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Hoc Analysis (hoc + analysis)
Kinds of Hoc Analysis Selected AbstractsPROGNOSIS OF UPPER GASTROINTESTINAL BLEEDING IN THE OLDEST-OLD PATIENTS: A POST HOC ANALYSIS OF A PROSPECTIVE STUDYJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2010Stéphane Nahon MD No abstract is available for this article. [source] Negligible Analgesic Tolerance Seen with Extended Release Oxymorphone: A Post Hoc Analysis of Open-Label Longitudinal DataPAIN MEDICINE, Issue 8 2010R. Norman Harden MD Abstract Objective., To examine the development of analgesic tolerance in patients on oxymorphone extended-release (OxymER). Design.,Post hoc analysis of data from a previously conducted prospective 1 year multi-center open-label extension study in which patients were able to titrate as needed. Patients., Sample of 153 hip and knee osteoarthritis (OA) subjects on OxymER. Primary analyses were limited to study completers (n = 62) due to the large amount of missing data for the noncompleters (n = 91). Outcome Measures., Main outcome measures included OxymER doses (pill counts) and pain intensity ratings using a visual analog scale at monthly visits. Results., There were significant dose increases from weeks 1 to 2 and 2 to 6 (P < 0.05). Doses stabilized around week 6, suggesting the completion of what we defined as "titration." Both doses and pain ratings were stable when this titration phase was excluded from the analysis (P = 0.751; P = 0.056, respectively). Only 28% of the patients had any dose changes following this titration. While there was a significantly greater dose at week 52 compared with week 10 (P = 0.010), the increase in dose became insignificant after excluding four subjects who required two dose increases (P = 0.103). Conclusions., The results showed that most of the titration/dose stabilization changes occurred within the first 10 weeks. A minority (28%) of subjects required dosage increases after this (defined) titration period. Pain reports stabilized statistically after 2 weeks. The findings of this post hoc analysis suggest a lack of opioid tolerance in the majority (72%) of these OA patients who completed this study following a defined titration period on OxymER. Summary., This post hoc analysis of oxymorphone ER consumption in osteoarthritis pain vs pain report showed that most dose changes occurred during an initial "titration period" as defined. Following this titration few subjects increased dose and analgesia remained stable. These findings suggest a lack of longitudinal opioid tolerance in the majority of those OA subjects who completed the trial. [source] Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Martin M. Miner MD ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source] Treatment of Anemia With Darbepoetin Alfa in Heart FailureCONGESTIVE HEART FAILURE, Issue 3 2010William T. Abraham MD Anemia is common in heart failure (HF) patients. A prespecified pooled analysis of 2 randomized, double-blind, placebo-controlled studies evaluated darbepoetin alfa (DA) in 475 anemic patients with HF (hemoglobin [Hb], 9.0,12.5 g/dL). DA was administered subcutaneously every 2 weeks and titrated to achieve and maintain a target Hb level of 14.0±1.0 g/dL. By week 27, mean (SD) Hb concentrations did not increase with placebo but increased with DA from 11.5 (0.7) to 13.3 (1.3) g/dL. Hazard ratios (HRs) for DA compared with placebo for all-cause death or first HF hospitalization (composite end point), all-cause death, and HF hospitalization by month 12 were 0.67 (95% confidence interval [CI], 0.44,1.03; P=.067), 0.76 (95% CI, 0.39,1.48; P=.419), and 0.66 (95% CI, 0.40,1.07; P=.093), respectively. Incidence of adverse events was similar in both groups. In post hoc analyses, improvement in the composite end point was significantly associated with the mean Hb change from baseline (adjusted HR, 0.40; P=.017) with DA treatment. There was no increased risk of all-cause mortality or first HF hospitalization with DA in patients with reduced renal function or elevated baseline B-type natriuretic peptide, a biomarker of worse HF. These results suggest that DA is well tolerated, corrects HF-associated anemia, and may have favorable effects on clinical outcomes., Congest Heart Fail. 2010;16:87,95. © 2010 Wiley Periodicals, Inc. [source] Cardiovascular drugs as antidiabetic agents: evidence for the prevention of type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 7 2008D. P. Macfarlane Given the long-term health consequences and increasing incidence of type 2 diabetes, there is great interest to potentially prevent or delay its onset. Primary prevention studies have demonstrated that intensive exercise and weight reduction, and to a lesser extent certain antidiabetic agents, can reduce new onset diabetes in at-risk individuals. Results from post hoc analyses and secondary end-point outcomes of large randomized controlled trials of cardiovascular drugs suggest that these may also have beneficial effects, reducing the incidence