“Erick Turner”

INTRODUCTION: Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression...

BACKGROUND: A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified...

BACKGROUND: Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range. AIMS: To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and panic disorder. METHOD: Fifty-six trials of second-generation antidepressants for the short-term treatment of an anxiety disorder were included...

A gene-level targeted enrichment method for direct detection of epigenetic modifications is described. The approach is demonstrated on the CGG-repeat region of the FMR1 gene, for which large repeat expansions, hitherto refractory to sequencing, are known to cause fragile X syndrome. In addition to achieving a single-locus enrichment of nearly 700,000-fold, the elimination of all amplification steps removes PCR-induced bias in the repeat count and preserves the native epigenetic modifications of the DNA. In conjunction with the single-molecule real-time sequencing approach, this enrichment method enables direct readout of the methylation status and the CGG repeat number of the FMR1 allele(s) for a clonally derived cell line...

BACKGROUND: The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. METHODS AND FINDINGS: We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972-2008, and we determined whether those grants led to publications...

Humans monitor states of uncertainty that can guide decision-making. These uncertain states are evident behaviorally when humans decline to make a categorization response. Such behavioral uncertainty responses (URs) have also defined the search for metacognition in animals. While a plethora of neuroimaging studies have focused on uncertainty, the brain systems supporting a volitional strategy shift under uncertainty have not been distinguished from those observed in making introspective post-hoc reports of categorization uncertainty...

IMPORTANCE: Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered. OBJECTIVE: To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases inflate estimates of drug efficacy. DATA SOURCES AND STUDY SELECTION: We included reviews obtained from the US Food and Drug Administration (FDA) for premarketing trials of 9 second-generation antidepressants in the treatment of anxiety disorders...

We measured the concentration of petroleum hydrocarbons in 405 wetland sediment samples immediately before the April 2010 Deepwater Horizon disaster led to their broad-scale oiling, and on nine trips afterwards. The average concentrations of alkanes and PAHs were 604 and 186 times the pre-spill baseline values, respectively. Oil was distributed with some attenuation up to 100m inland from the shoreline for alkanes, but increased for aromatics, and was not well-circumscribed by the rapid shoreline assessments (a...

BACKGROUND: Randomized trials can show whether a treatment effect is statistically significant and can describe the size of the effect. There are, however, no validated methods available for establishing the clinical relevance of these outcomes. Recently, it was proposed that a standardized mean difference (SMD) of 0.50 be used as cutoff for clinical relevance in the treatment of depression. METHODS: We explore what the effect size means and why the size of an effect has little bearing on its clinical relevance...

No abstract text is available yet for this article.

Publication bias undermines the integrity of the evidence base by inflating apparent drug efficacy and minimizing drug harms, thus skewing the risk-benefit ratio. This paper reviews the topic of publication bias with a focus on drugs prescribed for psychiatric conditions, especially depression, schizophrenia, bipolar disorder, and autism. Publication bias is pervasive; although psychiatry/psychology may be the most seriously afflicted field, it occurs throughout medicine and science. Responsibility lies with various parties (authors as well as journals, academia as well as industry), so the motives appear to extend beyond the financial interests of drug companies...

OBJECTIVES: To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. DESIGN: Cross sectional study. DATA SOURCES: Cochrane Database of Systematic Reviews. SELECTION CRITERIA: Systematic reviews of drug interventions published in 2010 in the Cochrane Database of Systematic Reviews, with review content classified as up to date in 2008 or later and with results from one or more randomised controlled trials...

BACKGROUND: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. METHODS AND FINDINGS: FDA Drug Approval Packages for eight second-generation antipsychotics-aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone--were used to identify a cohort of 24 FDA-registered premarketing trials...

No abstract text is available yet for this article.

CONTEXT: Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs. OBJECTIVE: To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs...

Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort.

Growth hormone (GH) therapy has been appropriate for severely GH-deficient children and adolescents since the 1960s. Use for other conditions for which short stature was a component could not be seriously considered because of the small supply of human pituitary-derived hormone. That state changed remarkably in the mid-1980s because of Creutzfeldt-Jakob disease associated with human pituitary tissue-derived hGH and the development of a (nearly) unlimited supply of recombinant, 22 kDa (r)hGH. The latter permitted all GH-deficient children to have access to treatment and one could design trials using rhGH to increase adult height in infants, children and adolescents with causes of short stature other than GH deficiency, as well as trials in adult GH-deficient men and women...

OBJECTIVE: To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases. DESIGN: Secondary analysis of a published systematic literature review. DATA SOURCES: Placebo controlled trials of antidepressants previously submitted to the US Food and Drug Administration (FDA) and matching journal publications. METHODS: Publication biases were identified using novel contour enhanced funnel plots, a regression based adjustment method, Egger's test, and the trim and fill method...

No abstract text is available yet for this article.

BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications...