- Email: [email protected]
Poor elevated-blood-pressure recognition in the outpatient setting
Translating Best Evidence into Best Care EDITOR’S NOTE: Studies for this issue were identified using the Clinical Queries feature of PubMed, “hand” searching JAMA Pediatrics, Pediatrics, and The Journal of Pediatrics, and from customized EvidenceUpdates alerts. EBM PEARL: EQUIVALENCE STUDIES (ES): There are 3 basic types of randomized therapeutic trials: superiority (most common), equivalence, and noninferiority. The question asked in ES is: Is the primary therapeutic effect of these two treatments essentially the same (equivalent)? The key issue for a reader of ES studies is to note, in the “statistics” section, which clinical equivalence range the investigators chose. If the 95% CI falls within the investigators’ chosen equivalence range, the study has demonstrated equivalence. An example of this is the AFRINEST study (amoxicillin versus injectable procaine benzylpenicillin plus gentamicin) (see the piece by Agweyu on page 778). The investigators chose an absolute risk reduction 95% CI of +/-5%, which was achieved in the intention-to-treat results. LITERATURE SEARCH PEARL: MACPLUS FEDERATED SEARCH: Haynes et al from McMaster University have developed an evidence-based filtering search system that partitions evidence retrieved by the “6S” pyramid: studies (at the base), synopses of studies, syntheses (eg, systematic reviews), synopses of syntheses, summaries (eg, UpToDate), and systems (at the top). Evidence is reviewed from the top of the pyramid down. Multiple evidence sources are assembled at each level, ensuring that one need not rely on a single source. MacPLUS (plus.mcmaster.ca/MacPLUSFS) provides other resources as well, such as evidence alerts (previously discussed in this column, J Pediatr 2014;165:1068) and links to PubMed. Access to MacPLUS is largely reserved for McMaster University and affiliates. However, others may participate as well, though some of the resources require a subscription (eg, UpToDate). —Jordan Hupert, MD
Amoxicillin equivalent to parenteral antibiotics in the treatment of resource-deficient infants with tachypnea African Neonatal Sepsis Trial (AFRINEST) group, Tshefu A, Lokangaka A, Ngaima S, Engmann C, Esamai F, Gisore P, et al. Oral amoxicillin compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with fast breathing when referral is not possible: a randomised, open-label, equivalence trial. Lancet 2015;385:1758-66. Question Among young infants with tachypnea and in the absence of other signs of serious infection, what is the therapeutic efficacy of oral amoxicillin, compared with injectable procaine benzylpenicillin–gentamicin, in tachypnea resolution? Design Randomized, open-label, equivalence trial. Setting 5 community-based sites in DR Congo, Kenya, and Nigeria. Participants Infants aged 0-59 days with fast breathing as the only sign of serious illness whose parents did not accept hospital referral. Intervention Oral amoxicillin vs injectable procaine benzylpenicillin–gentamicin. Primary Outcome Treatment failure by day 8 after enrollment. Main Results Amoxicillin demonstrated equivalence with benzylpenicillin-gentamicin: absolute risk reduction, per 778
protocol analysis 2.6% (95% CI –6.0 to 0.8), intention-totreat analysis 1.8% (95% CI –5.0 to 1.5). Conclusions Young infants with tachypnea can be effectively managed in a setting where referral is not possible. Commentary World Health Organization guidelines for the treatment of young infants with possible serious bacterial infection recommend inpatient care with parenteral antibiotics.1 In Sub-Saharan Africa, where infant mortality is particularly high, poor access to health facilities is a major barrier to care. This rigorously conducted multicenter trial demonstrated equivalence between oral and injectable therapy— findings that are consistent with existing evidence from Asian countries.2,3 Results of this study provide important data for use in the development of evidence-based guidelines for the management of sick young infants in low-income settings. National programs considering incorporating the findings of this study into policy will need to consider the feasibility of: (1) effective community-based follow up; (2) education of caregivers on signs of clinical deterioration; and (3) strengthening the training of health workers to exclude other signs of severe illness associated with high mortality (eg, hypoxia). Despite the low mortality reported, these findings do not obviate the need to improve access to inpatient services for severely-ill young infants, in whom mortality is generally high. Ambrose Agweyu, MMed, MSc KEMRI-Wellcome Trust Research Programme Nairobi, Kenya
Vol. 167, No. 3 September 2015
References 1. World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses with Limited Resources. 2nd ed. Geneva: WHO; 2013. 2. Zaidi AK, Ganatra HA, Syed S, Cousens S, Lee AC, Black R, et al. Effect of case management on neonatal mortality due to sepsis and pneumonia. BMC Public Health 2011;11(Suppl 3):S13. 3. Sazawal S, Black RE. Effect of pneumonia case management on mortality in neonates, infants, and preschool children: a meta-analysis of community-based trials. Lancet Infec Dis 2003;3:547-56.
