The
n e w e ng l a n d j o u r na l
study completion dates, publication dates, and journal names could help to identify journals more likely to publish specific types of studies, to evaluate 10-year trends in studies funded by the National Heart, Lung, and Blood Institute (NHLBI), and to assess the effect of more recent developments in publishing, such as open access and electronic publication ahead of print. Adequately powered, well-funded clinical trials with relevant clinical end points will always be of interest to journal editors. However, smaller studies with surrogate end points have an important role to play and deserve timely publication as well. Identifying the most appropriate journals for these studies before submission may contribute to more opportune publication of NHLBI-funded studies. Frank J. Rodino, M.H.S., P.A. Churchill Outcomes Research Maplewood, NJ [email protected] No potential conflict of interest relevant to this letter was reported. 1. Gordon D, Taddei-Peters W, Mascette A, Antman M,
Kaufmann PG, Lauer MS. Publication of trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med 2013; 369:1926-34. DOI: 10.1056/NEJMc1315653
of
m e dic i n e
date appeared in 50 different journals. They appeared with the greatest frequency in the New England Journal of Medicine (30 publications, with 23 [77%] focused on clinical end points), JAMA (27 publications, with 13 [48%] focused on clinical end points), Archives of Internal Medicine (14 publications, with 1 [7%] focused on clinical end points), and Circulation (7 publications, with none focused on clinical end points). We considered the Journal, JAMA, and Lancet (which published three trials) to be “general journals,” with interests that transcend internal medicine and its subspecialties. In a multivariable logistic regression model adjusting for all the confounders listed in Table 1 of our article, the most powerful independent predictor, by far, of publication in a general journal (as opposed to a specialty journal) was focus on clinical end points (adjusted odds ratio, 21.4; 95% confidence interval, 2.90 to 157.87; P = 0.003). It thus seems reasonable to “target” surrogate end point trials to specialty journals. We acknowledge, though, that we did not collect systematic data on each trial’s primary target journal. David J. Gordon, M.D., Ph.D. Michael S. Lauer, M.D. National Heart, Lung, and Blood Institute Bethesda, MD [email protected]
The Authors Reply: Mr. Rodino asks an intriguing question. The primary results of the 156 trials that were published before our common censor
Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1315653
Natural Disasters, Armed Conflict, and Public Health To the Editor: Leaning and Guha-Sapir (Nov. 7 issue)1 do not mention one important challenge in the delivery of health care during disasters. For example, during the 2011–2012 drought in Somalia, $1.3 billion was used to provide services during a disaster that threatened approximately 3.7 million people.2 In contrast, in Malawi, health care is provided in a continuous emergency situation. Our hospital serves 680,000 persons in inpatient and outpatient settings per year, providing therapy in a wide variety of specialties (e.g., 12,000 surgical operations) with a budget of $5.5 million. On a per capita basis, my colleagues and I could comfort and treat the entire affected Somalian population for 40 years with these resources. 782
Malawian mothers in villages who are waiting for basic services do not understand how logistics could explain this striking financial gap; is there something we are missing? Gregor Pollach, M.D. University of Malawi Blantyre, Malawi [email protected] No potential conflict of interest relevant to this letter was reported. 1. Leaning J, Guha-Sapir D. Natural disasters, armed conflict,
and public health. N Engl J Med 2013;369:1836-42.
2. Darcy J, Bonard P, Dini S. IASC real-time evaluation of the hu-
manitarian response to the Horn of Africa drought crisis: Somalia 2011–2012. United Nations Office for the Coordination of Humanitarian Affairs (OCHA), May 2012 (http://reliefweb.int/sites/ reliefweb.int/files/resources/IASC-RTE%20Somalia%202012.pdf). DOI: 10.1056/NEJMc1315507
n engl j med 370;8 nejm.org february 20, 2014
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
To the Editor: Leaning and Guha-Sapir present strong evidence that climate-related and geophysical events cause substantial illness and death. They point out that armed conflicts have decreased; however, by far the greatest harm from military activity comes from the diversion of money that could be used for beneficial purposes into wasteful military expenditures.1 Global military expenditures in 2012 amounted to $1753 billion — equivalent to 2.5% of the global gross domestic product.2,3 Spending in 2010–2012 was higher in real terms than at the previous peak in 1998, near the end of the Cold War.2,3 Military activity is immensely harmful, not primarily because of the horrible injuries caused by armed conflicts, nor even because of the much larger indirect effect of epidemics, famines, and social disruption on morbidity and mortality, but because of the enormous amount of money wasted on military expenditures that could be used for benefit rather than harm.1 Frank Shann, M.D. Royal Children’s Hospital Melbourne, VIC, Australia No potential conflict of interest relevant to this letter was reported. This letter was updated on February 21, 2014, at NEJM.org. 1. Shann F. Warfare and children. J Paediatr Child Health 2010;
46:217-21. 2. Perlo-Freeman S, Sköns E, Solmirano C, Wilandh H. Fact sheet: trends in world military expenditure, 2012. Stockholm: Stockholm International Peace Research Institute (SIPRI), April 2013. 3. Stockholm International Peace Research Institute (SIPRI) military expenditure database. Stockholm: SIPRI, 2013 (http:// web.sipri.org/contents/milap/milex/mex_database1.html). DOI: 10.1056/NEJMc1315507
To the Editor: We think that the article by Leaning and Guha-Sapir contains a serious omission. The article focused almost entirely on the physical consequences of disaster and to a limited extent on the social and ethical aspects, but it says almost nothing about psychological aspects. Except for one mention of “psychosocial support,” the authors are silent on both the psychological impact of disaster and its management. Although disasters can lead to numerous diagnosable psychiatric disorders,1,2 mental health concerns often take a backseat to physical disorders.3 We are concerned that the lack of focus on mental health might further cement such attitudes among clinicians and relevant authorities.
