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Cough and cold products—still in use despite the FDA advisory
July 2015 Volume 167 Number 1
Compliance with national guidelines for pediatric hypertension — Stephen R. Daniels, MD, PhD
Cough and cold products—still in use despite the FDA advisory — Denise M. Goodman, MD, MSc
Seats are not for sleeping — Thomas R. Welch, MD
Copyright ª 2015 by Elsevier Inc.
C
linical guidelines are developed to guide clinicians in making evidence–based decisions in the course of complex clinical care. After guidelines are produced, it is important to evaluate the extent to which they actually are implemented in practice. Often, uptake of guidelines is poor and the time between establishment of best evidence and real implementation can be quite long. In this issue of The Journal, Dobson et al used billing data to evaluate the prevalence of the diagnosis of hypertension, the use of echocardiography to evaluate left ventricular hypertrophy, and the frequency of prescriptions for antihypertensive agents. Although the prevalence of the diagnosis of hypertension has increased, compliance with national clinical guidelines is quite low. Of children with a diagnosis of hypertension who had an echocardiogram, 1 in 12 was abnormal. The use of antihypertensive medication is low. These results emphasize the need for better approaches to assist clinicians in the implementation of clinical guidelines for pediatric hypertension and likely in other areas as well. Article page 92<
O
n January 17, 2008, the US Food and Drug Administration issued a Public Health Advisory recommending that over-the-counter cough and cold products not be used to treat infants and children less than 2 years of age, citing “serious and potentially life-threatening side effects.” O’Donnell et al took advantage of two large cohort studies of children in this age range with bronchiolitis, one from 2004-2006 and the other from 2007-2010. In each cohort, caregivers were asked about the use of “decongestant or cough medicine.” Reassuringly, use decreased from 25% of children to 7% after the advisory, although in the oldest age group (12-23.9 months), use was still significant, approaching 20%. More interesting, in the postadvisory group, use was directly associated with maternal smoking during pregnancy and inversely associated with breast feeding. There are at least two important messages for pediatricians. Because maternal smoking during pregnancy is related to health literacy, these findings underscore the need for clinicians to assess the beliefs and knowledge of caregivers as these form the foundation upon which decisions are made. In addition, use of over-the-counter preparations may be interpreted as benign by families, or not of importance during history taking, or there may be an assumption of safety by the very presence of these agents in a pharmacy. Specific focused questions are needed to elicit a history of their use. Article page 196<
I
t is undisputed that car seats save lives. Like any other consumer item, however, they are only safe when used as directed. There have been recent disturbing reports of infants dying in car seats or other carrying devices. The current issue of The Journal contains an important report from Batra et al, which analyzes data from the Consumer Product Safety Commission. They identified 47 deaths of children < 2 years of age during a 4-year period. The deaths occurred while children were
1
placed outside a car in a car seat (n = 31) or other infant sitting/carrying device (eg, strollers, bouncers). The analysis showed that more than one-half of the deaths were from strangulation because of straps not being secured appropriately. The others were from unrecognized positional asphyxia. The authors provide very specific, actionable advice that pediatricians should share with all their patients’ parents. The advice boils down to: “Properly used car seats save thousands of infant lives. However, these and similar devices are not designed for unsupervised infant sleep!” Article page 183<
Obesity, physical activity, and blood pressure — Stephen R. Daniels, MD, PhD
Reassuring safety information for monovalent rotavirus vaccine — Sarah S. Long, MD
2
O
besity is an important risk factor for elevated blood pressure. As the prevalence and severity of obesity have risen in children and adolescents in the US, so has the average blood pressure and the prevalence of hypertension. In this issue of The Journal, Vale et al evaluated the role of physical activity in relationship with obesity and elevation of blood pressure. They found that elevated blood pressure was much more common in preschool children who were overweight or obese and had low levels of moderate to vigorous physical activity. These results suggest the importance of all children achieving the goal of 60 minutes a day of moderate to vigorous physical activity. In addition, these results emphasize the importance of physical activity in weight management programs. Future research should evaluate whether increasing physical activity is associated with lowering of blood pressure independent of changes in weight or body mass index. Article page 98<
R