Proactive perinatal care for extremely premature infants decreases morbidity without affecting neurodevelopmental outcomes Serenius F, Blennow M, Marsal K, Sj€ ors G, K€allen K, for the EXPRESS Study Group. Intensity of perinatal care for extremely preterm infants: outcomes at 2.5 years. Pediatrics 2015;135:e1163-72. Question Among extremely premature infants, what are the survival and neurodevelopmental outcomes with proactive obstetric and neonatal care, compared with less proactive care?
with neurodevelopmental problems. Outcomes for babies 22 and 23 weeks’ gestation, in particular, are attended with a high risk of severe morbidity, such as cerebral palsy and severe learning difficulties. Despite common perceptions, the majority of babies who survive, do so without these outcomes. Although there are other challenges to face for surviving children—which should not be minimized—this report promotes a timely discussion of our approach to care for this small but vulnerable population of children. Neil Marlow, DM, FMedSci University College London London, United Kingdom
References 1. Marlow N. The elephant in the delivery room. N Engl J Med 2015;372: 1856-7. 2. Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015;372:1801-11. 3. Serenius F, Sjors G, Blennow M, Fellman V, Holmstrom G, Marsal K, et al. EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden. Acta Paediatr 2014;103:27-37.
Design A prospective observational study. Setting National survey in Sweden. Participants Infants, including stillborns, 22-27 weeks’ gestation, alive at mothers’ admission. Intervention Level of obstetric and neonatal care. Outcomes 1-year mortality, and death or neurodevelopmental disability (NDI). Main Results Each 5-point increment in activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% CI 0.83–0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI 0.78–0.91). There was no difference in NDI risk at 2.5 years corrected age. Conclusions Proactive perinatal care decreased mortality without increasing the risk of NDI. Commentary Outcomes for infants born at extremely low gestations are dependent on the attitude of the attending physicians and their willingness to promote survival in this group1 and varies widely in the US.2 In this national study, Serenius et al have attempted to score the “intensity” of the interventions used in Sweden and relate this to mortality and morbidity outcomes. Previously, they had shown variation in mortality—particularly at 22 and 23 weeks—among different Swedish regions.3 This study provides evidence underpinning these differences, in that high intensity-scores were associated with a 35% reduction in mortality before or after birth through improved survival up to 12 hours after birth. The size of this reduction was similar to that produced by major effective interventions such as antenatal steroids and surfactant. Later mortality and morbidity at 2 years of age was unrelated to this score and increased survival was not associated with an increase in the proportion of children
Clindamycin and trimethoprim– sulfamethoxazole equally effective in treating skin infection Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, et al. Clindamycin versus Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Infections. N Engl J Med 2015;372:1093-103. Question Among children with cellulitis and/or skin abscesses, what is therapeutic efficacy of clindamycin, compared with trimethoprim–sulfamethoxazole (TMPSMX), in infection resolution? Design Randomized controlled trial. Setting 4 clinical settings across the US. Participants 524 patients with cellulitis and/or abscess; 30% children. Intervention Clindamycin compared with TMP-SMX. Outcomes Clinical cure 7 to 10 days after the end of treatment. Main Results 80.3% in the clindamycin group and 77.7% in the TMP-SMX group were cured; absolute risk reduction, 2.6%; 95% CI 10.2% to 4.9%. Conclusions There was no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile. Commentary This well conducted study of the treatment of abscess and cellulitis in adults and children has a few methodological issues worth noting. First, patients with abscess appropriately underwent incision and drainage. Staphylococcus aureus was the etiology in 73% of these cases, of which 779
THE JOURNAL OF PEDIATRICS
