Comparison of Approaches for Notification and Authorization in Pragmatic Clinical Research Evaluating Commonly Used Medical Practices.

BACKGROUND: For pragmatic clinical research comparing commonly used treatments, questions exist about if and how to notify participants about it and secure their authorization for participation. OBJECTIVE: To determine how patients react when they seek clinical care and encounter one of several different pragmatic clinical research studies. RESEARCH DESIGN: In an online survey using a between-subjects experimental design, respondents read and responded to 1 of 24 hypothetical research scenarios reflecting different types of studies and approaches to notification and authorization (eg, general notification, oral consent, written consent). SUBJECTS: English-speaking US adults 18 years and older. MEASURES: Willingness to participate in the hypothetical study, acceptability of the notification and authorization approach, understanding of the study, perceptions of benefit/harm, trust, and perception of amount of study information received. RESULTS: Willingness to participate did not differ by notification and authorization approach. Some (21%-36%) of the patients randomized to general notification with an explicit opt-out provision were not aware they would be enrolled by default. Acceptability was greatest for and similar among notification and authorization approaches that actively engaged the patient (eg, oral or written consent) and lower for approaches with less engagement (eg, general notification). Problems of understanding were found among 20%-55% of respondents, depending on the particular scenario. Most respondents (77%-94%) felt that participation in the hypothetical study posed no risks of harm to their health or privacy. CONCLUSIONS: Current attitudes about notification and authorization approaches and difficulties understanding pragmatic clinical research pose significant challenges for pragmatic research. Data from this study provide a starting point to developing solutions to these surprisingly complex issues.

Human beta defensin-1 is involved in the susceptibility to adeno-tonsillar hypertrophy.

INTRODUCTION: Innate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity. Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy. The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity. METHODS: Ninety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy). The specimen discarded from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry. RESULTS: Functional polymorphisms within DEFB1 gene, encoding the human beta defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adeno-tonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina. CONCLUSION: Our findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adeno-tonsillar hypertrophy development.