Ethical considerations for critical care research

Lapses at the New England Journal of Medicine

Professional advancement in academic plastic surgery may depend on scholarly activity. The authors evaluate gender-based publishing characteristics in three international plastic surgery journals. A retrospective review of all articles published in 2016 in the following journals was undertaken: Plastic and Reconstructive Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, European Journal of Plastic Surgery, Annals of Surgery, and New England Journal of Medicine. Data were collected on lead author gender (first or senior author) and differences in author gender proportions, by journal, by article topic, and by geographic location were evaluated. Overall, 2610 articles were retrieved: 34.1 percent were from plastic surgery journals, 12.8 percent were from the Annals of Surgery, and 53.1 percent were from the New England Journal of Medicine. There was a lower proportion of female lead authors among plastic surgery journals compared with the Annals of Surgery and the New England Journal of Medicine (31 percent versus 39 percent versus 39 percent; p = 0.001). There were no differences in female lead author geographic location in the Annals of Surgery or the New England Journal of Medicine; within the plastic surgery journals, there were differences (p = 0.005), including a lower proportion arising from East Asia (15 percent) and a higher proportion arising from Canada (48 percent). Within plastic surgery, Plastic and Reconstructive Surgery had the lowest proportion of female lead author (p < 0.001). The proportion of female lead author varied by article topic (p < 0.001) and was notably higher in breast (45.6 percent) and lower in head and neck/craniofacial-orientated articles (25.0 percent). There are gender disparities in three mainstream plastic surgery journals-Plastic and Reconstructive Surgery, the Journal of Plastic, Reconstructive and Aesthetic Surgery, the European Journal of Plastic Surgery-and there are lower proportions of lead female authorship compared with the Annals of Surgery and the New England Journal of Medicine. Further research should focus on understanding any geographic disparities that may exist.

Kathy Stern, the Graphic Arts Director at the New England Journal of Medicine (NEJM), is familiar with the adage “A picture is worth a thousand words.” Over her 29-year career with the NEJM, Kathy has drawn and overseen countless images telling myriad stories and has thus contributed millions of “words” to the information shared with NEJM readers. Images range from in-house illustrations drawn by medical illustrators, to line art graphs, photographs submitted by physician-authors, still images captured from videos created in-house, interactive online elements, and more. In this interview, Kathy discusses how she started in the production department back in the days of paste-up layout and now oversees a department of more than 20 employees working with state-of-the-art digital tools. Science Editor: How did you get started with your career at the New England Journal of Medicine (NEJM)? Kathy Stern: I started out working in a production facility that wasn’t even part of the editorial office. We communicated with a production coordinator in Boston (where the NEJM editorial offices are located) who worked directly with the editors. NEJM was one of several products that the production facility of the Massachusetts Medical Society served, but it was, by far, the biggest product. It was a massive amount of detail work. Everything was done with manual layout with precision cutting knives, acetate, and wax. We would create 14 different proofs that went out to 14 different people. Our main focus was the level of detail; everything had to be exactly right. If […]

Breast cancer is a disease associated with aging. In the US, the median age of breast cancer diagnosis and death is 61 years and 68 years, respectively. The number of older adults in the US is rising, and the number of individuals age 65 and older is expected to double by the year 2030. This demographic shift will lead to an increase in the number of individuals diagnosed with breast cancer. It is estimated that from 2010 to 2030 there will be a 57% growth in the number of new cases of breast cancer in patients age 65 and older.1 A challenge in caring for older adults with breast cancer is that they have been historically underrepresented in clinical trials that set the standard for breast cancer care.2 However, a growing body of evidence-based literature can be utilized to inform and optimize the care of the older adults with breast cancer. This presentation will focus on the treatment of early stage breast cancer in older adults, including the risks and benefits of local and systemic therapies, as well as survivorship issues. Recently reported phase III studies have led to advances in the treatment of older adults with breast cancer. A phase III randomized study evaluated the role of radiation therapy following lumpectomy in patients age 70 and older with stage I hormone receptor (HR) positive breast cancer who received treatment with tamoxifen. Receipt of radiation therapy was associated with a decrease in the risk of locoregional recurrence; however, there was no difference in overall survival. The study results underscore the importance of competing comorbidity as a cause of death in older adults with early stage breast cancer.3 The role of axillary lymph node dissection was evaluated in a randomized study of women over age 60 with node-negative, HR positive breast cancer who received treatment with tamoxifen. Patients were randomized to breast surgery and axillary dissection, or breast surgery alone. There was no difference between disease-free and overall survival in the 2 study arms.4 A phase III randomized study evaluated the efficacy of standard adjuvant IV chemotherapy (doxorubicin and cyclophosphamide [AC] or cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) versus oral chemotherapy (capecitabine) in patients age 65 and older with stage I-III breast cancer. Those patients who received standard chemotherapy showed improvement in progression-free and overall survival compared with patients who received capecitabine. This study demonstrates that IV polychemotherapy regimens remain the standard of care for older adults who are prescribed adjuvant chemotherapy.5 These phase III studies advance our understanding in the care of older adults with breast cancer. Furthermore, they demonstrate the feasibility and importance of accruing older adults to phase III trials, which will improve our evidence-based care of this growing population.