www.jpeds.com
83% were methicillin-resistant S aureus (MRSA). Cure was 80% in both arms. Systemic antibiotics may delay time to recurrence but otherwise do not improve outcomes, and as such, are not routinely recommended in this setting.1 In this study, the cure rate was 73% when clindamycin was used for clindamycin-resistant S aureus abscesses, which suggests a high rate of spontaneous resolution and questions the benefit of systemic antibiotics for cutaneous abscess. Second, TMP-SMX is not recommended for the treatment of cellulitis,1 as group A Streptococci is the most common pathogen,2 and TMP-SMX has limited anti-Streptococcal activity.1,2 TMP-SMX was likely included given the concern for MRSA as an increasing cause of cellulitis.3 Regardless, there was no difference in cure, which makes one question if TMP-SMX has better than appreciated anti-Streptococcal activity and/or if MRSA was more common in this study. Third, the doses of clindamycin and TMP-SMX for skin infection have not been well defined. The cure rates reported by Miller et al are reassuring given the frequency with which these drugs are prescribed for uncomplicated skin infections. Further research is needed in more critically ill and/or immunocompromised patients and to better define the most appropriate doses. Shellee A. Grim, PharmD, MS-CTS Loyola University Medical Center Maywood, Illinois
References 1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-52. 2. Jeng A, Beheshti M, Li J, Nathan R. The role of b-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine 2010;89:217-26. 3. Chira S, Miller LG. Staphylococcus aureus is the most common identified cause of cellulitis: a systemic review. Epidemiol Infect 2010;138:313-7.
Poor elevated-blood-pressure recognition in the outpatient setting Beacher DR, Chang SZ, Rosen JS, Lipkin GS, McCarville MM, Quadri-Sheriff M, et al. Recognition of elevated blood pressure in an outpatient pediatric tertiary care setting. J Pediatr 2015;166:1233-9. Question Among pediatric outpatient care centers, what is the rate of elevated blood pressure recognition?
Vol. 167, No. 3 Main Results Among those with $3 elevated blood pressure measurements, the median frequency of identification by division/service was 17%. Conclusions The identification of patients with elevated blood pressure measurements was low. Commentary Over the last several decades, the prevalence of pediatric hypertension has risen three-fold, with 3%-5% of all children currently hypertensive.1 Hypertension in childhood often is clinically silent. However, children with hypertension are much more likely to have hypertension in adulthood, where the sequelae result in significant morbidity and mortality.2 Primary and secondary prevention of hypertension, therefore, is of paramount importance in decreasing the cardiovascular disease risk of both children and adults. This study by Beacher et al notes that pediatric healthcare providers identify themselves as playing a role in the diagnosis and treatment of hypertension in youth. Despite this, more than 80% of elevated blood pressures were unrecognized in this study, leaving a substantial number of children with missed opportunities for early prevention and treatment. Although many of the children with elevated blood pressure in this study likely do not have hypertension, (hypertension is defined by the sustained elevation of blood pressure), it should be noted that they are at significantly increased risk for the development of hypertension. Children with an initial elevated blood pressure that normalizes during the same encounter are 5.9 times more likely to develop hypertension than those with an initial normal blood pressure.3 This important study by Beacher et al highlights the need for better systems to assist providers to accurately identify elevated blood pressure in children, particularly in those without obvious cardiovascular disease risk factors. Tammy M. Brady, MD, PhD Johns Hopkins University Baltimore, Maryland
References 1. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-76. 2. Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens 1995;8:657-65. 3. Redwine KM, Acosta AA, Poffenbarger T, Portman RJ, Samuels J. Development of hypertension in adolescents with pre-hypertension. J Pediatr 2012;160:98-103.
