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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 112) Sort By: Publication Date Relevance Took: 1.677 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 5 1 2 3 4 > Last >> (112 articles found) Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial. Jun 2008 I Jon Russell,Philip J Mease,Timothy R Smith,Daniel K Kajdasz,Madelaine M Wohlreich,Michael J Detke,Daniel J Walker,Amy S Chappell,Lesley M Arnold The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patient... ( view more )s meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20mg/day, 60mg/day, or 120mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60mg/day and 120mg/day appears to be safe and efficacious in patients with fibromyalgia. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex. Jun 2008 Madelaine M Rosenberg,Fang Yang,Monica Giovanni,Jesse L Mohn,Murali K Temburni,Michele H Jacob The neuronal nicotinic synapse plays a central role in normal cognitive and autonomic function. Molecular mechanisms that direct the assembly of this synapse remain poorly defined, however. We show here that adenomatous polyposis coli (APC) organizes a multi-molecular complex that is essential for ... ( view more )targeting alpha3(*)nAChRs to synapses. APC interaction with microtubule plus-end binding protein EB1 is required for alpha3(*)nAChR surface membrane insertion and stabilization. APC brings together EB1, the key cytoskeletal regulators macrophin and IQGAP1, and 14-3-3 adapter protein at nicotinic synapses. 14-3-3, in turn, links the alpha3-subunit to APC. This multi-molecular APC complex stabilizes the local microtubule and F-actin cytoskeleton and links postsynaptic components to the cytoskeleton--essential functions for controlling the molecular composition and stability of synapses. This work identifies macrophin, IQGAP1 and 14-3-3 as novel nicotinic synapse components and defines a new role for APC as an in vivo coordinator of nicotinic postsynaptic assembly in vertebrate neurons. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Transcription factors Pcr1 and Atf1 have distinct roles in stress- and Sty1-dependent gene regulation. May 2008 Miriam Sansó,Madelaine Gogol,José Ayté,Chris Seidel,Elena Hidalgo The mitogen-activated protein kinase Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. Upon stress activation, Sty1 reversibly accumulates in the nucleus, where it stimul... ( view more )ates gene expression via the Atf1 transcription factor. The Atf1 protein forms a heterodimer with Pcr1, but the specific role of this association is controversial. We have carried out a comparative analysis of strains lacking these proteins individually. We demonstrate that Atf1 and Pcr1 have similar but not identical roles in S. pombe, since cells lacking Pcr1 do not share all the phenotypes reported for Deltaatf1 cells. Northern blot and microarray analyses demonstrate that the responses to specific stresses of cells lacking either Pcr1 or Atf1 do not fully overlap, and even though most Atf1-dependent genes induced by osmotic stress are also Pcr1 dependent, a subset of genes require only the presence of Atf1 for their induction. Whereas binding of Atf1 to most stress-dependent genes requires the presence of Pcr1, we demonstrate here that Atf1 can bind to the Pcr1-independent promoters in a Deltapcr1 strain in vivo. Furthermore, these analyses show that both proteins have a global repressive effect on stress-dependent and stress-independent genes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Epi-illumination microscopy coupled to in situ hybridization and its utility in the study of evolution and development in non-model species. May 2008 Madelaine E Bartlett,Bruce K Kirchoff,Chelsea D Specht Evolutionary developmental biology often combines methods for examining morphology (e.g., scanning electron microscopy, SEM) with analyses of gene expression (e.g., RNA in situ hybridization). Due to differences in tissue preparation for SEM and gene expression analyses, the same specimen cannot be... ( view more ) used for both sets of techniques. To aid in the understanding of morphological variation, it would be particularly useful to have a high-magnification image of the very same sample in which gene expression is subsequently analyzed. To address this need, we developed a method that couples extended depth of field (EDF) epi-illumination microscopy to in situ hybridization in a sequential format, enabling both surface microscopy and gene expression analyses to be carried out on the same specimen. We first created a digital image of inflorescence apices using epi-illumination microscopy and commercially available EDF software. We then performed RNA in situ hybridizations on photographed apices to assess the expression of two developmental genes: Knotted1 (Kn1) in Zea mays (Poaceae) and a PISTILLATA (PI) homolog in Musa basjoo (Musaceae). We demonstrate that expression signal is neither altered nor reduced in the imaged apices as compared with the unphotographed controls. The demonstrated method reduces the amount of sample material necessary for developmental research, and enables individual floral development to be placed in the context of the entire inflorescence. While the technique presented here is particularly relevant to floral developmental biology, it is applicable to any research where observation and description of external features can be fruitfully linked with analyses of gene expression. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The spatial scale of attention strongly modulates saccade latencies. Apr 2008 Mark R Harwood,Laurent Madelain,Richard J Krauzlis,Josh Wallman We have previously shown that when a stimulus consisting of two concentric rings moves, saccade latencies are much longer (by 150 ms) when attention is directed to the larger ring than to the smaller ring. Here, we investigated whether this effect can be explained by a deferral of the "cost" of mak... ( view more )ing a saccade while the target remains inside the attentional field, or by purely visual factors (eccentricity or contrast). We found 1) latencies were shorter when attention was directed to small features irrespective of retinal eccentricity; 2) saccade latency distributions were systematically determined by the ratio between the amplitude of the stimulus step and the diameter of the attended ring: stimulus steps that were larger than the attended ring resulted in short latencies, whereas steps smaller than the attended ring resulted in proportionally longer and more variable latencies; 3) this effect was not seen in manual reaction times to the same target movement; and 4) suprathreshold changes in the contrast of targets, mimicking possible attentional effects on perceived contrast and saliency, had little effect on latency. We argue that the spatial scale of attention determines the urgency of saccade motor preparation processes by changing the rate and rate variability of the underlying decision signal, to defer the cost of saccades that result in little visual benefit. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Efficacy of duloxetine for the treatment of depression: relationship to most recent antidepressant trial. 2008 Timothy Petersen,Roy H Perlis,Chris Ticknor,Jim Lohr,H Brent Solvason,John P O'Reardon,Madelaine M Wohlreich,Charissa Andreotti,Michael Wilson,Maurizio Fava To describe and examine, in a sample of depressed outpatients, the relationship between level of response to a previous SSRI or SNRI antidepressant trial and subsequent response to duloxetine hydrochloride. Data collected from a multicenter trial that evaluated the safety and efficacy of duloxetine... ( view more ) for the treatment of major depressive disorder were analyzed to determine the relationship between response to previous antidepressant treatment and degree of response to duloxetine. Time to first response, first remission, sustained response, and sustained remission during the first 12 weeks of duloxetine treatment were compared across patient groups. Principal Observations: Response and remission with duloxetine treatment ranged between 57 and 68% and 29 and 57%, respectively, and did not differ significantly across previous response levels. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Dating conflicts: rethinking dating violence and youth conflict. Dec 2007 Madelaine Adelman,Sang Hea Kil Dating couples are tied to each other's friends who have expectations about dating, such as who constitutes an acceptable date and how to balance friendship and dating. We explore the place of friends in dating conflicts (i.e., conflicts and violence associated with heterosexual teen dating) and as... ( view more )k: (a) How are friends implicated in teen dating/violence not only as targets or confidants, but also as participants in conflict that stems from their friends' relationships, and (b) in what ways do dating conflicts conserve or challenge the power of gender and sexual conformity that underlies heterosexual dating and dating violence? ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A comparison of initial duloxetine dosing strategies in patients with major depressive disorder. Dec 2007 Virgil G Whitmyer,David L Dunner,Susan G Kornstein,Adam L Meyers,Craig H Mallinckrodt,Madelaine M Wohlreich,Jill S Gonzales,John H Greist OBJECTIVE: To compare the effects of starting doses of duloxetine taken with or without food on tolerability and efficacy in patients with major depressive disorder (MDD). METHOD: This double-blind, concurrent-dose-controlled, parallel-design trial contained a variable expected-duration placebo lea... ( view more )d-in period and was conducted in adult outpatients with DSM-IV-TR-defined MDD at psychiatric outpatient sites between October 2004 and January 2006. In actuality, patients received placebo for 1 week and then were randomly assigned to duloxetine 30 mg once daily in the morning (q.a.m.) (N = 219), 30 mg twice daily (b.i.d.) (N = 213), or 60 mg q.a.m. (N = 215) for 1 week along with 1 of 2 instructions about food: take study drug with food or do not take within 1 hour of eating. For the remaining 5 weeks of acute treatment, all patients received 60 mg once daily. The primary objective was to compare incidence of treatment-emergent nausea at 30 mg q.a.m. versus 60 mg q.a.m. using item 112 (nausea) of the Association for Methodology and Documentation in Psychiatry adverse event scale (AMDP-5). Secondary outcome measures included mean change on AMDP-5 item 112, discontinuations due to adverse events, mean changes in AMDP-5 items and subscales, spontaneously reported treatment-emergent adverse events, and vital signs. Efficacy was evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17). RESULTS: The primary analysis, which combined data from both food groups, showed no significant difference in the incidence