Disease-specific adverse events following nonlive vaccines: a paradoxical placebo effect or a nocebo phenomenon?

Vaccines can cause adverse reactions (AR), i.e. adverse events following immunization (AEFIs) due to the vaccine, such as local reactions or fever. In addition, live attenuated vaccines which replicate in vaccinees can cause disease-specific AR, e.g. measles-like rash following measles vaccination. However, nonlive vaccines because they are inactivated and they do not replicate in vaccinees, are not likely to cause disease-specific AR. The aim of the study was to assess whether safety signals could be generated by an undescribed bias in spontaneous reporting of disease-specific AEFIs with nonlive vaccines. All AEFIs of Sanofi Pasteur MSD vaccines spontaneously reported in France from January 2000 to June 2010, coded according to MedDRA terms and collected in the company's pharmacovigilance database were analyzed. Vaccine-event pairs of interest were selected a priori. The disproportionality reporting rate methodology was used, comparing the proportion of a given event reported following a given vaccine to its proportion reported following all other studied vaccines. The Reporting Odds Ratio (ROR) was used for signals detection for each vaccine-event pair selected. A total of 33,275 AEFIs were analyzed. The calculated ROR showed a statistically disproportionate reporting rate and generated false safety signals for almost all the pairs tested. Three nonlive vaccine pairs were striking: gynaecological symptoms and the quadrivalent human papillomavirus (qHPV) vaccine; trismus and tetanus vaccines; hepatobiliary disorders and hepatitis B vaccines. In conclusion we have identified a new vaccine AE spontaneous reporting bias: "disease-specific adverse events following nonlive vaccines", showing that vaccinees and healthcare professionals tend to report preferentially the symptoms of the disease against which the nonlive vaccine was administered. We suggest that bias is subordinate to a paradoxical placebo effect and/or a nocebo phenomenon.

Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France--The EDiTH VI study.

BACKGROUND: The incidence of oropharyngeal cancers has gradually increased over the last decades. Recent studies suggest an association between human papillomavirus (HPV) infection and several head and neck cancers, especially oropharyngeal and oral cavity invasive carcinomas. OBJECTIVES: The objective was to assess the overall and type specific HPV prevalence in oropharyngeal and oral cavity carcinomas in France. STUDY DESIGN: Paraffin-embedded tumour specimens were retrospectively collected in 12 French centres and centrally tested for HPV detection and genotyping (INNO-LiPA assay). RESULTS: A total of 523 cases (77% males) were collected, among which 60% were oropharyngeal and 40% oral cavity carcinomas. The most frequent anatomical sites were tonsil (58.9%) and base of tongue (13.7%) for the oropharynx and floor of mouth (41.1%) and oral tongue (38.3%) for the oral cavity. Overall HPV prevalence was 46.5% in oropharyngeal carcinomas and 10.5% in oral cavity carcinomas and was higher in female than in male cases (63.5% vs 42.2% in oropharynx and 17.2% vs 8.0% in oral cavity). About 95% of HPV-positive cases were infected by a single HPV type. HPV 16 was the most prevalent type and was found in 89.7% and 95.5% of HPV-positive oropharyngeal and oral cavity carcinoma cases, respectively. All other HPV types had prevalence below 5%. CONCLUSIONS: Our results indicate that HPV is common among oropharyngeal and oral cavity carcinoma cases in France and emphasize the predominance of HPV 16. The potential benefit of HPV vaccination on the occurrence of head and neck carcinomas should be further evaluated.

Human papillomavirus genotype distribution in tonsil cancers.

BACKGROUND: The incidence of tonsil cancers has increased in several countries. French data on HPV prevalence in tonsil cancers are scarce. The objective of this study was thus to assess the overall and type specific HPV prevalence in tonsil histological samples. METHODS: This French retrospective multicenter study involved 12 centres located throughout the country. Were included 185 histological samples collected from year 2000 to 2009 with a validated diagnosis of tonsil invasive carcinomas. HPV prevalence was studied according to gender, age and histological type of cancer. RESULTS: Overall HPV prevalence was 57% in tonsil cancers. Mean age of diagnosis was comparable in HPV positive tonsils cases (60 ± 11.2) and HPV negative tonsil cases (59 ± 9.6). HPV prevalence was significantly higher in female than in male cases (28/35 versus 78/150 in tonsil cases, respectively, P = 0.003). About 53% of tonsil cases were infected by a single HPV type. Only eight (4%) samples were infected by more than one HPV type. Among HPV positive samples, HPV 16 was found in 89% of tonsil cases. All other HPV types had prevalence below 5%. CONCLUSIONS: Our results indicate that HPV is common in tonsil carcinomas and emphasize the predominant role of HPV 16.

Methodology of the sensitivity analysis used for modeling an infectious disease.

Mathematical models may be used to help clarify dynamics of several infectious diseases. Because of the complexity of some models and the high degree of uncertainty in estimating many parameters, the present study proposes a rigorous framework for sensitivity analyses of mathematical models using as example a model to assess varicella and herpes zoster incidence. Its main steps are to assess the uncertainty of the factors to be studied, to evaluate qualitatively and quantitatively the impacts of these factors on model results, and to conduct an univariate and multivariate sensitivity analysis. The application of this technique may have considerable utility in the analysis of a wide variety of complex biological and epidemiological models.

[Readability and information density in biomedical research]. / Lisibilité et densité d'information en recherche biomédicale.

OBJECTIVE: This study was performed in order to compare the lexicosyntactic readability, and the information density in the informed consent forms used in biomedical research, in comparison with standard scientific texts dedicated to the general population. In addition, we studied whether there is a correlation between information readability and density. METHODS: Fifteen informed consent forms, 6 articles from "Sciences et Avenir" and 6 articles from "Sciences et Vie Junior" were analyzed. The lexicosyntactic readability was calculated using the Flesh score, and the information density using the number of information bits related to the number of words. RESULTS: The lexicosyntactic readability was lower in the informed consent forms (25, 17-32) compared with "Sciences et Avenir" (32, 29-38), but even higher in "Sciences et Vie Junior" (42, 38-57). Conversely, the information density was similar in "Sciences et Vie Junior" (0.24, [0.21-0.27]) and the informed consent forms (0.24, [0.22-0.26]), but higher in "Sciences et Avenir" (0.32, [0.26-0.38]). CONCLUSION: Informed consent forms are less readable, but paradoxically less dense than scientific papers dedicated to the general population. There is no correlation between density and readability.