Design Retrospective single cohort study. Setting Single tertiary-care pediatric outpatient center. Participants 20 000 patients (2-17 years old). Intervention Blood pressure measurement. Outcomes Recognition rate of elevated blood pressures. 780
Combined clinical and ultrasound assessment enhance appendicitis diagnostic accuracy Bachur RG, Callahan MJ, Monuteaux MC, Rangel SJ. Integration of ultrasound findings and a clinical score in the diagnostic evaluation of pediatric appendicitis. J Pediatr 2015;166:1134-9.
CURRENT BEST EVIDENCE
September 2015 Question Among children with possible appendicitis, what is the diagnostic accuracy of ultrasound (US) combined with clinical findings, compared with surgical pathology or computed tomography (among patients undergoing interval appendectomy), in diagnosing appendicitis? Design Prospective, observational study of children evaluated for possible appendicitis. Setting Boston Children’s Hospital emergency department. Participants 728 children, 3-18 years old, who had an US for possible appendicitis. Intervention US for appendicitis combined with clinical assessment based on the Pediatric Appendicitis Score (PAS). Outcomes Positive and negative predictive values for PAS combined with US. Main Results The negative predictive value of US decreased with increasing PAS-based risk assignment: low risk 1.00 (95% CI, 0.97-1.00), medium risk 0.94 (0.91-0.97), and high risk 0.81 (0.73-0.89). With increasing PAS, the positive predictive value of US increased: low risk 0.73 (0.47-0.99), medium risk 0.90 (0.82-0.98), and high risk 0.97 (0.95-1.0). Conclusions US findings in children with possible appendicitis should be integrated with clinical assessment, such as the PAS, to determine next steps in management. Commentary The diagnosis of acute appendicitis remains elusive, with high rates of perforation.1 Clinical scoring systems and US, when evaluated independently, have low to moderate sensitivity. This study adds to the existing litera-
ture supporting integration of the PAS with US, to enhance diagnostic accuracy.2,3 The PAS, when considered independently, correlated with the likelihood of appendicitis. However, among the high-risk group (PAS 7-10), the false negative rate was 19%; within the low risk group (PAS 03), 27% of US results were false positive. When US results were discordant with clinical suspicion, the authors recommended serial examination or further imaging. Notable limitations include: (1) enrollment bias; (2) requirement of an advanced imaging study or surgical consultation to be eligible; (3) PAS was calculated retrospectively and could not be ascertained in 16.4% of patients; and (4) results are not generalizable to the community hospital setting. Jay Pershad, MD Le Bonheur Children’s Hospital Memphis, Tennessee
References 1. Blakely ML, Williams R, Dassinger MS, Eubanks JW 3rd, Fischer P, Huang EY, et al. Early vs interval appendectomy for children with perforated appendicitis. Arch Surg 2011;146:660-5. 2. Saucier A, Huang EY, Emeremni CA, Pershad J. Prospective evaluation of a clinical pathway for suspected appendicitis. Pediatrics 2014;133:e88-95. 3. Toprak H, Kilincaslan H, Ahmad IC, Yildiz S, Bilgin M, Sharifov R, et al. Integration of ultrasound findings with Alvarado score in children with suspected appendicitis. Pediatrics Int 2014;56:95-9.