Citations rule the world—at least the world of academic medicine. Because of the importance of the impact factor, medical journals are dependent on being cited as often as possible in other medical journals. This is also true of Deutsches Arzteblatt International, which, after its inclusion in the Science Citation Index in 2009, is expecting its first impact factor in 2011 (1). In this situation, it is easy to forget that citations in the lay press too are important for medical journals. Being mentioned in the general media may not enhance the impact factor, but is a sign of how important the public deems a journal. By studying the German lay press one can gain an impression as to whether the prejudice that medicine is completely anglicized is correct. Is it really true that only English language journals are important in the work of a German medical journalist? We have analyzed how often leading German lay media mentioned German and English language medical journals in the course of the preceding eight years. The analysis was based on six medical journals, which are comparable, as they all appear weekly and all cover a variety of medical subjects: the New England Journal of Medicine, JAMA, the British Medical Journal, Deutsche Medizinische Wochenschrift, Munchener Medizinische Wochenschrift, and Deutsches Arzteblatt (for details of the methods, see the Box). Box The frequency was examined of the citations of the scientific content of the following weekly medical journals: the New England Journal of Medicine, the Journal of the American Medical Association (JAMA), the British Medical Journal (BMJ), Deutsche Medizinische Wochenschrift, Munchener Medizinische Wochenschrift—Fortschritte der Medizin, and Deutsches Arzteblatt. The journals selected were all clinically orientated magazines for general medicine (rather than specialized journals). The survey was based on the results of a search in the online search machines of FAZ, Welt, SZ, Spiegel, and Zeit. The search only covered central printed products, so that, for example, the Frankfurter Allgemeinen Sonntagszeitung (Sunday Newspaper), the SZ Magazin and Spiegel Online were excluded. For reasons of capacity, we could only consider five of the important and serious printed media in Germany. All journal names were searched for under their complete titles (e.g. New England Journal of Medicine, Munchener Medizinische or Munchener Medizinische Wochenschrift—Fortschritte der Medizin) and their conventional abbreviations (NEJM, N Engl J Med, or MMW or MMW Fortschr Med). Different cases (e.g. Deutsche/r Medizinische/n Wochenschrift) or other close variants (e.g. Munchener/Munchner Medizinische Wochenschrift) were considered. A citation was only counted if it was a direct reference to the scientific content of one of the six medical journals. Thus, a reference to the appointments section of Deutsches Arzteblatt or the announcements of its publishers were not counted as scientific citations. The English edition of Deutsches Arzteblatt, Deutsches Arzteblatt International, was excluded from the evaluation. On the other hand, in a subanalysis, the citations for Deutsches Arzteblatt which related to its political reporting were counted seperately. To ensure a reliable check of the citation of a scientific journal, the full text of the lay journal or newspaper was always searched for. The search took place between November 2008 and March 2009.

Comparison of survival of medically and surgically treated coronary disease patients in Seattle Heart Watch: a nonrandomized study.

When I was in my teens, I built a small radio transmitter from individual components. It was my first homebrew project, and I was anxious to see whether I could connect with someone far away from my home in St. Louis. After hours on the air desperately sending “CQ CQ CQ this is WAOAJX” in Morse code, I gave up. I had raised no one. Despite my broadcasts, nobody, it seemed, was aware of my work. I set the project aside. A few months later, I received a postcard from Mexico. Someone had picked up my signal, but I could not hear his response. Although I had succeeded in transmitting, the time frame and the mechanism of response were not what I had expected. Article see p 1755 What does this have to do with cardiovascular research? In this issue of Circulation , an article by Ranasinghe and coworkers looks at “poorly cited articles” in peer-reviewed cardiovascular journals.1 The authors’ premise is that articles that are infrequently cited are of limited impact and therefore “may reflect inefficiency and waste in the research enterprise.” Their key assumption is that impact can be measured by citations within the first 5 years from publication. If your work is important to others, they will cite it when they report their own work; this will happen within a few years of publication. This assumption may often be true, but is it also true that if no one rapidly cites your work, it is unimportant? By their statement about “inefficiency and waste in the research enterprise,” Ranasinghe et al seem to think so. But just as I had to wait to learn that my meager radio signal had reached a faraway place, recognition of the …

1 Department of Paediatric Intensive Care, Great North Children's Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 2 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. *See also p. 301. Dr. Agbeko's institution received funding from the National Institute for Health and Care Research; she received funding from the British Medical Journal.

