Genetic variants of TSLP and asthma in an admixed urban population

Background

Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.

Objectives

To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population.

Methodology and Main Results

Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09–2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04–3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93–1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10–2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07–1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08–1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94–1.17, p = 0.33).

Conclusions

Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.     

Determinants of Allergic Rhinitis in Young Children with Asthma

Background

In the preschool period, allergic rhinitis (AR) is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma.

Methods

We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema) were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens) and environmental parameters were also collected.

Results

Forty one of the children (18.1%) had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002); food allergy (OR = 4.31; p = 0.026); mold exposure (OR = 3.81 p<0.01) and parental history of AR (OR = 1.42; p = 0.046). Due to the strong link between food allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR.

Conclusions & Clinical Relevance

These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.     

Impact of Loading Phase, Initial Response and CFH Genotype on the Long-Term Outcome of Treatment for Neovascular Age-Related Macular Degeneration

Objective

Factors influencing the outcome of anti-VEGF treatment in neovascular AMD are still investigated. We analyzed the impact of a loading phase, the significance of an initial response for the long-term and the effect of the CFH polymorphism (p.His402Tyr) on treatment outcome.

Methods

Patients treated with ranibizumab for neovascular AMD were analyzed over a period of 24 months by assessing effects of loading phase, initial response and genotype of CFH rs1061170 (c.1204C>T, p.His402Tyr).

Results

204 eyes were included. A change of +5.0 [−1;+11] letters and +1.5 [−5.5;+9.5] was observed with a median of 4 [3]; [7] and 10 [7]; [14] ranibizumab injections during 12 and 24 months, respectively. Loading phase was no significant predictor for treatment as VA outcome in eyes with and without loading phase was similar (p = 0.846 and p = 0.729) at 12 and 24 months. In contrast, initial response was a significant predictor for improving vision of 5 or more letters at 12 (p = 0.001; OR = 6.75) and 24 months (p = 0.01; OR = 4.66). Furthermore, the CT genotype at CFH rs1061170 was identified as a significant predictor for a favorable VA outcome at 12 and 24 months (OR = 6.75, p = 0.001 and OR = 4.66, p = 0.01).

Conclusions

Our data suggest that clinical decisions regarding treatment may be guided by observing patients’ initial response as well as their genotype of SNP rs1061170, while the criterion of loading phase may not bear the customary value.     

Interruption and defaulting of multidrug therapy against leprosy: population-based study in Brazil's Savannah Region

Background

Low adherence to multidrug therapy against leprosy (MDT) is still an important obstacle of disease control, and may lead to remaining sources of infection, incomplete cure, irreversible complications, and multidrug resistance.

Methodology/Principal Finding

We performed a population-based study in 78 municipalities in Tocantins State, central Brazil, and applied structured questionnaires on leprosy-affected individuals. We used two outcomes for assessment of risk factors: defaulting (not presenting to health care center for supervised treatment for >12 months); and interruption of MDT. In total, 28/936 (3.0%) patients defaulted, and 147/806 (18.2%) interrupted MDT. Defaulting was significantly associated with: low number of rooms per household (OR = 3.43; 0.98–9.69; p = 0.03); moving to another residence after diagnosis (OR = 2.90; 0.95–5.28; p = 0.04); and low family income (OR = 2.42; 1.02–5.63: p = 0.04). Interruption of treatment was associated with: low number of rooms per household (OR = 1.95; 0.98–3.70; p = 0.04); difficulty in swallowing MDT drugs (OR = 1.66; 1.03–2.63; p = 0.02); temporal non-availability of MDT at the health center (OR = 1.67; 1.11–2.46; p = 0.01); and moving to another residence (OR = 1.58; 95% confidence interval: 1.03–2.40; p = 0.03). Logistic regression identified temporal non-availability of MDT as an independent risk factor for treatment interruption (adjusted OR = 1.56; 1.05–2.33; p = 0.03), and residence size as a protective factor (adjusted OR = 0.89 per additional number of rooms; 0.80–0.99; p = 0.03). Residence size was also independently associated with defaulting (adjusted OR = 0.67; 0.52–0.88; p = 0.003).

Conclusions

Defaulting and interruption of MDT are associated with some poverty-related variables such as family income, household size, and migration. Intermittent problems of drug supply need to be resolved, mainly on the municipality level. MDT producers should consider oral drug formulations that may be more easily accepted by patients. Thus, an integrated approach is needed for further improving control, focusing on vulnerable population groups and the local health system.     

Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque

Objective

Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque.

Methods

In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high-definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque.

Results

Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23–2.37, Bonferroni-corrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18–1.45, Bonferroni-corrected p = 1.4×10⁻⁵), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32–0.74, Bonferroni-corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52–0.78, Bonferroni-corrected p = 4.9×10⁻⁴). Some interactions with a nominal p≤0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes.

Conclusion

We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations.     

A geographically-restricted but prevalent Mycobacterium tuberculosis strain identified in the West Midlands Region of the UK between 1995 and 2008

Background

We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.

Methodology/Principal Findings

Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the “Mercian” strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95%CI = 4.56–17.87, p<0.01), Black Caribbean (OR = 5.68, 95%CI = 2.96–10.91, p<0.01) resident in Wolverhampton (OR = 9.29, 95%CI = 5.69–15.19, p<0.01) and negatively associated with age >65 years old (OR = 0.25, 95%CI = 0.09–0.67, p<0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95%CI = 2.00–46.78, p<0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95%CI = 1.45–27.02, p = .01) were observed as social risk factors for infection.

Conclusions/Significance

The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain.     

Adoptive immunotherapy in postoperative hepatocellular carcinoma: a systemic review

Purpose

The effectiveness of immunotherapy for postoperative hepatocellular carcinoma patients is still controversial. To address this issue, we did a systemic review of the literatures and analyzed the data with emphasis on the recurrence and survival.

Methods

We searched six randomized controlled trials that included adoptive immunotherapy in the postoperative management of hepatocellular carcinoma and compared with non-immunotherapy postoperation. A meta-analysis was carried out to examine one- and 3-year recurrence and survival.

Results

The overall analysis revealed significantly reduced risk of 1-year recurrence in patients receiving adoptive immunotherapy (OR = 0.35; 95% CI, 0.17 to 0.71; p = 0.003), in that the risk of 3-year recurrence with a pooled OR estimated at 0.31 (95% CI 0.16 to 0.61; p = 0.001). However, no statistically significant difference was observed for 3-year survival between groups with adoptive immunotherapy and without adjuvant treatment (OR = 0.91; 95% CI, 0.45 to 1.84; P = 0.792).

Conclusions

Adjuvant immunotherapy with cytokine induced killer cells or lymphokine activated killer cells may reduce recurrence in postoperative hepatocellular carcinoma patients, but may not improve survival.     

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background

Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS).

Objective

To evaluate the possible association between CCSVI and MS, using a population-based control design.

Methods

A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled.

Results

CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4).

Conclusions

A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.     

Association of OPA1 Polymorphisms with NTG and HTG: A Meta-Analysis

Background

Genetic polymorphisms of the Optic atrophy 1 gene have been implicated in altering the risk of primary open angle glaucoma (POAG), especially the susceptibility to normal tension glaucoma (NTG), but the results remain controversial.

Methods

Multiple electronic databases (up to January 20, 2012) were searched independently by two investigators. A meta-analysis was performed on the association between Optic atrophy 1 polymorphisms (rs 166850 and rs 10451941) and normal tension glaucoma (NTG)/high tension glaucoma (HTG). Summary odds ratios (ORs) and 95% confidence intervals (CI) were estimated.

Results

Seven studies of 713 cases and 964 controls for NTG and five studies of 1200 cases and 971 controls for HTG on IVS8+4C>T (rs 166850) and IVS8+32T>C (rs10451941) were identified. There were significant associations between the OPA1 rs10451941polymorphism and NTG susceptibility for all genetic models(C vs. T OR = 1.26, 95% CI 1.09–1.47, p = 0.002; CC vs. TT: OR = 1.52, 95% CI 1.04–2.20, p = 0.029; CC vs. CT+TT: OR = 1.64, 95% CI 1.16–2.33, p = 0.005; CC+CT vs. TT: OR = 1.21, 95% CI 1.02–1.44, p = 0.032). However, no evidence of associations was detected between the OPA1 IVS8+32C>T polymorphism and POAG susceptibility to HTG. Similarly, clear associations between the rs 166850 variant and NTG were observed in allelic and dominant models (T vs. C OR = 1.52, 95% CI 1.16–1.99, p = 0.002; TT+TC vs. CC OR = 1.50, 95% CI 1.13–2.01, p = 0.006) but not to HTG. In subgroup analyses by ethnicity, we detected an association between both OPA1 polymorphisms and risk for NTG in Caucasians but not in Asians. By contrast, no significant findings were noted between OPA1 variants for HTG, either in Caucasians or in Asians.