Sathya Prakash, M.D. Piyali Mandal, M.D., D.C.H. All India Institute of Medical Sciences New Delhi, India [email protected] No potential conflict of interest relevant to this letter was reported. 1. Norris FH, Friedman MJ, Watson PJ, Byrne CM, Diaz E,
Kaniasty K. 60,000 Disaster victims speak: Part I. An empirical review of the empirical literature, 1981-2001. Psychiatry 2002; 65:207-39. 2. Goldmann E, Galea S. Mental health consequences of disasters. Annu Rev Public Health 2013 October 25 (Epub ahead of print). 3. Adams RE, Laraque D, Chemtob CM, Jensen PS, Boscarino JA. Does a one-day educational training session influence primary care pediatricians’ mental health practice procedures in response to a community disaster? Results from the Reaching Children Initiative (RCI). Int J Emerg Ment Health 2013;15:3-14. DOI: 10.1056/NEJMc1315507
The Authors Reply: Pollach notes the great discrepancy between the high costs of emergency logistics for humanitarian relief and the routine ongoing costs of managing clinics and hospitals in resource-constrained regions. The notion is often raised that funds allocated to relieve the distress of people trapped in acute crises are in competition with funds to ease the long-term effects of poverty and desperation. Practically, however, the planning horizons, the political alignments, and the budgetary lines are very different. His point, however, serves to underscore the cost of inaction: were the world more strategically poised to make investments in health, education, economic development, and social justice, then late and very expensive emergency measures would become less necessary.1 This reasoning is behind our call at the end of our article for much greater world attention to early action to prevent or forestall these massive disasters and destructive wars against civilian populations. Shann criticizes the diversion of global resources away from public goods into military expenditures (including the costs of preparing for war as well as the costs of active conflict). Weighing the appropriate balance to some extent depends on where one sits, but we believe his concern is well grounded. A recent book, Warfare Ecology,2 undertakes to explore in some detail the environmental and public health effects of war on our ecosystem — effects that climate change is likely to exacerbate. We agree with Prakash and Mandal that psychosocial factors in disasters and armed conflict
n engl j med 370;8 nejm.org february 20, 2014
783
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
are prevalent in all phases of these crises. Evi- Debarati Guha-Sapir, Ph.D. dence-based mental health responses have been University of Louvain rolled out more recently within the humanitar- Brussels, Belgium Since publication of their article, the authors report no further ian response system, and our mention of psy- potential conflict of interest. chosocial support in a brief list of main public 1. Anand S, Desmond C, Fuje H, Marques N. The cost of inachealth interventions was not meant to diminish tion: case studies from Rwanda and Angola. Boston: FXB Center the importance of this service in particular. for Health and Human Rights and Harvard University Press, 2012. 2. Machlis GE, Hanson T, Špirić Z, McKendry JE, eds. Warfare ecology. NATO science for peace and security series. Dordrecht, the Netherlands: Springer, 2011.
