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Treatment Trials (treatment + trials)
Selected AbstractsMore Confusing Messages From the Hypertension Treatment TrialsJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2006Marvin Moser MD Editor in Chief First page of article [source] New-Onset Diabetes in the Hypertension Treatment Trials: A Point of ViewJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2004Marvin Moser MD Editor in Chief First page of article [source] Recommendations on Use of Biomarkers in Alcoholism Treatment TrialsALCOHOLISM, Issue 10 2003John P. Allen Background: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome. Methods: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported. Results: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status. Conclusions: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context. [source] Using Acquired Knowledge and New Technologies in Alcoholism Treatment TrialsALCOHOLISM, Issue 3 2002Barbara A. Flannery This article represents the proceedings of a symposium held at the 2001 RSA meeting in Montreal, Canada. The organizer and chair was Barbara A. Flannery and the discussant was Raye Z. Litten. The presentations were (1) The use of biomarkers in alcohol-dependence treatment trials, by John P. Allen; (2) Strategies for enhancing patient compliance in clinical treatment trials, by Helen M. Pettinati; (3) The predictive utility of an alcohol-craving measure, by Barbara A. Flannery; (4) What should be the primary outcome measures in a clinical trial, by Damaris J. Rohsenow; (5) Innovative strategies for assessing functional outcomes in alcoholism treatment clinical trials, by Ron A. Cisler. [source] Who Will Consent to Emergency Treatment Trials for Subarachnoid Hemorrhage?ACADEMIC EMERGENCY MEDICINE, Issue 4 2009Angela Del Giudice MD Abstract Objectives:, Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disorder that still requires much clinical study. However, the decision to participate in a randomized clinical trial, particularly a neuroemergency trial, is a complex one. The purposes of this survey were to determine who would participate in a randomized clinical trial that intended to examine transfusion practices after SAH, to identify who could serve as potential proxy decision-makers, and to find which patient characteristics were associated with the decision to participate. Methods:, This was a cross-sectional study using a self-administered questionnaire, composed of a brief description of the proposed trial followed by questions about participation using a 5-point Likert scale. Information sought included potential decision-maker, demographic data, setting and reason for current health care access, and personal or family history of neurologic injury. Results:, Nine-hundred five subjects were enrolled during emergency department (ED) visits, office visits, hospital admissions, or online, during a 1-month period: 63% were women and 46% were white. Nonneurologic problems were the leading reason (90%) for health care access, but 45% had a personal or family history of neurologic injury. Overall, 54% (95% confidence interval [CI] = 51% to 57%) of subjects stated they would definitely or probably consent to participate. No subject characteristics were associated with this decision: age (p = 0.28), sex (p = 0.16), race/ethnicity (p = 0.07), education (p = 0.44), religion (p = 0.42), clinical setting (p = 0.14), reason for visit (p = 0.58), and/or history of neurologic injury (p = 0.33). The vast majority (88%) identified a family member as the proxy decision-maker, again without differences among groups. Conclusions:, Greater than half of respondents stated they would participate in a proposed emergency treatment trial for SAH. Our survey suggests that the decision to participate is highly individualized, because no demographic, pathologic, historical, or access-related predictors of choice were found. Educational materials designed for this type of trial would need to be broad-based. Family members should be considered as proxy decision-makers where permitted by federal and local regulations. [source] Assessment of gestational age and neuromaturationDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2005Marilee C. Allen Abstract Neuromaturation is the functional development of the central nervous system (CNS). It is by its very nature a dynamic process, a continuous interaction between the genome and first the intrauterine environment, then the extrauterine environment. Understanding neuromaturation and being able to measure it is fundamental to infant neurodevelopmental assessment. Fetal and preterm neuromaturation has become easier to observe with the advent of prenatal ultrasonography and neonatal intensive care units. A number of measures of degree of fetal maturation have been developed and used to estimate gestational age (GA) at birth. The most reliable measures of GA are prenatal measures, especially from the first trimester. Postnatal GA measurements tend to be least accurate at the extremes of gestation, that is, in extremely preterm and post-term infants. Observations of measures of neuromaturation