Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

BackgroundTranslating the extraordinary scientific and technological advances occurring in medical research laboratories into care for patients in communities throughout the country has been a major challenge. One contributing factor has been the relative absence of community practitioners from the US biomedical research enterprise. Identifying and addressing the barriers that prevent their participation in research should help bridge the gap between basic research and practice to improve quality of care for all Americans.MethodsWe interviewed over 200 clinicians and other healthcare stakeholders from 2004 through 2005 to develop a conceptual framework and set of strategies for engaging a stable cadre of community clinicians in a clinical research program.ResultsLack of engagement of community practitioners, lack of necessary infrastructure, and the current misalignment of financial incentives and research participation emerged as the three primary barriers to community clinician research participation. Although every effort was made to learn key motivators for engagement in clinical research from interviewees, we did not observe their behavior and self-report by clinicians does not always track with their behavior.ConclusionsA paradigm shift involving acknowledgement of the value of clinicians in the context of community research, establishment of a stable infrastructure to support a cohort of clinicians across time and research studies, and realignment of incentives to encourage participation in clinical research is required.

The cAMP response element-binding protein (CREB) is a nuclear transcription factor that is critical for normal and neoplastic hematopoiesis. Previous studies have demonstrated that CREB is a proto-oncogene whose overexpression promotes cellular proliferation in hematopoietic cells. Transgenic mice that overexpress CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously develop acute myeloid leukemia. In this study, we used retroviral insertional mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice. Our mutagenesis screen identified several integration sites, including oncogenes Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as a gene that cooperates with CREB in myeloid leukemogenesis. We show that the transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus increases survival and self-renewal of cells in vitro. Furthermore, leukemic blasts from the majority of acute myeloid leukemia patients have higher CREB, phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse bone marrow cells results in increased expression of CREB target genes. We also demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation assays. These results indicate that Sox4 and CREB cooperate and contribute to increased proliferation of hematopoietic progenitor cells.

BackgroundNew National Institutes of Health policies call for expansion of practice-based research to improve the clinical research enterprise and facilitate dissemination of evidence-based medicine.ObjectiveThis paper describes organizational strategies that influence clinicians' decisions to participate in clinical research.DesignWe reviewed the literature and interviewed over 200 clinicians and stakeholders.ResultsThe most common barriers to community clinician participation in clinical research relate to beliefs that clinical research is too burdensome and has little benefit for the participating clinician or patient. We identified a number of approaches healthcare organizations can use to encourage clinicians to participate in research, including an outreach campaign to promote the benefits of clinical research; selection of study topics of interest to clinicians; establishment and enforcement of a set of research principles valuing the clinician and patient; development of a transparent schedule of reimbursement for research tasks; provision of technological and technical assistance to practices as needed; and promotion of a sense of community among clinicians involved in practice-based research.ConclusionsMany types of existing healthcare organizations could provide the technical and intellectual assistance community clinicians need to participate in clinical research. Multiple approaches are possible.