Jennifer Leaning, M.D. Harvard School of Public Health Boston, MA [email protected]
DOI: 10.1056/NEJMc1315507
Case 35-2013: A Man with Confusion and Malaise To the Editor: In the Case Record involving a 77-year-old man with high-grade lymphoma, Barnes and colleagues (Nov. 14 issue)1 note that the patient reported “numbness of the lower lip and chin bilaterally.” We would like to draw attention to the fact that the symptom described by the patient is part of the “numb chin syndrome” described in 1830 by Charles Bell.2 In Bell’s description of a patient with metastatic breast cancer, he writes: “an elderly maiden lady consulted me on account of a cancer in the breast; but of all her more formidable symptoms, none gave her so much anxiety as an insensibility of the lower lip.” The numb chin syndrome, which is caused by sensory neuropathy of the mental nerve, is associated either with a local dental disease or with a metastatic condition (mainly breast cancer and lymphoma).3 This syndrome may be the first manifestation of high-grade lymphoblastic lymphoma,4 as in the patient described by Barnes et al. Familiarity with this unique entity should alert physicians to the possibility of an ongoing metastatic process. Eytan Cohen, M.D. Elad Goldberg, M.D. Ilan Krause, M.D. Rabin Medical Center Petah Tikva, Israel [email protected]
No potential conflict of interest relevant to this letter was reported. 1. Case Records of the Massachusetts General Hospital (Case
35-2013). N Engl J Med 2013;369:1946-57.
2. Furukawa T. Charles Bell’s description of numb chin syn-
drome. Neurology 1988;38:331. 3. Lossos A, Siegal T. Numb chin syndrome in cancer patients: etiology, response to treatment, and prognostic significance. Neurology 1992;42:1181-4. 4. Baskaran RK, Krishnamoorthy, Smith M. Numb chin syndrome — a reflection of systemic malignancy. World J Surg Oncol 2006;4:52. DOI: 10.1056/NEJMc1315560
The Discussants Reply: We thank Cohen and colleagues for highlighting the clinical finding of facial numbness, which, as we observed in the Case Record, may be seen in patients with high-grade lymphomas, acute leukemias, and metastatic solid tumors with extensive bone marrow infiltration and associated mental-nerve injury. Jeffrey A. Barnes, M.D., Ph.D. Jeremy S. Abramson, M.D. Massachusetts General Hospital Boston, MA Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1315560
C4 Dense-Deposit Disease To the Editor: Dense-deposit disease is a com- lary-wall C3 staining on immunofluorescence plement-mediated disorder characterized by a microscopy, and large intramembranous osmioproliferative glomerulonephritis, bright capil- philic dense deposits that markedly thicken the 784
n engl j med 370;8 nejm.org february 20, 2014
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
study completion dates, publication dates, and journal names could help to identify journals more likely to publish specific types of studies, to evaluate 10-year trends in studies funded by the National Heart, Lung, and Blood Institute (NHLBI), and to assess the effect of more recent developments in publishing, such as open access and electronic publication ahead of print. Adequately powered, well-funded clinical trials with relevant clinical end points will always be of interest to journal editors. However, smaller studies with surrogate end points have an important role to play and deserve timely publication as well. Identifying the most appropriate journals for these studies before submission may contribute to more opportune publication of NHLBI-funded studies. Frank J. Rodino, M.H.S., P.A. Churchill Outcomes Research Maplewood, NJ [email protected] No potential conflict of interest relevant to this letter was reported. 1. Gordon D, Taddei-Peters W, Mascette A, Antman M,
Kaufmann PG, Lauer MS. Publication of trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med 2013; 369:1926-34. DOI: 10.1056/NEJMc1315653
of
m e dic i n e
date appeared in 50 different journals. They appeared with the greatest frequency in the New England Journal of Medicine (30 publications, with 23 [77%] focused on clinical end points), JAMA (27 publications, with 13 [48%] focused on clinical end points), Archives of Internal Medicine (14 publications, with 1 [7%] focused on clinical end points), and Circulation (7 publications, with none focused on clinical end points). We considered the Journal, JAMA, and Lancet (which published three trials) to be “general journals,” with interests that transcend internal medicine and its subspecialties. In a multivariable logistic regression model adjusting for all the confounders listed in Table 1 of our article, the most powerful independent predictor, by far, of publication in a general journal (as opposed to a specialty journal) was focus on clinical end points (adjusted odds ratio, 21.4; 95% confidence interval, 2.90 to 157.87; P = 0.003). It thus seems reasonable to “target” surrogate end point trials to specialty journals. We acknowledge, though, that we did not collect systematic data on each trial’s primary target journal. David J. Gordon, M.D., Ph.D. Michael S. Lauer, M.D. National Heart, Lung, and Blood Institute Bethesda, MD [email protected]
The Authors Reply: Mr. Rodino asks an intriguing question. The primary results of the 156 trials that were published before our common censor
Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1315653
Natural Disasters, Armed Conflict, and Public Health To the Editor: Leaning and Guha-Sapir (Nov. 7 issue)1 do not mention one important challenge in the delivery of health care during disasters. For example, during the 2011–2012 drought in Somalia, $1.3 billion was used to provide services during a disaster that threatened approximately 3.7 million people.2 In contrast, in Malawi, health care is provided in a continuous emergency situation. Our hospital serves 680,000 persons in inpatient and outpatient settings per year, providing therapy in a wide variety of specialties (e.g., 12,000 surgical operations) with a budget of $5.5 million. On a per capita basis, my colleagues and I could comfort and treat the entire affected Somalian population for 40 years with these resources. 782
Malawian mothers in villages who are waiting for basic services do not understand how logistics could explain this striking financial gap; is there something we are missing? Gregor Pollach, M.D. University of Malawi Blantyre, Malawi [email protected] No potential conflict of interest relevant to this letter was reported. 1. Leaning J, Guha-Sapir D. Natural disasters, armed conflict,
and public health. N Engl J Med 2013;369:1836-42.
