Chronic Obstructive Pulmonary Disease and Altered Risk of Lung Cancer in a Population-Based Case-Control Study

Background

Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking.

Methodology/Principal Findings

The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5–2.5), emphysema (OR = 1.9, 95% CI = 1.4–2.8), or COPD (OR = 2.5, 95% CI = 2.0–3.1). Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30–0.78).

Conclusions/Significance

These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis.     

Assessment of Risk Factors for Delayed Colonic Post-Polypectomy Hemorrhage: A Study of 15553 Polypectomies from 2005 to 2013

Background and Aim

Delayed colonic postpolypectomy bleeding is the commonest serious complication after polypectomy. This study aimed to utilize massive sampling data of polypectomy to analyze risk factors for delayed postpolypectomy bleeding.

Patients and Methods

The endoscopic data of 5600 patients with 15553 polyps removed (2005 to 2013) were analyzed retrospectively through univariate analysis and multiple logistic regression analysis to evaluate the risk factors for delayed bleeding.

Results

Delayed postpolypectomy bleeding occurred in 99 polyps (0.6%). The rates of bleeding for different polypectomy methods including hot biopsy forcep, biopsy forcep, Argon Plasma Coagulation (APC), Endoscopy piecemeal mucosal resection (EPMR), Endoscopic Mucosal Resection (EMR), and snare polypectomy were 0.1%, 0.0%, 0.0%, 6.9%, 0.9% and 1.0%, respectively. The risk factors for delayed bleeding were the size of polyps over 10 mm (odds ratio [OR] = 4.6, 95% CI, 2.9–7.2), pathology of colonic polyps (inflammatory/hyperplastic, OR = 1; adenomatous, OR = 1.4, 95% CI, 0.7–2.6; serrated, OR = 1.5, 95% CI, 0.2–11.9; juvenile, OR = 4.3, 95% CI, 1.8–11.0; Peutz-Jegher, OR = 3.3, 95% CI, 1.0–10.7), and immediate postpolypectomy bleeding (OR = 2.9, 95% CI, 1.4–5.9). In addition, although polypectomy method was not a risk factor, compared with hot biopsy forcep, snare polypectomy, EMR, and EPMR had increased risks of delayed bleeding, with ORs of 3.2 (0.4–23.3), 2.8 (0.4–21.7) and 5.1 (0.5–47.7), respectively.

Conclusion

Polyp size over 10 mm, pathology of colonic polyps (especially juvenile, Peutz-Jegher), and immediate postpolypectomy bleeding were significant risk factors for delayed postpolypectomy bleeding.     

Colorectal Advanced Neoplasms Occur through Dual Carcinogenesis Pathways in Individuals with Coexisting Serrated Polyps

Background

Individuals with serrated polyps (SP) are at higher risk for synchronous colorectal advanced neoplasms (AN) and cancers. However, it remains unclear whether there is a unique involvement of the serrated pathway and/or the classical adenoma-carcinoma sequence in this setting.

Methods

Colorectal ANs, which include tubular adenomas ≥10 mm, adenomas with villous histology, high-grade intraepithelial neoplasms, and cancers, were collected retrospectively. The groups included ANs with (AN+SP) or without (AN-only) coexisting SPs. Clinicopathological findings were compared between groups. BRAF and KRAS mutations in ANs and SPs, and methylation levels at long interspersed element-1 (LINE-1) in adjacent mucosa were determined by pyrosequencing.

Results

Seventy-five ANs from 40 patients in the AN+SP group, and 179 ANs from 119 patients in the AN-only group were analyzed. There were no significant differences in clinicopathological findings between the two groups, except that intraepithelial neoplasia in the AN+SP group was more likely to be located in the right colon (P = 0.018). BRAF mutations were significantly more frequent in the AN+SP group (P = 0.003), while KRAS mutations showed no significant differences between groups (P = 0.142). The majority of high-grade intraepithelial neoplasms in both groups showed a contiguous component of conventional adenoma. Individuals with large and right-sided SPs had significantly more conventional adenomas compared to those without such SPs (P = 0.027 and P = 0.031, respectively). Adjacent mucosa from individuals with multiple and large SPs showed significantly lower methylation levels at LINE-1 compared to individuals without such associated SPs (P = 0.049 and P = 0.015, respectively).

