HIV incidence and risk factors for acquisition in HIV discordant couples in Masaka, Uganda: an HIV vaccine preparedness study

Objectives

To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.

Methods

HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.

Results

495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1–6]; and 4.3 [2.8–6.4] and 4.4 [2.5–8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18–24 (aRR = 4.1, 95% CI 1.6–10.8) and 25–34 (aRR = 2.7, 95% CI 1.2–5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1–6); and reported genital discharge (aRR = 3.4, 95% CI 1.6–7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2–0.8); always (aRR = 0.1, 95% CI 0.02–0.9)]. In the follow-up risk analysis, young age [18–24 (aRR = 6.2, 95% CI 2.2–17.3) and 25-34 (aRR = 2.3, 95% CI 1.1–5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1–5.5), serological syphilis (aRR 3.2, 95% CI 1.3–7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4–16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.

Conclusions

The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population.     

The efficacy of exercise in reducing depressive symptoms among cancer survivors: a meta-analysis

Introduction

The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms.

Methods

We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis.

Results

We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d ₊ = −0.13 (95% CI: −0.26, −0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (β = −0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (β = −0.26, p = 0.01) and when cancer survivors were between 47–62 yr (β = 0.27, p = 0.01).

Conclusion

Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose-response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47–62 yr, or when exercise sessions were supervised.     

Predictive Accuracy of 29-Comorbidity Index for In-Hospital Deaths in US Adult Hospitalizations with a Diagnosis of Venous Thromboembolism

Background

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant source of mortality and morbidity worldwide. By analyzing data of the 2010 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality (AHRQ), we evaluated the predictive accuracy of the AHRQ’s 29-comorbidity index with in-hospital death among US adult hospitalizations with a diagnosis of VTE.

Methods

We assessed the case-fatality and prevalence of comorbidities among a sample of 153,518 adult hospitalizations with a diagnosis of VTE that comprised 87,605 DVTs and 65,913 PEs (with and without DVT). We estimated adjusted odds ratios and 95% confidence intervals with multivariable logistic regression models by using comorbidities as predictors and status of in-hospital death as an outcome variable. We assessed the c-statistics for the predictive accuracy of the logistic regression models.

Results

In 2010, approximately 41,944 in-hospital deaths (20,212 with DVT and 21,732 with PE) occurred among 770,137 hospitalizations with a diagnosis of VTE. When compared separately to hospitalizations with VTE, DVT, or PE that had no corresponding comorbidities, congestive heart failure, chronic pulmonary disease, coagulopathy, liver disease, lymphoma, fluid and electrolyte disorders, metastatic cancer, other neurological disorders, peripheral vascular disorders, pulmonary circulation disorders, renal failure, solid tumor without metastasis, and weight loss were positively and independently associated with 10%−125% increased likelihoods of in-hospital death. The c-statistic values ranged from 0.776 to 0.802.

Conclusion

The results of this study indicated that comorbidity was associated independently with risk of death among hospitalizations with VTE and among hospitalizations with DVT or PE. The AHRQ 29-comorbidity index provides acceptable to excellent predictive accuracy for in-hospital deaths among adult hospitalizations with VTE and among those with DVT or PE.     

Craniectomy for malignant cerebral infarction: prevalence and outcomes in US hospitals

Object

Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.

Methods

Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.

Results

After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999–2000 to 14.46 in 2007–2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18–59 year old group was found to be 24%(p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.

Conclusions

Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure.     

Association of MDM2 SNP309 Variation with Lung Cancer Risk: Evidence from 7196 Cases and 8456 Controls

Background

Evidence suggests that MDM2 T309G polymorphism may be a risk factor for several cancers. Increasing investigations have been conducted on the association of MDM2 T309G polymorphisms with lung cancer risk and have yielded conflicting results. Previous meta-analyses on this issue have reported inconclusive data. The aim of the present study was to derive a more precise estimation of the relationship.

