Interaction between drug and placebo effects: a cross-over balanced placebo design trial

<p>Abstract</p> <p>Background</p> <p>The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.</p> <p>Methods</p> <p>180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.</p> <p>Results</p> <p>The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).</p> <p>Conclusions</p> <p>Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identification number - NCT00426010.</p

Sustainability, epistemology, ecocentric business and marketing strategy:ideology, reality and vision

This conceptual article examines the relationship between marketing and sustainability through the dual lenses of anthropocentric and ecocentric epistemology. Using the current anthropocentric epistemology and its associated dominant social paradigm, corporate ecological sustainability in commercial practice and business school research and teaching is difficult to achieve. However, adopting an ecocentric epistemology enables the development of an alternative business and marketing approach that places equal importance on nature, the planet, and ecological sustainability as the source of human and other species' well-being, as well as the source of all products and services. This article examines ecocentric, transformational business, and marketing strategies epistemologically, conceptually and practically and thereby proposes six ecocentric, transformational, strategic marketing universal premises as part of a vision of and solution to current global un-sustainability. Finally, this article outlines several opportunities for management practice and further research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Fun, friend, or foe: Youth perceptions and definitions of online gambling

This article discusses youth consumption of high-speed Internet technology and online youth gambling based on examination of an Australian youth and young adults sample ranging in age from 13 to 30 years of age. This article explores the impact of online gambling on youth well-being and presents organization of the issues confronting youth and gambling behavior online. The article covers current research related to youth and offers a set of narrative definitions of online gambling as offered by 175 youth and young adults. Coupled with this, is a set of industry comments from Australian gambling sector representatives related to this cohort; these offer clarity on how this cohort interacts with current online gambling service providers. There is no doubt that youth underestimate the possible dangers of online gambling and define gambling and online gambling in terms of fun and gaming rather that fully appreciating the risks related to gambling. It is evident there is some legislation and practice protocols ranging in effectiveness that assist in minimizing the access of youth to online gambling

Lack of Gender and Racial Differences in Surgery and Mortality in Hospitalized Medicare Beneficiaries with Bleeding Peptic Ulcer

OBJECTIVE: Determine the relation of race and gender to outcome from bleeding peptic ulcer. DESIGN: Retrospective cohort study. SETTING: All acute care hospitals in the United States. PATIENTS: A 100% sample of hospitalized Medicare beneficiaries older than 64 years (n = 82,868) with a primary discharge diagnosis of peptic ulcer with hemorrhage. MEASUREMENTS AND MAIN RESULTS: Surgical treatment was performed in 6.9% of patients, 30-day mortality was 8.5%, and average length of stay was 9.4 days. Surgery was somewhat more common in men than women (7.3% vs 6.5%, p < .001), and in whites than African Americans (6.9% vs 6.3%, p < .001), but neither race nor gender was associated with surgery in multivariable analysis adjusting for potentially confounding factors. Mortality rates were similar in African Americans and whites (8.5%), and somewhat higher in men than women (10.7% vs 9.3%, p < .001). In multivariable analysis, there was no difference in mortality across gender and racial groups. Although unadjusted and adjusted lengths of stay were longer for African Americans and shorter for men, the differences were modest (i.e., 16% increase and 6% decrease in multivariable analysis, respectively, p < .0001). CONCLUSIONS: In this national sample, there is no significant gender or racial difference in therapy and outcome for patients with hemorrhagic peptic ulcer. The findings raise the possibility that studies that have shown race and gender differences in management of coronary artery disease and cancer may not be generalizable to other common diagnoses