We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
AbstractSmoking during pregnancy is associated with a multitude of health behaviors and with the psychosocial and socio-economic circumstances of pregnant women. Limited research has so far been ...conducted on the clustering of these characteristics and on their effect on pregnancy outcomes. This study aimed to identify different groups of pregnant women based on their behavioral, psychosocial and socio-economic characteristics and their pregnancy outcomes. In total, 2455 women who were 12 weeks pregnant completed a questionnaire on smoking behavior, health behaviors and psychosocial and socio-economic characteristics. Neonatal and maternal outcomes were extracted from the Dutch perinatal registration. Subgroups were identified with latent class analysis and adverse pregnancy outcomes were compared between subgroups with logistic regression. Women were classified into four latent classes. Two classes represented the healthy higher-educated pregnant women who did not smoke: one group of multigravida women and one of primigravida women, also characterized by less pregnancy-specific knowledge and more pregnancy-related stress. The remaining women were grouped into two less healthy groups. One group frequently quit smoking, reported less healthy eating, less physical activity and comparable stress levels as the healthy higher-educated groups. The last group contained the most smokers, had the highest scores on psychosocial and pregnancy-related stress and the most adverse socio-economic circumstances. This group had an increased risk of adverse maternal outcomes, in particular developing diabetes during pregnancy. A comprehensive and integrated approach is needed to improve outcomes in pregnancies with a combination of adverse health, psychosocial, and socio-economic conditions.
Management of early arthritis is based upon early recognition of individuals at high risk of developing persistent arthritis. Therefore, this study investigates whether the number of risk factors for ...persistent disease or treatment determines the clinical course of early arthritis by comparing the chance at (sustained) DMARD-free remission ((S)DFR) after 2 years follow-up.
Data from the tREACH trial, a stratified single-blinded multicentre strategy trial with a treat-to-target approach were used. We selected all patients with ≥1 swollen joint who did not fulfil 1987 and/or 2010 criteria for RA. The number of risk factors present; autoantibody-positivity, polyarthritis (>4), erosive disease and elevated acute phase reactants, determined risk group stratification. Multivariate logistic regression analyses were performed with (S)DFR as dependent variables and baseline disease activity score (DAS), treatment, symptom duration and number of risk factors present as independent variables.
In total, 130 early arthritis patients were included and respectively 31, 66 and 33 had 0, 1 and ≥2 risk factors present. DFR rates were respectively 74%, 48% and 45% for early arthritis patients with 0, 1 and ≥2 risk factors present. In accordance SDFR rates were 61%, 32% and 30%. In our logistic model (S)DFR was not influenced by the initial treatment strategies when stratified for risk groups.
The chance at (S)DFR in early arthritis diminishes when more risk factors are present, which is irrespective of the given initial treatment. Our data point out to a stratified management approach in early arthritis based on their risk profile, but validation is needed.
ISRCTN registry: ISRCTN26791028 (http://www.isrctn.com/ISRCTN26791028).
We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple-injection therapy ...(MIT) using a continuous subcutaneous glucose sensor.
A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA(1c) 7.8 +/- 0.9%) and 33 patients on MIT (HbA(1c) 8.7 +/- 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA(1c), diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated.
Nocturnal hypoglycaemia < or = 3.9 mmol/l occurred in 33.3% of both the CSII- (8/24) and MIT-treated patients (11/33). Mean (+/- sd; median, interquartile range) duration of hypoglycaemia < or = 3.9 mmol/l was 78 (+/- 76; 57, 23-120) min per night for the CSII- and 98 (+/- 80; 81, 32-158) min per night for the MIT-treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia.
Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.
To determine the efficacy of influenza vaccination in elderly people.
Randomized double-blind placebo-controlled trial.
Fifteen family practices in the Netherlands during influenza season 1991-1992.
...A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.
Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n = 927) or intramuscular placebo containing physiological saline solution (n = 911).
Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).
The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk RR, 0.50; 95% confidence interval CI, 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.
In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift).
Based on data from the Dutch Central Bureau of Statistics, the impact of influenza on mortality in The Netherlands was estimated for a 22.5-year period (1967-1989) in four age groups and three ...entities of disease, using Poisson regression techniques. Our analysis suggests that, on average, more than 2000 people died from influenza in The Netherlands each year, but in only a fraction of these deaths was influenza recognized as the cause of death. For each case of death registered as caused by influenza (registered influenza mortality), 2.6 additional cases of death registered as due to causes other than influenza, nevertheless, were influenza-related (non-registered influenza mortality). Therefore, the overall impact of influenza on mortality is estimated to be greater than registered influenza mortality by a factor of 3.6. Those under 60 years of age accounted for 5% of all non-registered influenza deaths, whereas people aged 60-69, 70-79 years and > 80 years accounted for 12%, 29% and 54% of such deaths, respectively. When extrapolating the figures for the Dutch population of 1989, we could attribute, on average per season-year, 82 deaths per 100,000 people > 60 years, 143 in people > 70 years, and 280 in people > 80 years. Of all non-registered influenza cases of death, 47% were estimated to occur in people with heart disease as a primarily reported cause of death, 23% in those with lung disease, and 30% in those with other diseases. This study stresses the serious effects of influenza, mainly in the elderly (95% of non-registered influenza mortality).
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