Wednesday, December 29, 2010

Sucrose Analgesia for Infants: State of the Science

From Medscape Pediatrics > Viewpoints

Analgesic Effects of Sweet-Tasting Solutions for Infants: Current State of Equipoise

Harrison D, Bueno M, Yamada J, Adams-Webber T, Stevens B
Pediatrics. 2010;126:894-902

Study Summary

This article describes a meta-analysis of multiple randomized controlled trials that evaluated oral sucrose (or other sugar product) for acute, painful procedures in infants. Harrison and colleagues examined whether a state of equipoise (equilibrium about whether an intervention is likely to be helpful) still exists in regard to the use of oral sucrose for pain amelioration.

They noted that many randomized, placebo-controlled trials have been conducted despite the fact that reviews published throughout the 2000s demonstrated overwhelming evidence of clinical effectiveness. In addition to conducting a meta-analysis of the literature, this study sought to identify research questions or areas upon which future studies could focus.

The investigators reviewed 4 online literature databases and existing evidence-based reviews on the topic. They identified 125 primary research studies on the topic, with 49% using heel lance as the painful procedure, 14% using venipuncture or intramuscular injection, and 6% studying pain relief related to circumcision.

In 103 studies (93%), the use of sucrose or other sweet solution reduced pain response. One of 8 studies evaluating pain control with circumcision had negative results, but the other 7 (87.5%) demonstrated benefit. The solutions used in the trial varied greatly, but the most common was sucrose.

In general, sweeter solutions (higher concentrations) tended to have higher rates of success. The investigators concluded that there is no longer ethical justification for placebo groups in trials investigating the use of sweet solutions to limit short-term procedural pain. They pointed out the following knowledge gaps that could ethically be the focus of future investigation:

* Are sweet solutions effective in mitigating procedural pain for extremely premature infants?
* Are repeated administrations of the solution more effective than single administrations?
* Are sweet solutions effective over extended hospitalizations?
* How do sweet solutions compare with narcotic pain medications for short procedures?
* What is the effectiveness of sweet solutions for longer noxious procedures?
* Are sweet solutions effective in this setting for older children?

Harrison and coworkers suggested that these unanswered questions should be the focus of future research.

Tuesday, December 28, 2010

Complementary, Alternative Medicine Linked to Adverse Events in Children

From Medscape Medical News

Laurie Barclay, MD

December 27, 2010 — The use of complementary and alternative medicine (CAM) can be associated with serious, and even fatal, adverse events in children, according to the results of a monthly active surveillance study reported online December 22 in the Archives of Disease in Childhood.

"...CAM is commonly administered to children," write Dr. Alissa Lim, from Royal Children's Hospital in Melbourne, Australia, and colleagues. "As CAM is frequently regarded as natural and therefore safe, adverse events may go unreported."

The goal of the study was to assess the types of adverse events linked to use of CAM that came to the attention of Australian pediatricians. Between January 2001 and December 2003, a total of 39 cases of adverse events associated with CAM use were reported to the Australian Paediatric Surveillance Unit, and a physician completed the questionnaire.

Almost two thirds of the reported cases (64%) were considered to be severe, life threatening, or fatal. Reported adverse events included constipation, bleeding, pain, allergic reactions, mouth ulcers, seizures, vomiting, stunted growth, infections, and malnutrition.

Several areas of concern were apparent that posed significant risks, including those related to failure to use conventional medicine because CAM therapy was substituted, those associated with medication changes made by CAM practitioners, and those caused by dietary restriction in the belief that this would cure symptoms. There were 4 reported deaths associated with a failure to use conventional medicine because a CAM treatment was substituted.

"CAM use has the potential to cause significant morbidity and fatal adverse outcomes," the study authors write. "The diversity of CAM therapies and their associated adverse events demonstrate the difficulty addressing this area and the importance of establishing mechanisms by which adverse effects may be reported or monitored."

Limitations of this study include lack of information about the products used, information collected only from pediatricians, and underreporting by families and also by clinicians because of time pressures and uncertainly about causality and severity of outcome. Although 46 instances of adverse events associated with CAM were reported during the study period, only 40 questionnaires were completed, and one of these was a duplicate, leaving 39 cases for analysis.

"Discussions with families about CAM use may empower them to talk about any medication changes suggested by a CAM practitioner before altering or ceasing the medication," the study authors conclude. "However, many of the adverse events associated with failure to use conventional medicine resulted from the family's belief in CAM and determination to use it despite medical advice."

The study authors have disclosed no relevant financial relationships.

Arch Dis Child. Published online December 22, 2010. Abstract

Monday, December 20, 2010

Moderate vs Low ICS Doses May Not Give Added Benefit in Childhood Asthma

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

December 8, 2010 — Compared with low doses, moderate doses of inhaled corticosteroids (ICSs) may not give an added benefit to children with mild to moderate persistent asthma, according to the results of a systematic review and meta-analysis reported online December 6 in Pediatrics.

"...ICSs are currently considered the first-line treatment for persistent childhood asthma; however, uncertainty remains regarding the optimal dose," write Linjie Zhang, MD, PhD, from the Maternal and Child Health Unit, Faculty of Medicine, Federal University of Rio Grande in Rio Grande, Brazil, and colleagues.

"The most recent asthma guidelines recommend a dose of up to 400 μg/day beclomethasone dipropionate (BDP)-hydrofluoroalkane equivalent for children with mild-to-moderate persistent asthma, but these recommendations are generally based on results from individual randomized trials rather than a body of evidence that has been critically appraised by a systematic review."

