- Email: [email protected]
MgSO4 for neuroprotection
August 2014 Volume 165 Number 2
The Journal implements CrossMark — Monica L. Helton, BA — William F. Balistreri, MD
Man’s best friend, except . — Sarah S. Long, MD
Copyright ª 2014 Elsevier Inc.
nsuring the integrity of the medical literature is a high priority of the Editors of The Journal and its publisher, Elsevier Inc. When an error is brought to our attention, we maintain the accuracy of the literature by publishing an update as appropriate: (1) erratum (minor publishing error); (2) correction (minor author error); or (3) retraction (major error). According to the Committee on Publication Ethics, retractions are reserved for articles with clear evidence that the findings are unreliable (either as a result of misconduct or honest error); have been previously published elsewhere without proper cross-referencing, permission, or justification; contain plagiarized material; and/or report unethical research (http://publicationethics.org/files/ retraction%20guidelines.pdf). Although the update itself links to the previously published article, how do readers know by looking at an article whether an update has been published? In the past, it was not always easy to find. To solve that problem, CrossRef, makers of CrossCheck and FundRef, have created CrossMark, a multipublisher initiative that allows journals to create an interactive reading experience that notifies readers when updates have been made. Beginning with this issue, the CrossMark logo (as depicted on the left) in print articles indicates that The Journal is an active participant in the CrossMark program. However, the logo comes to life in the online version of The Journal’s articles. By clicking the CrossMark logo, readers will be directed to a page that states whether the article is current or an update has been published. If a correction, erratum, retraction, etc, has been published for an article, readers will be provided with a direct link and citation to the update. There is no charge to access CrossMark information; however, the CrossMark logo does not indicate whether the article itself is freely available. Additional information about CrossMark is available at http://www.crossref.org/crossmark. We hope that you find CrossMark to be a useful tool when reading The Journal, as well as other journals participating in this program.
E
J
ust about everyone who owns and loves a pet, likely cannot imagine life without “man’s best friend.” There is no question of a pet’s value to the happiness and well-being of children. Pet-associated infectious risks for patients with cancer (and other immunocompromised children) also are clear. Guidance for patients with cancer targets personal hygiene, as well as types and ages of animals suited/not suited as pets: dogs and cats under 6 months of age more likely carry Campylobacter and Bartonella species; reptiles, amphibians, and exotic animal species are nearly obligate Salmonella carriers; poultry and rodents have Salmonella and other communicable bacteria; and rodents can harbor lymphocytic choriomeningitis virus. Veterinary, medical, public health, and population health departments teamed up to develop and administer a questionnaire to children cared for at the Children’s Hospital of Eastern Ontario to assess knowledge and attitudes toward pet ownership, perceived infectious risks, and ownership practices. They solicited enrollment of
217
children diagnosed with cancer as the group of interest and children with diabetes (as also having a chronic condition, with less risk of infection) as “controls” to assess effects of knowledge and education on action. Sixty-five percent of parents/guardians completed the questionnaire (64 whose child had cancer and 150 whose child had diabetes). At diagnosis, 45% of respondents had a household pet; few found them a new home. Twenty percent of patients with cancer acquired a pet after diagnosis, 77% of which were high-risk pets. These findings and more, which can be found in the authors’ report, provide convincing evidence of the need for improved education of households with immunocompromised children, as well as that of pediatric and veterinary healthcare professionals. Article page 348
Bones, breaks, and BMI — Thomas R. Welch, MD
An evaluation of pediatric clinical trial design — Robert W. Wilmott, MD
218
I
t seems that just about any childhood travail is somehow linked to obesity. Some of these associations are consistently reproducible, and others are less so. One of the more interesting of these is the association between obesity and fracture risk. Studies of this association have been mixed in their results, and are confounded by things like activity levels, sports participation, etc. This issue of The Journal contains an article by Sabhaney et al that brings some clarity to the matter and has a surprising finding. These investigators studied over 2000 children who came to one of two emergency departments with a non penetrating extremity injury. The children were classified according to body mass index, and the authors examined the risk of having a fracture as a function of obesity status. Overweight children had a small but significant decreased risk of fracture compared with those of normal weight. Underweight children, however, had a significantly increased risk of fracture. It is not immediately clear what we should do with this information. As the authors point out, weight status may have been a surrogate for bone mineral density, which could have been the major (unmeasured) risk factor. It also should be considered that these are generally low-severity upper extremity fractures, which may be the often-unavoidable consequence of an active childhood! Article page 313
S
