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Last Observation (last + observation)
Selected AbstractsA double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorderDEPRESSION AND ANXIETY, Issue 1 2007Mark H. Pollack M.D. Abstract To date, no large-scale, controlled trial comparing a serotonin,norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75,mg/day or 150,mg/day), or paroxetine 40,mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions,Severity (CGI-S) and ,Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder. Depression and Anxiety 24:1,14, 2007. © 2006 Wiley-Liss, Inc. [source] Early response and 8-week treatment outcome in GAD ,DEPRESSION AND ANXIETY, Issue 8 2006Moira Rynn M.D. Abstract Our objective was to compare the predictive value of early response to treatment outcome in patients with generalized anxiety disorder (GAD) treated with benzodiazepines, serotonin receptor (5HT-1A) partial agonists, or placebo. Data from two double-blind GAD studies were combined. Subjects were evaluated with the Hamilton Anxiety Scale (HAM-A) and the Clinical Global Impression of Improvement (CGI-I) scale over 8 weeks. Categories of response at weeks 1 and 2 were defined by the HAM-A total score. Analyses of covariance and Kaplan,Meier survival analyses were the primary analyses used to assess 8-week end point treatment outcomes as a function of early improvement. HAM-A change from baseline to weeks 1 and 2 significantly predicted last observation carried forward (LOCF) response at week 8 for both medications and for placebo (P<.001). Early improvement was a strong predictor for treatment outcome irrespective of whether active medication or placebo was the treatment agent. Depression and Anxiety 23:461,465, 2006. Published 2006 Wiley-Liss, Inc. [source] Using the Lee,Carter Method to Forecast Mortality for Populations with Limited Data,INTERNATIONAL STATISTICAL REVIEW, Issue 1 2004Nan Li Summary The Lee,Carter method for modeling and forecasting mortality has been shown to work quite well given long time series of data. Here we consider how it can be used when there are few observations at uneven intervals. Assuming that the underlying model is correct and that the mortality index follows a random walk with drift, we find the method can be used with sparse data. The central forecast depends mainly on the first and last observation, and so can be generated with just two observations, preferably not too close in time. With three data points, uncertainty can also be estimated, although such estimates of uncertainty are themselves highly uncertain and improve with additional observations. We apply the methods to China and South Korea, which have 3 and 20 data points, respectively, at uneven intervals. Résumé La méthode Lee,Carter de modélisation et de prévision de la mortalité a prouvé son bon fonctionnement avec des séries de données existant sur une longue période. Nous envisageons ici son utilisation lorsqu'on ne dispose que de quelques observations à intervalles irréguliers. En supposant que le modèle sous-jacent est correct et que l'indice de mortalité suit une marche aléatoire avec dérive, nous trouvons que cette méthode peut êetre utilisée avec des données éparses. La prévision centrale dépend alors principalement de la première et de la dernière observation. Elle peut donc êetre générée à partir de deux observations seulement, de préférence pas trop proches dans le temps. Avec trois points, on peut aussi estimer l'aléa, bienqu'un tel estimateur de l'aléa soit lui-mêeme très aléatoire. Il s'améliore cependant lorsqu'on dispose d'observations supplémentaires. Nous appliquons notre méthode àla Chine et à la Corée du Sud, pour lesquelles nous avons respectivement 3 et 20 points àintervalles irréguliers. [source] Time to establishment success for introduced signal crayfish in Sweden , a statistical evaluation when success is partially knownJOURNAL OF APPLIED ECOLOGY, Issue 5 2010Ullrika Sahlin Summary 1.,The signal crayfish Pacifastacus leniusculus is an invasive species in Sweden, threatening the red-listed nobel crayfish Astacus astacus through spreading the crayfish plague. Time-to-event models can handle censored data on such introduced populations for which the state (successful or not) is only partially known at the last observation, but even though data on introduced populations most often are censored, this type of model is usually not used for likelihood-based inference and predictions of the dynamics of establishing populations. 2.,We specified and fitted a probabilistic time-to-event model to be used to predict the time to successful establishment of signal crayfish populations introduced into Sweden. Important covariates of establishment success were found by the methods of ,model averaging' and ,hierarchical partitioning', considering model uncertainty and multi-colinearity, respectively. 3.,The hazard function that received the highest evidence based on the empirical data showed that the chances of establishment were highest in the time periods immediately following the first introduction. The model predicts establishment success to be <50% within 5 years after first introduction over the current distributional range of signal crayfish in Sweden today. 