in infants born to mothers with pregnancy complications, including intrauterine growth restriction, multiple gestation, and chronic hypertension, have led to the discovery that stressed pregnancies may accelerate fetal pulmonary and CNS maturation. This acceleration of neuromaturation does not occur before 30 weeks' gestation and has a cost with respect to cognitive limitations manifested in childhood. The ability to measure fetal and preterm neuromaturation provides an assessment of neurodevelopmental progress that can be used to reassure parents or identify at risk infants who would benefit from limited comprehensive follow-up and early intervention services. In addition, measures of neuromaturation have the potential to provide insight into mechanisms of CNS injury and recovery, much-needed early feedback in intervention or treatment trials and a measure of early CNS function for research into the relationships between CNS structure and function. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:21,33. [source] Review of bupropion for smoking cessationDRUG AND ALCOHOL REVIEW, Issue 2 2003ROBYN RICHMOND Abstract The advent of bupropion hydrochloride sustained release (Zyban) has heralded a major change in the options available for smoking cessation pharmacotherapy. Bupropion is a selective re-uptake inhibitor of dopamine and noradrenalin which prevents or reduces cravings and other features of nicotine withdrawal. Bupropion is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation. For this review a total of 221 papers were reviewed plus poster presentations. This review examines in detail original clinical trials on efficacy, categorised according to whether they were acute treatment trials in healthy smokers; studies in specific populations such as people with depression, chronic obstructive pulmonary disease (COPD) or cardiovascular disease; or relapse prevention studies. Overall, these studies in varying populations comprising over four thousand subjects, showed bupropion consistently produces a positive effect on smoking cessation outcomes. The evidence highlights the major public health role that bupropion has in smoking cessation. The methodological issues of published clinical trials reporting one year outcomes were examined in detail including: completeness of follow-up; loss to follow-up; intention to treat analysis; blindness of assessment; and validation of smoking status. The review discusses contraindications, adverse effects, dose and overdose, addictive potential, and the role of bupropion in reducing cessation-related weight gain. Bupropion combined with or compared to other pharmacotherapies (nicotine patch; nortriptyline) is considered. Impressive evidence exists for the use of bupropion in smoking cessation among difficult patients who are hard-core smokers such as those with cardiovascular disease, chronic obstructive pulmonary disease (COPD) and depression. Bupropion reduces withdrawal symptoms as well as weight gain and is effective for smoking cessation for people with and without a history of depression or alcoholism. Serious side effects of bupropion use are rare. The major safety issue with bupropion is risk of seizures (estimated at approximately 0.1%) and it should not be prescribed to patients with a current seizure disorder or any history of seizures. In clinical trials of bupropion for smoking cessation no seizures were reported. Allergic reactions occur at a rate of approximately 3% and minor adverse effects are common including dry mouth and insomnia. [source] Development of antiinflammatory therapy for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Paul S. Aisen Abstract Inflammatory mechanisms are active in the Alzheimer's disease (AD) brain. Studies that range from epidemiological surveys to therapeutic trials in transgenic mice provide growing support for the theory that antiinflammatory drugs may be useful in the prevention and/or treatment of the disease. Randomized controlled trials in humans have not yet confirmed this theory. However, prevention and treatment trials continue to test specific antiinflammatory strategies for AD. Drug Dev. Res. 56:421,427, 2002. © 2002 Wiley-Liss, Inc. [source] Introduction to therapy of hepatitis CHEPATOLOGY, Issue 5B 2002Karen L. Lindsay 1640 Marengo St. Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. [source] Introduction to therapy of hepatitis CHEPATOLOGY, Issue S1 2002Karen L. Lindsay M.D. Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. (HEPATOLOGY 2002;36:S114,S120). [source] Adefovir dipivoxil: review of a novel acyclic nucleoside analogueINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2004M. Danta Summary Adefovir dipivoxil (ADF) is a novel acyclic nucleoside analogue that has recently been approved for the treatment of chronic hepatitis B virus (HBV). Adefovir was initially assessed at higher doses for the treatment of human immunodeficiency virus (HIV) infection. However, in these studies, nephrotoxicity proved a dose-limiting side effect. Large randomised controlled studies have recently shown that ADF results in histological, virological and biochemical improvement in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic HBV. While the rate of HBeAg seroconversion at 1 year (12%) was lower than both lamivudine and interferon, this increases with prolonged treatment. The clinical improvements occurred without serious side effects or the development of resistance at the dose of 10 mg daily, in treatment trials of up to 2 years, although resistance has now been observed. In addition, the drug is efficacious in HBV/HIV co-infection and hepatitis B-infected liver transplant recipients, particularly in those who have developed lamivudine resistance. ADF can be added as a treatment option to existing treatment options (interferon-alpha and lamivudine) and assumes a role in the ongoing management of chronic HBV. The optimal use of ADF as either a monotherapy or as part of combination therapy requires further assessment. [source] Changes in psychopathology and symptom severity in bulimia nervosa between 1993 and 2003INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 2 2008Amanda S. Vaught BA Abstract Objective: This study investigated changes in symptom severity and the psychopathology of patients with bulimia nervosa between 1993 and 2003. Method: Pretreatment data of patients diagnosed with bulimia nervosa, collected between 1993 and 1997 from two multisite studies (N = 263), and from 2001 to 2003 from a third multisite study (N = 233) were compared for differences in psychopathology, eating disorder symptoms, and demographic characteristics. Results: There was a significant increase in baseline age between the cohorts (1993M = 28.7 ± 7.9, 2001M = 30.3 ± 8.7, p = 0.036) together with a decrease in personality disorders and in several aspects of eating disorder psychopathology. After controlling for age however, significant pretreatment differences were found only in the restraint subscale on the EDE. Conclusion: Results suggest that the presentation of individuals with bulimia nervosa has changed between 1993 and 2003, in that participants were older and demonstrated less dietary restraint. Hence, comparisons between samples and treatment trials over time must be made with caution. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [source] What can dropouts teach us about retention in eating disorder treatment studies?INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 7 2007Renee Rienecke Hoste PhD Abstract Objective: To describe strategies used to retain adolescents with bulimia nervosa (BN) in a randomized clinical trial, and to compare treatment completers and dropouts on baseline demographic and symptom severity information. Method: Adolescents with BN (N = 80) completed a demographic questionnaire, the Eating Disorder Examination, Rosenberg Self-esteem Scale, Family Adaptability and Cohesion Evaluation Scales, and Beck Depression Inventory prior to beginning treatment. Results: Several strategies were used to promote treatment retention (e.g., encouraging parental involvement in treatment, prompt rescheduling of cancelled appointments). Six participants (7.50%) voluntarily dropped out of treatment and three additional participants (3.75%) were asked to terminate treatment for medical/psychiatric reasons. Compared with treatment completers, noncompleters reported significantly longer duration of illness (p < .01). Sixty-two percent of treatment completers and only 22% of dropouts were from intact families. Conclusion: Examining factors related to retention in adolescent treatment trials is important, and could be utilized to improve retention in adult studies where drop out rates are higher. © 2007 by Wiley Periodicals, Inc. [source] Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegenerationJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 6 2007K. Freeman Abstract Background Pantothenate kinase-associated neurodegeneration (PKAN), an extremely rare autosomal recessive disorder resulting in iron accumulation in the brain, has a diverse phenotypic expression. Based on limited case studies of one or two patients, intellectual impairment is considered part of PKAN. Investigations of cognitive functioning have utilized specific neuropsychological tests, without attention to general intellectual skills or adaptive behaviour. Methods Sixteen individuals with PKAN completed measures of global intellectual functioning, and participants or care providers completed measures of adaptive behaviour skills and day-to-day functional limitations. Clinicians provided global ratings of condition severity. Results Testing with standardized measures documented varied phenotypic expression, with general cognitive skills and adaptive behaviour ranging from high average to well below average. Age of disease onset correlated with measures of intellectual functioning, adaptive functioning and disease severity. Conclusions Findings support previously described clinical impressions of varied cognitive impairment and the association between age of onset and impairment. Further, they add important information regarding the natural history of the disease and suggest assessment strategies for use in treatment trials. [source] Conventional MRI in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 