Conclusions

Both the IVS8+4C>T and IVS8+32T>C variants may affect individual susceptibility to NTG. Moreover, stratified analyses for NTG detecting the effects of both OPA1 polymorphisms seemed to vary with ethnicity. Further investigations are needed to validate the association.     

Prostate cancer postoperative nomogram scores and obesity

Purpose

Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms'' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.

Methods

We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).

Results

In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28–0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01–1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11–1.90).

Conclusion

Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.     

Increased risk of temporomandibular joint closed lock: a case-control study of ANKH polymorphisms

Objectives

This study aimed to carry out a histological examination of the temporomandibular joint (TMJ) in ank mutant mice and to identify polymorphisms of the human ANKH gene in order to establish the relationship between the type of temporomandibular disorders (TMD) and ANKH polymorphisms.

Materials and Methods

Specimens from the TMJ of ank mutant and wild-type mice were inspected with a haematoxylin and eosin staining method. A sample of 55 TMD patients were selected. Each was examined with standard clinical procedures and genotyping techniques.

Results

The major histological finding in ank mutant mice was joint space narrowing. Within TMD patients, closed lock was more prevalent among ANKH-OR homozygotes (p = 0.011, OR = 7.7, 95% CI 1.6–36.5) and the elder (p = 0.005, OR = 2.4, 95% CI 1.3–4.3).

Conclusions

Fibrous ankylosis was identified in the TMJ of ank mutant mice. In the human sample, ANKH-OR polymorphism was found to be a genetic marker associated with TMJ closed lock. Future investigations correlating genetic polymorphism to TMD are indicated.     

Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis

Background

Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in the epidermal growth factor (EGF) gene. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. Therefore, we performed a meta-analysis of several studies covering a large population to address this controversy.

Methods

PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between EGF 61*A/G polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

Eight studies were chosen in this meta-analysis, involving 1,304 HCC cases (1135 Chinese, 44 Caucasian and 125 mixed) and 2,613 controls (1638 Chinese, 77 Caucasian and 898 mixed). The EGF 61*G allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.29, 95% CI = 1.16–1.44, p<0.001), homozygote comparison (OR = 1.79, 95% CI = 1.39–2.29, p<0.001) and a recessive genetic model (OR = 1.34, 95% CI = 1.16–1.54, p<0.001), while patients carrying the EGF 61*A/A genotype had significantly lower risk of HCC than those with the G/A or G/G genotype (A/A vs. G/A+G/G, OR = 0.66, 95% CI = 0.53–0.83, p<0.001).

Conclusion

The 61*G polymorphism in EGF is a risk factor for hepatocarcinogenesis while the EGF 61*A allele is a protective factor. Further large and well-designed studies are needed to confirm this conclusion.     

Smoking among young rural to urban migrant women in China: a cross-sectional survey

Background

Rural-to-urban migrant women may be vulnerable to smoking initiation as they are newly exposed to risk factors in the urban environment. We sought to identify correlates of smoking among rural-to-urban migrant women in China.

Methods/Principal Findings

A cross-sectional survey of rural-to-urban migrant women working in restaurants and hotels (RHW) and those working as commercial sex workers (CSW) was conducted in ten provincial capital cities in China. Multiple logistic regression was conducted to identify correlates of smoking. We enrolled 2229 rural-to-urban migrant women (1697 RHWs aged 18–24 years and 532 CSWs aged 18–30 years). Of these, 18.4% RHWs and 58.3% CSWs reported ever tried smoking and 3.2% RHWs and 41.9% CSWs reported current smoking. Participants who first tried smoking after moving to the city were more likely to be current smokers compared to participants who first tried smoking before moving to the city (25.3% vs. 13.8% among RHWs, p = 0.02; 83.6% vs. 58.6% among CSWs, p = <0.01). Adjusting for other factors, “tried female cigarette brands” had the strongest association with current smoking (OR 5.69, 95%CI 3.44 to 9.41) among participants who had ever tried smoking.

Conclusions/Significance

Exposure to female cigarette brands may increase the susceptibility to smoking among rural-to-urban migrant women. Smoke-free policies and increased taxes may be effective in preventing rural-to-urban migrant women from smoking initiation.     

