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Small increases in prednisolone can prevent relapse during upper respiratory infections in patients with nephrotic syndrome
Bacterial meningitis score is valid in other populations of children
children with suspected meningitis. That is, until we find the “ultimate” score.
Dubos F, De la Rocque F, Levy C, Bingen E, Aujard Y, Cohen R, et al. Sensitivity of the bacterial meningitis score in 889 children with bacterial meningitis. J Pediatr 2008;152:378-82. Question In children with bacterial meningitis, how well does a previously validated bacterial meningitis score (BMS) correctly identify affected children?
Secondary analysis of prospective data for children presenting with bacterial meningitis to hospital emergency departments between January 2001 and February 2005. Design
Setting
France.
900 children aged 29 days to 18 years with acute bacterial meningitis.
Participants
Intervention The BMS was applied to all children with acute bacterial meningitis with the same inclusion criteria proposed by the authors of the rule. Outcome
Sensitivity of the BMS rule.
Results Use of the BMS correctly identified 884 children with bacterial meningitis, for 99.6% sensitivity (95% CI, 98.9%-99.8%). Conclusions The sensitivity of the BMS in detecting disease
was very high, but a few cases of bacterial meningitis were missed. Further refinements of the BMS may be warranted to lower the false-negative rate. Commentary In recent years, we have become “score hunt-
ers,” looking for evidence-based ways to justify our gestalt for determining who has bacterial meningitis and who does not. The French Surveillance Network should be applauded for getting us even closer to understanding scoring for bacterial meningitis. In this study, they try to validate the most recently developed score, by Nigrovic et al,1 by using a large cohort of children ⬎29 days old from a different geographic location. They succeeded in finding a very high sensitivity rate (99.6%) and bringing the confidence interval to almost 100%. Yet, even in a large cohort like this (n ⫽ 889), 5 children with meningitis would have been “missed” with the score. Beyond enhancing the level of evidence of the score and supporting its use with caution, the study illustrates that we may never reach a score that will apply to all infants and children with bacterial meningitis, no matter what population or during what era we try to do so. Furthermore, with such a good (but not a perfect) score, we should consider the ethical question related to investigating, prescribing antibiotics, admitting and spending large amounts of money on hundreds of children to find the few with true bacterial meningitis. We can potentially “save” so much if we decide to “accept” a score and with it the remote possibility of discharging home from the emergency department a small percentage of children with bacterial meningitis. It seems that the current consensus is that this rate is 0%, and we should be investigating and treating all 146
Ran D. Goldman, MD University of British Columbia Vancouver, BC, Canada
REFERENCE 1. Nigrovic LE, Kuppermann N, Macias CG, Cannavino CR, Moro-Sutherland DM, Schremmer RD, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007;297:52-60.
Small increases in prednisolone can prevent relapse during upper respiratory infections in patients with nephrotic syndrome Abeyagunawardena AS, Trompeter RS. Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial. Arch Dis Child 2008;93:226-8. Question In children with nephrotic syndrome, does a small
short-term increase in the dose of prednisolone reduce the risk of relapse during viral upper respiratory tract infections (URTIs), compared with placebo? Design Randomized, double-blind, placebo-controlled crossover trial. Setting
Nephrology clinic at a tertiary referral center in Sri
Lanka. Participants 48 children receiving low-dose (⬍0.6 mg/kg) prednisolone on alternate days as maintenance therapy were recruited, and 40 completed the trial (29 male, 11 female). Age at entry ranged from 1.5 to 13.2 years (median, 5.3 years). Intervention At the first sign of a URTI, patients were randomized to receive either placebo or prednisolone on the days when they were not regularly scheduled to get prednisolone. The intervention lasted 7 days (ie, 3 or 4 extra doses of prednisolone) and the prednisolone dose (or placebo dose) was identical to the patient’s usual alternative day prednisolone dose. During a subsequent URTI, the patients crossed over interventions.
Relapse, defined as the presence of 3⫹ proteinuria for 3 consecutive days.
