Design of the Advance Directives Cohort: a study of end-of-life decision-making focusing on Advance Directives

<p>Abstract</p> <p>Background</p> <p>ADs are documents in which one can state one's preferences concerning end-of-life care, aimed at making someone's wishes known in situations where he/she is not able to do so in another manner. There is still a lot unclear about ADs. We designed a study aimed at investigating the whole process from the formulating of an AD to its actual use at the end of life.</p> <p>Methods/Design</p> <p>The study has mixed methods: it's longitudinal, consisting of a quantitative cohort-study which provides a framework for predominantly qualitative sub-studies. The members of the cohort are persons owning an AD, recruited through two Dutch associations who provide the most common standard ADs in the Netherlands, the NVVE (Right to Die-NL), of which 5561 members participate, and the NPV (Dutch Patient Organisation), of which 1263 members participate. Both groups were compared to a sample of the Dutch general public. NVVE-respondents are more often single, higher educated and non-religious, while amongst NPV-respondents there are more Protestants compared to the Dutch public. They are sent a questionnaire every 1,5 year with a follow-up of at least 7,5 years. The response rate after the second round was 88% respectively 90% for the NVVE and NPV. Participants were asked if we were allowed to approach close-ones after their possible death in the future. In this way we can get insight in the actual use of ADs at the end of life, also by comparing our data to that from the Longitudinal Aging Study Amsterdam, whose respondents generally do not have an AD.</p> <p>Discussion</p> <p>The cohort is representative for people with an AD as is required to study the main research questions. The longitudinal nature of the study as well as the use of qualitative methods makes it has a broad scope, focusing on the whole course of decision-making involving ADs. It is possible to compare the end of life between patients with and without an AD with the use of data from another cohort.</p

Towns with extremely low mortality due to ischemic heart disease in Spain

BACKGROUND: The cause of coronary disease inframortality in Spain is unknown. The aim of this study is to identify Spanish towns with very low ischemic heart disease mortality, describe their health and social characteristics, and analyze the relationship with a series of contextual factors. METHODS: We obtained the number of deaths registered for each of 8,122 Spanish towns in the periods 1989-1998 and 1999-2003. Expected deaths, standardized mortality ratio (SMR), smoothed Relative Risk (RR), and Posterior Probability (PP) of RR > 1 were calculated using Bayesian hierarchical models. Inframortality was defined as any town that displayed an RR below the 10th percentile, an SMR of under 1 for both sexes, and a PP of RR > 1 less than or equal to 0.002 for male and 0.005 for female mortality, during the two periods covered. All the remaining towns, except for those with high mortality classified as "tourist towns", were selected as controls. The association among socioeconomic, health, dietary, lifestyle and vascular risk factors was analyzed using sequential mixed logistic regression models, with province as the random-effects variable. RESULTS: We identified 32 towns in which ischemic heart disease mortality was half the national rate and four times lower than the European Union rate, situated in lightly populated provinces spread across the northern half of Spain, and revealed a surprising pattern of geographic aggegation for 23 of the 32 towns. Variables related with inframortality were: a less aged population (OR 0.93, 95% CI 0.89-0.99); a contextual dietary pattern marked by a high fish content (OR 2.13, 95% CI 1.38-3.28) and wine consumption (OR 1.50, 95% CI 1.08-2.07); and a low prevalence of obesity (OR 0.47, 95% CI 0.22-1.01); and, in the case of towns of over 1000 inhabitants, a higher physician-population ratio (OR 3.80, 95% CI 1.17-12.3). CONCLUSIONS: Results indicate that dietary and health care factors have an influence on inframortality. The geographical aggregation suggests that other factors with a spatial pattern, e.g., genetic or environmental might also be implicated. These results will have to be confirmed by studies in situ, with objective measurements at an individual level.This study was funded by research study grant no. PI06/0656 from Spain's Health Research Fund (Fondo de Investigación Sanitaria).S

Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort

Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed. Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk

Promoting advance planning for health care and research among older adults: A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Family members are often required to act as substitute decision-makers when health care or research participation decisions must be made for an incapacitated relative. Yet most families are unable to accurately predict older adult preferences regarding future health care and willingness to engage in research studies. Discussion and documentation of preferences could improve proxies' abilities to decide for their loved ones. This trial assesses the efficacy of an advance planning intervention in improving the accuracy of substitute decision-making and increasing the frequency of documented preferences for health care and research. It also investigates the financial impact on the healthcare system of improving substitute decision-making.</p> <p>Methods/Design</p> <p>Dyads (<it>n </it>= 240) comprising an older adult and his/her self-selected proxy are randomly allocated to the experimental or control group, after stratification for type of designated proxy and self-report of prior documentation of healthcare preferences. At baseline, clinical and research vignettes are used to elicit older adult preferences and assess the ability of their proxy to predict those preferences. Responses are elicited under four health states, ranging from the subject's current health state to severe dementia. For each state, we estimated the public costs of the healthcare services that would typically be provided to a patient under these scenarios. Experimental dyads are visited at home, twice, by a specially trained facilitator who communicates the dyad-specific results of the concordance assessment, helps older adults convey their wishes to their proxies, and offers assistance in completing a guide entitled <it>My Preferences </it>that we designed specifically for that purpose. In between these meetings, experimental dyads attend a group information session about <it>My Preferences</it>. Control dyads attend three monthly workshops aimed at promoting healthy behaviors. Concordance assessments are repeated at the end of the intervention and 6 months later to assess improvement in predictive accuracy and cost savings, if any. Copies of completed guides are made at the time of these assessments.</p> <p>Discussion</p> <p>This study will determine whether the tested intervention guides proxies in making decisions that concur with those of older adults, motivates the latter to record their wishes in writing, and yields savings for the healthcare system.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN89993391">ISRCTN89993391</a></p

Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between pre-diagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested-case control study was conducted within the EPIC cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function and alpha-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95%CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable=1.30; 95%CI:1.14-1.48). The association was stronger among cases diagnosed within two years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC=0.86). For cases diagnosed within two years, the combination of OPN and AFP was best able to predict HCC risk (AUC=0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within two years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis

Adecuación de la ingesta dietética de la cohorte del Estudio Prospectivo Europeo sobre Nutrición y Cáncer (EPIC)-Granada a las ingestas recomendadas y objetivos nutricionales

Journal Article;BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.YesIntroducción: Se ha evaluado la ingesta de energía y de nutrientes de la cohorte EPIC-Granada (Estudio Prospectivo Europeo sobre Nutrición y Cáncer) en relación con la adecuación a los Objetivos Nutricionales españoles(ON) y a las ingestas recomendadas (IR). Métodos: Durante el reclutamiento (1992-1996), 7,789 participantes (de 35-69 años de edad) fueron entrevistados sobre su dieta mediante el método de historia de dieta. La ingesta de nutrientes se ha comparado con los NO y con las IR. El riesgo de ingesta inadecuada se ha estimado como porcentaje de participantes con ingestas: ≤ 1/3 IR (riesgo elevado), ≤ 2/3 IR-> 1/3 IR (riesgo moderado), ≤ IR-> 2/3 IR, > IR. Se han analizado diferencias según sexo, edad, hábito tabáquico e Índice de Masa Corporal(IMC). Resultados: La ingesta dietética no cumple los ON debido a que la contribución de proteínas y lípidos sobre la ingesta energética total excede estas recomendaciones. La mayoría de los nutrientes satisfacen las IR, excepto hierro, magnesio, vitamina D y E: entre las mujeres de 20-49 años un 55% presentaron riesgo moderado de ingesta inadecuada de hierro, y un 20% lo presentaron para el magnesio. En ambos sexos se encontró un elevado riesgo de ingesta inadecuada de vitamina D, que puede compensarse por la exposición solar. Los no fumadores mostraron un mejor cumplimiento de los ON. Conclusión: El perfil calórico de la dieta en la cohorte EPIC está desequilibrado. La ingesta inadecuada de los nutrientes hierro, magnesio y vitamina E podría ser atribuible a hábitos dietéticos inadecuados, y podría tener implicaciones para el desarrollo futuro de enfermedades

Transcriptional changes in human Caco-2 colon cancer cells following exposure to a recurrent non-toxic dose of polyphenol-rich chokeberry juice

Berries and red fruits are important dietary sources of polyphenols [1]. In vitro and animal studies have demonstrated the bioavailability and the anti-proliferative and anticarcinogenic properties of these fruits or of their phenolic components [2, 3]. Consumption of berries may contribute to the reduction of colon cancer by mechanisms not yet understood. Gene expression analysis using microarrays allows for a more comprehensive study of the possible molecular mechanisms by which food or food components may prevent certain cancers of the gastrointestinal tract [4]. The aim of this research is to investigate the anti-proliferative effects of a polyphenol-rich berry juice on a human model of colon cancer cells and its association to transcriptional changes in relation to colon cancer