inha et al from the University of Sydney, Australia, asked whether recently published randomized controlled trials of pharmacologic agents in children demonstrated any more risk of bias than similar trials performed in adults. This was investigated by evaluating 100 trials involving only children and matching them by drug class and therapeutic area with similar trials completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials. The results were reassuring in that the published randomized control trials involving children had a largely similar risk of bias compared with the randomized controlled trials in adults, suggesting that pediatric clinical investigators have a similar capability to conduct and report randomized controlled trials to their adult colleagues. The study demonstrated several areas where bias potentially exists in pediatric trials, although, in most areas, the pediatric trials were slightly better than the adult ones. However, these areas will need close attention in the future. An important message from this study is that we have the capability in pediatrics to perform robust, randomized, controlled trials in children, so there is no reason to neglect assessing drugs in the pediatric population. Article page 367
Vol. 165, No. 2
A healthy mind in a healthy body — Thomas R. Welch, MD
MgSO4 for neuroprotection — Alan H. Jobe, MD, PhD
August 2014
T
he concept that overall physical fitness is positively associated with academic performance has been in circulation for a long time. In this issue of The Journal, Esteban-Cornejo et al advance this area of study considerably, with a study that is impressive for the number of children involved and the detail with which the association was tested. In a group of over 2000 children, these authors performed standardized measures of three components of fitness: muscle strength, cardiorespiratory capacity, and motor fitness. These were examined in relation to four measures of academic achievement. Cardiorespiratory capacity and motor fitness were positively associated with all academic measures, but muscular strength had no independent association. Obviously, this work does not demonstrate cause and effect, but the results are striking. Their findings should stimulate carefully-designed interventional studies. Article page 306
S
urvivors of very preterm birth often have neurodevelopmental abnormalities that are certainly multifactoral in origin. Both antenatal and postnatal exposures can contribute to these adverse outcomes. One of the few interventions that has been tested in randomized controlled trials is maternal treatment with MgSO4 prior to very preterm delivery. This intervention, developed based on the frequent use of MgSO4 as a tocolytic for preterm labor, decreased cerebral palsy diagnosed at 2 years of age. In this issue of The Journal, Chollat et al report the school-age outcomes for one of the MgSO4 trials. Although not statistically significant, infants exposed to MgSO4 had less motor dysfunction, fewer behavioral disorders, fewer cognitive difficulties, less frequent repeating of school grade, and less use of special education services than the control infants. An unsatisfying aspect of this therapy is that the mechanism of action of MgSO4 on the very preterm fetus/newborn is unknown. Nevertheless, all assessments were in the direction of benefit, at least demonstrating no harm, from the MgSO4 exposure at school age. Article page 398
219
The Journal implements CrossMark — Monica L. Helton, BA — William F. Balistreri, MD
Man’s best friend, except . — Sarah S. Long, MD
Copyright ª 2014 Elsevier Inc.
nsuring the integrity of the medical literature is a high priority of the Editors of The Journal and its publisher, Elsevier Inc. When an error is brought to our attention, we maintain the accuracy of the literature by publishing an update as appropriate: (1) erratum (minor publishing error); (2) correction (minor author error); or (3) retraction (major error). According to the Committee on Publication Ethics, retractions are reserved for articles with clear evidence that the findings are unreliable (either as a result of misconduct or honest error); have been previously published elsewhere without proper cross-referencing, permission, or justification; contain plagiarized material; and/or report unethical research (http://publicationethics.org/files/ retraction%20guidelines.pdf). Although the update itself links to the previously published article, how do readers know by looking at an article whether an update has been published? In the past, it was not always easy to find. To solve that problem, CrossRef, makers of CrossCheck and FundRef, have created CrossMark, a multipublisher initiative that allows journals to create an interactive reading experience that notifies readers when updates have been made. Beginning with this issue, the CrossMark logo (as depicted on the left) in print articles indicates that The Journal is an active participant in the CrossMark program. However, the logo comes to life in the online version of The Journal’s articles. By clicking the CrossMark logo, readers will be directed to a page that states whether the article is current or an update has been published. If a correction, erratum, retraction, etc, has been published for an article, readers will be provided with a direct link and citation to the update. There is no charge to access CrossMark information; however, the CrossMark logo does not indicate whether the article itself is freely available. Additional information about CrossMark is available at http://www.crossref.org/crossmark. We hope that you find CrossMark to be a useful tool when reading The Journal, as well as other journals participating in this program.