Outcomes
Results The relapse rate after viral URTI was 19 of 40 (48%) in the placebo group and 7 of 40 (18%) in the prednisolone group (P ⫽ .014, number needed to treat [NNT] ⫽ 4). The mean dose of alternate day prednisolone was 0.36 mg/kg (range, 0.1-0.6 mg/kg). No significant adverse effects of the increased prednisolone were noted.
Additional doses of prednisolone during URTIs in patients with glucocorticoid-dependent nephrotic syndrome maintained on alternative day prednisone decreases the relapse rate without notable adverse effects.
Conclusions
The Journal of Pediatrics • July 2008
Comment The treatment of patients with frequently relapsing nephrotic syndrome, glucocorticoid-dependent nephrotic syndrome, or both poses many challenges for clinicians and families. In many patients, prolonged low-dose alternate-day glucocorticoid therapy provides adequate control without significant adverse effects. In this study, a URTI triggered relapse in ⬎50% of the patients treated with placebo. This trial provides evidence that an additional 3 to 4 relatively low doses of prednisolone can reduce the relapse rate in these difficultto-treat patients by ⬎60% during URTIs. This confirms the earlier findings of Mattoo and Mahmoud.1 This study did not describe how long after a URTI a relapse would be ascribed to a treatment group or the number of relapses deemed not related to URTIs. In 1 older study, 70% of relapses were associated with URTIs.2 Thus, this relatively benign strategy could have a major impact on the overall incident of relapse in
Clinical Research Abstracts for Pediatricians
these patients. For those patients who continue to relapse on alternate-day glucocorticoid therapies, there are a variety of immunomodulating agents that can be used, often associated with significant costs and adverse effects. Definitive controlled trials are needed in this area, and this study strongly supports the inclusion of a daily glucocorticoid during URTIs in the intervention arm in such trials. David Kershaw, MD University of Michigan Ann Arbor, Michigan
REFERENCES 1. Mattoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 2000;85:343-5. 2. MacDonald NE, Wolfish N, McLaine P, Phipps P, Rossier E. Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr 1986;108:378-82.
147
children with suspected meningitis. That is, until we find the “ultimate” score.
Dubos F, De la Rocque F, Levy C, Bingen E, Aujard Y, Cohen R, et al. Sensitivity of the bacterial meningitis score in 889 children with bacterial meningitis. J Pediatr 2008;152:378-82. Question In children with bacterial meningitis, how well does a previously validated bacterial meningitis score (BMS) correctly identify affected children?
Secondary analysis of prospective data for children presenting with bacterial meningitis to hospital emergency departments between January 2001 and February 2005. Design
Setting
France.
900 children aged 29 days to 18 years with acute bacterial meningitis.
Participants
Intervention The BMS was applied to all children with acute bacterial meningitis with the same inclusion criteria proposed by the authors of the rule. Outcome
Sensitivity of the BMS rule.
Results Use of the BMS correctly identified 884 children with bacterial meningitis, for 99.6% sensitivity (95% CI, 98.9%-99.8%). Conclusions The sensitivity of the BMS in detecting disease
was very high, but a few cases of bacterial meningitis were missed. Further refinements of the BMS may be warranted to lower the false-negative rate. Commentary In recent years, we have become “score hunt-
ers,” looking for evidence-based ways to justify our gestalt for determining who has bacterial meningitis and who does not. The French Surveillance Network should be applauded for getting us even closer to understanding scoring for bacterial meningitis. In this study, they try to validate the most recently developed score, by Nigrovic et al,1 by using a large cohort of children ⬎29 days old from a different geographic location. They succeeded in finding a very high sensitivity rate (99.6%) and bringing the confidence interval to almost 100%. Yet, even in a large cohort like this (n ⫽ 889), 5 children with meningitis would have been “missed” with the score. Beyond enhancing the level of evidence of the score and supporting its use with caution, the study illustrates that we may never reach a score that will apply to all infants and children with bacterial meningitis, no matter what population or during what era we try to do so. Furthermore, with such a good (but not a perfect) score, we should consider the ethical question related to investigating, prescribing antibiotics, admitting and spending large amounts of money on hundreds of children to find the few with true bacterial meningitis. We can potentially “save” so much if we decide to “accept” a score and with it the remote possibility of discharging home from the emergency department a small percentage of children with bacterial meningitis. It seems that the current consensus is that this rate is 0%, and we should be investigating and treating all 146
Ran D. Goldman, MD University of British Columbia Vancouver, BC, Canada
REFERENCE 1. Nigrovic LE, Kuppermann N, Macias CG, Cannavino CR, Moro-Sutherland DM, Schremmer RD, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007;297:52-60.