4.,Among covariates related to temperature, fish species and physical properties of the habitat, the length of the growing season was the most important and consistent covariate of establishment success. We found that establishment success of signal crayfish is expected to increase with the number of days when growth is possible, and decrease with the number of days with extremely high temperatures, which can be seen to approximate conditions of stress. 5.,Synthesis and applications. The results demonstrate lower establishment success of signal crayfish further north in Sweden, which may decrease the incentives of additional illegal introductions that may threaten the red-listed noble crayfish Astacus astacus. We provide a fully probabilistic statistical evaluation that quantifies uncertainty in the duration of the establishment stage that is useful for management decisions of invasive species. The combination of model averaging and hierarchical partitioning provides a comprehensive method to address multi-colinearity common to retrospective data on establishment success of invasive species. [source] The adjustment of prediction intervals to account for errors in parameter estimationJOURNAL OF TIME SERIES ANALYSIS, Issue 3 2004Paul Kabaila Abstract., Standard approximate 1 , , prediction intervals (PIs) need to be adjusted to take account of the error in estimating the parameters. This adjustment may be aimed at setting the (unconditional) probability that the PI includes the value being predicted equal to 1 , ,. Alternatively, this adjustment may be aimed at setting the probability that the PI includes the value being predicted equal to 1 , ,, conditional on an appropriate statistic T. For an autoregressive process of order p, it has been suggested that T consist of the last p observations. We provide a new criterion by which both forms of adjustment can be compared on an equal footing. This new criterion of performance is the closeness of the coverage probability, conditional on all of the data, of the adjusted PI and 1 , ,. In this paper, we measure this closeness by the mean square of the difference between this conditional coverage probability and 1 , ,. We illustrate the application of this new criterion to a Gaussian zero-mean autoregressive process of order 1 and one-step-ahead prediction. For this example, this comparison shows that the adjustment which is aimed at setting the coverage probability equal to 1 , , conditional on the last observation is the better of the two adjustments. [source] Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome , results of two randomized, placebo-controlled studiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009D. A. DROSSMAN Summary Background, Effective treatments for irritable bowel syndrome with constipation (IBS-C) are lacking. Aim, To assess the efficacy and safety of lubiprostone in IBS-C. Methods, A combined analysis was performed among 1171 patients with a Rome II diagnosis of IBS-C in two phase-3 randomized trials of lubiprostone 8 mcg vs. placebo twice daily for 12 weeks. Using a balanced seven-point Likert scale ranging from significantly relieved (+3), to significantly worse (,3), patients responded on their electronic diary to the question: ,How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?'. The primary efficacy endpoint was the percentage of overall responders. Results, Using an intent-to-treat analysis with last observation carried forward, a significantly higher percentage of lubiprostone-treated patients were considered overall responders compared with those treated with placebo (17.9% vs. 10.1%, P = 0.001). Patients treated with lubiprostone reported a similar incidence of adverse events to those treated with placebo. Conclusions, The percentage of overall responders based on patient-rated assessments of IBS-C symptoms was significantly improved in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo. Lubiprostone was well tolerated with a favourable safety profile. [source] Mid-term effects of steroid therapy on childhood-onset IgA nephropathyNEPHROLOGY, Issue 2001S Watanabe Purpose: IgA nephropathy (IgAN) is considered the most common glomerular disease in the world. Although treatment of children with severe IgAN with predonisolone (PSL) has been reported, the mid-term prognosis of paediatric patients treated with PSL is unclear. In the present study we examined the mid-term effects of PSL therapy. Method: Thirty-seven paediatric patients with IgAN (18 males, 19 females), whose biopsy findings showed acute segmental lesions including cellular crescent and adhesion in more than 10% of glomeruli examined, were prospectively treated with PSL plus heparin-warfarin and dipyridamole (Tx) for 1.5 years and followed up over 1 years after Tx end. Fifteen age and histological grade-matched children with IgAN (six males, nine females), who had never been treated with PSL, were also evaluated as a historical control. The mean observation period was 5.0 ± 1.8 years (range, 2.5,8.6 years). The histological grade (acute lesion) and stage (chronic lesion) were scored semiquantitatively based on the Shigematsu's grade-stage system.1 Result: Proteinuria decreased 1.48 g/day/1.73 m2 at the start of Tx to 0.32 g/day/1.73 m2 at the end of Tx. Eighteen patients (48.6%) achieved complete remission (CR). No patient developed chronic renal failure in Tx group, while two of the controls deteriorated renal function in the last observation. The pattern of responsiveness to Tx were divided into three