of nausea between starting doses of 30 mg q.a.m. and 60 mg q.a.m. (23% vs. 29%, respectively; p = .207). However, mean changes on the AMDP-5 nausea item revealed a significant main effect of food (p = .010) and a significant interaction between food and starting dose (p = .033). The food-by-dose interaction indicated that the benefit from taking drug with food was greatest in patients started at 60 mg q.a.m., and the benefit of starting at 30 mg q.a.m. was greatest in patients taking drug without food. In patients who took study drug without food, there was a significant difference across initial-dose groups for discontinuation due to adverse events (30 mg q.a.m. = 3.6%, 30 mg b.i.d. = 14.0%, 60 mg q.a.m. = 10.2%; 30 mg q.a.m. vs. 30 mg b.i.d., p = .008; 30 mg q.a.m. vs. 60 mg q.a.m., p = .066); however, in patients who took study drug with food, discontinuations due to adverse events did not significantly differ (30 mg q.a.m. = 5.4%, 30 mg b.i.d. = 7.5%, 60 mg q.a.m. = 7.4%; all p values > .50). Patients who started at 30 mg b.i.d. or 60 mg q.a.m. without food did not differ regarding mean changes (i.e., increases) in the common adverse events score after 1 week of treatment but had significantly greater mean changes than patients who started at 30 mg q.a.m. without food (0.87, 0.82, and 0, respectively; p < .05 vs. 30 mg b.i.d. and 60 mg q.a.m.). No significant differences were found between initial-dose groups in vital signs. CONCLUSIONS: These data imply that starting dulox-etine at 30 mg q.a.m. for 1 week with or without food or starting duloxetine at the therapeutic dose of 60 mg q.a.m. with food can improve the initial tolerability of the medication. Adding this information to existing knowledge of duloxetine will enable the clinician to tailor therapy most appropriately for the individual patient. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT 00191061. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Evidence for the efficacy of duloxetine in treating mild, moderate, and severe depression. Nov 2007 Richard C Shelton,Anne C Andorn,Craig H Mallinckrodt,Madelaine M Wohlreich,Joel Raskin,John G Watkin,Michael J Detke Clinicians need to know whether duloxetine is effective in patients across a broad range of depressive symptoms and depression severity. Data were pooled from nine randomized, double-blind, placebo-controlled studies in major depressive disorder (total N=2227) comparing duloxetine (40-120 mg/day) w... ( view more )ith placebo for 8-9 weeks. Patients were retrospectively stratified by baseline score on the HAMD17 into mild (< or =19; n=682), moderate (n=1099), or severe (> or =25; n=446) groups. Duloxetine produced significantly greater baseline-to-endpoint mean change than placebo in HAMD17 total score, Maier and retardation subscales, and the Clinical Global Impressions-Severity of Illness scale in all three cohorts. Significant improvement was seen in HAMD17 items 1 (depressed mood), 3 (suicide), 7 (work and activities), and 10 (psychic anxiety) regardless of severity. The HAMD17 anxiety subscale and items 13 (somatic symptoms-general) and 15 (hypochondriasis) showed significant improvement only in moderately and severely ill patients. Significant improvement in the HAMD17 Maier subscale was seen in all groups by week 1. In all three groups, placebo was significantly superior to duloxetine at early visits on HAMD17 item 12 (somatic symptoms-GI). Mildly and severely ill patients exhibited significant reduction in visual analog scale overall pain severity at the study endpoint. The studies contained fewer patients with very mild or very severe illness, limiting our ability to draw conclusions in these patient populations. Duloxetine demonstrated superior efficacy in the treatment of major depressive disorder, when compared with placebo, regardless of the baseline severity of depressive symptoms, although effect sizes were largest in the most severely depressed patients. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Control of sensorimotor variability by consequences. Oct 2007 Laurent Madelain,Lucie Champrenaut,Alan Chauvin Studies of reaction-time distributions provide a useful quantitative approach to understand decision processes at the neural level and at the behavioral level. A strong relationship between the spread of latencies and the median is generally accepted even though there has been no attempt to disenta... ( view more )ngle experimentally these two parameters. Here we test the ability to independently control the median and the variability in reaction times. Reaction times were measured in human subjects instructed to make a discrimination between a target and a distractor in a 2AFC task. In a first experiment, saccadic latencies were measured. In a second experiment, we used manual response reaction times. Subjects were trained to produce four different reaction-time distributions. A reinforcing feedback was given depending on both the variability and the median of the latency distributions. When low variability was reinforced, the standard deviation (SD) of reaction-time distributions were reduced by a factor of two and when high variability was reinforced, the SD returned to baseline level. Our procedure independently affected the spread and the median of the distribution patterns. By fitting the latency distributions using the Reddi and Carpenter LATER model, we found that these effects could be simulated by changing the