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.     

Sex‐ and Gender‐specific Research Priorities in Cardiovascular Resuscitation: Proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Resuscitation Research Workgroup

Significant sex and gender differences in both physiology and psychology are readily acknowledged between men and women; however, data are lacking regarding differences in their responses to injury and treatment and in their ultimate recovery and survival. These variations remain particularly poorly defined within the field of cardiovascular resuscitation. A better understanding of the interaction between these important factors may soon allow us to dramatically improve outcomes in disease processes that currently carry a dismal prognosis, such as sudden cardiac arrest. As part of the 2014 Academic Emergency Medicine consensus conference “Gender‐Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes,” our group sought to identify key research questions and knowledge gaps pertaining to both sex and gender in cardiac resuscitation that could be answered in the near future to inform our understanding of these important issues. We combined a monthly teleconference meeting of interdisciplinary stakeholders from largely academic institutions with a focused interest in cardiovascular outcomes research, an extensive review of the existing literature, and an open breakout session discussion on the recommendations at the consensus conference to establish a prioritization of the knowledge gaps and relevant research questions in this area. We identified six priority research areas: 1) out‐of‐hospital cardiac arrest epidemiology and outcome, 2) customized resuscitation drugs, 3) treatment role for sex steroids, 4) targeted temperature management and hypothermia, 5) withdrawal of care after cardiac arrest, and 6) cardiopulmonary resuscitation training and implementation. We believe that exploring these key topics and identifying relevant questions may directly lead to improved understanding of sex‐ and gender‐specific issues seen in cardiac resuscitation and ultimately improved patient outcomes.     

Successful Immunosuppressive Treatment of Erythroid Aplasia Appearing after Thymectomy

S ummary . A unique case of red cell aplasia appearing 2 yr after removal of a thymoma and a transient episode of myasthenic crisis is presented. When the marrow cells of this patient were incubated in vitro a marked increase in haem synthesis occurred, suggesting that the marrow had been freed from an inhibitor of erythroid function. An antibody to erythroblast nuclei was also present. The patient failed to respond to an initial course of immunosuppressive therapy, but after splenectomy he had a second course of immunosuppressive treatment which was followed by a complete haematologic remission. Guidelines for the future therapeutic use of immunosuppressive agents in pure erythroid aplasia are presented.     

Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation

Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.     

Longitudinal trends in antibiotic resistance in US nursing homes, 2000-2004.

We evaluated antibiotic resistance trends in US nursing homes using the Minimum Data Set. Significant increases in the number and proportion of infections caused by antibiotic-resistant bacteria were documented over the 5-year study. Further research on antibiotic resistance in nursing homes is urgently needed.     

Extrapulmonary tuberculosis active infection misdiagnosed as cancer: Mycobacterium tuberculosis disease in patients at a Comprehensive Cancer Center (2001-2005)

BACKGROUND: Extrapulmonary tuberculosis is an uncommon disease in the U.S., even in immunosuppressed cancer patients. This study evaluated characteristics and frequency of extrapulmonary tuberculosis in patients at a tertiary care referral cancer center. METHODS: The records of all consecutive patients with Mycobacterium tuberculosis diagnosed during January 2001 through April 2005 at the M. D. Anderson Cancer Center were reviewed after obtaining institutional review board approval. RESULTS: There were 26 patients with active tuberculosis during the period studied; 18 of them were cancer patients and the others had been referred for a presumed cancer but did not have cancer. The overall rate of active tuberculosis during this period was 0.2 in 1000 new cancer diagnoses. There were 18 men (69%), the median age was 54 years (range, 3-84 yrs), and 16 patients (62%) were born in the U.S. Thirteen (72%) of the 18 cancer patients had solid-organ tumors; 3 of the 5 patients with a hematologic malignancy had non-Hodgkin lymphoma. Three patients (12%) had diabetes mellitus, and 2 patients (8%) had received high-dose (>1 mg/kg of prednisone daily) corticosteroids in the previous week. No patient had a recent history (within the past 4 wks) of chemotherapy; 4 patients had neutropenia. Cough was a prominent symptom (31%), followed by bone pain (19%), dyspnea (15%), and fever (12%). Fifteen patients (58%) had extrapulmonary infection, including 5 patients with concurrent pulmonary involvement; 7 noncancer patients (88%) and 8 cancer patients (44%, P = 0.22) had extrapulmonary disease. In 11 patients (42%), the lungs were the only site of active tuberculosis. Cavitary pneumonia was seen radiographically in 3 of 16 patients (19%) with pulmonary tuberculosis. All M. tuberculosis isolates were susceptible to isoniazid, rifampin, ethambutol, and pyrazinamide; streptomycin resistance was noted in 1 of 22 (5%) isolates tested. Twenty-two patients (85%) received appropriate antituberculosis treatment; all had a clinical and radiographic response. In 3 patients (12%) the cause of death was attributed to M. tuberculosis disease; 2 of 18 cancer patients (11%) died of progressive M. tuberculosis, and they had advanced solid-organ cancer, whereas 1 of 8 patients (13%) without cancer died and the tuberculosis diagnosis was made only on postmortem examination. Univariate analysis showed no significant differences in patients or disease characteristics between non-U.S.-born and U.S.-born patients, whereas noncancer patients (age 52 yrs) and those with extrapulmonary tuberculosis (age 53 yrs) were younger compared with cancer patients (63 yrs; P < 0.007) and those with pulmonary disease (age 60 yrs; P = 0.09). CONCLUSIONS: Extrapulmonary tuberculosis was relatively common in younger patients with active M. tuberculosis infection, and was often initially misdiagnosed as cancer.