of new onset diabetes in addition to their proven cardiovascular benefits. Multiple meta-analyses confirm that drugs primarily acting on the renin,angiotensin system (RAS) reduce the incidence of diabetes in the populations studied, perhaps via improved insulin sensitivity and/or effects on pancreatic beta cells. However, results from the recent Diabetes REduction Approaches with Medication study specifically failed to show a significant reduction in the incidence of diabetes with ramipril in individuals with abnormal glucose tolerance at baseline. There is only limited evidence that statins improve glucose tolerance, and although beta-blockers tend to have detrimental effects on glucose tolerance, newer agents with vasodilatory properties may confer benefits. With current guidelines, the use of cardiovascular drugs modifying the RAS will increase in at-risk individuals, but at present, they cannot be recommended to prevent diabetes. [source] Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to CarbamazepineEPILEPSIA, Issue 5 2005Jerzy Majkowski Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source] Relational Factors and Family Treatment Engagement among Low-Income, HIV-Positive African American MothersFAMILY PROCESS, Issue 1 2003Victoria B. Mitrani Ph.D. Clinically derived hypotheses regarding treatment engagement of families of low-income, HIV-positive, African American mothers are tested using univariate and multivariate logistic regression models. Predictors are baseline family relational factors (family support, mother's desire for involvement with family, and family hassles) and mother's history of substance dependence. The study examines a subsample of 49 mothers enrolled in a clinical trial testing the efficacy of Structural Ecosystems Therapy (SET). SET is a family-based intervention intended to relieve and prevent psychosocial distress associated with HIV/AIDS. Participants in the subsample were randomly assigned to SET and attended at least two therapy sessions. Findings reveal that family relational factors predicted family treatment engagement (family support, p < 004; mother's desire for involvement with family, p < 008; family hassles, p < 027). Family support predicted family treatment engagement beyond the prediction provided by the other relational factors and the mother's own treatment engagement (p < 016). History of substance dependence was neither associated with family treatment engagement nor family support. Post hoc analyses revealed that family hassles (p < 003) and mother's desire for involvement with family (p < 018) were differentially related to family treatment engagement in low-versus high-support families. Implications for clinical practice and future research are discussed. [source] Characteristics of Migraine Attacks and Responses to Almotriptan Treatment: A Comparison of Menstrually Related and Nonmenstrually Related MigrainesHEADACHE, Issue 2 2008Merle L. Diamond MD Objectives., To compare the clinical characteristics of menstrually related migraines (MRMs) and nonmenstrually related migraines (nonMRMs) and to investigate the efficacy of almotriptan in the treatment of these migraine subtypes. Design/Methods., These are post hoc analyses of data from the AXERT® Early miGraine Intervention Study (AEGIS), a multicenter, double-blind, parallel-group trial that evaluated adults with IHS-defined migraine with and without aura. Patients were randomized 1 : 1 to treat 3 consecutive headaches with almotriptan 12.5 mg or matching placebo at the first sign of headache typical of their usual migraine, at any level of pain intensity but within 1 hour of onset. MRMs were defined as those occurring ±2 days of the first day of menstrual flow. Post hoc analyses to describe headache characteristics pooled all migraine attacks experienced by patients who reported ,1 menses during the study regardless of assigned treatment group. The post hoc efficacy analyses included outcomes of almotriptan treatment compared with placebo treatment for all migraines in patients with a menstrual record. Results., Of the 275 women in the AEGIS intent-to-treat population, 190 (69.1%; 97 almotriptan, 93 placebo; aged 18-54 years) reported ,1 menses during the trial. Of the 506 migraines reported by these patients, 95 (18.8%) occurred ±2 days of the first day of menstrual flow and were defined as MRM. Aura was associated with 11.7% of MRM and 15.0% of nonMRM. Allodynia-associated symptoms were present with 62.8% of MRM and 57.0% of nonMRM. Prior to treatment, 19.1% of MRM were associated with normal functional ability, 68.1% with disturbed functional ability, and 12.8% required bed rest compared with 18.9%, 68.8%, and 12.3%, respectively, of nonMRM. Pretreatment pain intensity was mild in 40.0%, moderate in 47.4%, and severe in 12.6% of MRM compared with 43.6%, 47.2%, and 9.2%, respectively, of nonMRM. Almotriptan treatment efficacy outcomes for MRM vs nonMRM, respectively, were: 2-hour pain relief, 77.4% vs 68.3%; 2-hour pain free, 35.4% vs 35.9%; and