNCR, and gas reburn with SNCR. Isothermal physical flow modeling and computational fluid dynamics simulation (CFD) were applied to understand the boiler flow patterns, the combustible distributions and the impact of combustion modifications on boiler operation and SNCR performance. The modeling results were compared with field data for model validation and verification. The study demonstrates that a comprehensive process design using advanced engineering tools is beneficial to the success of a layered low NOX system. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Equilibrium theory analysis of rectifying PSA for heavy component productionAICHE JOURNAL, Issue 8 2002Armin D. Ebner An isothermal equilibrium theory analysis, based on linear isotherms and a binary feed stream, was carried out to evaluate the feasibility of a rectifying PSA process for producing a pure heavy component at high recovery. Analytic expressions were derived to describe the performance of this process at the periodic state. The performance was also analyzed in terms of the different concentration and velocity profiles exhibited during various cycle steps that included the analysis of complex shock and simple wave interactions. Based on a parametric study, periodic behavior was established for a wide range of process conditions; and a design study with the PCB activated carbon,H2,CH4 system at 25°C further demonstrated the feasibility of a rectifying PSA cycle for producing a 100% CH4 stream from a dilute feed stream (y = 0.01) with a respectable recovery (80%), and reasonable process conditions. It also demonstrated the potential usefulness of an actual rectifying PSA process for bulk gas separation and purification. [source] Quality by design: Optimization of a liquid filled pH-responsive macroparticles using Draper-Lin composite designJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009Hasan Rafati Abstract In this study, pH responsive macroparticles incorporating peppermint oil (PO) were prepared using a simple emulsification/polymer precipitation technique. The formulations were examined for their properties and the desired quality was then achieved using a quality by design (QBD) approach. For this purpose, a Draper-Lin small composite design study was employed in order to investigate the effect of four independent variables, including the PO to water ratio, the concentration of pH sensitive polymer (hydroxypropyl methylcellulose phthalate), acid and plasticizer concentrations, on the encapsulation efficiency and PO loading. The analysis of variance showed that the polymer concentration was the most important variable on encapsulation efficiency (p,<,0.05). The multiple regression analysis of the results led to equations that adequately described the influence of the independent variables on the selected responses. Furthermore, the desirability function was employed as an effective tool for transforming each response separately and encompassing all of these responses in an overall desirability function for global optimization of the encapsulation process. The optimized macroparticles were predicted to yield 93.4% encapsulation efficiency and 72.8% PO loading, which were remarkably close to the experimental values of 89.2% and 69.5%, consequently. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2401,2411, 2009 [source] Analgesic Effects of Ethanol Are Influenced by Family History of Alcoholism and NeuroticismALCOHOLISM, Issue 8 2010Elizabeth Ralevski Background:, Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. Methods:, Forty-eight healthy subjects participated in this study; thirty-one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double-blind, placebo-controlled, randomized, within-subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low-exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high-exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60-minute infusion mark. Results:, The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. Conclusion:, These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol. [source] Theoretical design study on multifunctional triphenyl amino-based derivatives for OLEDsJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2009Lu-Yi Zou Abstract The use of triphenyl amino-based derivatives in organic light-emitting diodes (OLEDs) can significantly improve their efficiency and stability and especially their electroluminescence characteristics , most of the new hole-transport materials have this feature. In this study, a series of triphenyl amino-based compounds were computed, including two newly designed molecules. They can function as charge transport materials and emitters with high efficiency and stability. To reveal the relationship between the properties and structures of these bifunctional and multifunctional electroluminescent materials, the ground and excited state geometries were optimized at the B3LYP/6-31G(d), HF/6-31G(d), TD-B3LYP/6-31G(d), and CIS/6-31G(d) levels, respectively. The ionization potentials (IPs) and electron affinities (EAs) were computed. The lowest excitation energies, the maximum absorption, and emission wavelengths of these compounds were calculated by employing the time-dependent density functional theory (TD-DFT) method. Also, the mobilities of holes and electrons were studied computationally based on the Marcus electron transfer theory. The CH2Cl2 solvent effect on the absorption spectra of N,N,-di-1-naphthyl- N,N,-diphenylbenzidine (NPB) was considered by polarizable continuum model (PCM). The results obtained for these compounds are in good agreement with the experimental values. These data show that the proposed compounds 1 and 2 (N,B-di-1-naphthyl-N,B-diphenylbenzidine and Mes2N[p-4,4,-biphenyl-NPh(1-naphthyl)]), are