A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers

Background and Aims

Chronic infection with the hepatitis B virus (HBV) is a major health issue worldwide. Recently, single nucleotide polymorphisms (SNPs) within the human leukocyte antigen (HLA)-DP locus were identified to be associated with HBV infection in Asian populations. Most significant associations were observed for the A alleles of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535, which conferred a decreased risk for HBV infection. We assessed the implications of these variants for HBV infection in Caucasians.

Methods

Two HLA-DP gene variants (rs3077 and rs9277535) were analyzed for associations with persistent HBV infection and with different clinical outcomes, i.e., inactive HBsAg carrier status versus progressive chronic HBV (CHB) infection in Caucasian patients (n = 201) and HBsAg negative controls (n = 235).

Results

The HLA-DPA1 rs3077 C allele was significantly associated with HBV infection (odds ratio, OR = 5.1, 95% confidence interval, CI: 1.9–13.7; p = 0.00093). However, no significant association was seen for rs3077 with progressive CHB infection versus inactive HBsAg carrier status (OR = 2.7, 95% CI: 0.6–11.1; p = 0.31). In contrast, HLA-DPB1 rs9277535 was not associated with HBV infection in Caucasians (OR = 0.8, 95% CI: 0.4–1.9; p = 1).

Conclusions

A highly significant association of HLA-DPA1 rs3077 with HBV infection was observed in Caucasians. However, as a differentiation between different clinical courses of HBV infection was not possible, knowledge of the HLA-DPA1 genotype cannot be translated into personalized anti-HBV therapy approaches.     

Associations between APOE variants and metabolic traits and the impact of psychological stress

Objective

In a previous study, we observed that associations between APOE rs439401 and metabolic traits were moderated by chronic stress. Thus, in a population of stressed and non-stressed Danish men, we examined whether associations between APOE rs439401 and a panel of metabolic quantitative traits, all metabolic traits which may lead to T2D and CVD were moderated by psychological stress.

Methods

Obese young men (n = 475, BMI≥31.0 kg/m²) and a randomly selected control group (n = 709) identified from a population of 141,800 men were re-examined in two surveys (S-46: mean age 46, S-49: mean age 49 years) where anthropometric and biochemical measures were available. Psychological stress factors were assessed by a self-administered 7-item questionnaire. Each item had the possible response categories “yes” and “no” and assessed familial problems and conflicts. Summing positive responses constituted a stress item score, which was then dichotomized into stressed and non-stressed. Logistic regression analysis, applying a recessive genetic model, was used to assess odds ratios (OR) of the associations between APOE rs439401 genotypes and adverse levels of metabolic traits.

Results

The APOE rs439401 TT-genotype associated positively with BMI (OR = 1.09 [1.01; 1.17]), waist circumference (OR = 1.09 [1.02; 1.17]) in stressed men at S-46. Positive associations were observed for fasting plasma glucose (OR = 1.42 [1.07; 1.87]), serum triglycerides (OR = 1.41 [1.05; 1.91]) and with fasting plasma insulin (OR = 1.48 [1.05; 2.08]) in stressed men at S-49. Rs439401 TT-genotype also associated positively with surrogate measures of insulin resistance (HOMA-IR; OR = 1.21 [1.03; 1.41]) and inversely with insulin sensitivity (Stumvoll index; OR = 0.90 [0.82; 0.99], BIGTT-S_I; OR = 0.60 [0.43; 0.85]) in stressed men. No significant associations were observed in non-stressed men, albeit the estimates showed similar but weaker trends as in stressed men.

Conclusion

The present results suggest that the APOE rs439401 TT-genotype is associated with an adverse metabolic profile in a population of psychologically stressed Danish men.     

The Comparative Clinical Course of Pregnant and Non-Pregnant Women Hospitalised with Influenza A(H1N1)pdm09 Infection

Introduction

The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.

Methods

A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical ''hubs'' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15–44 years, using univariate and multivariable techniques.

Results

Of the 395 women aged 15–44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30–0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20–0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46–1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.

Conclusions

Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups.     

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru

Background

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.

Methodology and Results

A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.

Conclusions

Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.     

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective

To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years.

Design

Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s.

Exposure definition

Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life.

Outcome definition

Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age.

Data synthesis

Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.

Results

We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I² = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I² = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I² = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.

Conclusions

Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.