sustained pain free, 22.9% vs 23.8%. Almotriptan was similarly effective in relieving migraine-associated symptoms and improving functional disability associated with both MRM and nonMRM. Conclusions., Prior to treatment, the presence of migraine-associated characteristics including aura, allodynia-associated symptoms, photophobia, phonophobia, and nausea were similar for both MRM and nonMRM attacks. The pretreatment levels of pain intensity and functional disability were likewise similar across the migraine subtypes. Almotriptan was equally effective in the treatment of both MRM and nonMRM attacks and was associated with an adverse event profile that was similar to placebo treatment. [source] Eletriptan for the Acute Treatment of Migraine in Adolescents: Results of a Double-Blind, Placebo-Controlled TrialHEADACHE, Issue 4 2007Paul Winner DO Background.,Eletriptan is a potent 5-HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults. Objective.,To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). Methods.,A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. Results.,Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-naïve status (ie, no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. Conclusions.,The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose. [source] Osteoporosis management: a perspective based on bisphosphonate data from randomised clinical trials and observational databasesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2009S. Boonen Summary Aims:, The efficacy of treatments for osteoporosis can be evaluated using a variety of study designs. This article aims to comprehensively review the evidence for bisphosphonate anti-fracture efficacy in postmenopausal women, discussing the strengths and limitations associated with each study method. Methods:, Literature analysis included English-language publications reporting results of randomised controlled trials (RCTs), post hoc analyses, meta analyses and observational studies evaluating the efficacy of alendronate (ALN), ibandronate (IBN), risedronate (RIS) and zoledronate (ZOL), with an initial sample size , 100 patients, and follow-up data for at least 1 year. Results:, Primary and secondary analyses of RCT data suggest differences among bisphosphonates with regard to site-specific anti-fracture efficacy and onset of fracture risk reduction. While some observational studies indicate differences in clinical outcomes among these agents, others report similar effectiveness. ALN and RIS data demonstrate sustained fracture protection for up to 10 and 7 years of treatment respectively. The efficacy of IBN and ZOL has been evaluated for up to 3 and 5 years respectively. Conclusions:, Understanding of the benefits of bisphosphonate treatment can be maximised by evaluating complementary data from RCTs and observational database studies. Fracture risk reduction with bisphosphonates is shown in RCTs and in real-world clinical settings. [source] A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezilINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2004Sanford I. Finkel Abstract Objective To examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer's disease (AD) in outpatients treated with donepezil. Methods and materials Patients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score ,2 in at least one domain), were treated with donepezil (5,10,mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation therapy with either sertraline (50,200,mg) or placebo. Primary efficacy measures were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. Results 24 patients were treated with donepezil+sertraline and 120 patients with donepezil+placebo. There were no statistically significant differences at endpoint on any of the three primary efficacy measures. However, a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil+sertraline. Moreover, in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia, 60% of patients on sertraline vs 40% on placebo (p,=,0.006) achieved a response (defined as ,;50% reduction in a four-item NPI-behavioral subscale). One adverse event (diarrhea) was significantly (p,<,0.05) more common in the donepezil+sertraline group compared to the donepezil+placebo group. Conclusion Sertraline augmentation was well-tolerated in this sample of AD outpatients. In addition, post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinically and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia. Copyright © 2004 John Wiley & Sons, Ltd. [source] The Impact of Multiple Dimensions of Ethnic Identity on Discrimination and Adolescents' Self-EsteesJOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 11 2003Andrea J. Romero The rejection-identification model is investigated with multiple dimensions of ethnic identity in a sample of Mexican American youth. It is hypothesized that more perceived discrimination will be associated with higher ethnic identity in general, but that the multiple dimensions of ethnic identity will be associated differentially with