distribution of the noise affecting the decision process. Our results demonstrate that learned contingencies can affect reaction time variability and support the view that the so-called noise level in decision processes can undergo long-term changes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update] Oct 2007 E Porret,J Madelaine,F Galateau-Sallé,E Bergot,G Zalcman Malignant pleural mesothelioma (MPM) is a rare tumour due to occupational asbestos exposure. The incidence of MPM will continue to increase until 2020-2030. The incidence reaches 100 cases/million/year in occupationally exposed populations as opposed to 1 case/million/year in the general population... ( view more ), leading to 800 to 1,000 cases per year in France. The molecular carcinogenesis of MPM is incompletely understood but alterations to genes NF2, c-met, WT1 RASSF and p16 have been described. These genes are involved in cell invasion and motility, cell division and apoptosis control. Histological diagnosis remains difficult and depends on immunohistochemical analysis as described by the French Mesopath group. Clinical diagnosis relies on thoracoscopy and large pleural biopsies, with increasing use of CT-PET for the evaluation of disease extent. Therapeutic strategy includes prophylactic irradiation following drainage or thoracoscopy to prevent tumour nodule development along drainage channels and puncture sites. In selected patients, extensive extra-pleural pneumonectomy can be performed with curative intent. First line chemotherapy is based on a combination of pemetrexed and cisplatin that has demonstrated an improvement in overall survival and quality of life in phase 3 trials. Antiangiogenic agents such as bevacizumab (Avastatin) may be of interest but need to be tested in phase 3 trials. The Mesothelioma Avastatin Pemetrexed Study (MAPS) is ongoing, coordinated by the French Thoracic Cancer Intergroup (IFCT). ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. Jul 2007 Anita Clayton,Susan Kornstein,Apurva Prakash,Craig Mallinckrodt,Madelaine Wohlreich INTRODUCTION: Depression and antidepressant therapy have been associated with sexual dysfunction in short-term and point-prevalence trials. AIM: This report describes effects of duloxetine and escitalopram on sexual functioning during acute and long-term treatment of major depressive disorder (MDD)... ( view more ). METHODS: In this 8-month, double-blind, placebo-controlled study, adult outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-defined MDD were randomized to duloxetine 60 mg/day (N = 273; 173 female), escitalopram 10 mg/day (N = 274; 186 female), or placebo (N = 137; 87 female). After the first 8 weeks of treatment, dose increases were permitted to optimize treatment. MAIN OUTCOME MEASURE: The 14-item Changes in Sexual Functioning Questionnaire (CSFQ) was used to assess sexual functioning. RESULTS: Of the 114 patients who did not meet total CSFQ score criteria for global sexual dysfunction at baseline (duloxetine, N = 51; escitalopram, N = 39; placebo, N = 24), the incidence of treatment-emergent sexual dysfunction was significantly higher for escitalopram compared with placebo at 4 and 8 weeks, and significantly higher compared with duloxetine at 4 weeks. At 8 weeks, the incidence of treatment-emergent sexual dysfunction was 17/51 (33.3%) for duloxetine-treated patients; 19/39 (48.7%) for escitalopram-treated patients; and 4/24 (16.7%) for placebo-treated patients (P = 0.01 escitalopram vs. placebo; P = 0.13 duloxetine vs. placebo). After 12 weeks, no significant differences were observed between active drugs. At 8 months, the incidence of treatment-emergent sexual dysfunction was 33.3% for duloxetine, 43.6% for escitalopram, and 25.0% for placebo. Regardless of treatment, patients who achieved remission of MDD showed improvement in global sexual functioning, whereas worsening was observed for patients who did not achieve remission (P < 0.001). Discontinuation rates for sexual side effects did not differ between duloxetine (N = 2) and escitalopram (N = 7) (P = 0.07). CONCLUSIONS: Short-term treatment demonstrated a higher incidence of treatment-emergent sexual dysfunction with escitalopram compared with duloxetine and placebo. After 12 weeks, there were no statistically significant differences between drugs; however, MDD outcome (regardless of treatment) had a significant impact on improvement in global sexual functioning. ( view less ) View Full Abstract View Article Details   Related Articles Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription. Jun 1, 2007 Bing Li,Madelaine Gogol,Mike Carey,Samantha G Pattenden,Chris Seidel,Jerry L Workman The presence of Set2-mediated methylation of H3K36 (K36me) correlates with transcription frequency throughout the yeast genome. K36me targets the Rpd3S complex to deacetylate transcribed regions and suppress cryptic transcription initiation at certain genes. Here, using a genome-wide approach, we r... ( view more )eport that the Set2-Rpd3S pathway is generally required for controlling acetylation at coding regions. When using acetylation as a functional readout for this pathway, we discovered that longer genes and, surprisingly, genes transcribed at lower frequency exhibit a stronger dependency. Moreover, a systematic screen using high-resolution tiling microarrays allowed us to identify a group of genes that rely on Set2-Rpd3S to suppress spurious transcripts. Interestingly, most of these