Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer : a case-control study in a population with relatively low folate intake

Peer reviewedPublisher PD

Predisposing and precipitating risk factors for delirium in gastroenterology and hepatology: Subgroup analysis of 718 patients from a hospital-wide prospective cohort study

BACKGROUND AND AIMS Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined. PATIENTS AND METHODS Prospective 1-year hospital-wide cohort study in 29'278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients. RESULTS Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31-693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84-15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85-129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11-4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61-12.26], p = 0.004) and liver disease (OR 2.22 [1.12-4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001). CONCLUSION Delirium in GI- and HPB-disease was not associated with higher age per se, but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs

Qualitative Study of Factors Contributing to Fertility Service Use Among Cancer Survivors of Reproductive Age in the US

Cancer remains the second leading cause of death in the United States; however, there has been a decline in incidence and mortality due to advances in screening and treatment. Currently 16.9 million survivors are thriving within the United States, and the population of cancer survivors has been projected to grow to 22.2 million by 2030. Although cancer survivors report an increased surge of vitality and vigor, they often face physical, mental, psychosocial, or financial challenges that threaten their quality of life. A late treatment effect of particular concern for cancer survivors of reproductive age that has both physical and psychosocial implications is infertility. Current guidelines are in place to ensure that survivors are made aware of how treatment can impact their plans for building a family and pose viable options for preserving their fertility; however, studies indicate under-utilization of fertility preservation among cancer survivors. The aim of this study was to examine how a cancer diagnosis influenced parenthood motivation and family building strategies among individuals of reproductive age. The study identified contributors to access and use of fertility services by using a conceptual model based on Andersen’s Behavioral Model of Health Services, Lea’s model of Age-appropriate Care, and Kilbourne’s Health Services Research Framework to Advance Health Disparities. The conceptual model elucidates factors that impact cancer survivors’ use of fertility services, equitable access to services, and policy actions that assure equitable access to fertility services. A phenomenological qualitative study was conducted to allow deep exploration of these issues through the review and analysis of survivors’ stories as told through online narratives and in-depth interviews. Study findings showed a cancer diagnosis had not altered an individual’s desire to have children. Although fertility preservation was not always utilized by cancer survivors of reproductive age to conceive or sire a child, most survivors sought out some form of fertility service post treatment. Access and subsequent use of fertility services was grossly dependent on both survivor and provider factors as well as successful clinical encounters between the patient and the provider. These findings have implications for clinical care, public health policy, practice, and research

Genetic variation in DNA-repair pathways and response to radiochemotherapy in esophageal adenocarcinoma: A retrospective cohort study of the Eastern Cooperative Oncology Group

Background: Recent data in esophageal cancer suggests the variant allele of a single-nucleotide polymorphism (SNP) in XRCC1 may be associated with resistance to radiochemotherapy. However, this SNP has not been assessed in a histologically homogeneous clinical trial cohort that has been treated with a uniform approach. In addition, whether germline DNA may serve as a surrogate for tumor genotype at this locus is unknown in this disease. Our objective was to assess this SNP in relation to the pathologic complete response (pCR) rate in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy in a multicenter clinical trial (Eastern Cooperative Oncology Group 1201). As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA.Methods: Eighty-one eligible treatment-naïve subjects with newly diagnosed resectable esophageal adenocarcinoma received radiotherapy (45 Gy) concurrent with cisplatin-based chemotherapy, with planned subsequent surgical resection. The primary endpoint was pCR, defined as complete absence of tumor in the surgical specimen after radiochemotherapy. Using germline DNA from 60 subjects, we examined the base-excision repair SNP, XRCC1 Arg399Gln, and 4 other SNPs in nucleotide excision (XPD Lys751Gln and Asp312Asn, ERCC1 3' flank) and double-stranded break (XRCC2 5' flank) repair pathways, and correlated genotype with pCR rate. Paired tumor tissue was used to estimate the frequency of allelic imbalance at the XRCC1 SNP.Results: The variant allele of the XRCC1 SNP (399Gln) was detected in 52% of subjects. Only 6% of subjects with the variant allele experienced a pCR, compared to 28% of subjects without the variant allele (odds ratio 5.37 for failing to achieve pCR, p = 0.062). Allelic imbalance at this locus was found in only 10% of informative subjects, suggesting that germline genotype may reflect tumor genotype at this locus. No significant association with pCR was noted for other SNPs.Conclusions: Assessed for the first time in a prospective, interventional trial cohort of esophageal adenocarcinoma, XRCC1 399Gln was associated with resistance to radiochemotherapy. Further investigation of this genetic variation is warranted in larger cohorts. In addition, these data indicate that germline genotype may serve as a surrogate for tumor genotype at this locus. © 2011 Yoon et al; licensee BioMed Central Ltd

