Human Salmonellosis: Estimation of Dose-Illness from Outbreak Data

The quantification of the relationship between the amount of microbial organisms ingested and a specific outcome such as infection, illness, or mortality is a key aspect of quantitative risk assessment. A main problem in determining such dose-response models is the availability of appropriate data. Human feeding trials have been criticized because only young healthy volunteers are selected to participate and low doses, as often occurring in real life, are typically not considered. Epidemiological outbreak data are considered to be more valuable, but are more subject to data uncertainty. In this article, we model the dose-illness relationship based on data of 20 Salmonella outbreaks, as discussed by the World Health Organization. In particular, we model the dose-illness relationship using generalized linear mixed models and fractional polynomials of dose. The fractional polynomial models are modified to satisfy the properties of different types of dose-illness models as proposed by Teunis et al . Within these models, differences in host susceptibility (susceptible versus normal population) are modeled as fixed effects whereas differences in serovar type and food matrix are modeled as random effects. In addition, two bootstrap procedures are presented. A first procedure accounts for stochastic variability whereas a second procedure accounts for both stochastic variability and data uncertainty. The analyses indicate that the susceptible population has a higher probability of illness at low dose levels when the combination pathogen-food matrix is extremely virulent and at high dose levels when the combination is less virulent. Furthermore, the analyses suggest that immunity exists in the normal population but not in the susceptible population.     

Who does not cut down? Comparing characteristics and drinking motives of drinkers and abstainers during the exam periods

Objective: Drinking alcohol during the exams can affect academic performance and future career options, but is rarely investigated. Drinking motives, sociodemographics and personality characteristics are investigated in nonabstainers and weekly drinkers during the exams. Participants: 7,181 Belgian university students who anonymously responded to an email invitation to an online survey. Methods: Logistic regressions and mixed design analysis of variance on cross-sectional data. Results: One-third of the students continued drinking during the exams, with 40% drinking weekly. Nonabstainers were mainly men, elder, internally motivated when drinking, and housed with parents or independently. Weekly drinkers were similar, except mainly housed in student apartments or independently. Personality characteristics were nonsignificant. All drinking motives were less pronounced during the exams, with smaller differences for internal motives. Conclusions: Mainly linked to internal drinking motives, drinking during the exams in higher education is underestimated. The characteristics and motives of students doing so can be used in future interventions.     

Modelling PK/QT relationships from Phase I dose‐escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose‐escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose‐concentration and concentration‐QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug–drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose‐escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision‐making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd.     

Ethical uneasiness and the need for open-ended reflexivity: the case of research into older people with a wish to die

This article focuses on research ethics in highly intimate research with possible impact on life and death. In order to stimulate an open-ended dialogue about research ethics, we reflect on four ethical challenges that came up during our research into older people with a wish to die. Drawing on our experiences, we discuss (1) the possibly confirming influence of our research on the death wish (moral experience of whether or not to disregard responsibility); (2) the suggested duty to intervene (moral experience of whether or not to compromise the person’s autonomy); (3) the researcher’s authority and power over the data (moral experience of threatening a person’s self-narrative) and (4) the dilemma of intimacy (moral experience of encountering the tragic). For guidance in addressing these challenges, we draw upon work on research ethics from phenomenological and care ethics scholars, as well as from those writing about relational ethics in health research. We suggest that being open about ethical uneasiness is important, because in most cases of a grey area, there are only open-ended answers needing an enquiring mind, rather than clear and fixed guidelines. Acknowledgement of ethical uneasiness and open-ended reflexivity are indispensable to constitute a morally good research practice.     

Development of a Quantitative Microbial Risk Assessment for Human Salmonellosis Through Household Consumption of Fresh Minced Pork Meat in Belgium

A quantitative microbial risk assessment (QMRA) according to the Codex Alimentarius Principles is conducted to evaluate the risk of human salmonellosis through household consumption of fresh minced pork meat in Belgium. The quantitative exposure assessment is carried out by building a modular risk model, called the METZOON-model, which covers the pork production from farm to fork. In the METZOON-model, the food production pathway is split up in six consecutive modules: (1) primary production, (2) transport and lairage, (3) slaughterhouse, (4) postprocessing, (5) distribution and storage, and (6) preparation and consumption. All the modules are developed to resemble as closely as possible the Belgian situation, making use of the available national data. Several statistical refinements and improved modeling techniques are proposed. The model produces highly realistic results. The baseline predicted number of annual salmonellosis cases is 20,513 ( SD 9061.45). The risk is estimated higher for the susceptible population (estimate  4.713 × 10⁻⁵; SD 1.466 × 10⁻⁵  ) compared to the normal population  (estimate 7.704 × 10⁻⁶; SD 5.414 × 10⁻⁶)  and is mainly due to undercooking and to a smaller extent to cross-contamination in the kitchen via cook's hands.     

Comparison of causal effect estimators under exposure misclassification

Over the past decades, various principles for causal effect estimation have been proposed, all differing in terms of how they adjust for measured confounders: either via traditional regression adjustment, by adjusting for the expected exposure given those confounders (e.g., the propensity score), or by inversely weighting each subject's data by the likelihood of the observed exposure, given those confounders. When the exposure is measured with error, this raises the question whether these different estimation strategies might be differently affected and whether one of them is to be preferred for that reason. In this article, we investigate this by comparing inverse probability of treatment weighted (IPTW) estimators and doubly robust estimators for the exposure effect in linear marginal structural mean models (MSM) with G-estimators, propensity score (PS) adjusted estimators and ordinary least squares (OLS) estimators for the exposure effect in linear regression models. We find analytically that these estimators are equally affected when exposure misclassification is independent of the confounders, but not otherwise. Simulation studies reveal similar results for time-varying exposures and when the model of interest includes a logistic link.     