otavirus vaccines (RVs) are remarkably effective in averting this previously inescapable cause of gastroenteritis in young children. The benefit of RVs in developing countries primarily are saving lives, and in developed countries they are preventing hospitalizations. Since the implementation of pentavalent human-bovine reassortant vaccine (RV5) and monovalent human vaccine (RV1) in multiple countries, it has become apparent that both vaccines are associated with a small but measurable increase in cases of intussusception following immunization, especially in the first week and especially after the first dose. The rate of vaccine-associated intussusception has varied by country and likely is related to existing differences in rates of nonvaccine associated intussusception, as well as diet, maternal antibodies, and prevalence of enteropathogens – to name just a few. Young age, when intussusception is uncommon and when some maternal antibody to rotavirus is still present, is thought to be protective against RV-associated intussusception. The vast safety studies leading to licensure of RVs entered only young infants. Recommendation in the US is that the first dose of RV vaccination should be given at 2 months of age routinely and vaccination should be initiated only if the infant is 14 weeks and 6 days of age or younger. The study from Singapore reported in this issue of The Journal adds further data from a geographic area with higher incidence of background intussusception, a slightly older age at first dose, and dominant use of RV1 compared with the US. The analysis of cases and timing of intussusception in infants who received RV1 versus unimmunized infants suggests that a program achieving 90% vaccine coverage would prevent 71% of rotavirus hospitalizations, require 340 infants to be immunized to prevent one hospitalization, and would result in one excess intussusception hospitalization for every 64 668 infants immunized. These data, in this setting, are reassuring to the conclusion that the benefits of RVs far outweigh risk. Article page 163<
Vol. 167, No. 1
Cerebral palsy and brain cooling — Alan H. Jobe, MD, PhD
Inadequate testing for infectious diseases in infants with sudden unexpected death — Sarah S. Long, MD
July 2015
his month in The Journal there are 3 articles that discuss cerebral palsy (CP) and the use of hypothermia to decrease brain injury in newborns. Garfinkel et al used a Canadian CP registry to estimate that about 5% of CP could be prevented with the effective use of therapeutic hypothermia of asphyxiated term infants delivered in Canada. This low effectiveness results from the multiple factors pointed out in the editorial by Berg. Most cases of CP are not the result of the acute sentinel asphyxial events associated with deliveries, and many of the infants do not qualify for hypothermia treatment. Furthermore, the therapy is not highly effective. This discouraging overall effect of therapeutic hypothermia is compounded in low and middle-income countries (LMIC) as pointed out by the Commentary by Tagin et al. Hypoxic ischemic encephalopathy is responsible for an estimated 25% of all neonatal deaths worldwide, and asphyxia is responsible for a large number of fresh stillborns in LMIC countries. Although therapeutic hypothermia is an effective therapy in high resource environments, it has not been demonstrated to be effective in LMIC in a few trials. Although the therapy is relatively simple to deliver in any modern neonatal intensive care unit, there are multiple obstacles to its effective use in LMIC. Identification of the infant that qualifies for hypothermia treatment by the criteria used in high resource environments requires trained personnel and infrastructure, and, thus, is not easily accomplished. More lives could be saved by upgrading obstetric services to decrease stillborns and providing effective resuscitation, than by developing the infrastructure necessary for the rapid identification and treatment of the asphyxiated infant with hypothermia. Therapies to improve outcomes that are effective in one environment may not work in another. Even though therapeutic hypothermia is a major advance as the first treatment that can decrease brain injury in asphyxiated term infants, its overall impact on the incidence of CP and birth asphyxia will be small within the context of worldwide infant mortality. Article page 25< Article page 58< Editorial page 8<
T
P
reviously in the US, many academic children’s hospital pathologists performed autopsies with permission and gratitude of medical examiners when an infant died suddenly and unexpectedly (SUID). A variety of hurdles make this uncommon currently. Brooks et al show with a survey of US medical examiners and coroners that when autopsies are performed through their offices for SUID, patients are inadequately evaluated for infectious diseases. Infectious diseases have been shown to contribute to a conservatively estimated 20% of SUID cases. Many reasons likely account for lack of testing. Cases of SUID are infrequent among medical examiners/coroners workload, protocols for investigation are not established, knowledge of pathologists/examiners regarding molecular testing and other new methodologies may not be current, and testing may not be perceived as important. Knowledge of the burden of infectious diseases, especially of attendant deaths, is a critical first step to considering strategies for prevention. Beyond the personal tragedy of loss of an infant without apparent cause, a half-century old approach to investigation seems unacceptable. Article page 178<
3
Compliance with national guidelines for pediatric hypertension — Stephen R. Daniels, MD, PhD
Cough and cold products—still in use despite the FDA advisory — Denise M. Goodman, MD, MSc
Seats are not for sleeping — Thomas R. Welch, MD
Copyright ª 2015 by Elsevier Inc.
