Half-life Estimation of Pertussis-Specific Maternal Antibodies in (Pre)Term Infants After In-Pregnancy Tetanus, Diphtheria, Acellular Pertussis Vaccination.

BACKGROUND: To reduce the risk of pertussis-related morbidity and mortality in early life, an increasing number of countries recommend maternal pertussis vaccination. However, there is limited knowledge about half-lives of vaccine-induced pertussis-specific maternal antibodies, especially in preterm infants, and factors potentially influencing them. METHODS: We compared 2 different approaches to provide estimates of the half-lives of pertussis-specific maternal antibodies in infants and explored potential effects on the half-life in 2 studies. In the first approach, we estimated the half-lives per child and used these estimates as responses in linear models. In the second approach, we used linear mixed effect models on a log2 transformed scale of the longitudinal data to use the inverse of the time parameter as an estimate for the half-lives. RESULTS: Both approaches provided similar results. The identified covariates partly explain differences in half-life estimates. The strongest evidence we observed was a difference between term and preterm infants, with the preterm infants showing a longer half-life. Among others, a longer interval between vaccination and delivery increases the half-life. CONCLUSIONS: Several variables influence the decay speed of maternal antibodies. Both approaches have advantages and disadvantages, while the choice is secondary when assessing the half-life of pertussis-specific antibodies. CLINICAL TRIALS REGISTRATION: NCT02408926 and NCT02511327.

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics. METHODS: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland. FINDINGS: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group. INTERPRETATION: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation.

Effectiveness of computer-based interventions for community-dwelling people with cognitive decline: a systematic review with meta-analyses.

BACKGROUND: Cognitive deficits arise with age and can increase the risk for subjective cognitive decline (SCD) and mild cognitive impairment (MCI), which may result in dementia, leading to health problems, care dependency and institutionalization. Computer-based cognitive interventions (CCIs) have the potential to act as important counteraction functions in preserving or improving cognition concomitant to available pharmacological treatment. The aim was to assess the effectiveness of CCIs performed individually with a personal or tablet computer, game console, virtual, augmented, or mixed reality application on cognition in community-dwelling people with SCD, MCI and dementia. METHODS: A systematic review with meta-analyses of randomized controlled trials (RCTs) was performed. The systematic literature search was conducted in MEDLINE, CINAHL, Embase, Cochrane CENTRAL, IEEE Xplore Digital Library, Web of Science, Scopus and PsycINFO. In addition, a search for gray literature and backward citation searching were carried out. To judge on the evidence, two reviewers independently used the Cochrane Risk of Bias Tool. The standardized mean difference (SDM) for pooling comparable studies using the random-effects model was applied. RESULTS: Twenty-four RCTs were identified, of which 1 RCT examined CCIs in individuals with SCD, 18 RCTs with MCI, and 6 RCTs with dementia. Most interventions were conducted with personal computers. Meta-analyses with 12 RCTs showed significant effects of computer-based cognitive interventions for people with MCI in the domains memory, working memory, attention/concentration/processing speed and executive functioning, but no significant improvements in global cognition and language. Regarding dementia a meta-analysis pooled with 4 RCTs demonstrated a tendency towards, but no significant increase of memory functions (SMD 0.33, CI 95% [-0.10, 0.77]). One RCT regarding SCD reported significant improvements in memory functions for participants conducting a cognitive training on a personal computer. CONCLUSIONS: The results demonstrated that CCIs have beneficial effects on domain-specific cognition in people with MCI but no significant effects on people with dementia. In terms of SCD, one study showed significant improvements in memory functions. It seems that the beneficial effect for cognitive preservation or improvement due to CCIs occurs at the earliest intervention state. However, more research on SCD is needed. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CDR42020184069.

Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm-Born Infants.

BACKGROUND: Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants. METHODS: Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327). RESULTS: Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. CONCLUSIONS: Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response.

Modelling longitudinal binary outcomes with outcome dependent observation times: an application to a malaria cohort study.

