Niel Hens

Mining social mixing patterns for infectious disease models based on a two-day population survey in Belgium

BackgroundUntil recently, mathematical models of person to person infectious diseases transmission had to make assumptions on transmissions enabled by personal contacts by estimating the so-called WAIFW-matrix. In order to better inform such estimates, a population based contact survey has been carried out in Belgium over the period March-May 2006. In contrast to other European surveys conducted simultaneously, each respondent recorded contacts over two days. Special attention was given to holiday periods, and respondents with large numbers of professional contacts.MethodsParticipants kept a paper diary with information on their contacts over two different days. A contact was defined as a two-way conversation of at least three words in each others proximity. The contact information included the age of the contact, gender, location, duration, frequency, and whether or not touching was involved.For data analysis, we used association rules and classification trees. Weighted generalized estimating equations were used to analyze contact frequency while accounting for the correlation between contacts reported on the two different days.A contact surface, expressing the average number of contacts between persons of different ages was obtained by a bivariate smoothing approach and the relation to the so-called next-generation matrix was established.ResultsPeople mostly mixed with people of similar age, or with their offspring, their parents and their grandparents. By imputing professional contacts, the average number of daily contacts increased from 11.84 to 15.70. The number of reported contacts depended heavily on the household size, class size for children and number of professional contacts for adults. Adults living with children had on average 2 daily contacts more than adults living without children. In the holiday period, the daily contact frequency for children and adolescents decreased with about 19% while a similar observation is made for adults in the weekend. These findings can be used to estimate the impact of school closure.ConclusionWe conducted a diary based contact survey in Belgium to gain insights in social interactions relevant to the spread of infectious diseases. The resulting contact patterns are useful to improve estimating crucial parameters for infectious disease transmission models.

Efficacy of daily intake of Lactobacillus casei Shirota on respiratory symptoms and influenza vaccination immune response: a randomized, double-blind, placebo-controlled trial in healthy elderly nursing home residents

BACKGROUNDnAge is associated with immune dysregulation, which results in an increased infection rate and reduced effectiveness of vaccination.nnnOBJECTIVEnWe assessed whether an intervention with Lactobacillus casei Shirota (LcS) in elderly nursing home residents reduced their susceptibility to respiratory symptoms and improved their immune response to influenza vaccination.nnnDESIGNnBetween October 2007 and April 2008, a randomized, double-blind, placebo-controlled trial was conducted in 737 healthy people aged ≥ 65 y in 53 nursing homes in Antwerp, Belgium. Volunteers were randomly assigned to receive a probiotic (n = 375; 2 bottles of fermented milk that contained ≥ 6.5 × 10(9) live LcS/bottle) or a placebo (n = 362; similar drink with no bacteria) for 176 d. After 21 d, all subjects received an influenza vaccination. Primary outcome parameters were the number of days with respiratory symptoms, the probability of respiratory symptoms, and antiinfluenza antibody titer by hemagglutination inhibition after vaccination.nnnRESULTSnUnivariate and multivariate modeling showed no effect of the probiotic on clinical outcome parameters. Generalized linear mixed modeling showed no effect of the probiotic itself on the probability of respiratory symptoms [OR of probiotic: 0.8715; 95% CI: 0.6168, 1.2887). No significant difference regarding the influenza-vaccination immune response was shown.nnnCONCLUSIONnThe results of this study show that daily consumption of a fermented milk drink that contains LcS has no statistically or clinically significant effect on the protection against respiratory symptoms. This trial was registered at clinicaltrials.gov as NCT00849277.

Estimating the population prevalence and force of infection directly from antibody titres

The use of threshold values in order to diagnose individual subjects as being ‘susceptible’ or ‘infected or recovered/immune’ for a specific infection is virtually always prone to false positive, false negative or inconclusive classifications. Such misclassifications might lead to biased estimates for epidemiological parameters, such as the prevalence and the force of infection. In this article, we propose to estimate these epidemiological parameters directly from antibody titres, using an underlying mixture model. The method is applied to estimate the Salmonella serological prevalence in pigs and the age-dependent force of infection using serological data on the Varicella-Zoster virus (VZV) in humans. The threshold and direct method are compared through a simulation study.

Data mining for longitudinal data under multicollinearity and time dependence using penalized generalized estimating equations

Penalized generalized estimating equations with Elastic Net or L2-Smoothly Clipped Absolute Deviation penalization are proposed to simultaneously select the most important variables and estimate their effects for longitudinal Gaussian data when multicollinearity is present. The method is able to consistently select and estimate the main effects even when strong correlations are present. In addition, the potential pitfall of time-dependent covariates is clarified. Both asymptotic theory and simulation results reveal the effectiveness of penalization as a data mining tool for longitudinal data, especially when a large number of variables is present. The method is illustrated by mining for the main determinants of life expectancy in Europe.

A systematic review and meta-regression analysis of mivacurium for tracheal intubation

We systematically reviewed factors associated with intubation conditions in randomised controlled trials of mivacurium, using random‐effects meta‐regression analysis. We included 29 studies of 1050 healthy participants. Four factors explained 72.9% of the variation in the probability of excellent intubation conditions: mivacurium dose, 24.4%; opioid use, 29.9%; time to intubation and age together, 18.6%. The odds ratio (95% CI) for excellent intubation was 3.14 (1.65–5.73) for doubling the mivacurium dose, 5.99 (2.14–15.18) for adding opioids to the intubation sequence, and 6.55 (6.01–7.74) for increasing the delay between mivacurium injection and airway insertion from 1 to 2 min in subjects aged 25 years and 2.17 (2.01–2.69) for subjects aged 70 years, p < 0.001 for all. We conclude that good conditions for tracheal intubation are more likely by delaying laryngoscopy after injecting a higher dose of mivacurium with an opioid, particularly in older people.

Revealing age-specific past and future unrelated costs of pneumococcal infections by flexible generalized estimating equations

We aimed to study the excess health-care expenditures for persons with a known positive isolate of Streptococcus pneumoniae. The data set was compiled by linking the database of the largest Belgian Sickness Fund with data obtained from laboratories reporting pneumococcal isolates. We analyzed the age-specific per-patient cumulative costs over time, using generalized estimating equations (GEEs). The mean structure was described by fractional polynomials. The quasi-likelihood under the independence model criterion was used to compare different correlation structures. We show for all age groups that the health-care costs incurred by diagnosed pneumococcal patients are significantly larger than those incurred by undiagnosed matched persons. This is not only the case at the time of diagnosis but also long before and after the time of diagnosis. These findings can be informative for the current debate on unrelated costs in health economic evaluation, and GEEs could be used to estimate these costs for other diseases. Finally, these results can be used to inform policy on the expected budget impact of preventing pneumococcal infections.