C
linical guidelines are developed to guide clinicians in making evidence–based decisions in the course of complex clinical care. After guidelines are produced, it is important to evaluate the extent to which they actually are implemented in practice. Often, uptake of guidelines is poor and the time between establishment of best evidence and real implementation can be quite long. In this issue of The Journal, Dobson et al used billing data to evaluate the prevalence of the diagnosis of hypertension, the use of echocardiography to evaluate left ventricular hypertrophy, and the frequency of prescriptions for antihypertensive agents. Although the prevalence of the diagnosis of hypertension has increased, compliance with national clinical guidelines is quite low. Of children with a diagnosis of hypertension who had an echocardiogram, 1 in 12 was abnormal. The use of antihypertensive medication is low. These results emphasize the need for better approaches to assist clinicians in the implementation of clinical guidelines for pediatric hypertension and likely in other areas as well. Article page 92<
O
n January 17, 2008, the US Food and Drug Administration issued a Public Health Advisory recommending that over-the-counter cough and cold products not be used to treat infants and children less than 2 years of age, citing “serious and potentially life-threatening side effects.” O’Donnell et al took advantage of two large cohort studies of children in this age range with bronchiolitis, one from 2004-2006 and the other from 2007-2010. In each cohort, caregivers were asked about the use of “decongestant or cough medicine.” Reassuringly, use decreased from 25% of children to 7% after the advisory, although in the oldest age group (12-23.9 months), use was still significant, approaching 20%. More interesting, in the postadvisory group, use was directly associated with maternal smoking during pregnancy and inversely associated with breast feeding. There are at least two important messages for pediatricians. Because maternal smoking during pregnancy is related to health literacy, these findings underscore the need for clinicians to assess the beliefs and knowledge of caregivers as these form the foundation upon which decisions are made. In addition, use of over-the-counter preparations may be interpreted as benign by families, or not of importance during history taking, or there may be an assumption of safety by the very presence of these agents in a pharmacy. Specific focused questions are needed to elicit a history of their use. Article page 196<
I
t is undisputed that car seats save lives. Like any other consumer item, however, they are only safe when used as directed. There have been recent disturbing reports of infants dying in car seats or other carrying devices. The current issue of The Journal contains an important report from Batra et al, which analyzes data from the Consumer Product Safety Commission. They identified 47 deaths of children < 2 years of age during a 4-year period. The deaths occurred while children were
1
placed outside a car in a car seat (n = 31) or other infant sitting/carrying device (eg, strollers, bouncers). The analysis showed that more than one-half of the deaths were from strangulation because of straps not being secured appropriately. The others were from unrecognized positional asphyxia. The authors provide very specific, actionable advice that pediatricians should share with all their patients’ parents. The advice boils down to: “Properly used car seats save thousands of infant lives. However, these and similar devices are not designed for unsupervised infant sleep!” Article page 183<
Obesity, physical activity, and blood pressure — Stephen R. Daniels, MD, PhD
Reassuring safety information for monovalent rotavirus vaccine — Sarah S. Long, MD
2
O
besity is an important risk factor for elevated blood pressure. As the prevalence and severity of obesity have risen in children and adolescents in the US, so has the average blood pressure and the prevalence of hypertension. In this issue of The Journal, Vale et al evaluated the role of physical activity in relationship with obesity and elevation of blood pressure. They found that elevated blood pressure was much more common in preschool children who were overweight or obese and had low levels of moderate to vigorous physical activity. These results suggest the importance of all children achieving the goal of 60 minutes a day of moderate to vigorous physical activity. In addition, these results emphasize the importance of physical activity in weight management programs. Future research should evaluate whether increasing physical activity is associated with lowering of blood pressure independent of changes in weight or body mass index. Article page 98<
R