Methods and Findings

Updated meta-analyses examining the association between MDM2 T309G polymorphism and lung cancer risk were performed. Separate analyses on ethnicity, smoking status, histological types and gender as well as source of controls were also implemented. Eligible studies were identified for the period up to Feb 2012. Lastly, ten publications including eleven case-control studies were selected for analysis. The overall data failed to indicate a significant association between MDM2 T309G polymorphism and lung cancer risk (GG vs TT OR = 1.14; 95%CI = 0.95−1.37; dominant model: OR = 1.05; 95%CI = 0.92−1.19; recessive model: OR = 1.12; 95%CI = 0.99−1.27). In a subgroup analysis by smoking status, increased lung cancer risk was shown among never-smokers (GG vs TT: OR = 1.76; 95%CI = 1.36−2.29; dominant model: OR = 1.48; 95%CI = 1.22−1.81; recessive model: OR = 1.37; 95%CI = 1.11−1.69). In subgroup analysis by gender, elevated risk was presented among women under a recessive model (OR = 1.29; 95%CI = 1.04−1.59). In the subgroup analysis by ethnicity, histological types and source of controls, no marked associations were observed.

Conclusions

Compared to the previous meta-analyses, the results of this study confirmed that MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers. However, the data failed to suggest a marked association between the G allele of MDM2 T309G and lung cancer risk among Asians. More interestingly, subgroup analysis by gender indicated that homozygous GG alleles might raise lung cancer risk among females.     

Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery

Background

Postoperative ventricular dysfunction (VnD) occurs in 9–20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery.

Methods

A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed.

Results

Over 100 SNPs were associated with VnD (P<10⁻⁴), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (P_{additive model} = 2.14×10⁻⁸). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, OR_{additive model} = 2.01, P = 0.0002), 3p14.2 (rs17061085, OR_{additive model} = 1.70, P = 0.0001) and 11q23.2 (rs12279572, OR_{recessive model} = 2.19, P = 0.001).

Conclusions

No SNPs were consistently associated with strong risk (OR_{additive model}>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.     

Association between Bone Mineral Density and Incidence of Breast Cancer

Introduction

Previous studies have suggested an inverse relationship between bone mineral density (BMD) and breast cancer incidence. The primary objective of this study was to assess whether BMD is associated with risk of subsequent breast cancer occurrence in the female population of southern Israel.

Methods

The electronic medical charts of women who underwent BMD at the Soroka Medical Center (SMC) between February 2003 and March 2011 were screened for subsequent breast cancer diagnoses. Women were divided by tertiles of BMD at 3 skeletal sites: lumbar spine (LS, L1–4), total hip (TH) and femoral neck (FN). The incidence of breast cancer was calculated.

Results

Of 15268 women who underwent BMD testing, 86 were subsequently diagnosed with breast cancer. Most women in the study were older than 50 years (94.2% and 92.7%, respectively; p = 0.597). Women who subsequently developed breast cancer had a higher mean body-mass index (BMI) (30.9±5.5 vs. 29.1±5.7 p = 0.004) and the mean BMD Z-score was significantly higher than in those without breast cancer for all 3 skeletal sites (LS: 0.36±1.58 vs. −0.12±1.42, p = 0.002; TH: 0.37±1.08 vs. 0.03±1.02, p = 0.002; FN: 0.04±0.99 vs. −0.18±0.94; p = 0.026). Women in the highest Z-score tertiles at the FN and TH had a higher chance of developing breast cancer compared to the lowest tertile; odds ratio of 2.15, 2.02, respectively (P = 0.004 and 0.01 respectively). No association was found between the BMD Z-score and the stage, histology, grade or survival from breast cancer.

Conclusions

This study provides additional support for an inverse association between BMD and the risk of breast cancer.     

The clinical characteristics and direct medical cost of influenza in hospitalized children: a five-year retrospective study in suzhou, china

Background

There have been few studies on children hospitalized with influenza published from mainland China. We performed a retrospective review of medical charts to describe the epidemiology, clinical features and direct medical cost of laboratory-proven influenza hospitalized children in Suzhou, China.

Methods

Retrospective study on children with documented influenza infection hospitalized at Suzhou Children Hospital during 2005–2009 was conducted using a structured chart review instrument.