groups according to the levels of proteinuria: CR, rebound (> 0.5 g/day/1.73 m2) and incomplete remission (< 0.5 g/day/1.73 m2). The rebound of proteinuria is usually accompanied with PSL reduction. The grade of glomerular pathology was improved with Tx (Gg: 0.8,0.3), while the stage of tubulo-interstitial change progressed (Sint: 0.7,1.2). Conclusions: The present study shows that Tx to children with IgAN showing acute lesions for 1.5 years is effective to subside acute glomerular injury. However, because clinical courses of treated patients vary in each patient, dosage and duration of PSL administration should be modified in their clinical setting. [source] A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic painPHYTOTHERAPY RESEARCH, Issue 9 2008C. Chrubasik Abstract This pilot surveillance included 152 patients with acute exacerbations of chronic pain, 124 (Back group) with non-specific low back pain (NSLBP), 20 with NSLBP overridden by osteoarthritic pain (Knee-Hip group), and eight with specific LBP (included in the safety analysis). Patients were recommended the rose hip and seed powder LitozinR at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Clinical symptoms and well-being were assessed every 6 weeks. The patients also kept a diary of their pain and the requirement for rescue medication. Data were analysed by intention to treat with last observation carried forward. Only 77 patients completed the year of surveillance. Multivariate analysis suggested an appreciable overall improvement during the surveillance, irrespective of group, and this was reflected for most of the individual measures in repeated measures ANOVA. The degree and time-course of improvement echoed that seen in similar surveillances of patients receiving an aqueous extract of Harpagophytum. Multiple regression analyses indicated that percentage changes from baseline tended to be greater in patients with greater degrees of pain and disability, but were otherwise largely unrelated to the patients' characteristics. There were no serious adverse events. The rose hip and seed powder, LitozinR, seems to deserve further, more definitive studies as a possible option in long-term management of NSLBP with or without osteoarthritic pain. Copyright © 2008 John Wiley & Sons, Ltd. [source] Improving the Sexual Quality of Life of Couples Affected by Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial of VardenafilTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2005William A. Fisher PhD ABSTRACT Introduction., Erectile dysfunction (ED) has a dual negative impact on men and their female partners; both are likely to face a drop in sexual quality of life and challenges to their intimate relationship as couples' sexual activities are curtailed by the loss of erectile function. Aim., The primary objective of this study was to compare the efficacy of vardenafil vs. placebo in terms of success of maintenance of erection in men with ED and improvement of their female partner's sexual quality of life. Methods., This was a randomized, double-blind, multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo for 12 weeks in men (,18 years) with ED of ,,6 months duration, and their female partners. Main Outcome Measures., Changes in patient's overall response rate to Sexual Encounter Profile question 3 (SEP3) "Did your erection last long enough for you to have sexual intercourse?" and female partner's response to the quality of life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL) at last observation carried forward (LOCF) were considered the primary efficacy measures. In addition, patient's response to SEP2 "Were you able to insert your penis into your partner's vagina?," the erectile function domain of the International Index of Erectile Function (IIEF-EF) and patient's mSLQQ-QOL score were also assessed. Results., Compared with placebo, vardenafil significantly improved overall least square (LS) mean per-patient SEP3 success rate (28% vs. 68%; P < 0.0001) and partner's LS mean (standard error [SE]) mSLQQ-QOL score at LOCF (32.14 [3.24] vs. 65.80 [3.10]; P < 0.0001). In addition, compared with placebo, vardenafil also improved overall LS mean per-patient SEP2 success rate (47% vs. 80%; P < 0.0001), LS mean (SE) IIEF-EF scores at LOCF (12.7 [0.8] vs. 22.8 [0.8]; P < 0.0001) and patient's LS mean (SE) mSLQQ-QOL (28.37 [3.46] vs. 63.85 [3.28]; P < 0.0001) at LOCF. Conclusions., Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple. Fisher WA, Rosen RC, Mollen M, Brock G, Karlin G, Pommerville P, Goldstein I, Bangerter K, Bandel T-J, Derogatis LR, and Sand M for the Vardenafil Study Group. Improving the sexual quality of life of couples affected by erectile dysfunction: a double-blind, randomized, placebo-controlled trial of vardenafil. J Sex Med 2005;2:699,708. [source] Two-year clinical and radiographic results with combination etanercept,methotrexate therapy versus monotherapy in early rheumatoid arthritis: A two-year, double-blind, randomized study,ARTHRITIS & RHEUMATISM, Issue 3 2010Paul Emery Objective To evaluate how continuation of and alterations to initial year 1 combination etanercept,methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. Methods Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score ,0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission. Results At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen. Conclusion