PACIFIC: Time for a surgical IIIA uprising

Acute myeloid leukemia is heterogeneous with respect to clinical outcome and molecular pathogenesis. Approximately 20% of AML cases are refractory to induction chemotherapy, and about 50% of patients ultimately relapse within a time interval that ranges from months to years. At the molecular level, diverse chromosomal abnormalities and genetic mutations have been observed across patients1. Although several clinical factors (age, white blood cell count), cytogenetic aberrations (t[15;17] translocation, loss of chromosome 5) 2-4, and genetic mutations (DNMT3A, FLT3) have been associated with differences in survival 5,6, these factors are of limited prognostic utility. Moreover, few studies have integrated sequence data with clinical and cytogentic factors to build predictive models of patient outcome. Here, we sought to identify genomic predictors of refractory disease or early relapse. We used whole genome and exome sequencing to analyze the genomes of 71 adult de novo AML patients treated with anthracycline and cytarabine-based induction chemotherapy. Of these, 34 had refractory disease or relapsed within 6 months, 12 relapsed in 6-12 months, and 25 had a long first remission (&amp;gt;12 months). We also developed an enhanced exome sequencing (EES) approach to identify and follow leukemia-associated variants over time. In 12 additional patients that achieved morphologic remission after induction chemotherapy, we used EES to identify and track variants at time of diagnosis, time of morphologic remission (roughly 30 days later), and a final time point corresponding to eventual relapse (n=8) or extended remission (n=4). No novel coding or non-coding variants present at the time of diagnosis were found to be predictive of refractory disease or early relapse. Using EES, however, we were able to detect leukemia-associated variants in the initial remission bone marrow in all eight patients who eventually relapsed. One persistent leukemia-associated variant was also detected in one patient still in remission, but all other variants in that patient were eliminated. We also detected 64 somatic variants that became enriched following chemotherapy, but were not detected in the original leukemic cells. These may represent relapse-specific variants or oligoclonal hematopoiesis after bone marrow recovery. Overall, our data suggest that the persistence of leukemia-associated variants after bone marrow recovery from cytotoxic therapy is strongly correlated with relapse, and may be used to complement more traditional, morphologic measures of leukemic cell clearance. 1. Cancer Genome Atlas Research N. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. The New England Journal of Medicine 2013;368:2059-74. 2. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002;100:4325-36. 3. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116:354-65. 4. Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. The New England Journal of Medicine 2008;358:1909-18. 5. Kihara R, Nagata Y, Kiyoi H, et al. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 2014;28:1586-95. 6. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. The New England Journal of Medicine 2010;363:2424-33. Citation Format: Jeffery M. Klco, Christopher A. Miller, Malachi Griffith, Allegra Petti, David H. Spencer, Shamika Ketkar-Kulkarni, Lukas D. Wartman, Matthew Christopher, Tamara L. Lamprecht, Jacqueline E. Payton, Jack Baty, Sharon E. Heath, Obi L. Griffith, Dong Shen, Jasreet Hundal, Gue Su Chang, Robert S. Fulton, Michelle O'laughlin, Catrina Fronick, Vincent Magrini, Ryan Demeter, David E. Larson, Shashikant Kulkarni, Bradley A. Ozenberger, John S. Welch, Matthew J. Walker, Timothy A. Graubert, Peter Westervelt, Jerald P. Radich, Daniel C. Link, Elaine R. Mardis, John F. DiPersio, Richard K. Wilson. Genomic approaches for risk assessment in acute myeloid leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR11.

Introduction: We report preliminary results of the mineralogy, petrology, and LA-ICPMS refractory trace element and REE analyses of six type A inclusions and one hibonite bearing inclusion from the Lance...

Articles in The New England Journal of Medicine get tremendous publicity, some justified and some not. Recently, 2 articles and an editorial (1)(2)(3) were published about the use of “high-sensitivity” cardiac troponin (cTn).1 These articles are welcome because they emphasize important concepts for clinicians. Some aspects, however, require clarification. Here we examine these articles and separate out new data from hype. No. Most of the assays used are contemporary assays (4), including the Siemens Ultra and Abbott Architect assays. Two new assays were included, both from Roche: a hs-cTnT assay (1) and a first description of a cTnI assay. There are no analytical data to evaluate the cTnI assay, but it appears similar to contemporary cTnI assays at best. The new hs-cTnT assay (2) is a novel high-sensitivity assay. Although there are no published analytical studies of the assay, there are several clinical publications. The hs-cTnT assay appears more analytically sensitive (4) than the others (see “What Does the Future Hold?” below). Despite that, the hs-cTnT assay was not statistically better clinically than the other assays for detection of acute myocardial infarction (AMI) (1). They are not novel. The findings are more robust because larger patient groups were used. But the concept is not new that if one uses ( a ) sensitive contemporary assays as opposed to many presently available insensitive assays and ( b ) the 99th percentile cutoff recommended by guidelines groups, then early diagnosis occurs frequently. It is the use of the 99th percentile value as a decision cutpoint that is key for early diagnosis. Similar findings were reported in 2006 and confirmed. The New England Journal of Medicine results (1)(2) are impressive, which likely reflects differences in the populations studied. Hopefully, the publicity associated with The New England Journal of Medicine …

Paying the Price: The psychiatric cost of war

We have read with great

Amylin, Eli Lilly, and Alkermes received a full response letter from the USFDA on the companies' New Drug Application (NDA) for their once-weekly exenatide, thereafter branded Bydureon.The USFDA's letter did not request any new clinical or preclinical data or data analysis, instead focusing on label fi nalization, Risk Evaluation and Mitigation Strategy (REMS), and clarifi cation