Conclusion

Our data suggest that both the adenoma-carcinoma sequence and the serrated pathway are operational in individuals with coexisting ANs and SPs. The reduced methylation levels at LINE-1 in the background mucosa suggest the possibility of an underlying ‘field defect’.     

Association between Chronic Obstructive Pulmonary Disease and Lung Cancer: A Case-Control Study in Southern Chinese and a Meta-Analysis

Background

Lung cancer and chronic obstructive pulmonary disease (COPD) share a common risk factor in cigarette smoking and a large portion of patients with lung cancer suffer from COPD synchronously. We therefore hypothesized that COPD is an independent risk factor for lung cancer. Our aim was to investigate the intrinsic linkage of COPD (or emphysema, chronic bronchitis and asthma) and lung cancer.

Methods

The present hospital-based case-control study included 1,069 patients with newly diagnosed lung cancer and 1,132 age frequency matched cancer-free controls. The odds ratios (ORs) for the associations between each previous pulmonary disease and lung cancer were estimated with logistic regression models, adjusting for age, sex, family history of cancer, BMI and pack year smoking. In meta-analysis, the pooled effects of previous pulmonary diseases were analyzed with random effects models; and stratification analyses were conducted on smoking status and ethnicity.

Results

In the case-control study, previous COPD was associated with the odds for increased risk of lung cancer (OR = 1.29, 95% confidence interval [CI] = 1.00∼1.68); so were emphysema (OR = 1.55, 95%CI = 1.03∼2.32) and chronic bronchitis (OR = 1.22, 95%CI = 0.99∼1.67); while asthma was associated with odds for decreased risk of lung cancer (OR = 0.29, 95%CI = 0.16∼0.53). These associations were more pronounced in smokers (P<.05 for all strata), but not in non-smokers. In meta-analysis, 35 studies (22,010 cases and 44,438 controls) were identified. COPD was significantly associated with the odds for increased risk of lung cancer (pooled OR = 2.76; 95% CI = 1.85–4.11), so were emphysema (OR = 3.02; 95% CI = 2.41–3.79) and chronic bronchitis (OR = 1.88; 95% CI = 1.49–2.36); and these associations were more pronounced in smokers than in non-smokers (P<.001 respectively). No significant association was observed for asthma.

Conclusion

Previous COPD could increase the risk of lung cancer, especially in smokers.     

Detection of Colorectal Serrated Polyps by Stool DNA Testing: Comparison with Fecal Immunochemical Testing for Occult Blood (FIT)

Objectives

Precursors to 1/3 of colorectal cancer (CRC), serrated polyps have been under-detected by screening due to their inconspicuous, non-hemorrhagic, and proximal nature. A new multi-target stool DNA test (multi-target sDNA) shows high sensitivity for both CRC and advanced adenomas. Screen detection of serrated polyps by this approach requires further validation. We sought to assess and compare noninvasive detection of sessile serrated polyps (SSP) ≥1 cm by sDNA and an occult blood fecal immunochemical test (FIT).

Methods

In a blinded prospective study, a single stool sample used for both tests was collected from 456 asymptomatic adults prior to screening or surveillance colonoscopy (criterion standard). All 29 patients with SSP≥1 cm were included as cases and all 232 with no neoplastic findings as controls. Buffered stool samples were processed and frozen on receipt; Exact Sciences performed sDNA in batches using optimized analytical methods. The sDNA multi-marker panel targets methylated BMP3 (mBMP3) and NDRG4, mutant KRAS, β-actin, and hemoglobin. FIT (Polymedco OC-FIT Check) was performed in separate lab ≤2 days post defecation and evaluated at cutoffs of 50 (FIT-50) and 100 ng/ml (FIT-100).

Results

Median ages: cases 61 (range 57–77), controls 62 (52–70), p = NS. Women comprised 59% and 51%, p = NS, respectively. SSP median size was 1.2 cm (1–3 cm), 93% were proximal, and 64% had synchronous diminutive polyps. Among multi-target sDNA markers, mBMP3 proved highly discriminant for detection of SSP≥1 cm (AUC = 0.87, p<0.00001); other DNA markers provided no incremental sensitivity. Hemoglobin alone showed no discrimination (AUC = 0.50, p = NS). At matched specificities, detection of SSP≥1 cm by stool mBMP3 was significantly greater than by FIT-50 (66% vs 10%, p = 0.0003) or FIT-100 (63% vs 0%, p<0.0001).