genes are within the group that depend on the same pathway to maintain a hypoacetylated state at coding regions. These data highlight the importance of using the functional readout of histone codes to define the roles of specific pathways. ( view less ) View Full Abstract View Article Details   Related Articles Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Jun 2007 Teresa A Pigott,Apurva Prakash,Lesley M Arnold,Scott T Aaronson,Craig H Mallinckrodt,Madelaine M Wohlreich BACKGROUND: Duloxetine and escitalopram were compared in an 8-month, randomized, double-blind, placebo-controlled trial in adult outpatients meeting DSM-IV criteria for major depressive disorder (MDD). The results regarding the primary objective of the study (onset of antidepressant action) have be... ( view more )en previously published. The current paper focuses on the longer-term (8-month) comparisons of efficacy and safety between duloxetine and escitalopram. RESEARCH DESIGN AND METHODS: Upon completion of the 8-week, fixed-dose, placebo-controlled, acute-treatment phase (duloxetine 60 mg/day (n = 273), escitalopram 10 mg/day (n = 274), placebo (n = 137)), patients remaining in the duloxetine (n = 188) and escitalopram (n = 208) groups were eligible for double-blind dose increases (duloxetine to 120 mg/day, escitalopram to 20 mg/day), and placebo non-responders were eligible for double-blind rescue to active drug. MAIN OUTCOME MEASURES: Efficacy was primarily assessed using the HAMD(17). Safety/tolerability assessments included spontaneously reported adverse events (AEs), overall rates and reasons for discontinuation, laboratory analyses, and vital signs. RESULTS: Both drugs demonstrated similar remission rates over the course of the study, with the probability of remission reaching 70% (duloxetine) and 75% (escitalopram) at 8 months (p = 0.44). Similar improvement was observed for both duloxetine and escitalopram on efficacy measures with the exception of the sleep subscale of the HAMD(17), wherein escitalopram had a statistically significant advantage over duloxetine in improving sleep. Over the entire 8-month study, discontinuation rates differed significantly for duloxetine (62%) compared with escitalopram (55%; p = 0.02). Rates of discontinuation due to AEs did not differ significantly between duloxetine (12.8%), escitalopram (12.0%), and placebo (10.2%) (p > 0.05 all pairwise comparisons). AEs associated with duloxetine tended to emerge early in treatment (e.g., nausea, dry mouth), whereas AEs associated with escitalopram tended to emerge later in treatment (e.g., diarrhea, weight increase). The incidence of sustained hypertension was similar between drugs (1.5 vs. 1.1% patients for duloxetine and escitalopram, respectively). Statistically significant drug differences were identified in the mean changes from baseline to study endpoint for pulse (+3.05 beats per minute (bpm), duloxetine; -0.89 bpm, escitalopram; p < 0.001) and systolic blood pressure (+3.73 mmHg, duloxetine; +0.31 mmHg, escitalopram; p < 0.05), but not diastolic blood pressure (+0.81 mmHg, duloxetine; -0.24 mmHg, escitalopram; p = 0.27). At 8 months, mean change in weight was significantly higher for escitalopram compared with duloxetine (+0.61 kg, duloxetine; +1.83 kg, escitalopram; p < 0.05), however, the incidence of treatment-emergent abnormal weight gain (> or = 7% increase in weight from baseline) was similar between drugs and was significantly greater for both duloxetine and escitalopram compared with placebo. LIMITATIONS: Because so few patients on placebo (n = 15), in comparison to duloxetine (n = 104) or escitalopram (n = 123), completed the entire 8-month study, the power to detect a difference between the active treatments and placebo after 8 weeks was significantly decreased and very likely insufficient. CONCLUSION: Throughout the 8-month study, similar improvement was observed for both duloxetine and escitalopram on most efficacy measures with the exception of the sleep subscale of the HAMD(17). Drug differences were identified in safety/tolerability measures. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. May 18, 2007 Bing Li,Madelaine Gogol,Mike Carey,Daeyoup Lee,Chris Seidel,Jerry L Workman Nucleosomes must be deacetylated behind elongating RNA polymerase II to prevent cryptic initiation of transcription within the coding region. RNA polymerase II signals for deacetylation through the methylation of histone H3 lysine 36 (H3K36), which provides the recruitment signal for the Rpd3S hist... ( view more )one deacetylase complex (HDAC). The recognition of methyl H3K36 by Rpd3S requires the chromodomain of its Eaf3 subunit. Paradoxically, Eaf3 is also a subunit of the NuA4 acetyltransferase complex, yet NuA4 does not recognize methyl H3K36 nucleosomes. In Saccharomyces cerevisiae, we found that methyl H3K36 nucleosome recognition by Rpd3S also requires the plant homeobox domain (PHD) of its Rco1 subunit. Thus, the coupled chromo and PHD domains of Rpd3S specify recognition of the methyl H3K36 mark, demonstrating the first combinatorial domain requirement within a protein complex to read a specific histone code. ( view less ) View Full Abstract View Article Details   Related Articles In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. May 2007 Nina Roos,Nicolas Poulalhon,Dominique Farge,Isabelle Madelaine,Alain Mauviel,Franck Verrecchia The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent organ rejection