E
J
ust about everyone who owns and loves a pet, likely cannot imagine life without “man’s best friend.” There is no question of a pet’s value to the happiness and well-being of children. Pet-associated infectious risks for patients with cancer (and other immunocompromised children) also are clear. Guidance for patients with cancer targets personal hygiene, as well as types and ages of animals suited/not suited as pets: dogs and cats under 6 months of age more likely carry Campylobacter and Bartonella species; reptiles, amphibians, and exotic animal species are nearly obligate Salmonella carriers; poultry and rodents have Salmonella and other communicable bacteria; and rodents can harbor lymphocytic choriomeningitis virus. Veterinary, medical, public health, and population health departments teamed up to develop and administer a questionnaire to children cared for at the Children’s Hospital of Eastern Ontario to assess knowledge and attitudes toward pet ownership, perceived infectious risks, and ownership practices. They solicited enrollment of
217
children diagnosed with cancer as the group of interest and children with diabetes (as also having a chronic condition, with less risk of infection) as “controls” to assess effects of knowledge and education on action. Sixty-five percent of parents/guardians completed the questionnaire (64 whose child had cancer and 150 whose child had diabetes). At diagnosis, 45% of respondents had a household pet; few found them a new home. Twenty percent of patients with cancer acquired a pet after diagnosis, 77% of which were high-risk pets. These findings and more, which can be found in the authors’ report, provide convincing evidence of the need for improved education of households with immunocompromised children, as well as that of pediatric and veterinary healthcare professionals. Article page 348
Bones, breaks, and BMI — Thomas R. Welch, MD
An evaluation of pediatric clinical trial design — Robert W. Wilmott, MD
218
I
t seems that just about any childhood travail is somehow linked to obesity. Some of these associations are consistently reproducible, and others are less so. One of the more interesting of these is the association between obesity and fracture risk. Studies of this association have been mixed in their results, and are confounded by things like activity levels, sports participation, etc. This issue of The Journal contains an article by Sabhaney et al that brings some clarity to the matter and has a surprising finding. These investigators studied over 2000 children who came to one of two emergency departments with a non penetrating extremity injury. The children were classified according to body mass index, and the authors examined the risk of having a fracture as a function of obesity status. Overweight children had a small but significant decreased risk of fracture compared with those of normal weight. Underweight children, however, had a significantly increased risk of fracture. It is not immediately clear what we should do with this information. As the authors point out, weight status may have been a surrogate for bone mineral density, which could have been the major (unmeasured) risk factor. It also should be considered that these are generally low-severity upper extremity fractures, which may be the often-unavoidable consequence of an active childhood! Article page 313
S
inha et al from the University of Sydney, Australia, asked whether recently published randomized controlled trials of pharmacologic agents in children demonstrated any more risk of bias than similar trials performed in adults. This was investigated by evaluating 100 trials involving only children and matching them by drug class and therapeutic area with similar trials completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials. The results were reassuring in that the published randomized control trials involving children had a largely similar risk of bias compared with the randomized controlled trials in adults, suggesting that pediatric clinical investigators have a similar capability to conduct and report randomized controlled trials to their adult colleagues. The study demonstrated several areas where bias potentially exists in pediatric trials, although, in most areas, the pediatric trials were slightly better than the adult ones. However, these areas will need close attention in the future. An important message from this study is that we have the capability in pediatrics to perform robust, randomized, controlled trials in children, so there is no reason to neglect assessing drugs in the pediatric population. Article page 367
Vol. 165, No. 2
A healthy mind in a healthy body — Thomas R. Welch, MD
MgSO4 for neuroprotection — Alan H. Jobe, MD, PhD
August 2014
T
he concept that overall physical fitness is positively associated with academic performance has been in circulation for a long time. In this issue of The Journal, Esteban-Cornejo et al advance this area of study considerably, with a study that is impressive for the number of children involved and the detail with which the association was tested. In a group of over 2000 children, these authors performed standardized measures of three components of fitness: muscle strength, cardiorespiratory capacity, and motor fitness. These were examined in relation to four measures of academic achievement. Cardiorespiratory capacity and motor fitness were positively associated with all academic measures, but muscular strength had no independent association. Obviously, this work does not demonstrate cause and effect, but the results are striking. Their findings should stimulate carefully-designed interventional studies. Article page 306
S
urvivors of very preterm birth often have neurodevelopmental abnormalities that are certainly multifactoral in origin. Both antenatal and postnatal exposures can contribute to these adverse outcomes. One of the few interventions that has been tested in randomized controlled trials is maternal treatment with MgSO4 prior to very preterm delivery. This intervention, developed based on the frequent use of MgSO4 as a tocolytic for preterm labor, decreased cerebral palsy diagnosed at 2 years of age. In this issue of The Journal, Chollat et al report the school-age outcomes for one of the MgSO4 trials. Although not statistically significant, infants exposed to MgSO4 had less motor dysfunction, fewer behavioral disorders, fewer cognitive difficulties, less frequent repeating of school grade, and less use of special education services than the control infants. An unsatisfying aspect of this therapy is that the mechanism of action of MgSO4 on the very preterm fetus/newborn is unknown. Nevertheless, all assessments were in the direction of benefit, at least demonstrating no harm, from the MgSO4 exposure at school age. Article page 398
219