781
Amoxicillin equivalent to parenteral antibiotics in the treatment of resource-deficient infants with tachypnea African Neonatal Sepsis Trial (AFRINEST) group, Tshefu A, Lokangaka A, Ngaima S, Engmann C, Esamai F, Gisore P, et al. Oral amoxicillin compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with fast breathing when referral is not possible: a randomised, open-label, equivalence trial. Lancet 2015;385:1758-66. Question Among young infants with tachypnea and in the absence of other signs of serious infection, what is the therapeutic efficacy of oral amoxicillin, compared with injectable procaine benzylpenicillin–gentamicin, in tachypnea resolution? Design Randomized, open-label, equivalence trial. Setting 5 community-based sites in DR Congo, Kenya, and Nigeria. Participants Infants aged 0-59 days with fast breathing as the only sign of serious illness whose parents did not accept hospital referral. Intervention Oral amoxicillin vs injectable procaine benzylpenicillin–gentamicin. Primary Outcome Treatment failure by day 8 after enrollment. Main Results Amoxicillin demonstrated equivalence with benzylpenicillin-gentamicin: absolute risk reduction, per 778
protocol analysis 2.6% (95% CI –6.0 to 0.8), intention-totreat analysis 1.8% (95% CI –5.0 to 1.5). Conclusions Young infants with tachypnea can be effectively managed in a setting where referral is not possible. Commentary World Health Organization guidelines for the treatment of young infants with possible serious bacterial infection recommend inpatient care with parenteral antibiotics.1 In Sub-Saharan Africa, where infant mortality is particularly high, poor access to health facilities is a major barrier to care. This rigorously conducted multicenter trial demonstrated equivalence between oral and injectable therapy— findings that are consistent with existing evidence from Asian countries.2,3 Results of this study provide important data for use in the development of evidence-based guidelines for the management of sick young infants in low-income settings. National programs considering incorporating the findings of this study into policy will need to consider the feasibility of: (1) effective community-based follow up; (2) education of caregivers on signs of clinical deterioration; and (3) strengthening the training of health workers to exclude other signs of severe illness associated with high mortality (eg, hypoxia). Despite the low mortality reported, these findings do not obviate the need to improve access to inpatient services for severely-ill young infants, in whom mortality is generally high. Ambrose Agweyu, MMed, MSc KEMRI-Wellcome Trust Research Programme Nairobi, Kenya
Vol. 167, No. 3 September 2015
References 1. World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses with Limited Resources. 2nd ed. Geneva: WHO; 2013. 2. Zaidi AK, Ganatra HA, Syed S, Cousens S, Lee AC, Black R, et al. Effect of case management on neonatal mortality due to sepsis and pneumonia. BMC Public Health 2011;11(Suppl 3):S13. 3. Sazawal S, Black RE. Effect of pneumonia case management on mortality in neonates, infants, and preschool children: a meta-analysis of community-based trials. Lancet Infec Dis 2003;3:547-56.
Proactive perinatal care for extremely premature infants decreases morbidity without affecting neurodevelopmental outcomes Serenius F, Blennow M, Marsal K, Sj€ ors G, K€allen K, for the EXPRESS Study Group. Intensity of perinatal care for extremely preterm infants: outcomes at 2.5 years. Pediatrics 2015;135:e1163-72. Question Among extremely premature infants, what are the survival and neurodevelopmental outcomes with proactive obstetric and neonatal care, compared with less proactive care?
with neurodevelopmental problems. Outcomes for babies 22 and 23 weeks’ gestation, in particular, are attended with a high risk of severe morbidity, such as cerebral palsy and severe learning difficulties. Despite common perceptions, the majority of babies who survive, do so without these outcomes. Although there are other challenges to face for surviving children—which should not be minimized—this report promotes a timely discussion of our approach to care for this small but vulnerable population of children. Neil Marlow, DM, FMedSci University College London London, United Kingdom
References 1. Marlow N. The elephant in the delivery room. N Engl J Med 2015;372: 1856-7. 2. Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015;372:1801-11. 3. Serenius F, Sjors G, Blennow M, Fellman V, Holmstrom G, Marsal K, et al. EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden. Acta Paediatr 2014;103:27-37.