Results

A total of 480 children were positive by immuno-fluorescent assay for influenza during 2005–2009. The hospitalizations for influenza occurred in 8–12 months of the year, most commonly in the winter with a second late summer peak (August-September). Influenza A accounted for 86.3%, and of these 286 (59.6%) were male, and 87.2% were <5 years of age. The median length of hospital stay was 7 days. Fever was the most common symptom, occurring in 398 (82.9%) children. There were 394 (82.1%) children with pneumonia and 70.2% of these hospitalized children had radiographic evidence of a pulmonary infiltrate. One hundred and twelve children (23.3%) required oxygen treatments and 13 (2.7%) were transferred to the ICU. Multivariable logistic regression showed that compared with the ≤6 months children, those aged >60 months old had shorter hospital stay (OR = 0.45); children with oxygen treatment tended to have longer hospital stays than those without oxygen treatment (OR = 2.14). The mean cost of each influenza-related hospitalization was US$ 624 (US$ 1323 for children referred to ICU and US$ 617 for those cared for on the wards). High risk children had higher total cost than low-risk patients.

Conclusion

Compared to other countries, in Suzhou, children hospitalized with influenza have longer hospital stay and higher percentage of pneumonia. The direct medical cost is high relative to family income. Effective strategies of influenza immunization of young children in China may be beneficial in addressing this disease burden.     

Evaluation of brain iron content based on magnetic resonance imaging (MRI): comparison among phase value, R2* and magnitude signal intensity

Background and Purpose

Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn''t commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron.

Methods

We measured both phase values and R2* in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2* and brain iron.

Results

We found phase value correlated with R2* in substantia nigra (r = −0.723, p<0.001) and putamen (r = −0.514, p = 0.010), while no correlations in red nucleus (r = −0.236, p = 0.268) and globus pallidus (r = −0.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = −0.593, p = 0.002), substantia nigra (r = −0.521, p = 0.009), globus pallidus (r = −0.750, p<0.001) and putamen (r = −0.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = −0.982, P<0.001).

Conclusions

Our study indicates that phase value may not be used for assessing the iron content in some brain regions especially globus pallidus. The new magnitude method is highly consistent with R2* especially in globus pallidus, and we assume that this approach may be acceptable as an index of iron content in iron-rich brain regions.     

Bradykinin β(2) Receptor -58T/C Gene Polymorphism and Essential Hypertension: A Meta-Analysis

Background

Research has shown that bradykinin β₂ receptor (BDKRB2) −58T/C gene polymorphism is correlated with the risk of essential hypertension (EH), but the results remain inconclusive.

Objective and Methods

The objective of this study was to explore the association between BDKRB2−58T/C gene polymorphism and EH. A meta-analysis of 11 studies with 3882 subjects was conducted. Pooled odds ratios (ORs) for the association between BDKRB2−58T/C gene polymorphism and EH and their corresponding 95% confidence intervals (CIs) were estimated using the random effects model.

Results

The BDKRB2−58T/C gene polymorphism was significantly correlated with EH under an allelic genetic model (OR = 1.24, 95% CI = 1.05–1.46; P = 0.01), a dominant genetic model (OR = 0.65, 95% CI = 0.47–0.90; P = 0.01), a recessive genetic model (OR = 1.146, 95% CI = 1.035–1.269; P = 0.009), a homozygote genetic model (OR = 1.134, 95% CI = 1.048–1.228; P = 0.002), and a heterozygote genetic model (OR = 1.060, 95% CI = 1.009–1.112; P = 0.019).

Conclusions

The BDKRB2−58T/C gene polymorphism is associated with increased EH risk. The results of this study suggest that carriers of the −58C allele are susceptible to EH.     

Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis

Background

A variety of studies have evaluated the associations between polymorphisms in the promoter regions of Matrix metalloproteinases (MMPs) and cancer metastasis. However, the results remain inconclusive. To better understand the roles of MMP polymorphisms in metastasis, we conducted a comprehensive meta-analysis.

Methods

Electronic databases were searched (from January 2000 to June 2011) for any MMP genetic association studies in metastasis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between MMP polymorphisms and metastasis. Statistical analysis was performed with Review Manager 5.0 and STATA11.0.