BACKGROUND : In spite of the global reduction of 21% in malaria incidence between 2010 and 2015, the disease still threatens many lives of children and pregnant mothers in African countries. A correct assessment and evaluation of the impact of malaria control strategies still remains quintessential in order to eliminate the disease and its burden. Malaria follow-up studies typically involve routine visits at pre-scheduled time points and/or clinical visits whenever individuals experience malaria-like symptoms. In the latter case, infection triggers outcome assessment, thereby leading to outcome-dependent sampling (ODS). Commonly used methods to analyze such longitudinal data ignore ODS and potentially lead to biased estimates of malaria-specific transmission parameters, hence, inducing an incorrect assessment and evaluation of malaria control strategies. METHODS : In this paper, a new method is proposed to handle ODS by use of a joint model for the longitudinal binary outcome measured at routine visits and the clinical event times. The methodology is applied to malaria parasitaemia data from a cohort of [Formula: see text] Ugandan children aged 0.5-10 years from 3 regions (Walukuba-300 children, Kihihi-355 children and Nagongera-333 children) with varying transmission intensities (entomological inoculation rate equal to 2.8, 32 and 310 infectious bites per unit year, respectively) collected between 2011-2014. RESULTS : The results indicate that malaria parasite prevalence and force of infection (FOI) increase with age in the region of high malaria intensity with highest FOI in age group 5-10 years. For the region of medium intensity, the prevalence slightly increases with age and the FOI for the routine process is highest in age group 5-10 years, yet for the clinical infections, the FOI gradually decreases with increasing age. For the region with low intensity, both the prevalence and FOI peak at the age of 1 year after which the former remains constant with age yet the latter suddenly decreases with age for the clinically observed infections. CONCLUSION : Malaria parasite prevalence and FOI increase with age in the region of high malaria intensity. In all study sites, both the prevalence and FOI are highest among previously asymptomatic children and lowest among their symptomatic counterparts. Using a simulation study inspired by the malaria data at hand, the proposed methodology shows to have the smallest bias, especially when consecutive positive malaria parasitaemia presence results within a time period of 35 days were considered to be due to the same infection.

Seroprevalence of IgG antibodies against SARS-CoV-2 - a serial prospective cross-sectional nationwide study of residual samples, Belgium, March to October 2020.

BackgroundTo control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken.AimTo assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000-4,000 residual samples during seven periods between 30 March and 17 October 2020.MethodsWe analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.ResultsThe weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0-2.6) to 5.3% (95% CrI: 4.2-6.4), implying a seroincidence of 3.4% (95% CrI: 2.4-4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1-5.2).ConclusionDuring lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.

COVID-19 mortality, excess mortality, deaths per million and infection fatality ratio, Belgium, 9 March 2020 to 28 June 2020.

BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.

Breast Milk Antibody Levels in Tdap-Vaccinated Women After Preterm Delivery.

BACKGROUND: Enrichment of breast milk (BM) with immunoglobulin (Ig) A and IgG through maternal vaccination could help infants combat targeted pathogens. However, evidence on this effect after preterm delivery is lacking. In this study, we investigated the total and anti-pertussis toxin (anti-PT)-specific IgA and IgG production in BM after term and preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination. METHODS: Serum and BM samples of lactating women who delivered at term or prematurely and did or did not receive Tdap vaccine (Boostrix, GSK Biologicals) during pregnancy were collected as part of a clinical study (N = 234). Anti-PT IgA/IgG (IBL assay; Meso Scale Discovery assay) and total IgA/IgG (Thermofisher, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours and 4, 8, and 12 weeks postpartum. RESULTS: BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (eg, colostrum anti-PT IgA, 5.39 IU/mL vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMCs in colostrum of vaccinated compared with unvaccinated women who delivered at term (0.110 IU/mL vs 0.027 IU/mL, P = .009). Anti-PT antibodies persisted up to 12 weeks postpartum. CONCLUSIONS: This study provides evidence that maternal Tdap vaccination induces high Ig levels in BM after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life. CLINICAL TRIAL REGISTRATION: NCT02511327.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

A data-driven metapopulation model for the Belgian COVID-19 epidemic: assessing the impact of lockdown and exit strategies.

