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association between BMI and mortality was similar in persons with a high level of physical activity and those with a low level (P = 0.19 for interaction in women and P = 0.37 for interaction in men). In a previous study, we found that BMI and physical activity were independently associated with the risk of death.1 In the Aerobics Center Longitudinal Study, a high BMI was the most important modifiable risk factor for low cardiorespiratory fitness, and obesity was found to offset the benefits of physical activity on fitness.2 Furthermore, weight loss through lifestyle interventions was highly effective in improving physical fitness.3 In response to Logue et al.: although our Nurses’ Health Study and Health Professionals Follow-up Study cohorts were enrolled in 1976 and 1986, respectively, our analyses included incident diabetes cases through January 1, 2010. Thus, our cohorts reflected contemporary populations of patients with diabetes. Because body weight is substantially influenced by disease severity and methods of treatment, it is important to use BMI before or at the time of a diabetes diagnosis. As shown in our data and those of others, weight loss is common in patients with diabetes, even shortly before the diagnosis. Therefore, use of the postdiagnosis weight increases the potential for reverse-causation biases. Dixon and Kral note that overweight and obesity might be protective against premature death in older populations by providing metabolic reserves, although this hypothesis has yet

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to be tested. However, among older participants (≥65 years of age) at diabetes diagnosis, we found no survival advantage associated with overweight or obesity. BMI is a less valid measure of excess body fat in elderly populations than in younger populations, owing to differential loss of muscle mass related to sarcopenia and increased frailty. Future studies involving elderly populations should pay particular attention to these methodologic issues, especially weight loss due to chronic diseases, and should also include measures of bodyfat distribution such as waist circumference. Deirdre Tobias, Sc.D. Harvard School of Public Health Boston, MA [email protected]

An Pan, Ph.D. National University of Singapore Singapore, Singapore

Frank B. Hu, M.D., Ph.D. Harvard School of Public Health Boston, MA Since publication of their article, the authors report no further potential conflict of interest. 1. Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson

JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 2004;351:2694-703. 2. Jackson AS, Sui X, Hébert JR, Church TS, Blair SN. Role of lifestyle and aging on the longitudinal change in cardiorespiratory fitness. Arch Intern Med 2009;169:1781-7. 3. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-54. DOI: 10.1056/NEJMc1401876

Acute Osteomyelitis in Children To the Editor: In their article on acute osteomyelitis in children, Peltola and Pääkkönen (Jan. 23 issue)1 proposed measurement of serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate, blood culture, and plain radiography for the primary evaluation of a child with presumed acute osteomyelitis. The first step in their algorithm that initiates action (further evaluation) is elevation of CRP levels or the erythrocyte sedimentation rate, whereas normal CRP levels and erythrocyte sedimentation rates indicate observation and later reevaluation or, if clinically indicated, the same evalu-

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ation as for an elevation of either value. Given that an elevated erythrocyte sedimentation rate is not specific for osteomyelitis,2,3 and that a normal rate persists long after the development of osteomyelitis (long after CRP levels become elevated),4 there is, in our opinion, no evidence for measuring the erythrocyte sedimentation rate in patients with acute disease. The relatively low cost of measuring the erythrocyte sedimentation rate may argue in its favor, but every test is expensive if it does not improve diagnostic specificity or sensitivity, particularly when ordered frequently. Furthermore, a false posi-

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correspondence

tive result can both introduce additional costs Edward P. Fink, M.D. and put the patient at risk from the effects of 2410 E. Carol Ave. Phoenix, AZ additional procedures. [email protected]

Rihard Trebše, M.D., Ph.D. Rene Mihalič, M.D.

No potential conflict of interest relevant to this letter was reported.

Valdoltra Orthopedic Hospital Ankaran, Slovenia [email protected]

1. Yagupsky P, Porsch E, St Geme JW III. Kingella kingae:

No potential conflict of interest relevant to this letter was reported.

DOI: 10.1056/NEJMc1402234

an emerging pathogen in young children. Pediatrics 2011;127: 557-65.

1. Peltola H, Pääkkönen M. Acute osteomyelitis in children.

N Engl J Med 2014;370:352-60. 2. Brigden M. The erythrocyte sedimentation rate: still a helpful test when used judiciously. Postgrad Med 1998;103:257-62, 272-4. 3. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. C-reactive protein versus erythrocyte sedimentation rate, white blood cell count and alkaline phosphatase in diagnosing bacteraemia in bone and joint infections. J Paediatr Child Health 2013;49(3):E189-E192. 4. Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H. Serum C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in acute hematogenous osteomyelitis of children. Pediatrics 1994;93:59-62. DOI: 10.1056/NEJMc1402234