2007Massimo Filippi MD ABSTRACT During the past 10 years, conventional magnetic resonance imaging (cMRI) has become an established tool for the assessment of patients with multiple sclerosis (MS) and to monitor treatment trials. This is mainly due to the sensitivity and reproducibility of cMRI in the detection of MS-related damage. A large effort has also been devoted to develop imaging strategies capable of providing accurate estimates of the extent of disease-related damage not only in the brain, but also in the spinal cord and optic nerve. Guidelines have been defined to integrate MR findings in the diagnostic evaluation of patients at presentation with clinically isolated syndromes suggestive of MS, and specific acquisition protocols have been offered for monitoring longitudinal changes in patients with established disease. Despite the fact that the role of cMRI in MS has been profoundly obviated by the advent of modern and quantitative MR techniques, several issues are still unresolved. Technical development in acquisition and postprocessing, as well as the introduction of high-field magnets in the clinical arena, are likely to increase our understanding of disease pathobiology, mainly through an increased ability to quantify the extent of gray matter damage. [source] Temporal Changes in Brain Volume and Cognition in a Randomized Treatment Trial of Vascular DementiaJOURNAL OF NEUROIMAGING, Issue 1 2001Joseph P. Broderick MD ABSTRACT Objective. To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. Methods. Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. Results. Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r= 0.51, P= .0024), as well as activities of daily living (r= 0.61, P= .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r= 0.74, P= .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P= .001) and the mean ischemic brain volume increased by 18% (P= .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. Conclusion. In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease. [source] Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndromeJOURNAL OF PINEAL RESEARCH, Issue 2 2009Yanina Romero-Zerbo Abstract:, Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental-retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental-retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental-retardation protein was bred. In the present study, fragile X mental retardation 1-knockout and wild-type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid-reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1-knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1-knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1-knockout mice, including abnormal context-dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1-knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease. [source] Factors Affecting %CDT Status at Entry Into a Multisite Clinical Treatment Trial: Experience from the COMBINE StudyALCOHOLISM, Issue 11 2006Raymond F. Anton Background: Carbohydrate-deficient transferrin (CDT) occurs as a higher percentage of normal transferrin (%CDT) in heavy drinkers. %CDT is used as a marker of both alcohol use disorder severity and treatment outcome both clinically and in treatment trials. Nevertheless, little is known about the parameters that predict which patients are %CDT positives at treatment entry. These parameters might include level of drinking, days of abstinence before testing, and severity of alcohol dependence before evaluation. Methods: %CDT levels were collected before randomization from participants of the COMBINE Study, a large federally sponsored multisite clinical trial evaluating medications and behavioral therapies in alcohol-dependent outpatients. %CDT (assayed in a central laboratory) was available in 1,193 individuals for whom drinking history in the 30 days before testing and measures of alcoholism severity were documented. The effects of drinking history and alcohol severity were evaluated for prediction of a %CDT-positive test status. Results: Less percent days abstinent (PDA) and more drinks per drinking day (DDD) were predictive of higher rates of %CDT-positive patients (maximum 67%). Up to 14 days of continuous abstinence before testing did not appear to significantly affect %CDT status. Rates of %CDT positives remained reasonably steady up to about 40% PDA. Years of drinking at dependence levels had an unexpected negative impact on %CDT-positive rates while previous treatment had a small but positive impact of %CDT-positive rates. ADS and DrInC scores had no predictive value over and above recent drinking amounts on %CDT status. Conclusions: %CDT is more likely to be positive in those who have more days of drinking and to a lesser degree in those who drink more per drinking day. It can remain positive even in those alcoholic subjects who stop drinking many days before testing. Alcoholic subjects with more treatment experiences appear to have a marginally higher %CDT-positive rate. [source] Outcome Variables and Their Assessment in Alcohol Treatment Studies: 1968-1998ALCOHOLISM, Issue 10 2003John W. Finney Background: This article provides a historical overview of the assessment of outcome variables in alcohol treatment studies that were first published between 1968 and 1998. The review focuses on changes over time in (1) the number of outcome variables and the number of different types of outcome variables assessed, (2) the likelihood of assessing specific types of outcome variables, (3) the methods used to assess outcome variables, and (4) the status of outcome assessment in more recent studies first published between 1990 and 1998. Methods: Reports of 357 alcohol treatment trials with two or more treatment/control groups were coded with respect to the number and types of outcome variables assessed, sources of outcome data, and methodological aspects of outcome assessment. Results: Although the number of outcome variables assessed in studies, on average, did not increase significantly over time, the number of different types of outcome variables did increase. An expected decrease in the assessment of categorical abstinence was not found, but another categorical variable, global ratings of drinking improvement, did decrease over time. More recent studies were more likely to assess such continuous variables as time abstinent, alcohol consumption, time drinking, dependence symptoms, and drinking-related problems. Physiological markers of drinking/alcohol misuse also were assessed more frequently in later years. Some aspects of outcome assessment methods exhibited improvement over time; validity data were more likely to be provided or cited, and self-reports of drinking behaviors were more likely to be corroborated in studies first published in more recent years. However, the percentages of studies that provided/cited reliability data for outcome measures, indicated that follow-up data collectors were not affiliated with treatment and were unaware of respondents' treatment conditions, and reported that respondents were alcohol-free at follow-up did not rise significantly over time. Conclusions: Although the methods of outcome assessment improved between 1968 and 1998, much room for improvement remains. [source] Using Acquired Knowledge and New Technologies in Alcoholism Treatment TrialsALCOHOLISM, Issue 3 2002Barbara A. Flannery This article represents the proceedings of a symposium held at the 2001 RSA meeting in Montreal, Canada. The organizer and chair was Barbara A. Flannery and the discussant was Raye Z. Litten. The presentations were (1) The use of biomarkers in alcohol-dependence treatment trials, by John P. Allen; (2) Strategies for enhancing patient compliance in clinical treatment trials, by Helen M. Pettinati; (3) The predictive utility of an alcohol-craving measure, by Barbara A. Flannery; (4) What should be the primary outcome measures in a clinical trial, by Damaris J. Rohsenow; (5) Innovative strategies for assessing functional outcomes in alcoholism treatment clinical trials, by Ron A. Cisler. [source] Meta-analysis: factors affecting placebo response rate in the irritable bowel syndromeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. C. Ford Aliment Pharmacol Ther 2010; 32: 144,158 Summary Background, Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract with a significant placebo response. Aim, To conduct a systematic review and meta-analysis examining the magnitude of placebo response rate in treatment trials for IBS. Methods, MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing pharmacological therapies with placebo in adult IBS patients. Studies reported either global assessment of IBS symptom cure or improvement or abdominal pain cure or improvement. Data were extracted as intention-to-treat analyses with drop-outs assumed to be treatment failures and pooled using a random-effects model. Proportion of placebo patients experiencing symptom improvement or resolution was reported with a 95% confidence interval (CI). Effect of trial characteristics on magnitude of placebo response was examined. Results, In all, 73 RCTs were eligible, including 8364 patients with IBS allocated to placebo. Pooled placebo response rate across all RCTs was 37.5% (95% CI 34.4,40.6%). Rates were higher in European RCTs, RCTs that used physician-reported outcomes and RCTs using shorter duration of therapy. Conclusions, Placebo response rates across RCTs of pharmacological therapies in IBS were high. Future research should identify patient characteristics predicting placebo response. [source] Meta-analysis: Helicobacter pylori eradication treatment efficacy in childrenALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007R. KHURANA Summary Background, Several meta-analyses assessing the efficacy of anti- Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. Aims, To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. Methods, We searched Medline, reference lists from published study reports, and conference proceedings for anti- H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. Results, Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2,6 weeks of nitroimidazole and amoxicillin, 