Results

Thirty-three studies addressing five MMP polymorphisms were analyzed among 10,516 cancer cases (4,059 metastasis-positive cases and 6,457 metastasis-negative cases). For MMP1 (−1607)1G/2G, genotype 2G/2G increased the overall risk of metastasis under the recessive model (OR = 1.44, 95% CI = 1.05–1.98). In subgroup analysis based on cancer type, associations were found in head/neck and breast cancer under the recessive model, and also in breast cancer under the dominant model. For MMP3 (−1171) 5A/6A, the polymorphism decreased the overall risk of metastasis under two genetic models (recessive: OR = 0.80, 95%CI = 0.64–0.99, dominant: OR = 0.72, 95%CI = 0.56–0.93). The polymorphisms of MMP7 (−181) A/G and MMP9 (−1562) C/T increased metastatic risk. However, no association was observed between MMP2 (−1306) C/T and metastasis.

Conclusions

Our investigations demonstrate that polymorphisms in the promoter regions of MMP1, 3, 7 and 9 might be associated with metastasis in some cancers. Further studies with large sample size for MMP2 should be conducted.     

Opposite associations of trunk and leg fat depots with plasma ferritin levels in middle-aged and older Chinese men and women

Background

Few data have been published on the associations of ferritin with trunk and leg fat depots. We aimed to investigate these associations in a Chinese population.

Methodology

Trunk fat mass and leg fat mass were determined in a cross-sectional sample of 1,150 Chinese (479 men and 671 women) aged 50–70 years by dual-energy X-ray absorptiometry scan. Fasting plasma ferritin was measured.

Principal Findings

Plasma ferritin was positively correlated with waist circumference, waist-to-hip ratio, total body fat and trunk fat mass, but inversely correlated with leg fat mass in men (r = 0.16, 0.26, 0.19, 0.22 and −0.12, respectively, all P<0.05) and women (r = 0.16, 0.16, 0.08, 0.17 and −0.12, respectively, all P<0.05). Multivariate regression analysis showed that ferritin levels increased with larger trunk fat mass (β = 0.33 ± 0.08 for men and β = 0.21 ± 0.05 for women, both P<0.001) while decreased with larger leg fat mass (β = −0.12 ± 0.09, P = 0.15 for men; and β = −0.14 ± 0.05, P = 0.005 for women). Moreover, plasma ferritin levels decreased with increasing tertile of leg fat mass among each tertile of trunk fat mass.

Conclusion

This is the first study to report the opposite associations of trunk and leg fat depots with plasma ferritin levels.     

LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer

Purpose

Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1) methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.

Experimental Design

LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1) on age(±5years), sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.

Results

LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84–83.47) compared to 81.67% (IQR: 80.35–83.03) among controls (p = 0.003, Wilcoxon). Compared to the lowest LINE-1 methylation quartile(Q1), the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2) = 1.84(1.20−2.81), OR(Q3) = 1.72(1.11−2.65) and OR(Q4) = 2.06(1.34−3.17), with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001) than former or never smokers (p-interaction = 0.03). To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.

Conclusions

Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis.     

Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies

Background

The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk.

Methods and Findings

Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR _{for 100 g/day increase}  = 1.17, 95% CI  = 1.05−1.31) and processed meat (RR _{for 50 g/day increase}  = 1.18, 95% CI  = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed.

Conclusions

High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.     

Lung function is associated with arterial stiffness in children

Background

In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life.

Objective

To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children.

Methods

Data on brachial blood pressure, lung function (FEV₁, FVC, FEV₁/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates.

Results

In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = −0.17,b = −6.72, partial R² = .02, p = 0.03), FVC (standardised β = −0.29, b = −9.31, partial R² = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R² = 0.02, p = 0.04).

Conclusion

Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.     

Serum cholesterol and nigrostriatal R2* values in Parkinson's disease

Background

The occurrence of Parkinson''s disease (PD) is known to be associated both with increased nigrostriatal iron content and with low serum cholesterol and PD, but there has been no study to determine a potential relationship between these two factors.

Methods

High-resolution MRI (T1-, T2, and multiple echo T2*-weighted imaging) and fasting lipid levels were obtained from 40 patients with PD and 29 healthy controls. Iron content was estimated from mean R2* values (R2* = 1/T2*) calculated for each nigrostriatal structure including substantia nigra, caudate, putamen, and globus pallidus. This was correlated with serum cholesterol levels after controlling for age, gender, and statin use.