BACKGROUND: In response to the ongoing COVID-19 pandemic, several countries adopted measures of social distancing to a different degree. For many countries, after successfully curbing the initial wave, lockdown measures were gradually lifted. In Belgium, such relief started on May 4th with phase 1, followed by several subsequent phases over the next few weeks. METHODS: We analysed the expected impact of relaxing stringent lockdown measures taken according to the phased Belgian exit strategy. We developed a stochastic, data-informed, meta-population model that accounts for mixing and mobility of the age-structured population of Belgium. The model is calibrated to daily hospitalization data and is able to reproduce the outbreak at the national level. We consider different scenarios for relieving the lockdown, quantified in terms of relative reductions in pre-pandemic social mixing and mobility. We validate our assumptions by making comparisons with social contact data collected during and after the lockdown. RESULTS: Our model is able to successfully describe the initial wave of COVID-19 in Belgium and identifies interactions during leisure/other activities as pivotal in the exit strategy. Indeed, we find a smaller impact of school re-openings as compared to restarting leisure activities and re-openings of work places. We also assess the impact of case isolation of new (suspected) infections, and find that it allows re-establishing relatively more social interactions while still ensuring epidemic control. Scenarios predicting a second wave of hospitalizations were not observed, suggesting that the per-contact probability of infection has changed with respect to the pre-lockdown period. CONCLUSIONS: Contacts during leisure activities are found to be most influential, followed by professional contacts and school contacts, respectively, for an impending second wave of COVID-19. Regular re-assessment of social contacts in the population is therefore crucial to adjust to evolving behavioral changes that can affect epidemic diffusion.

SARS-CoV-2 seroprevalence survey among health care providers in a Belgian public multiple-site hospital.

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is lasting for more than 1 year, the exposition risks of health-care providers are still unclear. Available evidence is conflicting. We investigated the prevalence of antibodies against SARS-CoV-2 in the staff of a large public hospital with multiple sites in the Antwerp region of Belgium. Risk factors for infection were identified by means of a questionnaire and human resource data. We performed hospital-wide serology tests in the weeks following the first epidemic wave (16 March to the end of May 2020) and combined the results with the answers from an individual questionnaire. Overall seroprevalence was 7.6%. We found higher seroprevalences in nurses [10.0%; 95% confidence interval (CI) 8.9-11.2] than in physicians 6.4% (95% CI 4.6-8.7), paramedical 6.0% (95% CI 4.3-8.0) and administrative staff (2.9%; 95% CI 1.8-4.5). Staff who indicated contact with a confirmed coronavirus disease 2019 (COVID-19) colleague had a higher seroprevalence (12.0%; 95% CI 10.7-13.4) than staff who did not (4.2%; 95% CI 3.5-5.0). The same findings were present for contacts in the private setting. Working in general COVID-19 wards, but not in emergency departments or intensive care units, was also a significant risk factor. Since our analysis points in the direction of active SARS-CoV-2 transmission within hospitals, we argue for implementing a stringent hospital-wide testing and contact-tracing policy with special attention to the health care workers employed in general COVID-19 departments. Additional studies are needed to establish the transmission dynamics.

Stable HEV IgG seroprevalence in Belgium between 2006 and 2014.

Recent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort-specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log-log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero-)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1-5.1) and 5.8% (121/2087, CI 4.8-6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.

How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018.

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6-30 months old) attending day care were collected in three periods over 2016-2018. Children's demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017-2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017-2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017-2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.

Sample size calculation for estimating key epidemiological parameters using serological data and mathematical modelling.

BACKGROUND: Our work was motivated by the need to, given serum availability and/or financial resources, decide on which samples to test in a serum bank for different pathogens. Simulation-based sample size calculations were performed to determine the age-based sampling structures and optimal allocation of a given number of samples for testing across various age groups best suited to estimate key epidemiological parameters (e.g., seroprevalence or force of infection) with acceptable precision levels in a cross-sectional seroprevalence survey. METHODS: Statistical and mathematical models and three age-based sampling structures (survey-based structure, population-based structure, uniform structure) were used. Our calculations are based on Belgian serological survey data collected in 2001-2003 where testing was done, amongst others, for the presence of Immunoglobulin G antibodies against measles, mumps, and rubella, for which a national mass immunisation programme was introduced in 1985 in Belgium, and against varicella-zoster virus and parvovirus B19 for which the endemic equilibrium assumption is tenable in Belgium. RESULTS: The optimal age-based sampling structure to use in the sampling of a serological survey as well as the optimal allocation distribution varied depending on the epidemiological parameter of interest for a given infection and between infections. CONCLUSIONS: When estimating epidemiological parameters with acceptable levels of precision within the context of a single cross-sectional serological survey, attention should be given to the age-based sampling structure. Simulation-based sample size calculations in combination with mathematical modelling can be utilised for choosing the optimal allocation of a given number of samples over various age groups.

