Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals

David Henry and colleagues examine compliance with new disclosure requirements of Medicines Australia, the pharmaceutical industry representative body, and argue that they fall short and instead more comprehensive reporting standards are needed

Acetylation of surface carbohydrates in bacterial pathogens requires coordinated action of a two-domain membrane-bound acyltransferase

Membrane bound acyltransferase-3 (AT3) domain-containing proteins are implicated in a wide range of carbohydrate O-acyl modifications, but their mechanism of action is largely unknown. O-antigen acetylation by AT3 domain-containing acetyltransferases of Salmonella spp. can generate a specific immune response upon infection and can influence bacteriophage interactions. This study integrates in situ and in vitro functional analyses of two of these proteins, OafA and OafB (formerly F2GtrC), which display an "AT3-SGNH fused" domain architecture, where an integral membrane AT3 domain is fused to an extracytoplasmic SGNH domain. An in silico-inspired mutagenesis approach of the AT3 domain identified seven residues which are fundamental for the mechanism of action of OafA, with a particularly conserved motif in TMH1 indicating a potential acyl donor interaction site. Genetic and in vitro evidence demonstrate that the SGNH domain is both necessary and sufficient for lipopolysaccharide acetylation. The structure of the periplasmic SGNH domain of OafB identified features not previously reported for SGNH proteins. In particular, the periplasmic portion of the interdomain linking region is structured. Significantly, this region constrains acceptor substrate specificity, apparently by limiting access to the active site. Coevolution analysis of the two domains suggests possible interdomain interactions. Combining these data, we propose a refined model of the AT3-SGNH proteins, with structurally constrained orientations of the two domains. These findings enhance our understanding of how cells can transfer acyl groups from the cytoplasm to specific extracellular carbohydrates.IMPORTANCE Acyltransferase-3 (AT3) domain-containing membrane proteins are involved in O-acetylation of a diverse range of carbohydrates across all domains of life. In bacteria they are essential in processes including symbiosis, resistance to antimicrobials, and biosynthesis of antibiotics. Their mechanism of action, however, is poorly characterized. We analyzed two acetyltransferases as models for this important family of membrane proteins, which modify carbohydrates on the surface of the pathogen Salmonella enterica, affecting immunogenicity, virulence, and bacteriophage resistance. We show that when these AT3 domains are fused to a periplasmic partner domain, both domains are required for substrate acetylation. The data show conserved elements in the AT3 domain and unique structural features of the periplasmic domain. Our data provide a working model to probe the mechanism and function of the diverse and important members of the widespread AT3 protein family, which are required for biologically significant modifications of cell-surface carbohydrates

Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians

Constructing public health policies in post crisis countries: lessons to learn from the associations between free-sugars consumption and diabetes, obesity and dental caries before, during and after sanctions in Iraq.

BACKGROUND: This article aims to provide evidence for an informed public health policy on free-sugar consumption in post-crisis countries. METHODS: Iraq was selected as a case study. A systematic search for published data on the prevalence/incidence of type-2 diabetes, overweight/obesity, dental caries and free-sugar consumption levels in Iraq was conducted using MEDLINE, the Iraqi Academic Scientific journals and relevant international organisations' websites. Comparable data before (1980-1990), during (1991-2002) and after (2003-2015) the United Nations sanctions (UNS) were included. RESULTS: Ten studies were included. Quality scores ranged between 3 and 7/8. Free-sugar consumption decreased dramatically during the UNS (from 50 to 16.3 kg/person/year) and started increasing afterwards (24.1 kg/person/year). Changes in type-2 diabetes, overweight/obesity and caries levels mirrored those of free-sugar consumption. Caries declined markedly during UNS and started increasing afterwards. Comparable data on diabetes and overweight/obesity were only available for the periods during and after the UNS. Both of these conditions started increasing with increased free-sugar consumption after lifting the UNS. CONCLUSIONS: There is a need to develop a public health policy in post-crisis countries to maintain the reduction in free-sugar consumption, and hence promote both general and dental health, by integrating the common risk factor approach into the social determinant framework

Establishing a library of resources to help people understand key concepts in assessing treatment claims—The “Critical thinking and Appraisal Resource Library” (CARL)