discrimination. Higher perceived discrimination will be associated with more ethnic exploration and less ethnic affirmation. Self-report questionnaires were completed by middle school students of Mexican descent (N= 881). Based on structural equation modeling, the data were found to fit the rejection-identification model (p < .05). Higher discrimination was associated with lower ethnic affirmation (p < .05) and lower ethnic exploration (p < .05). Post hoc analyses indicated a significant interaction between discrimination and ethnic affirmation (p < .01) such that youth with high ethnic affirmation who experienced high discrimination still reported high self-esteem. The findings are discussed in the context of understanding methods of coping with prejudice and discrimination that will enhance the mental well-being of minority youth. [source] Forensic nursing in secure environmentsJOURNAL OF FORENSIC NURSING, Issue 3 2009Deborah Shelton PhD Abstract There are few well-designed studies of corrections or prison nursing roles. This study seeks to describe the corrections or prison role of forensic nurses in the United States who provide care in secure environments. National data detailing the scope of practice in secure environments are limited. This pencil and paper survey describes the roles of 180 forensic nurses from 14 states who work in secure environments. Descriptive statistics are utilized. A repeated measures ANOVA with post hoc analyses was implemented. These nurses were older than average in age, but had 10 years or less experience in forensic nursing practice. Two significant roles emerged to "promote and implement principles that underpin effective quality and practice" and to "assess, develop, implement, and improve programs of care for individuals." Significant roles varied based upon the security classification of the unit or institution in which the nurses were employed. Access to information about these nurses and their nursing practice was difficult in these closed systems. Minimal data are available nationally, indicating a need for collection of additional data over time to examine changes in role. It is through such developments that forensic nursing provided in secure environments will define its specialization and attract the attention it deserves. [source] Intervention program to keep girls in the science pipeline: Outcome differences by ethnic statusJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 4 2003Toby Epstein Jayaratne This study evaluated a 2-week residential program aimed at enhancing the science interest and persistence of high-achieving 8th-grade girls. Questionnaires were administered to 38 program participants (14 of whom were of minority ethnicity) and 173 applicants who did not attend the program, at 3 time points: preprogram, 1 year postprogram, and 4 years postprogram. Outcomes, measured postprogram, included science self-concept and interest, persistence and aspirations in science, science activities, science course-taking in high school, and plans for a science college major. There was no main effect of program participation on any of the outcome measures, but a significant Participation,×,Ethnicity interaction effect occurred for all but one of the outcome variables. At Time 2, and especially Time 3, nonminority participants tended to have the most positive outcomes, whereas minority participants tended to have the most negative outcomes, compared with applicants. Post hoc analyses showed that although nonminority girls overall were more advantaged, this difference did not explain results. Several interpretations for these findings are discussed, the most likely that some global feature of the program, not any intervention component, interacted over time with the girls' postprogram experience. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 40: 393,414, 2003 [source] Glycemic Targets for Patients with Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227,233, 2009. © 2009 Mount Sinai School of Medicine [source] Novel pharmacology: asimadoline, a ,-opioid agonist, and visceral sensationNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008M. Camilleri Abstract, Asimadoline is a potent ,-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the , receptor, with IC50 of 5.6 nmol L,1 (guinea pig) and 1.2 nmol L,1 (human recombinant), and high selectively with , : , : , binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post- on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date. [source] Market Orientation and R&D Effectiveness in High-Technology Firms: An Empirical Investigation in the Biotechnology Industry,THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 3 2010Luigi M. De Luca There seems to be lack of consensus among informed scholars about the importance a of market orientation for high-technology firms. This paper gives a comprehensive review of existing empirical studies on the relationship between market orientation and innovation performance and pinpoints two limitations in this research