Genetic testing for hereditary nonpolyposis colorectal cancer

Approximately 80 per cent of patients with colorectal cancer have sporadic disease whereas the remaining 20 per cent seem to have a genetic component. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common autosomal dominant hereditary syndrome predisposing to colorectal cancer. Various methods have been described to screen for HNPCC and to directly test for mismatch repair gene mutations. This study evaluates the initial results of 1) microsatellite instability (MSI) and immunohistochemistry (IHC) staining of tumors and 2) genetic sequencing for mismatch repair gene mutations in patients suspected to have HNPCC. Appropriate patients for HNPCC testing were identified through a high-risk colorectal cancer clinic. Of those patients screened only those who met Amsterdam criteria (AC) for HNPCC or were young age onset (YAO) (<40 years of age) were eligible for testing. The tumors underwent testing for MSI and had IHC performed in those patients with available tumor specimens. MSI was performed on the five markers approved by the NIH consensus conference. MSI-High (MSI-H) was defined as two or more markers being unstable. IHC was done with commercially available stains for MLH1 and MSH2. All patients had sequencing of the MLH1 and MSH2 genes performed to search for mutations by a commercial laboratory. Genetic counseling was provided and written informed consent was obtained. Fourteen patients were part of kindreds that met the AC. An additional 10 patients were <40 years of age at diagnosis of colorectal cancer but lacked any family history. Testing for MSI and IHC was performed on those available tissue blocks. Of the AC patients five had MSH2 mutations and two had MLH1 variants. Of the five with MSH2 mutations three of four had MSI-H tumors and all four had loss of expression of MSH2 on IHC. Of the MLH1 variants only one had MSI-H tumor and lacked expression of MLH-1 on IHC. Of those patients with no mutation identified three of six had MSI-H tumors. For those patients YAO no genetic mutations were identified. Two of the seven had MSI-H tumors. Genetic testing for HNPCC even in those patients fulfilling the rigid AC yielded mutations in only five of 14 patients with variants of unknown significance being found in an additional two patients. Only one MSH2 variant of unknown significance was identified in the 10 YAO patients, which would suggest that screening in this group of patients with MSI and/or IHC would be appropriate.     

Health Implications of PAH Release from Coated Cast Iron Drinking Water Distribution Systems in the Netherlands

Background: Coal tar and bitumen have been historically used to coat the insides of cast iron drinking water mains. Polycyclic aromatic hydrocarbons (PAHs) may leach from these coatings into the drinking water and form a potential health risk for humans.Objective: We estimated the potential human cancer risk from PAHs in coated cast iron water mains.Method: In a Dutch nationwide study, we collected drinking water samples at 120 locations over a period of 17 days under various operational conditions, such as undisturbed operation, during flushing of pipes, and after a mains repair, and analyzed these samples for PAHs. We then estimated the health risk associated with an exposure scenario over a lifetime.Results: During flushing, PAH levels frequently exceeded drinking water quality standards; after flushing, these levels dropped rapidly. After the repair of cast iron water mains, PAH levels exceeded the drinking water standards for up to 40 days in some locations.Conclusions: The estimated margin of exposure for PAH exposure through drinking water was > 10,000 for all 120 measurement locations, which suggests that PAH exposure through drinking water is of low concern for consumer health. However, factors that differ among water systems, such as the use of chlorination for disinfection, may influence PAH levels in other locations.     

Investigation of the role of interleukin-6 and hepcidin antimicrobial peptide in the development of anemia with age

Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.     

Academic Help-Seeking Behavior Among Student Pharmacists

Objectives. To identify factors associated with academic help-seeking behavior among student pharmacists at a public university.Methods. Semi-structured focus group interviews were conducted to explore in depth perceptions of facilitators of and barriers to the help-seeking behavior and academic achievement of student pharmacists who had received a D or F grade in any year. A 4-part survey instrument was developed and administered to all student pharmacists and included sections for (1) attitudes and academic help-seeking behavior, (2) health status, (3) demographics, and (4) open comments. A structural equation modeling approach was used to assess relationships among domains of interest.Results. Three student focus groups noted that helpfulness of faculty members and school administrators were 2 prominent facilitators of help-seeking behavior and academic achievement. Diminished quality of life caused by stress and depression was the primary barrier to help-seeking and achievement. Three hundred four (68.6%) student pharmacists completed the survey instrument. Academic help-seeking behavior was influenced mostly by perceived academic competence and perceived faculty helpfulness. In contrast, ambivalence and perception of help-seeking as threatening were 2 factors that were negatively associated with academic help-seeking behavior.Conclusions. Academic help-seeking behavior was positively related to greater perceived academic competence and positive relationships among student pharmacists and faculty members.     

Local Leaders' Perspectives on Women Veterans’ Health Care: What Would Ideal Look Like?

Background

The Veterans Health Administration (VHA) faces challenges in providing comprehensive, gender-sensitive care for women. National policies have led to important advancements, but local leadership also plays a vital role in implementing changes and operationalizing national priorities. In this article, we explore the notions of ideal women veterans' health care articulated by women's health leaders at local VHA facilities and regional networks, with the goal of identifying elements that could inform practice and policy.

Family caregivers’ perspectives on medication adherence challenges in older people with dementia: a qualitative study

Abstract

Objectives: To achieve a better understanding of medication non-adherence determinants in older people with dementia from caregivers’ perspectives and possible management solutions to improve medication adherence.

Method: Semi-structured telephone interviews were conducted with 20 caregivers of older people with dementia living in the community. Data was analyzed using an inductive thematic analysis based on Braun and Clarke’s method.

Findings: Four themes emerged: dementia symptoms influence medication adherence, medication increases caregiver burden, lack of self-efficacy, medication aids and technology to enhance medication adherence. Caregivers’ lack of knowledge reduces their self-efficacy in managing medications and increases their burden of care. The majority of caregivers used technology and welcomed its use to assist them with their role.

Conclusion: Caregivers require knowledge and support such as a multifaceted technology based intervention to assist with medication adherence.