Conclusions

In a screening and surveillance setting, SSP≥1 cm can be detected noninvasively by stool assay of exfoliated DNA markers, especially mBMP3. FIT appears to have no value in SSP detection.     

Injection Drug Use Is a Risk Factor for HCV Infection in Urban Egypt

Objective

To identify current risk factors for hepatitis C virus (HCV) transmission in Greater Cairo.

Design and Setting

A 1∶1 matched case-control study was conducted comparing incident acute symptomatic hepatitis C patients in two “fever” hospitals of Greater Cairo with two control groups: household members of the cases and acute hepatitis A patients diagnosed at the same hospitals. Controls were matched on the same age and sex to cases and were all anti-HCV antibody negative. Iatrogenic, community and household exposures to HCV in the one to six months before symptoms onset for cases, and date of interview for controls, were exhaustively assessed.

Results

From 2002 to 2007, 94 definite acute symptomatic HCV cases and 188 controls were enrolled in the study. In multivariate analysis, intravenous injections (OR = 5.0; 95% CI = 1.2–20.2), medical stitches (OR = 4.2; 95% CI = 1.6–11.3), injection drug use (IDU) (OR = 7.9; 95% CI = 1.4–43.5), recent marriage (OR = 3.3; 95% CI = 1.1–9.9) and illiteracy (OR = 3.9; 95% CI = 1.8–8.5) were independently associated with an increased HCV risk.

Conclusion

In urban Cairo, invasive health care procedures remain a source of HCV transmission and IDU is an emerging risk factor. Strict application of standard precautions during health care is a priority. Implementation of comprehensive infection prevention programs for IDU should be considered.     

The Knowledge of Colorectal Cancer Symptoms and Risk Factors among 10,078 Screening Participants: Are High Risk Individuals More Knowledgeable?

Objectives

We tested the a priori hypothesis that self-perceived and real presences of risks for colorectal cancer (CRC) are associated with better knowledge of the symptoms and risk factors for CRC, respectively.

Methods

One territory-wide invitation for free CRC screening between 2008 to 2012 recruited asymptomatic screening participants aged 50–70 years in Hong Kong. They completed survey items on self-perceived and real presences of risks for CRC (advanced age, male gender, positive family history and smoking) as predictors, and knowledge of CRC symptoms and risk factors as outcome measures, respectively. Their associations were evaluated by binary logistic regression analyses.

Results

From 10,078 eligible participants (average age 59 years), the mean knowledge scores for symptoms and risk factors were 3.23 and 4.06, respectively (both score range 0–9). Male gender (adjusted odds ratio [AOR] = 1.34, 95% C.I. 1.20–1.50, p<0.01), self-perception as not having any risks for CRC (AOR = 1.12, 95% C.I. 1.01–1.24, p = 0.033) or uncertainty about having risks (AOR = 1.94, 95% C.I. 1.55–2.43, p<0.001), smoking (AOR 1.38, 95% C.I. 1.11–1.72, p = 0.004), and the absence of family history (AOR 0.61 to 0.78 for those with positive family history, p<0.001) were associated with poorer knowledge scores (≤4) of CRC symptoms. These factors remained significant for knowledge of risk factors.

Conclusions

Male and smokers were more likely to have poorer knowledge but family history of CRC was associated with better knowledge. Since screening of these higher risk individuals could lead to greater yield of colorectal neoplasm, educational interventions targeted to male smokers were recommended.     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Development and Validation of a Bedside Score to Predict Early Death in Cancer of Unknown Primary Patients

Background

We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients.

Methods

Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4).

Results

The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5×the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0–1], 2 and [3]–[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values.

Conclusions

We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy.     

Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends

Background

Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized.

Methods

We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors.

Results

We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade ≥3 vs0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade ≥3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (−3.4%, 28.5%)) and a downward trend in deaths (APC = −18.1% (−22.5%, −13.4%)).

Conclusions

Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.     

CYP2E1 RsaI/PstI Polymorphism and Gastric Cancer Susceptibility: Meta-Analyses Based on 24 Case-Control Studies

Background

Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a possible risk factor for several cancers. Published studies on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are controversial. This study aimed to determine this relationship accurately.