stream that might be at the origin of such controversy. First, extant research often overlooked key innovation outcomes for high-technology firms, such as those related to research and development (R&D) performance. Second, organizational conditions that can ensure an optimal integration of market knowledge in the innovation process have been less analyzed in the case of these firms. Against this background, the present study contributes to the literature by providing a test of the effect of market orientation on R&D effectiveness and the moderating role of knowledge integration in this relationship, using a sample of Italian biotechnology firms. The study's objectives are addressed in two steps. The first one consists of an in-depth qualitative study based on semistructured interviews in five biotechnology firms. The second step consists of a follow-up survey of 50 biotechnology firms. Results from hierarchical multiple regression analysis show that the different dimensions of a market orientation have diverse effects on R&D effectiveness of high-technology firms: whereas interfunctional coordination has a positive main effect, the effect of customer orientation is moderated by knowledge integration, and competitor orientation has no effect on R&D effectiveness. Post hoc analyses also show two additional results involving a broader set of dependent variables. First, R&D effectiveness mediates the effects of customer orientation and interfunctional coordination on organizational performance. Second, market orientation does not appear to significantly affect R&D efficiency. The present study contributes to current literature in two main respects. First, it adds to previous work on market orientation and innovation by proposing a new dependent variable,R&D effectiveness,which offers a better perspective to understand the impact of market orientation on innovation performance in high-technology contexts. Second, while part of the current debate on the role of market orientation in high-tech markets seems to be polarized by positions that sustain its potential drawbacks or, on the contrary, its advantages, this study's findings on the moderating role of knowledge integration shed light on important contingency factors, such as organizational capabilities. The authors discuss the study's limitations and provide directions for future research. [source] The efficacy and safety of abatacept in patients with non,life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 10 2010J. T. Merrill Objective To evaluate abatacept therapy in patients with non,life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis. Methods In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (,10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper. Results A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference ,3.5 [95% CI ,15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period). Conclusion Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non,life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment. [source] A post hoc analysis of multiple-stimulus preference assessment resultsBEHAVIORAL INTERVENTIONS, Issue 2 2002Richard B. Graff Fifteen individuals with developmental disabilities participated in multiple-stimulus without replacement preference assessments (seven assessment sessions, seven trials each). Twelve of 15 individuals completed a second set of preference assessments 6 months later. Post hoc analyses indicated that in 25 of 27 cases, the same most preferred stimulus was identified in the first three trials as the full seven trials. Additionally, five sessions of three trials each were sufficient to identify the most highly preferred stimulus in 22 of 27 instances. Copyright © 2002 John Wiley & Sons, Ltd. [source] Psychological therapies in bipolar disorder: the effect of illness history on relapse prevention , a systematic reviewBIPOLAR DISORDERS, Issue 5 2009Dominic H Lam Objectives:, Despite some encouraging outcomes and shared components of psychological therapies specific to bipolar disorders, not all studies found conclusively that the addition of a psychosocial intervention to pharmacological interventions improves outcomes. There was some tentative evidence from post hoc analyses that patients with more than 12 previous episodes did not benefit from psychoeducation or cognitive therapy. This paper presents a systematic review and meta-analysis which examines the overall efficacy of bipolar disorder-specific psychological therapies and the impact of the number of previous episodes on the efficacy of psychological therapies in relapse prevention. Methods:, Systematic literature searches of electronic databases and reference lists of existing reviews were carried out. The number of participants experiencing relapse in randomized, controlled studies was combined in a meta-analysis to determine the overall treatment effect in relapse prevention. Metaregression modeling was used to examine whether the number of previous episodes confounded the number of