after transplantation and has shown some efficacy to prevent the fibrotic complications that occur during autoimmune diseases such as systemic sclerosis or during graft-versus-host disease (GVHD). We tested th... ( view more )e hypothesis that MMF may exert direct effects on fibroblast extracellular matrix remodeling. Incubation of human lung fibroblast cultures with MMF led to dose- and time-dependent reduction in the synthesis and expression of type I collagen. Inhibition of COL1A1 and COL1A2 mRNA steady-state levels occurred at the level of transcription via repression of their promoters. In contrast, MMF significantly enhanced the expression and the synthesis of interstitial collagenase (matrix metalloproteinase-1). MMF was also found to diminish the capacity of fibroblast to contract mechanically unloaded collagen lattices and to reduce the synthesis of alpha-smooth muscle actin, a marker of the contractile myofibroblast phenotype. In addition, MMF diminished the fibroblasts motility. In conclusion, we provide novel mechanism by which MMF alters fibroblast functions important for wound healing and implicated in the development of tissue fibrosis, e.g., collagen production, extracellular matrix contraction, and cell migration. Such properties may contribute to the beneficial therapeutic effects of MMF against fibrotic lesions developing in systemic sclerosis or during GVHD. ( view less ) View Full Abstract View Article Details   Related Articles Bilateral periventricular nodular heterotopia, severe learning disability, and epilepsy in a male patient with 46,XY,der(19)t(X;19) (q11.1-11.2;p13.3). Mar 2007 Sevim Balci,Aysun Unal,Ozlem Engiz,Dilek Aktas,Thomas Liehr,Madelaine Gross,Kristin Mrasek,Serap Saygi Periventricular nodular heterotopia (PNH) is a rare neuronal migration disorder in which immature neurons fail to undergo a directed migration from the ventricular and subventricular zones to the cerebral cortex. Classic PNH occurs predominantly in females and is associated with periods of epilepsy... ( view more ) and near-normal intelligence. One gene associated with PNH was mapped to chromosome Xq28. PNH with learning disability is reported in 15 male patients with several syndromes and various congenital abnormalities such as craniosynostosis, frontonasal malformation, and agenesis of the corpus callosum. We present a 26-year-old male patient who was followed up with the diagnosis of epilepsy from the age of 1 year. Additionally the patient had severe learning disability, obesity, and hypogonadism. Imaging of his brain demonstrated PNH. Klinefelter syndrome was clinically suspected, and analysis of his chromosomes revealed a karyotype 46,XY,der(19)t(X;19) (q11.1-11.2;p13.3). Molecular techniques, such as subtelomere-specific fluorescent in-situ hybridization and multicolour banding, were also used. The same translocation was demonstrated in his mother and his maternal grandmother. This family might help to explain the gene localization of X-linked recessive PNH. In our patient, PNH is associated with familial (X;19) translocation. To our knowledge, this unique combination has not been reported in the medical literature. ( view less ) View Full Abstract View Article Details   Related Articles Asymmetric syntheses of 1-aryl-2,2,2-trifluoroethylamines via diastereoselective 1,2-addition of arylmetals to 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide. Feb 15, 2007 Vouy Linh Truong,Madeleine S Ménard,Madelaine S Ménard,Isabelle Dion Condensation of N-tert-butanesulfinamide (S)-1 with trifluoroacetaldehyde hydrate 2a afforded 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide 3. Without isolation and purification, imine 3 was added to various aryllithium reagents to give highly diastereomerically enriched adducts 5a-g.... ( view more ) Acidic methanolysis of 5a-g provided the desired 1-aryl-2,2,2-trifluoroethylamine hydrochloride compounds 6a-g. [reaction: see text]. ( view less ) View Full Abstract View Article Details   Related Articles Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Feb 2007 Andrew A Nierenberg,John H Greist,Craig H Mallinckrodt,Apurva Prakash,Angelo Sambunaris,Gary D Tollefson,Madelaine M Wohlreich OBJECTIVE: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment. The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reu... ( view more )ptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor). RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo- and active comparator-controlled study, in which patients (> or = 18 years) meeting DSM-IV criteria for Major Depressive Disorder (MDD) received duloxetine 60 mg once daily (QD; N = 273), escitalopram 10 mg QD (N = 274), or placebo (N = 137) for 8 weeks. The primary objective was to compare the onset of antidepressant efficacy, by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group. MAIN OUTCOME MEASURES: Onset of efficacy was defined as a 20% decrease from baseline on the 17-item Hamilton Rating Scale for Depression (HAMD(17)) Maier subscale that was maintained or exceeded at all subsequent visits. RESULTS: Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6% versus 35.2%, respectively (treatment difference = 7.4%; 95% confidence interval, -1.3% to 16.2%; p = 0.097). Both drugs showed significant improvement compared with placebo (p < or = 0.05) on the primary efficacy measure (Maier subscale) at Week 1 and endpoint (Week 8). No differences were found between duloxetine, escitalopram, and placebo rates of remission or response at 8 weeks. Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea, dry mouth, vomiting, yawning, and irritability. The rate of discontinuation due to adverse events did not differ significantly between treatment groups. LIMITATIONS: Given the difficulties in constructing appropriate dose comparisons, the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole. This study employed a fixed-dose design; flexible-dose designs are more likely to find a difference between antidepressants and placebo. CONCLUSION: In this study, both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8-week acute treatment period, while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks. Escitalopram at a starting dose of 10 mg QD was better tolerated than duloxetine at a starting dose of 60 mg QD. This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy, and the results show that duloxetine is at least as fast as (non-inferior to) escitalopram. ( view less ) View Full Abstract View Article Details   Related Articles [Primitive metastasizing bronchial carcinoid with long survival] Jan 2007 N Bouvier,V Zengerling,A Halley,V Le Pennec,J P Le Rochais,J Madelaine,F Galateau-Salle,E Bergot,G Zalcman BACKGROUND: Metastatic bronchial carcinoid tumours are rare but some patients have a prolonged survival. A new functional imagery now makes it possible to supplement the assessment of the extent of disease. OBSERVATION: A 57 year old patient was referred for dyspnoea on exertion revealing an upper ... ( view more )left lobar tumour, with carcinoid syndrome. The assessment enabled to find out a bronchial carcinoid tumour with liver and bone metastases, highlighted by positron-emission tomography and pentetreotide SPECT. A chemotherapy proved to be ineffective and upper left lobectomy was carried out because of the risk of pulmonary atelectasis. The patient was treated by somatostatin analogues then underwent liver transcatheter arterial chemo-embolization. The patient was alive 44 months after diagnosis (56 months after first computed tomography). CONCLUSION: Metastatic bronchial carcinoid tumours are rare. They keep a metastatic potential, the histological type remaining the major prognosis factor. Carcinoid syndrome is suggestive. The assessment of extra-thoracic disease extent benefits by contribution of new functional imagery techniques such as the pentetreotide SPECT and positron-emission tomography. The management is essentially symptomatic since there is no effective chemotherapy. However survival can be prolonged, even in multimetastatic patients. ( view less ) View Full Abstract View Article Details   Related Articles High-dose therapy and autologous stem-cell transplantation can improve event-free survival for indolent lymphoma: a study using patients as their own controls. Jan 1, 2007 Stéphane Vignot,Nicolas Mounier,Jérôme Larghero,Pauline Brice,Laurent Quero,Cédric de Bazelaire,Marjan Ertault,Josette Brière,Isabelle Madelaine,Christian Gisselbrecht BACKGROUND: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) remain controversial for indolent lymphoma patients. METHODS: The study was designed to evaluate the benefit of this strategy by retrospectively comparing for each patient the event-free survival (EFS) after ASCT wi... ( view more )th the duration of the disease phase just before the phase including ASCT (ie, the last qualifying phase, LQP). RESULTS: A total of 109 indolent lymphoma (mostly follicular lymphoma) patients were treated with HDT and ASCT. Before ASCT, patients experienced a median of 2 disease phases (range, 1-4). After a median 5-year follow-up from ASCT, overall survival was 67% and EFS was 43%. When each of the 92 patients experiencing recurrence was taken as her/his own control, EFS was longer after ASCT than the duration of LQP (62%, P < .01). During LQP, 86 patients (93%) experienced recurrence in less than 5 years, compared with only 58 (63%) who experienced recurrence in the 5 years after ASCT (P < .01). CONCLUSION: HDT and ASCT can significantly increase EFS in comparison with the duration of the LQP for indolent lymphoma patients and can change disease course. This methodology has been found useful for evaluating new strategies, especially with monoclonal antibodies. ( view less ) View Full Abstract View Article Details   Related Articles Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 2007 Madelaine M Wohlreich,Craig H Mallinckrodt,Apurva Prakash,John G Watkin,William P Carter Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. T... ( view more )o further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575]. ( view less ) View Full Abstract View Article Details   Related Articles [The place of targeted therapies in the management of non-small cell bronchial carcinoma. Biological mechanisms of bronchial carcinogenesis: towards a better understanding and the development of new therapies] Nov 2006 G Zalcman,N Richard,J Madelaine,E Bergot An increasing knowledge of cell signal transduction pathways has led to a better understanding of multi-step bronchial carcinogenesis. This new data has been used to design new drugs targeting specific proteins involved in epithelial cell transformation. New biotherapies are a major part of the evo... ( view more )lving strategies to fight lung cancer and actually represent a true revolution for subsets of patients. Future treatments in lung cancer patients will