Methods

Meta-analyses that assessed the association of CYP2E1 RsaI/PstI variations with gastric cancer were conducted. Subgroup analyses on ethnicity, smoking status, alcohol consumption, and source of controls were also performed. Eligible studies up to Mar 2012 were identified.

Results

After rigorous searching and screening, 24 case-control studies comprising 3022 cases and 4635 controls were selected for analysis. The overall data failed to indicate the significant associations of CYP2E1 RsaI/PstI polymorphisms with the gastric cancer risk [c2 vs. c1: odds ratio (OR) = 1.06; 95% confidence interval (CI) = 0.88–1.28; c2c2 vs. c1c1: OR = 1.23; 95% CI = 0.78–1.92; c2c2+c1c2 vs. c1c1: OR = 0.93; 95% CI = 0.79–1.10]. Similar results were observed in the subgroup analyses on ethnicity, drinking status, and source of controls. However, in the subgroup analysis on smoking status, a borderline increase in cancer risk was found among long-term smokers (c2c2+c1c2 vs. c1c1: OR = 1.39; 95% CI = 1.00–1.92).

Conclusion

CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to gastric cancer among individuals who have a smoking history. Large and well-designed studies are needed to confirm this conclusion.     

Four SNPs in the CHRNA3/5 Alpha-Neuronal Nicotinic Acetylcholine Receptor Subunit Locus Are Associated with COPD Risk Based on Meta-Analyses

Background

Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population. However, results from subsequent studies have been controversial, particularly in studies recruiting Asians. In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus.

Methods

A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group. The influence of individual studies on pooled measures was assessed, in addition to publication bias.

Results

A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10–1.18; rs8034191: OR = 1.29, 95%CI = 1.18–1.41; rs6495309: OR = 1.26, 95%CI = 1.09–1.45; rs16969968: OR = 1.27, 95%CI = 1.17–1.39) and genotype models. Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10–1.18), but not Asians (OR = 1.23, 95%CI = 0.91–1.67). Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status.

Conclusion

Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk. Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified. Additional studies will be necessary to assess the effect of rs6495309 on COPD. Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed.     

Role of a Genetic Variant on the 15q25.1 Lung Cancer Susceptibility Locus in Smoking-Associated Nasopharyngeal Carcinoma

Background

The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods

In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and alcohol consumption. Univariate and multivariate logistic regression analyses were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI).

Results

We found that individuals with CHRNA5 rs3841324 combined variant genotypes (ins/del+del/del) had a >1.5-fold elevated risk for NPC than those with the ins/ins genotype (adjusted OR = 1.52; 95% CI, 1.16–2.00), especially among ever smokers (adjusted OR = 2.07; 95% CI, 1.23–3.48). The combined variant genotypes acted jointly with cigarette smoking to contribute to a 4.35-fold increased NPC risk (adjusted OR = 4.35; 95% CI, 2.57–7.38). There was a dose-response relationship between deletion alleles and NPC susceptibility (trend test, P = 0.011).

Conclusions

Our results suggest that genetic variants on the 15q25.1 lung cancer susceptibility locus may influence susceptibility to NPC, particularly for smoking-associated NPC. Such work may be helpful to facilitate an understanding of the etiology of smoking-associated cancers and improve prevention efforts.     

Allergies and Diabetes as Risk Factors for Dengue Hemorrhagic Fever: Results of a Case Control Study

Background

The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with selected co-morbidities are at higher risk of developing DHF.

Methods

A matched case-control study was conducted in a dengue sero-positive population in two Brazilian cities. For each case of DHF, 7 sero-positive controls were selected. Cases and controls were interviewed and information collected on demographic and socio-economic status, reported co-morbidities (diabetes, hypertension, allergy) and use of medication. Conditional logistic regression was used to calculate the strength of the association between the co-morbidities and occurrence of DHF.

Results

170 cases of DHF and 1,175 controls were included. Significant associations were found between DHF and white ethnicity (OR = 4.70; 2.17–10.20), high income (OR = 6.84; 4.09–11.43), high education (OR = 4.67; 2.35–9.27), reported diabetes (OR = 2.75; 1.12–6.73) and reported allergy treated with steroids (OR = 2.94; 1.01–8.54). Black individuals who reported being treated for hypertension had 13 times higher risk of DHF then black individuals reporting no hypertension.

