Funding Mechanisms for Gender‐specific Research: Proceedings from a Panel Discussion at the 2014 Academic Emergency Medicine Consensus Conference

As part of the 2014 Academic Emergency Medicine (AEM) consensus conference “Gender‐Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes,” we assembled a diverse panel of representatives from federal and nonfederal funding agencies to discuss future opportunities for sex‐ and gender‐specific research. The discussion revolved around the mission and priorities of each organization, as well as its interest in promoting sex‐ and gender‐specific research. The panelists were asked to provide specific examples of funding lines generated or planned for as pertinent to emergency care. Training opportunities for future researchers in this area were also discussed.     

Organization,Execution and Evaluation of the 2014 Academic Emergency Medicine Consensus Conference on Gender‐Specific Research in Emergency Care – An Executive Summary

With the goal of reducing inequalities in patient care, the 2014 Academic Emergency Medicine (AEM) consensus conference, “Gender‐Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes,” convened a diverse group of researchers, clinicians, health care providers, patients, and representatives of federal agencies and policy‐makers in Dallas, Texas, in May 2014. The executive and steering committees identified seven clinical domains as key to gender‐specific emergency care: cardiovascular, neurological, trauma/injury, substance abuse, pain, mental health, and diagnostic imaging. The main aims of the conference were to: 1) summarize and consolidate current data related to sex‐ and gender‐specific research for acute care and identify critical gender‐related gaps in knowledge to inform an EM research agenda; 2) create a consensus‐driven research agenda that advances sex‐ and gender‐specific research in the prevention, diagnosis, and management of acute diseases and identify strategies to investigate them; and 3) build a multinational interdisciplinary consortium to disseminate and study the sex and gender medicine of acute conditions. Over a 2‐year period, this collaborative network of stakeholders identified key areas where sex‐ and gender‐specific research is most likely to improve clinical care and ultimately patient outcomes. The iterative consensus process culminated in a daylong conference on May 13, 2014, with a total of 133 registrants, with the majority being between ages 31 and 50 years (57%), females (71%), and whites (79%). Content experts led the consensus‐building workshops at the conference and used the nominal group technique to consolidate consensus recommendations for priority research. In addition, panel sessions addressed funding mechanisms for gender‐specific research as well as gender‐specific regulatory challenges to product development and approval. This special issue of AEM reports the results of the 2014 consensus conference as well as related original research with the goal of bringing high‐quality equitable care to male and female emergency patients.     

Gender‐specific Regulatory Challenges to Product Approval: A Panel Discussion

On May 13, 2014, a 1‐hour panel discussion session titled “Gender‐specific Regulatory Challenges to Product Approval” was held during the Academic Emergency Medicine consensus conference, “Gender‐specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” The session sought to bring together leaders in emergency medicine (EM) research, authors, and reviewers in EM research publications, as well as faculty, fellows, residents, and students engaged in research and clinical practice. A panel was convened involving a representative from the Office of Women's Health of the U.S. Food and Drug Administration, two pharmaceutical executives, and a clinical EM researcher. The moderated discussion also involved audience members who contributed significantly to the dialogue. Historical background leading up to the session along with the main themes of the discussion are reproduced in this article. These revolve around sex‐ and gender‐specific research, statistical analysis of sex and gender, clinical practice, financial costs associated with pharmaceutical development, adaptive design, and specific recommendations on the regulatory process as it affects the specialty of EM.     

Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3–3.0 μg/kg/d, s.c.) and epo (60–300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of  1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11–24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance ( P  < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100–500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or  2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.     

The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man.

A method has been developed to measure local glucose consumption in the various structures of the brain in man with three-dimensional resolution. [18F]-2-deoxy-2-fluoro-D-glucose is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissue. A mathematical model and derived operational equation are used which enable local cerebral glucose consumption to be calculated in terms of the following measurable variables. An intravenous bolus of [18F]-2-deoxy-2-fluoro-D-glucose is given and the arterial specific activity monitored for a predetermined period of from 30 to 120 minutes. Starting at 30 minutes, the activity in a series of sections through the brain is determined with three-dimensional resolution by an emission tomographic scanner. The method was used to measure local cerebral glucose consumption in two normal volunteers. The values in gray matter structures range from 5.79 mg/100 g per minute in the cerebellar cortex to 10.27 in the visual cortex, whereas, in white matter structures, the values range from 3.64 mg/100 g per minute in the corpus callosum to 4.22 in the occipital lobe. Average values for gray matter, white matter, and whole brain metabolic rates, calculated as a weighted average based on the approximate volume of each structure, are 8.05, 3.80, and 5.90 mg/100 g per minute, respectively. The value of 5.9 mg/100 g per minute compares favorably with values previously reported.     

Kaposi's sarcoma in human T-cell leukemia virus type I-associated adult T-cell leukemia

Kaposi's sarcoma (KS) developed in a patient with human T-cell leukemia virus type I (HTLV-I)-associated adult T-cell leukemia who was treated with a short-term course of monoclonal antibody immunotherapy. The presentation was transient and temporally related to the underlying clinical course. The association of KS in an HTLV-I infected, but not human immunodeficiency virus (HIV)-infected, individual should alert investigators to the occurrence of KS in retroviral-associated diseases other than acquired immunodeficiency disease syndrome. Recognition of the similarities and differences between HTLV-I and HIV infections may provide insights concerning the angiopathogenesis of KS.     

Controlled trial of bowel rest and nutritional support in the management of Crohn's disease.

To define the role of bowel rest as an independent variable from nutritional support a prospective, randomised controlled trial was undertaken in 51 patients with active Crohn's disease unresponsive to other medical management. Nutritional support for 21 days was randomised to total parenteral nutrition and nil by mouth (n = 17), defined formula diet administered through a nasogastric tube (n = 19), or partial parenteral nutrition and oral food (n = 15). Nutrient input in the first two groups provided 40 non-protein kcal/kg ideal body weight /d and 1g/ kg/d protein respectively, while the third group received 15 non-protein kcal/kg/d and 0.3 g/kg/d protein intravenously and ate unrestricted food. Clinical remissions occurred in 71% of patients on parenteral nutrition, in 58% on the defined formula diet and in 60% on partial parenteral nutrition; the probability for each group of being in remission at one year, after successful therapy was 42%, 55%, and 56% respectively. These differences were not significant. In patients with active Crohn's disease bowel rest was not a major factor in achieving a remission during nutritional support and did not influence outcome during one year's follow-up.