Background People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior. Objectives Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL). This library was to be in the form of a database containing learning resources for those who are responsible for encouraging critical thinking about treatment claims, and was to be made available online. We wished to include resources for groups we identified as ‘intermediaries’ of knowledge, i.e. teachers of schoolchildren, undergraduates and graduates, for example those teaching evidence-based medicine, or those communicating treatment claims to the public. In selecting resources, we wished to draw particular attention to those resources that had been formally evaluated, for example, by the creators of the resource or independent research groups. Methods CARL was populated with learning-resources identified from a variety of sources—two previously developed but unmaintained inventories; systematic reviews of learning-interventions; online and database searches; and recommendations by members of the project group and its advisors. The learning-resources in CARL were organised by ‘Key Concepts’ needed to judge the trustworthiness of treatment claims, and were made available online by the James Lind Initiative in Testing Treatments interactive (TTi) English (www.testingtreatments.org/category/learning-resources).TTi English also incorporated the database of Key Concepts and the Claim Evaluation Tools developed through the Informed Healthcare Choices (IHC) project (informedhealthchoices.org). Results We have created a database of resources called CARL, which currently contains over 500 open-access learning-resources in a variety of formats: text, audio, video, webpages, cartoons, and lesson materials. These are aimed primarily at ‘Intermediaries’, that is, ‘teachers’, ‘communicators’, ‘advisors’, ‘researchers’, as well as for independent ‘learners’. The resources included in CARL are currently accessible at www.testingtreatments.org/category/learning-resources Conclusions We hope that ready access to CARL will help to promote the critical thinking about treatment claims, needed to help improve healthcare choices

Knowledge of ghostwriting and financial conflicts-of-interest reduces the perceived credibility of biomedical research

<p>Abstract</p> <p>Background</p> <p>While the impact of conflicts-of-interest (COI) is of increasing concern in academic medicine, there is little research on the reaction of practicing clinicians to the disclosure of such conflicts. We developed two research vignettes presenting a fictional antidepressant medication study, one in which the principal investigator had no COI and another in which there were multiple COI disclosed. We confirmed the face validity of the COI vignette through consultation with experts. Hospital-based clinicians were randomly assigned to read one of these two vignettes and then administered a credibility scale.</p> <p>Findings</p> <p>Perceived credibility ratings were much lower in the COI group, with a difference of 11.00 points (31.42%) on the credibility scale total as calculated through the Mann-Whitney U test (95% CI = 6.99 - 15.00, <it>p </it>< .001). Clinicians in the COI group were also less likely to recommend the antidepressant medication discussed in the vignette (Odds Ratio = 0.163, 95% CI = .03 = 0.875).</p> <p>Conclusions</p> <p>In this study, increased disclosure of COI resulted in lower credibility ratings.</p

Obesity, the Endocannabinoid System, and Bias Arising from Pharmaceutical Sponsorship

Previous research has shown that academic physicians conflicted by funding from the pharmaceutical industry have corrupted evidence based medicine and helped enlarge the market for drugs. Physicians made pharmaceutical-friendly statements, engaged in disease mongering, and signed biased review articles ghost-authored by corporate employees. This paper tested the hypothesis that bias affects review articles regarding rimonabant, an anti-obesity drug that blocks the central cannabinoid receptor.A MEDLINE search was performed for rimonabant review articles, limited to articles authored by USA physicians who served as consultants for the company that manufactures rimonabant. Extracted articles were examined for industry-friendly bias, identified by three methods: analysis with a validated instrument for monitoring bias in continuing medical education (CME); analysis for bias defined as statements that ran contrary to external evidence; and a tally of misrepresentations about the endocannabinoid system. Eight review articles were identified, but only three disclosed authors' financial conflicts of interest, despite easily accessible information to the contrary. The Takhar CME bias instrument demonstrated statistically significant bias in all the review articles. Biased statements that were nearly identical reappeared in the articles, including disease mongering, exaggerating rimonabant's efficacy and safety, lack of criticisms regarding rimonabant clinical trials, and speculations about surrogate markers stated as facts. Distinctive and identical misrepresentations regarding the endocannabinoid system also reappeared in articles by different authors.The findings are characteristic of bias that arises from financial conflicts of interest, and suggestive of ghostwriting by a common author. Resolutions for this scenario are proposed