1,2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. Conclusions, Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high. [source] Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trialsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006S. J. O. VELDHUYZEN VAN ZANTEN Summary Background, Currently there is no consensus on the optimal method to measure the severity of dyspepsia symptoms in clinical trials. Aim, To validate the 7-point Global Overall Symptom scale. Methods, The Global Overall Symptom scale uses a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem. Validation was performed in two randomized-controlled trials (n = 1121 and 512). Construct validity: Global Overall Symptom was compared with the Quality of Life in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and 10 specific symptoms using Spearman correlation coefficients. Test,retest reliability: The Intraclass Correlation Coefficient was calculated for patients with stable dyspepsia defined by no change in Overall Treatment Effect score over two visits. Responsiveness: effect size and standardized response mean were also calculated. Results, Construct validity: Change in Global Overall Symptom score correlated significantly with Quality of Life for Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness: There was a positive correlation between change in Global Overall Symptom and change in symptom severity. The effect size and standardized response mean were 1.1 and 2.1, respectively. Conclusion, The Global Overall Symptom scale is a simple, valid outcome measure for dyspepsia treatment trials. [source] Methods of evaluation of musician's dystonia: Critique of measurement toolsMOVEMENT DISORDERS, Issue 3 2007June T. Spector MD Abstract Musician's dystonia is associated with significant morbidity. To assess treatment options, accurate and precise measurements of disease severity are critical. We describe current methods of quantitatively measuring musician's dystonia of the upper extremity including subjective, objective, and automated methods. The degree to which these methods satisfy rigorous measurement criteria, including their reliability, validity, responsiveness to treatment, and practicality, is examined. We report that most of these methods have not been properly evaluated. Therefore, treatment trials based on these methods are difficult to interpret. © 2006 Movement Disorder Society [source] Less is more, or almost as much: A 15-item quality-of-life instrument for myasthenia gravisMUSCLE AND NERVE, Issue 2 2008Ted M. Burns MD Abstract We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the "gold standard," the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG. Muscle Nerve, 2008 [source] Immunotherapy of idiopathic inflammatory neuropathiesMUSCLE AND NERVE, Issue 3 2003Peter D. Donofrio MD Abstract Evaluation of peripheral neuropathy is a common reason for referral to a neurologist. Recent advances in immunology have identified an inflammatory component in many neuropathies and have led to treatment trials using agents that attenuate this response. This article reviews the clinical presentation and treatment of the most common subacute inflammatory neuropathies, Guillain,Barré syndrome (GBS) and Fisher syndrome, and describes the lack of response to corticosteroids and the efficacy of treatment with plasma exchange and intravenous immunoglobulin (IVIG). Chronic inflammatory demyelinating polyneuropathy, although sharing some clinical, electrodiagnostic, and pathologic similarities to GBS, improves after treatment with plasma exchange and IVIG and numerous immunomodulatory agents. Controlled trials in multifocal motor neuropathy have shown benefit after treatment with IVIG and cyclophosphamide. Also discussed is the treatment of less common inflammatory neuropathies whose pathophysiology involves monoclonal proteins or antibodies directed against myelin-associated glycoprotein or sulfatide. Little treatment data exist to direct the clinician to proper management of rare inflammatory neuropathies resulting from osteosclerotic myeloma; POEMS syndrome; vasculitis; Sjögren's syndrome; and neoplasia (paraneoplastic neuropathy). Muscle Nerve 28: 273,292, 2003 [source] Biofeedback therapy in fecal incontinence and constipationNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2009P. Enck Abstract, We examine the collected evidence for efficacy of biofeedback therapy (BFT) in incontinence and constipation by means of meta-analysis of randomized controlled trials. PubMed search was performed to identify treatment trials that match quality criteria (adequate control groups, randomization). They were entered into meta-analyses using fixed effect models and computing odds ratio (OR) and 95% confidence interval (CI) of treatment effects. For constipation, eight BFT trials were identified. In four trials, electromyographic (EMG) BFT was compared to non-BFT treatments (laxatives, placebo, sham training and botox injection), while in the remaining four studies EMG BFT was compared to other BFT (balloon pressure, verbal feedback) modes. Meta-analyses revealed superiority of BFT to non-BFT (OR: 3.657; 95% CI: 2.127,6.290, P < 0.001) but equal efficacy of EMG BFT to other BF applications (OR: 1.436; CI: 0.692,3.089; P = 0.319). For fecal incontinence, a total of 11 trials were identified, of which six compared BFT to other treatment options (sensory training, pelvic floor exercise and electrical stimulation) and five compared one BFT option to other modalities of BFT. BFT was equal effective than non-BFT therapy (OR: 1.189, CI: 0.689,2.051, P = 0.535). No difference was found when various modes BFT were compared (OR: 1.278, CI: 0.736,2.220, P = 0.384). Included trials showed a substantial lack of quality and harmonization, e.g. variable endpoints and missing psychological assessment across studies. BFT for pelvic floor dyssynergia shows substantial specific therapeutic effect while BFT for incontinence is still lacking evidence for efficacy. However, in both conditions the mode of BFT seems to play a minor role. [source] Childhood developmental disorders: an academic and clinical convergence point for psychiatry, neurology, psychology and pediatricsTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 1-2 2009Allan L. Reiss Background:, Significant advances in understanding brain development and behavior have not been accompanied by revisions of traditional academic structure. Disciplinary isolation and a lack of meaningful interdisciplinary opportunities are persistent barriers in academic medicine. To enhance clinical practice, research, and training for the next generation, academic centers will need to take bold steps that challenge traditional departmental boundaries. Such change is not only desirable but, in fact, necessary to bring about a truly innovative and more effective approach to treating disorders of the developing brain. Methods:, I focus on developmental disorders as a convergence point for transcending traditional academic boundaries. First, the current taxonomy of developmental disorders is described with emphasis on how current diagnostic systems inadvertently hinder research progress. Second, I describe the clinical features of autism, a phenomenologically defined condition, and Rett and fragile X syndromes, neurogenetic diseases that are risk factors for autism. Finally, I describe how the fields of psychiatry, psychology, neurology, and pediatrics now have an unprecedented opportunity to promote an interdisciplinary approach to training, research, and clinical practice and, thus, advance a deeper understanding of developmental disorders. Results:, Research focused on autism is increasingly demonstrating the heterogeneity of individuals diagnosed by DSM criteria. This heterogeneity hinders the ability of investigators to replicate research results as well as progress towards more effective, etiology-specific interventions. In contrast, fragile X and Rett syndromes are ,real' diseases for which advances in research are rapidly accelerating towards more disease-specific human treatment trials. Conclusions:, A major paradigm shift is required to improve our ability to diagnose and treat individuals with developmental disorders. This paradigm shift must take place at all levels , training, research and clinical activity. As clinicians and scientists who are currently constrained by disciplinary-specific history and training, we must move towards redefining ourselves as clinical neuroscientists with shared interests and expertise that permit a more cohesive and effective approach to improving the lives of patients. [source] Annotation: The therapeutic alliance , a significant but neglected variable in child mental health treatment studiesTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 5 2006Jonathan Green Background:, There has been relatively little research into therapeutic alliance in child and adolescent mental health and virtually no incorporation of alliance measures as a variable in treatment trials in Child and Adolescent Mental Health Services (CAMHS). Method:, A selective literature review on studies in therapeutic alliance in adulthood and childhood along with a theoretical formulation of possible mechanisms of alliance. Results:, Therapeutic alliance is reliably measurable both by observation and questionnaire methods at all points in the treatment cycle. In both adult and child studies it shows a consistent, albeit modest, association with treatment outcome. In specific adult studies it has shown a high predictive validity in relation to outcome compared to other variables. In child studies alliance is particularly salient in externalising disorder and predicts outcome of inpatient treatment. Child alliance and parental alliance are independent factors. Theoretical models of alliance outlined in this paper suggest testable hypotheses regarding predictors for positive and negative alliance. Conclusions:, Therapeutic alliance in CAMHS is measurable and worth measuring. It is likely to be an important variable for treatment outcome studies and should be included in future trial designs. [source] Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2009Article first published online: 14 OCT 200 Abstract The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially on the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. [source] | ||||||||||||||||||||||||||||||||||