Results

In patients with PD, higher serum cholesterol levels were associated with lower iron content in the substantia nigra (R = −0.43, p = 0.011 for total-cholesterol, R = −0.31, p = 0.080 for low-density lipoprotein) and globus pallidus (R = −0.38, p = 0.028 for total-cholesterol, R = −0.27, p = 0.127 for low-density lipoprotein), but only a trend toward significant association of higher total-cholesterol with lower iron content in the striatum (R = −0.34, p = 0.052 for caudate; R = −0.32, p = 0.061 for putamen). After adjusting for clinical measures, the cholesterol-iron relationships held or became even stronger in the substantia nigra and globus pallidus, but weaker in the caudate and putamen. There was no significant association between serum cholesterol levels and nigrostriatal iron content for controls.

Conclusions

The data show that higher serum total-cholesterol concentration is associated with lower iron content in substantia nigra and globus pallidus in Parkinson''s disease patients. Further studies should investigate whether this is mechanistic or epiphenomenological relationship.     

Socioeconomic and Environmental Risk Factors among Rheumatic Heart Disease Patients in Uganda

Background

Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda.

Aims and Objective

The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients.

Methods

This was a case control study in which rheumatic heart disease cases and normal controls aged 5–60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person.

Results

486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/−14.6 years for cases and 35.75+/−12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/−3.0 versus 6.0+/−3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/−3.8 versus 3.3+/−12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05–8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1–1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05–1.42).

Conclusion

The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.     

Functional promoter -31G>C variant in survivin gene is associated with risk and progression of renal cell cancer in a Chinese population

Background

Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (−31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population.

Methods

We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC.

Results

Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [P = 0.006, adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08–1.76]. The polymorphism was associated with risk of developing advanced stage (OR = 2.02, 95%CI = 1.34–3.07) and moderately differentiated (OR = 1.75; 95%CI = 1.20–2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (P_trend = 0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC.

Conclusions

Our results suggest that the functional −31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings.     

Emergent Endovascular vs. Open Surgery Repair for Ruptured Abdominal Aortic Aneurysms: A Meta-Analysis

Objectives

To systematically review studies comparing peri-operative mortality and length of hospital stay in patients with ruptured abdominal aortic aneurysms (rAAAs) who underwent endovascular aneurysm repair (EVAR) to patients who underwent open surgical repair (OSR).

Methods

The Medline, Cochrane, EMBASE, and Google Scholar databases were searched until Apr 30, 2013 using keywords such as abdominal aortic aneurysm, emergent, emergency, rupture, leaking, acute, endovascular, stent, graft, and endoscopic. The primary outcome was peri-operative mortality and the secondary outcome was length of hospital stay.

Results

A total of 18 studies (2 randomized controlled trials, 5 prospective studies, and 11 retrospective studies) with a total of 135,734 rAAA patients were included. rAAA patients who underwent EVAR had significantly lower peri-operative mortality compared to those who underwent OSR (overall OR = 0.62, 95% CI = 0.58 to 0.67, P<0.001). rAAA patients with EVAR also had a significantly shorter mean length of hospital stay compared to those with OSR (difference in mean length of stay ranged from −2.00 to −19.10 days, with the overall estimate being −5.25 days (95% CI = −9.23 to −1.26, P = 0.010). There was no publication bias and sensitivity analysis showed good reliability.

Conclusions

EVAR confers significant benefits in terms of peri-operative mortality and length of hospital stay. There is a need for more randomized controlled trials to compare outcomes of EVAR and OSR for rAAA.     

Vascular Endothelial Growth Factor +936C/T, –634G/C, –2578C/A,and –1154G/A Polymorphisms with Risk of Preeclampsia: A Meta-Analysis

Background

Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual''s susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk.

Methods

A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08–2.12) or −634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03–1.50) was associated with the risk of PE, whereas there was no association between −2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82–1.16) or −1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94–1.78) polymorphism and PE risk in our study.

Conclusion

Our meta-analysis suggested that VEGF −2578C/A or −1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or −634G/C polymorphism and risk of PE.