relapses experienced by participants by the end of treatment. Results:, Meta-analysis of relapse calculated an overall relative risk of 0.74 [95% confidence interval (CI): 0.64,0.85] with some heterogeneity present (I2 = 43.3%). Metaregression of six studies showed no relationship between number of episodes and number of relapses by endpoint. Conclusion:, Psychological therapy specifically designed for bipolar disorder is effective in preventing or delaying relapses in bipolar disorders, and there is no clear evidence that the number of previous episodes moderated the effect. [source] Computer Self-Efficacy and Motivation to Learn in a Self-Directed Online CourseDECISION SCIENCES JOURNAL OF INNOVATIVE EDUCATION, Issue 1 2009Marcia J. Simmering ABSTRACT Despite the increased use of new learning technologies, there is still much to be learned about the role of learner characteristics in online learning. The purpose of this study was to examine how subjects' characteristics normally associated with effective training (i.e., initial motivation to learn and self-efficacy) related to learning in a self-directed online course. From an analysis of 190 respondents, computer and Internet usage prior to the start of class were positively related to individuals' computer self-efficacy and computer self-efficacy was positively related to learning. However, contrary to expectations, computer self-efficacy was not related to initial motivation to learn and motivation to learn was not related to learning in the class. Post hoc analysis of qualitative data enabled a rich explanation of the findings, including an evaluation of the unexpected relationships among the variables of interest and the nature of self-directed courses in virtual learning environments. [source] Depressive relapse during lithium treatment associated with increased serum thyroid-stimulating hormone: results from two placebo-controlled bipolar I maintenance studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2009M. A. Frye Objective:, To assess the relationship between depressive relapse and change in thyroid function in an exploratory post hoc analysis from a controlled maintenance evaluation of bipolar I disorder. Method:, Mean thyroid-stimulating hormone (TSH) and outcome data were pooled from two 18-month, double-blind, placebo-controlled, maintenance studies of lamotrigine and lithium monotherapy. A post hoc analysis of 109 subjects (n = 55 lamotrigine, n = 32 lithium, n = 22 placebo) with serum TSH values at screening and either week 52 (±14 days) or study drop-out was conducted. Results:, Lithium-treated subjects who required an intervention for a depressive episode had a significantly higher adjusted mean TSH level (4.4 ,IU/ml) compared with lithium-treated subjects who did not require intervention for a depressive episode (2.4 ,IU/ml). Conclusion:, Lithium-related changes in thyroid function are clinically relevant and should be carefully monitored in the maintenance phase of bipolar disorder to maximize mood stability and minimize the risk of subsyndromal or syndromal depressive relapse. [source] Depressive symptoms in the first year from diagnosis of Type 2 diabetes: results from the DESMOND trialDIABETIC MEDICINE, Issue 8 2010T. C. Skinner Diabet. Med. 27, 965,967 (2010) Abstract Aims, To describe the course of depressive symptoms during the first year after diagnosis of Type 2 diabetes. Methods,Post hoc analysis of data from a randomized controlled trial of self-management education for 824 individuals newly diagnosed with Type 2 diabetes. Participants completed the Depression scale of the Hospital Anxiety and Depression Scale after diagnosis and at 4, 8 and 12 months follow-up. Participants also completed the Problem Areas in Diabetes scale at 8 and 12 months follow-up. We present descriptive statistics on prevalence and persistence of depressive symptoms. Logistic regression is used to predict possible depression cases, and multiple regression to predict depressive symptomatology. Results, The prevalence of depressive symptoms in individuals recently diagnosed with diabetes (18,22% over the year) was not significantly different from normative data for the general population (12%) in the UK. Over 20% of participants indicated some degrees of depressive symptoms over the first year of living with Type 2 diabetes; these were mostly transient episodes, with 5% (1% severe) reporting having depressive symptoms throughout the year. At 12 months post diagnosis, after controlling for baseline depressive symptoms, diabetes-specific emotional distress was predictive of depressive symptomatology. Conclusions, The increased prevalence of depressive symptoms in diabetes is not manifest until at least 1 year post diagnosis in this cohort. However, there are a significant number of people with persistent depressive symptoms in the early stages of diabetes, and diabetes-specific distress may be contributing to subsequent development of depressive symptoms in people with Type 2 