Design options for molecular epidemiology research within cohort studies.

Past discussions of the relative strengths of nested case-control and case-cohort designs have not fully considered cohorts with stored biological samples in which biomarker analyses are planned. Issues related to biomarker analyses can affect an investigator's choice of design and the conduct of these two designs. The key issues identified are effects of analytic batch, long-term storage, and freeze-thaw cycles on biomarkers. In comparison with the nested case-control design, the case-cohort design is less able to handle these challenges. Problems arise because most implementations of the case-cohort design do not allow for simultaneous evaluation of biomarkers in cases and reference group members, and there is no matching. By design, the nested case-control study controls for storage duration and the batching of biological samples from cases and controls is logistically simple. The allowance for matching also means that subjects can be matched on the number of freeze-thaw cycles experienced by the biological sample. However, the matching generates complex data sets that can be more difficult to analyze, and the costly biomarker data generated from the controls has few uses outside of testing the specific hypotheses of the study. In addition, because the same subject can serve as a control and a case, or multiple times as a control, biomarker analyses and sample batching can be more complex than initially anticipated. However, in total, of the two designs, the nested case-control study is better suited for studying biomarkers that can be influenced by analytic batch, long-term storage, and freeze-thaw cycles.     

Migration,health, and socioenvironmental safety net among children of Dhaka,Bangladesh

This study quantifies the diarrhea burden among migrant children under age 5 (who have migrated due to environmental degradation) in Dhaka. We used a multifactor socioepidemiological as well as environmental approach with pretested questionnaires and observations. It was found that 52% of the children were affected by diarrhea. Disability-adjusted life years (DALYs) lost was reduced manifold with the increase of mothers' behavioral determinants. Health losses were 1,718 fold with significant coefficient (β) in the migrant group. DALYs lost were significantly associated with socioenvironmental factors such as mother's illiteracy (β = .18; p < .001), no hand wash before eating (β = .08; p = .004), and no hand wash after defecation (β = .10; p < .001). This puts emphasis clearly on the awareness at household level, especially of mothers and children under age 5 in Dhaka, Bangladesh, in formulating migration-related policies.     

Meta-analysis of self-gripping mesh (Progrip) versus sutured mesh in open inguinal hernia repair

BackgroundThis metaanalysis was designed to systematically analyse all published randomized controlled trials comparing self-gripping mesh (ProGrip) and sutured mesh to analyse early and long term outcomes for open inguinal hernia repair.MethodsA literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing self-gripping mesh with sutured mesh were included. Statistical analysis was performed using Review Manager Version 5.2 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, wound complications and perioperative complications.ResultsFive randomized trials were identified as suitable, including 1170 patients. There was no significant difference between the two types of mesh repairs in perioperative complications, wound haematoma, chronic groin pain and hernia recurrence. Wound infection was lower in self gripping mesh group compared to sutured mesh but this was not statistically significant (risk ratio (RR) 0.57, 95% confidence interval 0.30–1.06, P = 0.08). The duration of operation was significantly shorter with self-gripping mesh compared to sutured mesh with a mean difference of ?5.48 min [?9.31, ?1.64] Z = 2.80 (P = 0.005).ConclusionSelf-gripping mesh was associated with shorter operative time compared to sutured mesh. Both types of mesh repairs have comparable perioperative and long term outcomes.     

Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity.Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation.Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation.Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10^–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10^–11) and blood arsenic concentrations (p = 1.48 × 10^–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci.Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884     

Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center

Context

There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe

Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.