be tailored on the basis of routine molecular analysis of surgical and bronchoscopic biopsy specimens. Tyrosine-kinase EGFR inhibitors and VEGF inhibitors are the first molecules in this new class of therapies for lung cancer. Their mechanism of action and the resistance mechanisms that occur with these new drugs continue to be analysed, and this knowledge will help to improve the targeting of therapeutic regimes. In the same way, a better knowledge of the molecular resistance mechanisms to classical chemotherapy agents (platinum compounds, anti-metabolite agents or tubulin-interacting agents) will lead to a tailored use of these drugs, based again on the molecular characteristics of tumor specimens. The surprisingly long survivals observed among subsets of 'molecular-selected' patients, treated with frontline EGFR tyrosine-kinase inhibitors (TKIs) in still limited prospective clinical trials, could herald significant improvement in the global efficacy of lung cancer therapeutics. ( view less ) View Full Abstract View Article Details   Related Articles The prevalence of, associations between and conjugal transfer of antibiotic resistance genes in Escherichia coli isolated from Norwegian meat and meat products. Oct 2006 Marianne Sunde,Madelaine Norström OBJECTIVES: To investigate the distribution of, associations between and the transferability of antimicrobial resistance genes in resistant Escherichia coli strains isolated from Norwegian meat and meat products. METHODS: The 241 strains investigated were collected within the frame of the Norwegian... ( view more ) monitoring programme for antimicrobial resistance in bacteria from feed, food and animals (NORM-VET) during the years 2000-2003. PCR was carried out for detection of resistance genes. Conjugation experiments were carried out with the resistant isolates from meat as donor strains and E. coli DH5alpha as the recipient strain. Statistical analyses were performed with the SAS-PC-System version 9.1 for Windows. RESULTS: Resistance genes common in pathogenic E. coli were frequently found among the isolates investigated. Strains harbouring several genes encoding resistance to the same antimicrobial agent were significantly (P < 0.0001) more frequently multiresistant than others. Strong positive associations were found between the tet(A) determinant and the genetic elements sul1, dfrA1 and aadA1. Negative associations were found between resistance genes encoding resistance to the same antimicrobial agent: tet(A)/tet(B), sul1/sul2 and strA-strB/aadA1. The resistance genes were successfully transferred from 38% of the isolates. The transfer was more frequent from resistant isolates harbouring class 1 integrons (P < 0.001). CONCLUSIONS: Acquired resistance played a major role in conferring resistance among the isolates investigated. The possibility of transferring resistance increases both by increased multiresistance and by the presence of class 1 integrons. The conjugation experiments suggest that tet(A) and class 1 integrons are often located on the same conjugative plasmid. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Duloxetine in the treatment of major depressive disorder: comparisons of safety and efficacy in U.S. Hispanic and majority Caucasian patients. Sep 2006 Roberto Lewis-Fernández,Carlos Blanco,Craig H Mallinckrodt,Madelaine M Wohlreich,John G Watkin,John M Plewes OBJECTIVE: To evaluate new pharmacotherapies for the treatment of major depressive disorder (MDD) in Hispanic Americans, the largest ethnic minority group in the United States. METHOD: Efficacy and safety data were pooled from 7 double-blind, placebo-controlled clinical trials of duloxetine conduct... ( view more )ed from February 1999 through November 2002. English-speaking patients (aged > or = 18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/ day; Hispanic, N = 58; Caucasian, N = 748) or placebo (Hispanic, N = 62; Caucasian, N = 594) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, HAM-D-17 subscales, the Clinical Global Impressions-Severity of Illness scale, the Patient Global Impression of Improvement scale, and the Visual Analog Scales for pain. Safety was assessed using discontinuation rates, treatment-emergent adverse events, vital signs, and laboratory analyses. Three sets of data were analyzed using different pooling strategies, including exploratory analyses with 470 subjects (Hispanic, N = 51; Caucasian, N = 419) receiving the recommended dose of 60 mg. RESULTS: No evidence for a differential effect of duloxetine in Hispanic and Caucasian patients was found in efficacy outcomes. Discontinuation rates due to adverse events among duloxetine-treated patients were 14.0% for Hispanics and 17.0% for Caucasians, compared with 3.2% and 5.7%, respectively, for placebo-treated patients (p = .671). The type of adverse events and their individual rate of occurrence did not differ significantly between Hispanic and Caucasian patients. Mean changes from baseline for pulse, blood pressure, weight, and laboratory analytes were small and showed no significant differences between Hispanic and Caucasian patients. CONCLUSION: In this analysis of pooled data, no evidence for a differential effect of duloxetine in Hispanic and majority Caucasian patients was found in efficacy or safety outcomes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 5 1 2 3 4 > Last >> (112 articles found)

      
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