Design A prospective observational study. Setting National survey in Sweden. Participants Infants, including stillborns, 22-27 weeks’ gestation, alive at mothers’ admission. Intervention Level of obstetric and neonatal care. Outcomes 1-year mortality, and death or neurodevelopmental disability (NDI). Main Results Each 5-point increment in activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% CI 0.83–0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI 0.78–0.91). There was no difference in NDI risk at 2.5 years corrected age. Conclusions Proactive perinatal care decreased mortality without increasing the risk of NDI. Commentary Outcomes for infants born at extremely low gestations are dependent on the attitude of the attending physicians and their willingness to promote survival in this group1 and varies widely in the US.2 In this national study, Serenius et al have attempted to score the “intensity” of the interventions used in Sweden and relate this to mortality and morbidity outcomes. Previously, they had shown variation in mortality—particularly at 22 and 23 weeks—among different Swedish regions.3 This study provides evidence underpinning these differences, in that high intensity-scores were associated with a 35% reduction in mortality before or after birth through improved survival up to 12 hours after birth. The size of this reduction was similar to that produced by major effective interventions such as antenatal steroids and surfactant. Later mortality and morbidity at 2 years of age was unrelated to this score and increased survival was not associated with an increase in the proportion of children
Clindamycin and trimethoprim– sulfamethoxazole equally effective in treating skin infection Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, et al. Clindamycin versus Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Infections. N Engl J Med 2015;372:1093-103. Question Among children with cellulitis and/or skin abscesses, what is therapeutic efficacy of clindamycin, compared with trimethoprim–sulfamethoxazole (TMPSMX), in infection resolution? Design Randomized controlled trial. Setting 4 clinical settings across the US. Participants 524 patients with cellulitis and/or abscess; 30% children. Intervention Clindamycin compared with TMP-SMX. Outcomes Clinical cure 7 to 10 days after the end of treatment. Main Results 80.3% in the clindamycin group and 77.7% in the TMP-SMX group were cured; absolute risk reduction, 2.6%; 95% CI 10.2% to 4.9%. Conclusions There was no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile. Commentary This well conducted study of the treatment of abscess and cellulitis in adults and children has a few methodological issues worth noting. First, patients with abscess appropriately underwent incision and drainage. Staphylococcus aureus was the etiology in 73% of these cases, of which 779
THE JOURNAL OF PEDIATRICS
www.jpeds.com
83% were methicillin-resistant S aureus (MRSA). Cure was 80% in both arms. Systemic antibiotics may delay time to recurrence but otherwise do not improve outcomes, and as such, are not routinely recommended in this setting.1 In this study, the cure rate was 73% when clindamycin was used for clindamycin-resistant S aureus abscesses, which suggests a high rate of spontaneous resolution and questions the benefit of systemic antibiotics for cutaneous abscess. Second, TMP-SMX is not recommended for the treatment of cellulitis,1 as group A Streptococci is the most common pathogen,2 and TMP-SMX has limited anti-Streptococcal activity.1,2 TMP-SMX was likely included given the concern for MRSA as an increasing cause of cellulitis.3 Regardless, there was no difference in cure, which makes one question if TMP-SMX has better than appreciated anti-Streptococcal activity and/or if MRSA was more common in this study. Third, the doses of clindamycin and TMP-SMX for skin infection have not been well defined. The cure rates reported by Miller et al are reassuring given the frequency with which these drugs are prescribed for uncomplicated skin infections. Further research is needed in more critically ill and/or immunocompromised patients and to better define the most appropriate doses. Shellee A. Grim, PharmD, MS-CTS Loyola University Medical Center Maywood, Illinois
References 1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-52. 2. Jeng A, Beheshti M, Li J, Nathan R. The role of b-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine 2010;89:217-26. 3. Chira S, Miller LG. Staphylococcus aureus is the most common identified cause of cellulitis: a systemic review. Epidemiol Infect 2010;138:313-7.
Poor elevated-blood-pressure recognition in the outpatient setting Beacher DR, Chang SZ, Rosen JS, Lipkin GS, McCarville MM, Quadri-Sheriff M, et al. Recognition of elevated blood pressure in an outpatient pediatric tertiary care setting. J Pediatr 2015;166:1233-9. Question Among pediatric outpatient care centers, what is the rate of elevated blood pressure recognition?
