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

Improving the use of research evidence in guideline development: 4. Managing conflicts of interests

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the fourth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on conflicts of interest to answer the following questions: 1. What is the best way to obtain complete and accurate disclosures on financial ties and other competing interests? 2. How to determine when a disclosed financial tie or other competing interest constitutes a conflict of interest? 3. When a conflict of interest is identified, how should the conflict be managed? 4. How could conflict of interest policies be enforced? METHODS: We searched PubMed, the Cochrane Methodology Register and selectively searched for the published policies of several organizations, We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: What is the best way to obtain complete and accurate disclosures on financial ties and other competing interests? • Although there is little empirical evidence to guide the development of disclosure forms, minimal or open-ended formats are likely to be uninformative. We recommend the development of specific, detailed, structured forms that solicit as much information as possible about the nature and extent of the competing interests. How to determine when a disclosed financial tie or other competing interest constitutes a conflict of interest? • There is no empirical evidence to suggest that explicit criteria are preferable to ad hoc committee decisions when deciding if a disclosed financial tie is a conflict of interest. However, explicit criteria may make decision-making easier. When a conflict of interest is identified, how should the conflict be managed? • Descriptive studies suggest that appropriate management strategies are best determined on a case-by-case basis. Thus, WHO should use a wide range of management strategies to address disclosed conflicts of interest, with public disclosure of conflicts associated with each meeting as a minimum and recusal of conflicted individuals as the other extreme. How could conflict of interest policies be enforced? • Although there are no empirical studies of the enforcement of conflict if interest policies, descriptive studies of other organizations and institutions suggest that WHO convene a standing committee to review all financial disclosure statements prior to the commencement of committee meetings/hearings and to make management recommendations when necessary. A standard policy requiring all financial ties to be made public (i.e., recorded into the meeting minutes) should reduce the number of problematic cases. In instances where the conflicts seem intractable, a recommendation of recusal may be necessary to protect the greater interests of WHO and its constituents

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

<p>Abstract</p> <p>Background</p> <p>Expression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging.</p> <p>Methods</p> <p>We describe a method to identify the <it>trans-</it>acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed <it>co-regulatory expression quantitative trait locus </it>(creQTL) <it>mapping</it>-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping.</p> <p>Results</p> <p>Applying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNβ-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNβ-induced genes and the DNA damage response.</p> <p>Conclusions</p> <p>Because of the importance of IFNβ in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at <url>http://sites.google.com/site/kenkompass/</url>.</p