Factors Influencing Surrogate End-of-Life Healthcare Decision-Making for a Family Member with Alzheimer\u27s Disease

Alzheimer’s disease (AD), a chronic terminal disease, progressively impairs cognitive function resulting in deterioration of intellect, memory, and personality. With disease progression, the surrogate decision-maker becomes more involved in intervention choices and end-of-life (EOL) care, which may or may not be based on patients’ wishes or best practice guidelines. Yet surrogate decision outcomes involve important issues of medical futility, quality of life and death. The purpose of this study was to examine factors that influence surrogate health care decision-making for a family member during the terminal stage of AD. A descriptive, predictive design was used to address the research questions: 1.What is the relationship between surrogate gender and decision motives?; 2. Do structure (surrogate age and gender, attachment, interpersonal conflict), interactional context (elder image, caregiving beliefs), situational context (dementia level), and perception (burden) variables predict the type of decision motive (reward seeking, altruistic, distress reduction, punishment avoidance) used by surrogates’ when making healthcare decisions for their family member with AD?; 3. What healthcare decision choices do surrogate decision-makers make for a family member with AD? A convenience sample of 58 women (67.2%) and men surrogates between the ages of 43 to 84 years of age (M = 62.22, SD = 9.67) living in one urban and several rural cities in a southeastern state were recruited. Participants were recruited during facility meetings for families at 15 long-term care facilities and 1 dementia care assisted living facility. The majority of participants were Caucasian (84.5%). Questionnaires were distributed to participants at a facility meeting. After the study was explained, written informed consent was obtained. Each participant was asked to complete the questionnaire booklet and return via mail in a stamped self-addressed envelope to the researcher. Data were analyzed with descriptive and inferential statistics including frequencies, percentages, means, standard deviations, t-tests, and multiple linear regressions. Types of decision motives did not differ by gender. For the regression models, the independent variables included gender, feelings of attachment, interpersonal conflict with the elder, beliefs about caregiving, dementia level and caregiver burden. For the model predicting punishment avoidance decision motive, simultaneous multiple linear regression results indicated that the overall model significantly predicted the dependent variable. The regression model predicting reward seeking decision motive results indicated that the overall model significantly predicted the dependent variable. Two of the variables, dementia level and surrogate burden, significantly contributed to the variance in the reward seeking decision motive. When asked about the decisions they have been asked to make in the past 12 months, surrogates were asked to make life supportive interventions (pain management and nutritional supplements) more frequently than life extending interventions. The most frequent life extending interventions chosen in descending order of frequency include surgery, central line placement, and feeding tube placement. This study supports the importance of providing surrogate and family information on AD and end-of-life healthcare interventions in a therapeutic and supportive environment. Nursing implications address pain management of the cognitively impaired patient, advocacy for advance directive completion and non-futile care, and patient and family AD education. Health care implications include process for completion of an advance directive and the burden of medical futility

Rescuing Children from the Marriage Movement: The Case against Marital Restrictions on Adoption and Assisted Reproduction

Much of the current cultural debate about marriage in the United States focuses on the need for children to be raised by heterosexual married couples. In the current atmosphere, it is important to examine how marriage functions in contexts where parent-child relationships are determined by more than just genetics and marital presumptions. This Article argues that the favoritism toward marriage in adoption and assisted reproduction relates neither to the purposes of marriage nor to child welfare. Part I subjects marital restrictions on assisted reproduction to an interpretivist microscope, and Part II undertakes a comprehensive comparison of step-parent adoption and second-parent adoption. Both Parts raise concerns that are further addressed in Part III’s look at how the contemporary marriage movement, in advocating for favored treatment of married couples at all levels of society, ultimately undermines the welfare of children whose best hope lies with parents for whom marriage is not an option