diabetes. [source] Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapyEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2008J. M. Cooper Background and purpose:, A pilot study of high dose coenzyme Q10 (CoQ10)/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. Methods:, Fifty FRDA patients were randomly divided into high or low dose CoQ10/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. Results:, At baseline serum CoQ10 and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ10 and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ10 levels. Conclusions:, A high proportion of FRDA patients have a decreased serum CoQ10 level which was the best predictor of a positive clinical response to CoQ10/vitamin E therapy. Low and high dose CoQ10/vitamin E therapies were equally effective in improving ICARS scores. [source] Inter-hemispheric inhibition is impaired in mirror dystoniaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009S. Beck Abstract Surround inhibition, a neural mechanism relevant for skilled motor behavior, has been shown to be deficient in the affected primary motor cortex (M1) in patients with focal hand dystonia (FHD). Even in unilateral FHD, however, electrophysiological and neuroimaging studies have provided evidence for bilateral M1 abnormalities. Clinically, the presence of mirror dystonia, dystonic posturing when the opposite hand is moved, also suggests abnormal interhemispheric interaction. To assess whether a loss of inter-hemispheric inhibition (IHI) may contribute to the reduced surround inhibition, IHI towards the affected or dominant M1 was examined in 13 patients with FHD (seven patients with and six patients without mirror dystonia, all affected on the right hand) and 12 right-handed, age-matched healthy controls (CON group). IHI was tested at rest and during three different phases of a right index finger movement in a synergistic, as well as in a neighboring, relaxed muscle. There was a trend for a selective loss of IHI between the homologous surrounding muscles in the phase 50 ms before electromyogram onset in patients with FHD. Post hoc analysis revealed that this effect was due to a loss of IHI in the patients with FHD with mirror dystonia, while patients without mirror dystonia did not show any difference in IHI modulation compared with healthy controls. We conclude that mirror dystonia may be due to impaired IHI towards neighboring muscles before movement onset. However, IHI does not seem to play a major role in the general pathophysiology of FHD. [source] Strain differences in the behavioural outcome of neonatal ventral hippocampal lesions are determined by the postnatal environment and not genetic factorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001Graham K. Wood Abstract It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions. [source] Early Intervention With Almotriptan Improves Sustained Pain-free Response in Acute MigraineHEADACHE, Issue 10 2003Ninan T. Mathew MD Objective.,To determine whether treatment of migraine with almotriptan, when pain intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates compared with treatment when pain intensity is moderate or severe. Methods.,This was a post hoc analysis derived from an open-label, multicenter, long-term study of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who met International Headache Society criteria for migraine with or without aura were eligible. Patients were instructed to take a single dose of almotriptan 12.5 mg at the onset of a migraine attack. Rescue medication could be taken if migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5 mg could be taken if head pain recurred within 24 hours of the initial dose. Patients reported the intensity of pain at baseline and at 1 and 2 hours postmedication using a 4-point scale: no pain, mild, moderate, or severe pain. They also reported recurrence of pain (return of moderate or severe pain within 2 to 24 hours of taking the study medication) and use of rescue medication. Rescue medication consisted of supplemental analgesics taken for pain relief at 2 to 24 hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue medications. Based on these patient-reported end points, sustained pain-free rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and no use of rescue medication, were calculated. Results.,A higher proportion of migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with attacks of moderate or severe intensity (7.5%) (P < .001). Two-hour pain-free rates also were significantly higher with mild intensity pain (76.9%) compared to moderate or severe intensity (43.9%) (P < .001). In addition, recurrence rates and use of rescue medication were reduced when attacks were treated during mild pain. Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P < .001), and use of rescue medication was 9.4% for mild pain versus 17.2% for moderate or severe pain (P < .001). Sustained pain-free rates were nearly twice as high when attacks were treated during mild intensity pain (66.6%) compared with attacks treated during moderate or severe pain (36.6%) (P < .001). Conclusion.,Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity improves 1- and 2-hour pain-free and sustained pain-free responses. [source] Clinical Benefits of Early Triptan Therapy for MigraineHEADACHE, Issue 2002Julio Pascual MD Although triptans have been proven effective for acute treatment of migraine, reserving them for moderate or severe pain may produce suboptimal pain relief and higher rates of recurrence. Recent evidence indicates that early intervention at the onset of pain improves outcomes. Post hoc analysis of a long-term, open-label European study of almotriptan 12.5 mg found that the percentage of attacks rendered pain-free at 2 hours was significantly greater when patients treated mild pain (84%) than when the intervention occurred during moderate or severe pain (53%). A similar pattern emerged with respect to the consistency of pain relief, with a significant advantage for early intervention (88% versus 56%, respectively). A difference in favor of early intervention was also seen with respect to recurrence, need for rescue medication, and adverse events. The recurrence rate was significantly lower in patients treating mild pain (28%) than in those delaying treatment until the pain became moderate or severe (33%), which suggests that achieving pain freedom results in less recurrence. These results were generally replicated in post hoc analysis of a subgroup of patients from a randomized, placebo-controlled trial (the Spectrum Study) of oral sumatriptan 50 mg in migraineurs. This analysis demonstrated that with early intervention, pain was less likely to intensify, fewer attacks required redosing, more attacks remained pain-free 24 hours postdose, and normal function returned more quickly. In sum, early intervention with triptans can improve outcomes, avoiding much of the pain and disability associated with treating moderate or severe attacks. [source] Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational studyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2010Cecilia Adrianzén Abstract Objective To explore the relative association of adverse events with health-related quality of life (HRQL) in patients (N,=,16,091) with schizophrenia, treated with antipsychotic medication. Methods In this post hoc analysis of data from two 3-year observational studies, a mixed effects model with repeated measures was used to evaluate the association between HRQL (EuroQoL visual analogue scale (EQ-VAS)) and pre-specified covariates including: severity of illness, extrapyramidal symptoms, tardive dyskinesia, sexual dysfunction, and clinically significant weight gain (>,7% increase from baseline after ,,3 months of treatment). Results Mean EQ-VAS increased from 47.8,±,21.7 at baseline to 72.4,±,18.4 after 36 months. The rank order of the negative association of adverse events with HRQL was: sexual dysfunction (effect estimate ,4.04; 95% CI ,4.30 to ,3.79), extrapyramidal symptoms (effect estimate ,2.09; 95% CI ,2.43 to ,1.75), and tardive dyskinesia (effect estimate ,0.89; 95% CI ,1.46 to ,0.32). Conclusions Differences were observed in the direction and magnitude of the association between each adverse event and HRQL. Recognition of the relative association of adverse events with HRQL may contribute to improved adherence of patients with schizophrenia to antipsychotic therapy. Copyright © 2010 John Wiley & Sons, Ltd. [source] How long should a trial of escitalopram treatment be in patients with major depressive disorder, generalised anxiety disorder or social anxiety disorder?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2009An exploration of the randomised controlled trial database Abstract Objective To extend the knowledge of course of improvement in patients with major depressive disorder (MDD), social anxiety disorder (SAD) or generalised anxiety disorder (GAD) participating in randomised placebo-controlled trials (RCTs) and to infer the optimal duration of initial escitalopram treatment in clinical practice, after which intervention might be reasonable in case of non-response. Methods Post hoc analysis of pooled clinical trial database for escitalopram in MDD (14 studies), GAD (4 studies) and SAD (2 studies). ,Onset' of action was defined as a 20% or more decrease from baseline score in disorder-specific psychopathological rating scales: ,response' as a 50% or more decrease from baseline score. Results In MDD, the probability of responding at week 8 if no onset was apparent at week 2 was 43%; in patients with an onset of effect the probability was nearly 80%. Similar patterns were observed in GAD and SAD. The chance of responding beyond week 4 in MDD, GAD and SAD was 20% or less if no effect had occurred by week 2. Conclusions The pattern of response in these RCTs suggests that in patients with MDD, GAD or SAD in wider clinical practice, a period of at least 4,weeks is worthwhile before considering further intervention. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||||||||