Effectiveness of an educational intervention to increase knowledge and reduce use of risky behaviors associated with cumulative trauma in office workers

OBJECTIVE: This pilot project assessed the effectiveness of an intervention to increase knowledge and reduce risky behaviors related to cumulative trauma disorders (CTD) in office workers. STUDY DESIGN: All 124 employees from the administrative offices of a health maintenance organization were invited to participate. Subjects were followed across time using an identification number. Data were collected via questionnaire in June 1994 (pretest1) (N=84), August 1994 (pretest II) (N= 63) and September 1995 (posttest) (N=40). The yearlong intervention focused on functional activities to prevent CTD. RESULTS: of chi-square analyses for the 40 subjects who completed all surveys indicated this intervention significantly increased overall knowledge of CTD (p =.002). Significant changes in self-reported hand/wrist (p =.016) and neck/shoulder (p =.003) posture were also found. CONCLUSIONS: This study is a first step in identifying effective educational interventions to increase knowledge and reduce risk factors related to CTD in office workers.     

The Second Generation in Belgium

A growing proportion of second‐generation Moroccan and Turkish youngsters in Belgium are moving on to higher secondary education and beyond. This trend is greater among Moroccan youngsters than among their Turkish peers. Turkish girls in particular are still married off at a young age, which inevitably affects their educational opportunities. Despite higher participation rates for youngsters from immigrant backgrounds, the educational gap with Belgian pupils and students remains wide. This is largely attributable to differences in socioeconomic background. It appears that the concentration of second‐generation immigrant pupils in certain schools is also a major explanatory factor. Despite their increased participation in education, second‐generation immigrants are still not well represented in the labor market and they are, moreover, employed mostly in less favorable segments of that market. An interesting development among second‐generation immigrants is the polarization that is taking place in relation to the significance of Islam. A growing number of second‐generation youngsters are opting for a more secular way of life, while an increasingly large group is choosing Islamist ideologies or at least a more conscious form of Islam. For young people of the second generation, who often have little to hold on to socially, Islamism can provide a transparent, supportive, and all‐embracing frame of reference.     

NUSAP Method for Evaluating the Data Quality in a Quantitative Microbial Risk Assessment Model for Salmonella in the Pork Production Chain

The numeral unit spread assessment pedigree (NUSAP) system was implemented to evaluate the quality of input parameters in a quantitative microbial risk assessment (QMRA) model for Salmonella spp. in minced pork meat. The input parameters were grouped according to four successive exposure pathways: (1) primary production (2) transport, holding, and slaughterhouse, (3) postprocessing, distribution, and storage, and (4) preparation and consumption. An inventory of 101 potential input parameters was used for building the QMRA model. The characteristics of each parameter were defined using a standardized procedure to assess (1) the source of information, (2) the sampling methodology and sample size, and (3) the distributional properties of the estimate. Each parameter was scored by a panel of experts using a pedigree matrix containing four criteria (proxy, empirical basis, method, and validation) to assess the quality, and this was graphically represented by means of kite diagrams. The parameters obtained significantly lower scores for the validation criterion as compared with the other criteria. Overall strengths of parameters related to the primary production module were significantly stronger compared to the other modules (the transport, holding, and slaughterhouse module, the processing, distribution, and storage module, and the preparation and consumption module). The pedigree assessment contributed to select 20 parameters, which were subsequently introduced in the QMRA model. The NUSAP methodology and kite diagrams are objective tools to discuss and visualize the quality of the parameters in a structured way. These two tools can be used in the selection procedure of input parameters for a QMRA, and can lead to a more transparent quality assurance in the QMRA.     

Evaluation of Scenarios for Reducing Human Salmonellosis Through Household Consumption of Fresh Minced Pork Meat

Nontyphoidal salmonellosis is the second most frequently reported zoonotic disease in the European Union (EU) and is considered to be a major threat to human health worldwide. The most reported Salmonella serovar in the EU is S. Enteritidis, mainly associated with egg contamination, followed by S. Typhimurium, with the latter being the most predominant serovar isolated from pork. These findings suggest that reducing the Salmonella contamination in the pork production might be a good strategy to prevent and control human salmonellosis in the EU. Recently, a quantitative microbial risk assessment (QMRA) has been developed to assess the risks for human salmonellosis due to home consumption of fresh minced pork meat in Belgium.⁽ 1 ⁾ The newly developed risk model is called the METZOON model. In the current study, the METZOON model was used to evaluate the effectiveness of different hypothetical Salmonella mitigation strategies implemented at different stages of the minced pork production and consumption chain by means of a scenario analysis. To efficiently evaluate the mitigation strategies, model results were obtained by running simulations using the randomized complete block design. The effectiveness of a mitigation strategy is expressed using point and interval estimates of the effect size for dependent observations, expressed as the standardized difference in population means. The results indicate that the most effective strategies are taken during the slaughter processes of polishing, evisceration, and chilling, and during postprocessing, whereas interventions in the primary production and at the beginning of the slaughter process seem to have only a limited effect. Improving consumer awareness is found to be effective as well.