Vol. 167, No. 3 Main Results Among those with $3 elevated blood pressure measurements, the median frequency of identification by division/service was 17%. Conclusions The identification of patients with elevated blood pressure measurements was low. Commentary Over the last several decades, the prevalence of pediatric hypertension has risen three-fold, with 3%-5% of all children currently hypertensive.1 Hypertension in childhood often is clinically silent. However, children with hypertension are much more likely to have hypertension in adulthood, where the sequelae result in significant morbidity and mortality.2 Primary and secondary prevention of hypertension, therefore, is of paramount importance in decreasing the cardiovascular disease risk of both children and adults. This study by Beacher et al notes that pediatric healthcare providers identify themselves as playing a role in the diagnosis and treatment of hypertension in youth. Despite this, more than 80% of elevated blood pressures were unrecognized in this study, leaving a substantial number of children with missed opportunities for early prevention and treatment. Although many of the children with elevated blood pressure in this study likely do not have hypertension, (hypertension is defined by the sustained elevation of blood pressure), it should be noted that they are at significantly increased risk for the development of hypertension. Children with an initial elevated blood pressure that normalizes during the same encounter are 5.9 times more likely to develop hypertension than those with an initial normal blood pressure.3 This important study by Beacher et al highlights the need for better systems to assist providers to accurately identify elevated blood pressure in children, particularly in those without obvious cardiovascular disease risk factors. Tammy M. Brady, MD, PhD Johns Hopkins University Baltimore, Maryland
References 1. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-76. 2. Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens 1995;8:657-65. 3. Redwine KM, Acosta AA, Poffenbarger T, Portman RJ, Samuels J. Development of hypertension in adolescents with pre-hypertension. J Pediatr 2012;160:98-103.
Design Retrospective single cohort study. Setting Single tertiary-care pediatric outpatient center. Participants 20 000 patients (2-17 years old). Intervention Blood pressure measurement. Outcomes Recognition rate of elevated blood pressures. 780
Combined clinical and ultrasound assessment enhance appendicitis diagnostic accuracy Bachur RG, Callahan MJ, Monuteaux MC, Rangel SJ. Integration of ultrasound findings and a clinical score in the diagnostic evaluation of pediatric appendicitis. J Pediatr 2015;166:1134-9.
CURRENT BEST EVIDENCE
September 2015 Question Among children with possible appendicitis, what is the diagnostic accuracy of ultrasound (US) combined with clinical findings, compared with surgical pathology or computed tomography (among patients undergoing interval appendectomy), in diagnosing appendicitis? Design Prospective, observational study of children evaluated for possible appendicitis. Setting Boston Children’s Hospital emergency department. Participants 728 children, 3-18 years old, who had an US for possible appendicitis. Intervention US for appendicitis combined with clinical assessment based on the Pediatric Appendicitis Score (PAS). Outcomes Positive and negative predictive values for PAS combined with US. Main Results The negative predictive value of US decreased with increasing PAS-based risk assignment: low risk 1.00 (95% CI, 0.97-1.00), medium risk 0.94 (0.91-0.97), and high risk 0.81 (0.73-0.89). With increasing PAS, the positive predictive value of US increased: low risk 0.73 (0.47-0.99), medium risk 0.90 (0.82-0.98), and high risk 0.97 (0.95-1.0). Conclusions US findings in children with possible appendicitis should be integrated with clinical assessment, such as the PAS, to determine next steps in management. Commentary The diagnosis of acute appendicitis remains elusive, with high rates of perforation.1 Clinical scoring systems and US, when evaluated independently, have low to moderate sensitivity. This study adds to the existing litera-
ture supporting integration of the PAS with US, to enhance diagnostic accuracy.2,3 The PAS, when considered independently, correlated with the likelihood of appendicitis. However, among the high-risk group (PAS 7-10), the false negative rate was 19%; within the low risk group (PAS 03), 27% of US results were false positive. When US results were discordant with clinical suspicion, the authors recommended serial examination or further imaging. Notable limitations include: (1) enrollment bias; (2) requirement of an advanced imaging study or surgical consultation to be eligible; (3) PAS was calculated retrospectively and could not be ascertained in 16.4% of patients; and (4) results are not generalizable to the community hospital setting. Jay Pershad, MD Le Bonheur Children’s Hospital Memphis, Tennessee
References 1. Blakely ML, Williams R, Dassinger MS, Eubanks JW 3rd, Fischer P, Huang EY, et al. Early vs interval appendectomy for children with perforated appendicitis. Arch Surg 2011;146:660-5. 2. Saucier A, Huang EY, Emeremni CA, Pershad J. Prospective evaluation of a clinical pathway for suspected appendicitis. Pediatrics 2014;133:e88-95. 3. Toprak H, Kilincaslan H, Ahmad IC, Yildiz S, Bilgin M, Sharifov R, et al. Integration of ultrasound findings with Alvarado score in children with suspected appendicitis. Pediatrics Int 2014;56:95-9.
781