Small increases in prednisolone can prevent relapse during upper respiratory infections in patients with nephrotic syndrome Abeyagunawardena AS, Trompeter RS. Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial. Arch Dis Child 2008;93:226-8. Question In children with nephrotic syndrome, does a small
short-term increase in the dose of prednisolone reduce the risk of relapse during viral upper respiratory tract infections (URTIs), compared with placebo? Design Randomized, double-blind, placebo-controlled crossover trial. Setting
Nephrology clinic at a tertiary referral center in Sri
Lanka. Participants 48 children receiving low-dose (⬍0.6 mg/kg) prednisolone on alternate days as maintenance therapy were recruited, and 40 completed the trial (29 male, 11 female). Age at entry ranged from 1.5 to 13.2 years (median, 5.3 years). Intervention At the first sign of a URTI, patients were randomized to receive either placebo or prednisolone on the days when they were not regularly scheduled to get prednisolone. The intervention lasted 7 days (ie, 3 or 4 extra doses of prednisolone) and the prednisolone dose (or placebo dose) was identical to the patient’s usual alternative day prednisolone dose. During a subsequent URTI, the patients crossed over interventions.
Relapse, defined as the presence of 3⫹ proteinuria for 3 consecutive days.
Outcomes
Results The relapse rate after viral URTI was 19 of 40 (48%) in the placebo group and 7 of 40 (18%) in the prednisolone group (P ⫽ .014, number needed to treat [NNT] ⫽ 4). The mean dose of alternate day prednisolone was 0.36 mg/kg (range, 0.1-0.6 mg/kg). No significant adverse effects of the increased prednisolone were noted.
Additional doses of prednisolone during URTIs in patients with glucocorticoid-dependent nephrotic syndrome maintained on alternative day prednisone decreases the relapse rate without notable adverse effects.
Conclusions
The Journal of Pediatrics • July 2008
Comment The treatment of patients with frequently relapsing nephrotic syndrome, glucocorticoid-dependent nephrotic syndrome, or both poses many challenges for clinicians and families. In many patients, prolonged low-dose alternate-day glucocorticoid therapy provides adequate control without significant adverse effects. In this study, a URTI triggered relapse in ⬎50% of the patients treated with placebo. This trial provides evidence that an additional 3 to 4 relatively low doses of prednisolone can reduce the relapse rate in these difficultto-treat patients by ⬎60% during URTIs. This confirms the earlier findings of Mattoo and Mahmoud.1 This study did not describe how long after a URTI a relapse would be ascribed to a treatment group or the number of relapses deemed not related to URTIs. In 1 older study, 70% of relapses were associated with URTIs.2 Thus, this relatively benign strategy could have a major impact on the overall incident of relapse in
Clinical Research Abstracts for Pediatricians
these patients. For those patients who continue to relapse on alternate-day glucocorticoid therapies, there are a variety of immunomodulating agents that can be used, often associated with significant costs and adverse effects. Definitive controlled trials are needed in this area, and this study strongly supports the inclusion of a daily glucocorticoid during URTIs in the intervention arm in such trials. David Kershaw, MD University of Michigan Ann Arbor, Michigan
REFERENCES 1. Mattoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 2000;85:343-5. 2. MacDonald NE, Wolfish N, McLaine P, Phipps P, Rossier E. Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr 1986;108:378-82.
147