2. Darcy J, Bonard P, Dini S. IASC real-time evaluation of the hu-
manitarian response to the Horn of Africa drought crisis: Somalia 2011–2012. United Nations Office for the Coordination of Humanitarian Affairs (OCHA), May 2012 (http://reliefweb.int/sites/ reliefweb.int/files/resources/IASC-RTE%20Somalia%202012.pdf). DOI: 10.1056/NEJMc1315507
n engl j med 370;8 nejm.org february 20, 2014
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
To the Editor: Leaning and Guha-Sapir present strong evidence that climate-related and geophysical events cause substantial illness and death. They point out that armed conflicts have decreased; however, by far the greatest harm from military activity comes from the diversion of money that could be used for beneficial purposes into wasteful military expenditures.1 Global military expenditures in 2012 amounted to $1753 billion — equivalent to 2.5% of the global gross domestic product.2,3 Spending in 2010–2012 was higher in real terms than at the previous peak in 1998, near the end of the Cold War.2,3 Military activity is immensely harmful, not primarily because of the horrible injuries caused by armed conflicts, nor even because of the much larger indirect effect of epidemics, famines, and social disruption on morbidity and mortality, but because of the enormous amount of money wasted on military expenditures that could be used for benefit rather than harm.1 Frank Shann, M.D. Royal Children’s Hospital Melbourne, VIC, Australia No potential conflict of interest relevant to this letter was reported. This letter was updated on February 21, 2014, at NEJM.org. 1. Shann F. Warfare and children. J Paediatr Child Health 2010;
46:217-21. 2. Perlo-Freeman S, Sköns E, Solmirano C, Wilandh H. Fact sheet: trends in world military expenditure, 2012. Stockholm: Stockholm International Peace Research Institute (SIPRI), April 2013. 3. Stockholm International Peace Research Institute (SIPRI) military expenditure database. Stockholm: SIPRI, 2013 (http:// web.sipri.org/contents/milap/milex/mex_database1.html). DOI: 10.1056/NEJMc1315507
To the Editor: We think that the article by Leaning and Guha-Sapir contains a serious omission. The article focused almost entirely on the physical consequences of disaster and to a limited extent on the social and ethical aspects, but it says almost nothing about psychological aspects. Except for one mention of “psychosocial support,” the authors are silent on both the psychological impact of disaster and its management. Although disasters can lead to numerous diagnosable psychiatric disorders,1,2 mental health concerns often take a backseat to physical disorders.3 We are concerned that the lack of focus on mental health might further cement such attitudes among clinicians and relevant authorities.