Conclusions

This is the first study to find an association between DHF and diabetes, allergy and hypertension. Given the high case fatality rate of DHF (1–5%), we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in hospital.     

Access to Water Source,Latrine Facilities and Other Risk Factors of Active Trachoma in Ankober,Ethiopia

Objective

This study aims to determine the prevalence and correlates of active trachoma in Ankober, Ethiopia.

Methods

A cross-sectional community-based study was conducted during July 2007. A total of 507 children (ages 1–9 years), from 232 households were included in the study. All children were examined for trachoma by ophthalmic nurses using the WHO simplified clinical grading system. Interviews and observations were used to assess risk factors. Logistic regression procedures were used to determine associations between potential risk factors and signs of active trachoma.

Results

Overall, the prevalence of active trachoma was found to be 53.9% (95%CI 49.6%–58.2%). Presence of fly-eye (fly contact with the eyelid margin during eye examination) (Odds Ratio (OR) = 4.03 95% CI 1.40–11.59), absence of facial cleanliness (OR = 7.59; 95%CI 4.60–12.52), an illiterate mother (OR = 5.88; 95%CI 2.10–15.95), lack of access to piped water (OR = 2.19; 95%CI 1.14–6.08), and lack of access to latrine facilities (OR = 4.36; 95%CI 1.49–12.74) were statistically significantly associated with increased risk of active trachoma.

Conclusion

Active trachoma among children 1–9 years of age in Ankober is highly prevalent and significantly associated with a number of risk factors including access to water and latrine facilities. Trachoma prevention programs that include improved access to water and sanitation, active fly control, and hygiene education are recommended to lower the burden of trachoma in Ankober, Ethiopia.     

Respiratory Symptoms and Airway Obstruction in HIV-Infected Subjects in the HAART Era

Background

Prevalence and risk factors for respiratory symptoms and airway obstruction in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART) are unknown. We evaluated respiratory symptoms and measured airway obstruction to identify the impact of HAART and other risk factors on respiratory symptoms and pulmonary function.

Methodology/Principal Findings

Two hundred thirty-four HIV-infected adults without acute respiratory symptoms were recruited from an HIV clinic. All subjects were interviewed and performed spirometry. Multivariate linear and logistic regressions were performed to determine predictors of respiratory symptoms, forced expiratory volume in one second (FEV₁) percent predicted, and FEV₁/forced vital capacity (FEV₁/FVC). Thirty-one percent of subjects reported at least one respiratory symptom. Smoking status (current or former versus never) (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.41–5.22, p = 0.003), higher log plasma HIV viral levels (OR = 1.12, 95%CI = 1.02–1.24, p = 0.02), and lower FEV₁/FVC (OR = 1.06 for every 0.01 decrease in FEV₁/FVC, 95%CI = 1.02–1.14, p = 0.001) were independent predictors of respiratory symptoms. Age (p = 0.04), pack-year smoking history (p<0.001), previous bacterial pneumonia (p = 0.007), and HAART use (p = 0.04) were independent predictors of decreased FEV₁/FVC.

Conclusions/Significance

Respiratory symptoms remain common in HIV-infected subjects, especially in those with a smoking history. Subjects who were older, had a greater pack-year history of smoking, or previous bacterial pneumonia had lower FEV₁/FVC ratios. Interestingly, use of HAART was independently associated with a decreased FEV₁/FVC, possibly secondary to an immune response to subclinical infections, increased autoimmunity, or other factors associated with HAART use.     

New Insights of Microsporidial Infection among Asymptomatic Aboriginal Population in Malaysia

Background

Studies on microsporidial infection mostly focus on immunodeficiency or immunosuppressive individuals. Therefore, this cross-sectional study describes the prevalence and risk factors of microsporidiosis among asymptomatic individuals in Malaysia.

Methods/Findings

Four hundred and forty seven stool samples were collected and examined for microsporidia after staining with Gram-chromotrope Kinyoun. Demographic, socioeconomic, environmental, and behavioral information were collected by using a pre-tested questionnaire. Overall, 67 (15%) samples were positive for microsporidia. The prevalence of infection was significantly higher among individuals aged more than 15 years compared to those aged <15 years (OR = 1.97, 95% CI = 1.08, 3.62; P = 0.028). Furthermore, logistic regression analysis confirmed that the presence of other family members infected with microsporidia (OR = 8.45; 95% CI = 4.30, 16.62; P<0.001) and being a consumer of raw vegetables (OR = 2.05; 95% CI = 1.15, 3.66; P = 0.016) were the significant risk factors of this infection.

Conclusions

These findings clearly show that exposure to microsporidia is common among Aboriginal population. Further studies using molecular approach on microsporidia isolates from asymptomatic individuals is needed to determine species-specific. The risk factors associated with microsporidiosis will help in identifying more clearly the sources of the infection in the environment that pose a risk for transmission so that preventive strategies can be implemented.     

Absence of association between N-acetyltransferase 2 acetylator status and colorectal cancer susceptibility: based on evidence from 40 studies

Background and Objectives

N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens, whose phenotypes were reported to be related to individual susceptibility to colorectal cancer (CRC). However, the results remain conflicting. To assess the relationship between NAT2 phenotypes and CRC risk, we performed this meta-analysis.

Methods

A comprehensive literature search was conducted to identify all case-control or cohort studies of NAT2 acetylator status on the susceptibility of CRC by searching of PubMed and EMBASE, up to May 20, 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association.

Results

A total of over 40,000 subjects from 40 published literatures were identified by searching the databases. No significantly elevated CRC risk in individuals with NAT2 slow acetylators compared with fast acetylators was found when all studies pooled (OR = 0.95, 95% CI: 0.87–1.04, I² = 52.6%). While three studies contributed to the source of heterogeneity were removed, there was still null result observed (OR = 0.96, 95% CI: 0.90–1.03, P = 0.17 for heterogeneity, I² = 17.8%). In addition, we failed to detect any associations in the stratified analyses by race, sex, source of controls, smoking status, genotyping methods or tumor localization. No publication bias was observed in this study.

Conclusions

This meta-analysis suggests that the NAT2 phenotypes may not be associated with colorectal cancer development.     

Bed-Sharing in the Absence of Hazardous Circumstances: Is There a Risk of Sudden Infant Death Syndrome? An Analysis from Two Case-Control Studies Conducted in the UK

Objective

The risk of sudden infant death syndrome (SIDS) among infants who co-sleep in the absence of hazardous circumstances is unclear and needs to be quantified.

Design

Combined individual-analysis of two population-based case-control studies of SIDS infants and controls comparable for age and time of last sleep.

Setting

Parents of 400 SIDS infants and 1386 controls provided information from five English health regions between 1993–6 (population: 17.7 million) and one of these regions between 2003–6 (population:4.9 million).

Results

Over a third of SIDS infants (36%) were found co-sleeping with an adult at the time of death compared to 15% of control infants after the reference sleep (multivariate OR = 3.9 [95% CI: 2.7–5.6]). The multivariable risk associated with co-sleeping on a sofa (OR = 18.3 [95% CI: 7.1–47.4]) or next to a parent who drank more than two units of alcohol (OR = 18.3 [95% CI: 7.7–43.5]) was very high and significant for infants of all ages. The risk associated with co-sleeping next to someone who smoked was significant for infants under 3 months old (OR = 8.9 [95% CI: 5.3–15.1]) but not for older infants (OR = 1.4 [95% CI: 0.7–2.8]). The multivariable risk associated with bed-sharing in the absence of these hazards was not significant overall (OR = 1.1 [95% CI: 0.6–2.0]), for infants less than 3 months old (OR = 1.6 [95% CI: 0.96–2.7]), and was in the direction of protection for older infants (OR = 0.1 [95% CI: 0.01–0.5]). Dummy use was associated with a lower risk of SIDS only among co-sleepers and prone sleeping was a higher risk only among infants sleeping alone.

Conclusion

These findings support a public health strategy that underlines specific hazardous co-sleeping environments parents should avoid. Sofa-sharing is not a safe alternative to bed-sharing and bed-sharing should be avoided if parents consume alcohol, smoke or take drugs or if the infant is pre-term.     

Hospital Recorded Morbidity and Breast Cancer Incidence: A Nationwide Population-Based Case-Control Study

Introduction

Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth.

Methods

Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods.

Results

The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment.

Conclusions

There was no substantial association between morbidity measured with the CCI and breast cancer risk.