To the Editor: The statement by Peltola and Pääkkönen that acute osteomyelitis in children “is considerably more common in low-income countries” may be inaccurate. In many resourcepoor countries, timely access to proper medical care and treatment is not available. By the time most children with acute open fractures are seen, infection has already established itself and become chronic. Similarly, the referral of children with acute hematogenous osteomyelitis for care is often delayed, producing chronic osteomyelitis, for which the treatment considerations are very different. The authors also state that infections due to Kingella kingae are increasing. Although Yagupsky et al.1 report that the organism was associated with infection more than four decades ago, proper laboratory identification techniques were not recognized at that time. As more laboratories have begun to perform proper assays for the bacteria, their role as a causative agent is being more readily appreciated. However, there is no evidence that kingella produces higher rates of infection. Indeed, the inability to culture the organism in the past may explain the relatively high rate of culture negative cases that have been reported for decades.

The Authors Reply: Trebše and Mihalič question whether measurement of the erythrocyte sedimentation rate adds anything to the determination of the CRP level in a child with suspected acute osteomyelitis. The benefit is no doubt small, but in our prospective series of 265 osteoarticular infections, the sensitivity of the CRP level (cutoff point, 20 mg per liter) for diagnosis was 95%, but it was 98% with measurement of both the CRP level and the erythrocyte sedimentation rate (cutoff point, 20 mm per hour).1 The sensitivity of the erythrocyte sedimentation rate alone was 94%. Although the erythrocyte sedimentation rate performs as well as the CRP level for diagnostic purposes, the CRP level is a more valuable test overall, because the erythrocyte sedimentation rate reacts to treatment too slowly to be of much value in follow-up.1 Fink questions whether acute osteomyelitis is more common among children in low-income countries. The incidence is unknown in various parts of the world, but the day-to-day experience of colleagues working in low-income countries indicates that bone infections are rampant. The few available reports are usually from a single institution and lack population-based data. In KwaZulu-Natal, a rural province of South Africa, the incidence of hematogenous bone and joint sepsis was estimated to be 1 in 4000 among children younger than 15 years of age, which is high as compared with the incidences in North America and Europe.2 In Malawi, the incidence of septic arthritis is 1 in 5000 among children younger than 5 years of age,3 and osteomyelitis is usually twice as common as septic arthritis. Several factors may explain these high incidence rates. Malnutrition, poor hygiene, and trauma all are factors predisposing underprivileged children to infectious diseases. Similarly, salmonella osteomyelitis is not uncommon in the malar-

n engl j med 370;14 nejm.org april 3, 2014

The New England Journal of Medicine Downloaded from nejm.org at MIT LIBRARIES on November 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.

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ial regions of sub-Saharan Africa, where sickle Heikki Peltola, M.D. cell disease is also prevalent.4 Helsinki University Central Hospital Fink also argues that improved diagnostic Helsinki, Finland Since publication of their article, the authors report no furmethods alone account for the “emergence” of K. kingae infection in children with osteomyelitis. ther potential conflict of interest. This may sometimes be the case, but in Scandi- 1. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Sensitivity of navia K. kingae has been actively sought for dec- erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res 2010;468: ades but found only on occasion and only during 861-6. the past few years. The use of day care outside 2. Nunn T, Rollinson P. Haematogenous pyogenic bone and the home seems to be increasing the oropharyn- joint sepsis — reducing avoidable morbidity. S Afr Med J 2007; 97:456-60. geal colonization of K. kingae and invasive infec- 3. Lavy CB, Peek AC, Manjolo G. The incidence of septic arthrition,5 but this pathogen is clearly more common tis in Malawian children. Int Orthop 2005;29:195-6. 4. Ebong WW. Acute osteomyelitis in Nigerians with sickle cell in some countries than in others. disease. Ann Rheum Dis 1986;45:911-5.

Markus Pääkkönen, M.D.

5. Amit U, Dagan R, Yagupsky P. Prevalence of pharyngeal car-

Turku University Hospital Turku, Finland [email protected]

DOI: 10.1056/NEJMc1402234

riage of Kingella kingae in young children and risk factors for colonization. Pediatr Infect Dis J 2013;32:191-3.

Nephropathic Cystinosis — A Gap between Developing and Developed Nations To the Editor: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that, if untreated, leads to end-stage renal disease (ESRD) in the first decade of life because of

Renal Survival from Diagnosis (%)

100 90 80 70 60 50 40 Developed countries

30 No cysteamine treatment in developing countries

20 10 0

0

5

Cysteamine treatment in developing countries 10

15

20

25

Years to ESRD

Figure 1. Time to End-Stage Renal Disease (ESRD) in Patients with Nephropathic Cystinosis in Developed and Developing Countries, AUTHOR: Bertholet-Thomas According to the Use of Cysteamine. 1 of 1 between developed countries and developP

Acute osteomyelitis in children.

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