multifunctional and bifunctional materials similar to Mes2B[p -4,4,-biphenyl-NPh(1-naphthyl)] (BNPB) and NPB, respectively. Copyright © 2009 John Wiley & Sons, Ltd. [source] Salivary Acetaldehyde Concentration According to Alcoholic Beverage Consumed and Aldehyde Dehydrogenase-2 GenotypeALCOHOLISM, Issue 9 2008Akira Yokoyama Background:, Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers. Methods:, In a randomized cross-over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3-week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking. Results:, The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 ,M in saliva vs. 2 to 5 ,M in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 ,M in saliva vs. 12 to 25 ,M in blood), and they were 13 to 25 ,M higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes. Conclusions:, There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype. [source] Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiodJOURNAL OF SLEEP RESEARCH, Issue 2 2007GILLES VANDEWALLE Summary Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by the sleep,wake/rest,activity cycle as well as by endogenous circadian rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and investigated whether this rhythm can be shifted by repeated melatonin administration while exposed to an altered photoperiod. Eight healthy males (age 24.4 ± 4.4 years) participated in a double-blind cross-over design study. In both conditions, volunteers were scheduled to 16 h,8 h rest : wake and dark : light cycles for nine consecutive days preceded and followed by 29-h constant routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5 mg) or placebo was administered at the beginning of the extended sleep opportunities. For all polysomnographically verified wakefulness periods of the CR, we calculated the high- (HF) and low- (LF) frequency bands of the power spectrum of the R,R interval, the standard deviation of the normal-to-normal (NN) intervals (SDNN) and the square root of the mean-squared difference of successive NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase-advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than after placebo treatment. We conclude that endogenous circadian rhythmicity influences autonomic control of HR and that the timing of these endogenous rhythms can be altered by extended sleep/rest episodes and associated changes in photoperiod as well as by melatonin treatment. [source] Unipolar versus bipolar radiofrequency treatment of rhytides and laxity using a mobile painless delivery methodLASERS IN SURGERY AND MEDICINE, Issue 7 2008Macrene Alexiades-Armenakas MD Abstract Background Previous studies have shown that radiofrequency (RF) energy is a safe and effective treatment for rhytide-reduction. Objective This randomized, blinded, split-face study assesses the safety and efficacy of the unipolar versus bipolar handpieces on an RF device with a mobile delivery method for the treatment of rhytides and laxity using quantitative grading. Methods In this randomized, blinded, split-face design study, 10 subjects (aged 18,75 years) with a clinically observable excess of rhytides and laxity (minimum grade 2 out of 4) on the face received four treatments at 1-week intervals with random assignment of unipolar RF to one side and bipolar RF to the contralateral side. Each side received approximately four passes per treatment delivered in a mobile continuous manner. Results were evaluated by two blinded investigators of photographs employing a comprehensive 4-point grading scale at baseline, and 1- and 3-month follow-up visits after the final treatment. Results All subjects completed and responded to treatment. The blinded evaluations demonstrated the following mean percent improvements in grading scores of rhytides and laxity: for the unipolar side 6.0±4.6% and 4.6±4.8% versus the bipolar side 4.4±2.5 and 7.3±3.5%. The degree of improvement approached but did not achieve statistical significance for either handpiece, but demonstrated a trend toward improvement (P,=,0.5599 unipolar vs. 0.1108 bipolar). The treatment was painless (rated 0 out of 10 by all subjects) and side effects included minimal erythema which resolved within 1,3 hours. No crusting, dyspigmentation or scarring was observed. Conclusion This randomized, split-face study with blinded evaluations employing a quantitative grading scale demonstrated that minimal pass, mobile energy delivery serial treatments with either the unipolar or bipolar handpieces of a novel RF device appears to safe and painless. Each handpiece demonstrated minimal clinical efficacy which was not statistically significant, but with a trend toward improvement in rhytides and laxity of facial skin. Lesers Surg. Med. 40:446,453, 2008. © 2008 Wiley-Liss, Inc. [source] Olanzapine treatment for dopaminergic-induced hallucinationsMOVEMENT DISORDERS, Issue 5 2002William G. Ondo MD Abstract Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5,10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function. © 2002 Movement Disorder Society [source] NLST: India's National Large Solar TelescopeASTRONOMISCHE NACHRICHTEN, Issue 6 2010S.S. Hasan Abstract This article introduces the new Indian 2 m telescope which has been designed by MT Mechatronics in a detailed conceptual design study for the Indian Institute of Astrophysics, Bangalore. We describe the background of the project and the science goals which shall be addressed with this telescope. NLST is a solar telescope with high optical throughput and will be equipped with an integrated Adaptive Optics system. It is optimized for a site with the kind of seeing and wind conditions as they are expected at a lake site in the Himalayan mountains. The telescope can also be used for certain night time applications. We