Early sustained combination etanercept,MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk. [source] Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trialARTHRITIS & RHEUMATISM, Issue 4 2006Désirée van der Heijde Objective To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Methods Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. Results A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Conclusion Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX. [source] Marginal Analysis of Incomplete Longitudinal Binary Data: A Cautionary Note on LOCF ImputationBIOMETRICS, Issue 3 2004Richard J. Cook Summary In recent years there has been considerable research devoted to the development of methods for the analysis of incomplete data in longitudinal studies. Despite these advances, the methods used in practice have changed relatively little, particularly in the reporting of pharmaceutical trials. In this setting, perhaps the most widely adopted strategy for dealing with incomplete longitudinal data is imputation by the "last observation carried forward" (LOCF) approach, in which values for missing responses are imputed using observations from the most recently completed assessment. We examine the asymptotic and empirical bias, the empirical type I error rate, and the empirical coverage probability associated with estimators and tests of treatment effect based on the LOCF imputation strategy. We consider a setting involving longitudinal binary data with longitudinal analyses based on generalized estimating equations, and an analysis based simply on the response at the end of the scheduled follow-up. We find that for both of these approaches, imputation by LOCF can lead to substantial biases in estimators of treatment effects, the type I error rates of associated tests can be greatly inflated, and the coverage probability can be far from the nominal level. Alternative analyses based on all available data lead to estimators with comparatively small bias, and inverse probability weighted analyses yield consistent estimators subject to correct specification of the missing data process. We illustrate the differences between various methods of dealing with drop-outs using data from a study of smoking behavior. [source] Statistical methods for longitudinal research on bipolar disordersBIPOLAR DISORDERS, Issue 3 2003John Hennen Objectives: Outcomes research in bipolar disorders, because of complex clinical variation over-time, offers demanding research design and statistical challenges. Longitudinal studies involving relatively large samples, with outcome measures obtained repeatedly over-time, are required. In this report, statistical methods appropriate for such research are reviewed. Methods: Analytic methods appropriate for repeated measures data include: (i) endpoint analysis; (ii) endpoint analysis with last observation carried forward; (iii) summary statistic methods yielding one summary measure per subject; (iv) random effects and generalized estimating equation (GEE) regression modeling methods; and (v) time-to-event survival analyses. Results: Use and limitations of these several methods are illustrated within a randomly selected (33%) subset of data obtained in two recently completed randomized, double blind studies on acute mania. Outcome measures obtained repeatedly over 3 or 4 weeks of blinded treatment in active drug and placebo sub-groups included change-from-baseline Young Mania Rating Scale (YMRS) scores (continuous measure) and achievement of a clinical response criterion (50% YMRS reduction). Four of the methods reviewed are especially suitable for use with these repeated measures data: (i) the summary statistic method; (ii) random/mixed effects modeling; (iii) GEE regression modeling; and (iv) survival analysis. Conclusions: Outcome studies in bipolar illness ideally should be longitudinal in orientation, obtain outcomes data frequently over extended times, and employ large study samples. Missing data problems can be expected, and data analytic methods must accommodate missingness. [source] Advanced Statistics: Missing Data in Clinical Research,Part 1: An Introduction and Conceptual FrameworkACADEMIC EMERGENCY MEDICINE, Issue 7 2007Jason S. Haukoos MD Missing data are commonly encountered in clinical research. Unfortunately, they are often neglected or not properly handled during analytic procedures, and this may substantially bias the results of the study, reduce study power, and lead to invalid conclusions. In this two-part series, the authors will introduce key concepts regarding missing data in clinical research, provide a conceptual framework for how to approach missing data in this setting, describe typical mechanisms and patterns of censoring of data and their relationships to specific methods of handling incomplete data, and describe in detail several simple and more complex methods of handling such data. In part 1, the authors will describe relatively simple approaches to handling missing data, including complete-case analysis, available-case analysis, and several forms of single imputation, including mean imputation, regression imputation, hot and cold deck imputation, last observation carried forward, and worst case analysis. In part 2, the authors will describe in detail multiple imputation, a more sophisticated and valid method for handling missing data. [source] | |||||||||||||