Sathya Prakash, M.D. Piyali Mandal, M.D., D.C.H. All India Institute of Medical Sciences New Delhi, India [email protected] No potential conflict of interest relevant to this letter was reported. 1. Norris FH, Friedman MJ, Watson PJ, Byrne CM, Diaz E,
Kaniasty K. 60,000 Disaster victims speak: Part I. An empirical review of the empirical literature, 1981-2001. Psychiatry 2002; 65:207-39. 2. Goldmann E, Galea S. Mental health consequences of disasters. Annu Rev Public Health 2013 October 25 (Epub ahead of print). 3. Adams RE, Laraque D, Chemtob CM, Jensen PS, Boscarino JA. Does a one-day educational training session influence primary care pediatricians’ mental health practice procedures in response to a community disaster? Results from the Reaching Children Initiative (RCI). Int J Emerg Ment Health 2013;15:3-14. DOI: 10.1056/NEJMc1315507
The Authors Reply: Pollach notes the great discrepancy between the high costs of emergency logistics for humanitarian relief and the routine ongoing costs of managing clinics and hospitals in resource-constrained regions. The notion is often raised that funds allocated to relieve the distress of people trapped in acute crises are in competition with funds to ease the long-term effects of poverty and desperation. Practically, however, the planning horizons, the political alignments, and the budgetary lines are very different. His point, however, serves to underscore the cost of inaction: were the world more strategically poised to make investments in health, education, economic development, and social justice, then late and very expensive emergency measures would become less necessary.1 This reasoning is behind our call at the end of our article for much greater world attention to early action to prevent or forestall these massive disasters and destructive wars against civilian populations. Shann criticizes the diversion of global resources away from public goods into military expenditures (including the costs of preparing for war as well as the costs of active conflict). Weighing the appropriate balance to some extent depends on where one sits, but we believe his concern is well grounded. A recent book, Warfare Ecology,2 undertakes to explore in some detail the environmental and public health effects of war on our ecosystem — effects that climate change is likely to exacerbate. We agree with Prakash and Mandal that psychosocial factors in disasters and armed conflict
n engl j med 370;8 nejm.org february 20, 2014
783
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
are prevalent in all phases of these crises. Evi- Debarati Guha-Sapir, Ph.D. dence-based mental health responses have been University of Louvain rolled out more recently within the humanitar- Brussels, Belgium Since publication of their article, the authors report no further ian response system, and our mention of psy- potential conflict of interest. chosocial support in a brief list of main public 1. Anand S, Desmond C, Fuje H, Marques N. The cost of inachealth interventions was not meant to diminish tion: case studies from Rwanda and Angola. Boston: FXB Center the importance of this service in particular. for Health and Human Rights and Harvard University Press, 2012. 2. Machlis GE, Hanson T, Špirić Z, McKendry JE, eds. Warfare ecology. NATO science for peace and security series. Dordrecht, the Netherlands: Springer, 2011.
Jennifer Leaning, M.D. Harvard School of Public Health Boston, MA [email protected]
DOI: 10.1056/NEJMc1315507
Case 35-2013: A Man with Confusion and Malaise To the Editor: In the Case Record involving a 77-year-old man with high-grade lymphoma, Barnes and colleagues (Nov. 14 issue)1 note that the patient reported “numbness of the lower lip and chin bilaterally.” We would like to draw attention to the fact that the symptom described by the patient is part of the “numb chin syndrome” described in 1830 by Charles Bell.2 In Bell’s description of a patient with metastatic breast cancer, he writes: “an elderly maiden lady consulted me on account of a cancer in the breast; but of all her more formidable symptoms, none gave her so much anxiety as an insensibility of the lower lip.” The numb chin syndrome, which is caused by sensory neuropathy of the mental nerve, is associated either with a local dental disease or with a metastatic condition (mainly breast cancer and lymphoma).3 This syndrome may be the first manifestation of high-grade lymphoblastic lymphoma,4 as in the patient described by Barnes et al. Familiarity with this unique entity should alert physicians to the possibility of an ongoing metastatic process. Eytan Cohen, M.D. Elad Goldberg, M.D. Ilan Krause, M.D. Rabin Medical Center Petah Tikva, Israel [email protected]
No potential conflict of interest relevant to this letter was reported. 1. Case Records of the Massachusetts General Hospital (Case
35-2013). N Engl J Med 2013;369:1946-57.
2. Furukawa T. Charles Bell’s description of numb chin syn-
drome. Neurology 1988;38:331. 3. Lossos A, Siegal T. Numb chin syndrome in cancer patients: etiology, response to treatment, and prognostic significance. Neurology 1992;42:1181-4. 4. Baskaran RK, Krishnamoorthy, Smith M. Numb chin syndrome — a reflection of systemic malignancy. World J Surg Oncol 2006;4:52. DOI: 10.1056/NEJMc1315560
The Discussants Reply: We thank Cohen and colleagues for highlighting the clinical finding of facial numbness, which, as we observed in the Case Record, may be seen in patients with high-grade lymphomas, acute leukemias, and metastatic solid tumors with extensive bone marrow infiltration and associated mental-nerve injury. Jeffrey A. Barnes, M.D., Ph.D. Jeremy S. Abramson, M.D. Massachusetts General Hospital Boston, MA Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1315560
C4 Dense-Deposit Disease To the Editor: Dense-deposit disease is a com- lary-wall C3 staining on immunofluorescence plement-mediated disorder characterized by a microscopy, and large intramembranous osmioproliferative glomerulonephritis, bright capil- philic dense deposits that markedly thicken the 784
n engl j med 370;8 nejm.org february 20, 2014
The New England Journal of Medicine Downloaded from nejm.org at RUTGERS UNIV ALEXANDER LIBRARY on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