also give the scientific rationale for this class of telescope (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Multiple Imputation Methods for Treatment Noncompliance and Nonresponse in Randomized Clinical TrialsBIOMETRICS, Issue 1 2009L. Taylor Summary Randomized clinical trials are a powerful tool for investigating causal treatment effects, but in human trials there are oftentimes problems of noncompliance which standard analyses, such as the intention-to-treat or as-treated analysis, either ignore or incorporate in such a way that the resulting estimand is no longer a causal effect. One alternative to these analyses is the complier average causal effect (CACE) which estimates the average causal treatment effect among a subpopulation that would comply under any treatment assigned. We focus on the setting of a randomized clinical trial with crossover treatment noncompliance (e.g., control subjects could receive the intervention and intervention subjects could receive the control) and outcome nonresponse. In this article, we develop estimators for the CACE using multiple imputation methods, which have been successfully applied to a wide variety of missing data problems, but have not yet been applied to the potential outcomes setting of causal inference. Using simulated data we investigate the finite sample properties of these estimators as well as of competing procedures in a simple setting. Finally we illustrate our methods using a real randomized encouragement design study on the effectiveness of the influenza vaccine. [source] Association study of 5,-UTR polymorphisms of the human dopamine transporter gene with manic depressionBIPOLAR DISORDERS, Issue 5p1 2006Gerald Stöber Objectives:, To determine the degree of association of five single nucleotide polymorphisms at the 5,-untranslated region (5,-UTR) of the human dopamine transporter gene (hSLC6A3; hDAT1) in bipolar affective disorder. Methods:, In a case,control design study, the polymorphisms were genotyped for allelic and genotypic distribution between 105 index cases (50 males) with bipolar affective disorder according to DSM IV and 199 unaffected control subjects (120 males). Results:, At the 5,-UTR locus of hSLC6A3, no significant allelic or genotypic differences were observed between index cases and controls. However, distinct 5-locus genotypes accumulated in subjects with bipolar affective disorder compared to control subjects (p = 0.029, odds ratio 1.84, 95% confidence interval 1.12,3.02). Conclusions:, In conclusion, our data do not provide evidence for a major role of the 5,-UTR of the dopamine transporter gene in bipolar affective disorder. A minor contribution of distinct genotypes may be possible and warrants replication in extended samples. [source] Authors response to: Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to ZelenBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2006P-G Larsson No abstract is available for this article. [source] Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3ABRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2009Sandrine Turpault WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Numerous cocktails using concurrent administration of several cytochrome P450 (CYP) isoform-selective probe drugs have been reported to investigate drug,drug interactions in vivo. , This approach has several advantages: characterize the inhibitory or induction potential of compounds in development toward the CYP enzymes identified in vitro in an in vivo situation, assess several enzymes in the same trial, and have complete in vivo information about potential CYP-based drug interactions. WHAT THIS STUDY ADDS , This study describes a new cocktail containing five probe drugs that has never been published. , This cocktail can be used to test the effects of a new chemical entity on multiple CYP isoforms in a single clinical study: CYP1A2 (caffeine), CYP2C9 (warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol), and CYP3A (midazolam) and was designed to overcome potential liabilities of other reported cocktails. AIMS To assess the pharmacokinetics (PK) of selective substrates of CYP1A2 (caffeine), CYP2C9 (S-warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol) and CYP3A (midazolam) when administered orally and concurrently as a cocktail relative to the drugs administered alone. METHODS This was an open-label, single-dose, randomized, six-treatment six-period six-sequence William's design study with a wash-out of 7 or 14 days. Thirty healthy male subjects received 100 mg caffeine, 100 mg metoprolol, 0.03 mg kg,1 midazolam, 20 mg omeprazole and 10 mg warfarin individually and in combination (cocktail). Poor metabolizers of CYP2C9, 2C19 and 2D6 were excluded. Plasma samples were obtained up to 48 h for caffeine, metoprolol and omeprazole, 12 h for midazolam, 312 h for warfarin and the cocktail. Three different validated liquid chromatography tandem mass spectrometry methods were used. Noncompartmental PK parameters were calculated. Log-transformed Cmax, AUClast and AUC for each analyte were analysed with a linear mixed effects model with fixed term for treatment, sequence and period, and random term for subject within sequence. Point estimates (90% CI) for treatment ratios (individual/cocktail) were computed for each analyte Cmax, AUClast and AUC. RESULTS There was no PK interaction between the probe drugs when administered in combination as a cocktail, relative to the probes administered alone, as the 90% CI of the PK parameters was within the prespecified bioequivalence limits of 0.80, 1.25. CONCLUSION The lack of interaction between probes indicates that this cocktail could be used to evaluate the potential for multiple drug,drug interactions in vivo. [source] | ||||||||||||||||||||||||||||