Blockade of prostaglandin E2 receptor 4 ameliorates nephrotoxic serum nephritis.

Prostaglandin E2 (PGE2) signaling is known to modulate inflammation and vascular resistance. Receptors of PGE2 [E-type prostanoid receptors (EP)] might be an attractive pharmacological target in immune-mediated diseases such as glomerulonephritis. We hypothesized that selective EP4 antagonism improves nephrotoxic serum nephritis (NTS) by its anti-inflammatory properties. Mice were subjected to NTS and treated with the EP4 antagonist ONO AE3-208 (10 mg·kg body wt-1·day-1] or vehicle starting from disease initiation. In one set of experiments, treatment was started 4 days after NTS induction. Tubular epithelial cells were evaluated in vitro under starving conditions. EP4 antagonist treatment significantly improved the NTS phenotype without affecting blood pressure levels. Remarkably, the improved NTS phenotype was also observed when treatment was started 4 days after NTS induction. EP4 antagonism decreased tubular chemokine (C-X-C motif) ligand ( Cxcl) 1 and Cxcl-5 expression and thereby subsequently reduced interstitial neutrophil infiltration into the kidney. In vitro, tubular epithelial cells increasingly expressed Cxcl-5 mRNA and Cxcl-5 protein when treated with PGE2 or an EP4 agonist under starving conditions, which was blunted by EP4 antagonist treatment. Together, EP4 antagonism improves the NTS phenotype, probably by decreasing mainly Cxcl-5 production in tubular cells, thereby reducing renal neutrophil infiltration.

Mathematical models used to inform study design or surveillance systems in infectious diseases: a systematic review.

BACKGROUND: Mathematical models offer the possibility to investigate the infectious disease dynamics over time and may help in informing design of studies. A systematic review was performed in order to determine to what extent mathematical models have been incorporated into the process of planning studies and hence inform study design for infectious diseases transmitted between humans and/or animals. METHODS: We searched Ovid Medline and two trial registry platforms (Cochrane, WHO) using search terms related to infection, mathematical model, and study design from the earliest dates to October 2016. Eligible publications and registered trials included mathematical models (compartmental, individual-based, or Markov) which were described and used to inform the design of infectious disease studies. We extracted information about the investigated infection, population, model characteristics, and study design. RESULTS: We identified 28 unique publications but no registered trials. Focusing on compartmental and individual-based models we found 12 observational/surveillance studies and 11 clinical trials. Infections studied were equally animal and human infectious diseases for the observational/surveillance studies, while all but one between humans for clinical trials. The mathematical models were used to inform, amongst other things, the required sample size (n = 16), the statistical power (n = 9), the frequency at which samples should be taken (n = 6), and from whom (n = 6). CONCLUSIONS: Despite the fact that mathematical models have been advocated to be used at the planning stage of studies or surveillance systems, they are used scarcely. With only one exception, the publications described theoretical studies, hence, not being utilised in real studies.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. METHODS: The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. RESULTS: Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 µm (interquartile range 116.0-244.5) at baseline to 139.0 µm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. CONCLUSION: The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

Prevalence and incidence of toxoplasmosis: a retrospective analysis of mother-child examinations, Styria, Austria, 1995 to 2012.

In Austria, mandatory screening for the prevention of congenital toxoplasmosis stipulates a serological test for antibodies against Toxoplasma gondii as early as possible in pregnancy. In the case of a seronegative result, subsequent tests at intervals of 8 weeks are requested. We analysed serological data from Styria, an Austrian federal state, to determine the seroprevalence and incidence of Toxoplasma infections. The study included 353,599 tests from 103,316 women during 158,571 pregnancies from 1995 to 2012. The age-adjusted seroprevalence decreased from 43.3% in 1995 to 31.5% in 2012, with a yearly decline of 0.84% (95% confidence interval (CI): 0. 79 -0.88). The intergravid incidence showed an annual decrease of 4.2%. The average yearly incidence of intragravid and intergravid seroconversions was 0.52% (95% CI 0.45-0.61) and 0.72% (95% CI 0.67-0.77), respectively. If the difference between these rates (p < 0.001) can be explained by the effect of primary prevention such as avoiding raw meat and taking hygiene precautions when encountering cats or preparing vegetables, only ca two of seven (28%) infections were avoided by hygiene measures taken by pregnant women. Primary prevention may therefore have its limits.