Independent and combined effects of physical activity and body mass index on the development of Type 2 Diabetes - a meta-analysis of 9 prospective cohort studies.

BACKGROUND: The aim of this harmonized meta-analysis was to examine the independent and combined effects of physical activity and BMI on the incidence of type 2 diabetes. METHODS: Our systematic literature review in 2011 identified 127 potentially relevant prospective studies of which 9 fulfilled the inclusion criteria (total N = 117,878, 56.2 % female, mean age = 50.0 years, range = 25-65 years). Measures of baseline physical activity (low, intermediate, high), BMI-category [BMI < 18.4 (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), 30+ (obese)] and incident type 2 diabetes were harmonized across studies. The associations between physical activity, BMI and incident type 2 diabetes were analyzed using Cox regression with a standardized analysis protocol including adjustments for age, gender, educational level, and smoking. Hazard ratios from individual studies were combined in a random-effects meta-analysis. RESULTS: Mean follow-up time was 9.1 years. A total of 11,237 incident type 2 diabetes cases were recorded. In mutually adjusted models, being overweight or obese (compared with normal weight) and having low physical activity (compared with high physical activity) were associated with an increased risk of incident type 2 diabetes (hazard ratios 2.33, 95 % CI 1.95-2.78; 6.10, 95 % CI: 4.63-8.04, and 1.23, 95 % CI: 1.09-1.39, respectively). Individuals who were both obese and had low physical activity had 7.4-fold (95 % CI 3.47-15.89) increased risk of type 2 diabetes compared with normal weight, high physically active participants. CONCLUSIONS: This harmonized meta-analysis shows the importance of maintaining a healthy weight and being physically active in diabetes prevention.

Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.

Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2, IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease susceptibility to a different extent in preterm children, born with underdeveloped lungs, than in term children.

Syndromic surveillance for local outbreaks of lower-respiratory infections: would it work?

BACKGROUND: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. METHODS AND FINDINGS: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999-2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999-2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999-2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). CONCLUSIONS: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.

Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in infants. Only a proportion of children infected with RSV require hospitalization. Because known risk factors for severe disease, such as premature birth, cannot fully explain differences in disease severity, genetic factors have been implicated. METHODS: To study the complexity of RSV susceptibility and to identify the genes and biological pathways involved in its development, we performed a genetic association study involving 470 children hospitalized for RSV bronchiolitis, their parents, and 1008 random, population controls. We analyzed 384 single-nucleotide polymorphisms (SNPs) in 220 candidate genes involved in airway mucosal responses, innate immunity, chemotaxis, adaptive immunity, and allergic asthma. RESULTS: SNPs in the innate immune genes VDR (rs10735810; P=.0017), JUN (rs11688; P=.0093), IFNA5 (rs10757212; P=.0093), and NOS2 (rs1060826; P=.0031) demonstrated the strongest association with bronchiolitis. Apart from association at the allele level, these 4 SNPs also demonstrated association at the genotype level (P=.0056, P=.0285, P=.0372, and P=.0117 for the SNPs in VDR, JUN, IFNA5, and NOS2, respectively). The role of innate immunity as a process was reinforced by association of the whole group of innate immune SNPs when the global test for groups of genes was applied (P=.046). CONCLUSION: SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.

Poliovirus-specific memory immunity in seronegative elderly people does not protect against virus excretion.

BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and may have escaped natural infection because of reduced poliovirus circulation. We examined whether people with low or undetectable antibody levels are susceptible to infection and whether memory immunity provides protection against virus excretion. METHODS: A total of 429 elderly participants were challenged with monovalent oral poliovirus vaccine (type 1 or 3) and followed for 8 weeks. Immune responses and virus excretion were compared for 4 groups, defined on the basis of seronegativity for poliovirus type 1 or 3, natural immunity, and IPV-induced immunity. RESULTS: On the basis of the rapidity of the antibody response and the absence of immunoglobulin M, we saw clear evidence of memory immune responses in 33% of the participants without detectable antibodies against poliovirus type 1 and in 5% of the participants without detectable antibodies against poliovirus type 3. Fecal virus-excretion patterns were not significantly different for seronegative participants, regardless of whether they showed evidence of memory immunity. CONCLUSIONS: Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.