otavirus vaccines (RVs) are remarkably effective in averting this previously inescapable cause of gastroenteritis in young children. The benefit of RVs in developing countries primarily are saving lives, and in developed countries they are preventing hospitalizations. Since the implementation of pentavalent human-bovine reassortant vaccine (RV5) and monovalent human vaccine (RV1) in multiple countries, it has become apparent that both vaccines are associated with a small but measurable increase in cases of intussusception following immunization, especially in the first week and especially after the first dose. The rate of vaccine-associated intussusception has varied by country and likely is related to existing differences in rates of nonvaccine associated intussusception, as well as diet, maternal antibodies, and prevalence of enteropathogens – to name just a few. Young age, when intussusception is uncommon and when some maternal antibody to rotavirus is still present, is thought to be protective against RV-associated intussusception. The vast safety studies leading to licensure of RVs entered only young infants. Recommendation in the US is that the first dose of RV vaccination should be given at 2 months of age routinely and vaccination should be initiated only if the infant is 14 weeks and 6 days of age or younger. The study from Singapore reported in this issue of The Journal adds further data from a geographic area with higher incidence of background intussusception, a slightly older age at first dose, and dominant use of RV1 compared with the US. The analysis of cases and timing of intussusception in infants who received RV1 versus unimmunized infants suggests that a program achieving 90% vaccine coverage would prevent 71% of rotavirus hospitalizations, require 340 infants to be immunized to prevent one hospitalization, and would result in one excess intussusception hospitalization for every 64 668 infants immunized. These data, in this setting, are reassuring to the conclusion that the benefits of RVs far outweigh risk. Article page 163<
Vol. 167, No. 1
Cerebral palsy and brain cooling — Alan H. Jobe, MD, PhD
Inadequate testing for infectious diseases in infants with sudden unexpected death — Sarah S. Long, MD
July 2015
his month in The Journal there are 3 articles that discuss cerebral palsy (CP) and the use of hypothermia to decrease brain injury in newborns. Garfinkel et al used a Canadian CP registry to estimate that about 5% of CP could be prevented with the effective use of therapeutic hypothermia of asphyxiated term infants delivered in Canada. This low effectiveness results from the multiple factors pointed out in the editorial by Berg. Most cases of CP are not the result of the acute sentinel asphyxial events associated with deliveries, and many of the infants do not qualify for hypothermia treatment. Furthermore, the therapy is not highly effective. This discouraging overall effect of therapeutic hypothermia is compounded in low and middle-income countries (LMIC) as pointed out by the Commentary by Tagin et al. Hypoxic ischemic encephalopathy is responsible for an estimated 25% of all neonatal deaths worldwide, and asphyxia is responsible for a large number of fresh stillborns in LMIC countries. Although therapeutic hypothermia is an effective therapy in high resource environments, it has not been demonstrated to be effective in LMIC in a few trials. Although the therapy is relatively simple to deliver in any modern neonatal intensive care unit, there are multiple obstacles to its effective use in LMIC. Identification of the infant that qualifies for hypothermia treatment by the criteria used in high resource environments requires trained personnel and infrastructure, and, thus, is not easily accomplished. More lives could be saved by upgrading obstetric services to decrease stillborns and providing effective resuscitation, than by developing the infrastructure necessary for the rapid identification and treatment of the asphyxiated infant with hypothermia. Therapies to improve outcomes that are effective in one environment may not work in another. Even though therapeutic hypothermia is a major advance as the first treatment that can decrease brain injury in asphyxiated term infants, its overall impact on the incidence of CP and birth asphyxia will be small within the context of worldwide infant mortality. Article page 25< Article page 58< Editorial page 8<
T
P
reviously in the US, many academic children’s hospital pathologists performed autopsies with permission and gratitude of medical examiners when an infant died suddenly and unexpectedly (SUID). A variety of hurdles make this uncommon currently. Brooks et al show with a survey of US medical examiners and coroners that when autopsies are performed through their offices for SUID, patients are inadequately evaluated for infectious diseases. Infectious diseases have been shown to contribute to a conservatively estimated 20% of SUID cases. Many reasons likely account for lack of testing. Cases of SUID are infrequent among medical examiners/coroners workload, protocols for investigation are not established, knowledge of pathologists/examiners regarding molecular testing and other new methodologies may not be current, and testing may not be perceived as important. Knowledge of the burden of infectious diseases, especially of attendant deaths, is a critical first step to considering strategies for prevention. Beyond the personal tragedy of loss of an infant without apparent cause, a half-century old approach to investigation seems unacceptable. Article page 178<
3