The reviewers searched MEDLINE for articles published between 1950 and August 2009 describing randomized controlled trials that compared 2 or more different ICS doses in children aged 3 to 18 years with persistent asthma.
The analyses focused on study endpoints of morning and evening peak expiratory flow, forced expiratory volume in 1 second, asthma symptom score, use of β2-agonists, withdrawal for lack of efficacy, and adverse events.
The investigators used meta-analyses to compare moderate doses of ICSs (300 - 400 μg/day) vs low doses of ICSs (≤ 200 μg/day beclomethasone equivalent).

The 14 included randomized controlled trials enrolled a total of 5768 asthmatic children and evaluated 5 ICSs. Moderate vs low doses were slightly but statistically significantly more effective in improving forced expiratory volume in 1 second among children with mild to moderate asthma, based on the pooled standardized mean difference from 6 trials (standardized mean difference, 0.11; 95% confidence interval, 0.01 - 0.21). However, other efficacy outcomes were not significantly different between the 2 doses, and there was no evidence of a dose-response relationship at low to moderate doses. Local adverse events were uncommon.

"Compared with low doses, moderate doses of ICSs may not provide clinically relevant therapeutic advantage in children with mild-to-moderate persistent asthma," the study authors write. "Additional RCTs [randomized controlled trials] are needed to clarify the dose-response relationship of ICSs in persistent childhood asthma."

Limitations of this study include an unclear risk for bias in the included trials, as well as nonuniform reporting of continuous efficacy outcome results and incomplete reporting of data collection and adverse events. Because of the language limitation, 1 small randomized trial conducted in Germany was not included.

"Although ICSs are generally considered safe treatment for children with asthma, the potential systemic adverse effects such as adrenal suppression, linear growth retardation, and effects on bone mass, are still of concern," the study authors conclude. "A limited number of studies included in this review assessed adverse effects of ICSs given at different doses on linear growth and on hypothalamic-pituitary-adrenal function, and their findings were inconsistent. There are no suitable data for investigating dose-response relationship of systemic adverse effects of ICSs."

Dr. Zhang has received grants from the Brazilian government agency CAPES for postdoctoral training in the Institute for Clinical Research and Health Policy Studies (Tufts Medical Center, Boston, Massachusetts).

Pediatrics. Published online December 6, 2010.
Clinical Context

ICSs are first-line therapy for children with persistent asthma, but the long-term use of these medications among children raises concerns regarding significant long-term adverse effects. This issue was addressed in a review by Allen, which was published in Advances in Pediatrics in 2006. He notes that the use of ICSs alone at small doses does not appear to be associated with any significant systemic adverse events. Although ICSs can retard vertical linear growth when given at high doses, ICS use alone does not appear to affect final adult height. Routine ICS use also should not lead to significant adrenal suppression or bone loss.

Although ICSs at low doses may be safe for children, are they effective enough? The current study examines the dose response to ICSs among children with persistent asthma.

HPV Immunization for Male and Female Patients: Strategies to Reduce the Disease Burden

Kenneth A. Alexander, MD, PhD, Course Chair; Amanda Frisch Dempsey, MD, PhD, MPH; Maura L. Gillison, MD, PhD; Stephen E. Goldstone, MD

Contents of This CME Activity

1. Introduction
Kenneth A. Alexander, MD, PhD, Course Chair
Available As: Slides/Audio | Transcript
2. HPV Epidemiology: Infection to Genital Warts and Cancer
Maura L. Gillison, MD, PhD
Available As: Slides/Audio | Transcript
3. HPV Immunization: Making the Case for Males and Females
Stephen E. Goldstone, MD
Available As: Slides/Audio | Transcript
4. Incorporating HPV Into Adolescent Immunization
Amanda Frisch Dempsey, MD, PhD, MPH
Available As: Slides/Audio | Transcript
5. Talking to Patients and Parents
Available As: Slides/Audio | Transcript

Earn CME Credit »

FDA Hearing on Mercury-Based Dental Fillings Pleases Both Sides of Debate

From Medscape Medical News

Robert Lowes

December 18, 2010 — An advisory panel to the US Food and Drug Administration (FDA) concluded this week that there are no huge scientific flaws in the agency's 2009 finding that mercury-based dental fillings, known as dental amalgam, are safe for adults and children aged 6 years and older.

However, at the end of its 2-day hearing, the agency's dental products panel recommended that the FDA look at more data — and the latest data — on the possible health risks that the filling material poses to pregnant women and their fetuses and to young children, particularly nursing infants whose mothers have these fillings. The panel also said the agency should consider adding warnings for these groups to the material's product instructions.

In one sense, the outcome of the hearing temporarily preserves the status quo for dental amalgam — so much so that the American Dental Association immediately issued a press release praising the expert panel's recommendations. The American Dental Association maintains that dental amalgam is safe and warrants no further regulation by the FDA as a medical device.

At the same time, the panel's quest for more scientific data about vulnerable populations acknowledged the concerns of dental amalgam opponents, who link mercury exposure to dozens of diseases ranging from autism to Alzheimer's disease. At high enough levels, mercury exposure can damage the brain and kidneys.

"We have to recognize that some patients should not have amalgam," said panel member Amid Ismail, BDS, DrPH, a professor and dean at the Kornberg School of Dentistry at Temple University in Philadelphia, Pennsylvania.

"There is really no place for mercury in children," added Suresh Kotagal, MD, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota. "The bottom line is, do no harm."

An attorney for the International Academy of Oral Medicine and Toxicology (IAOMT), which advocates mercury-free dentistry, told Medscape Medical News that he was encouraged by the consensus positions of the panel (no formal votes were taken).

"There was a lot of support that risk assessment needs to be done again," said Jim Love, the attorney for the group. "I thought it was a very constructive dialogue."

The FDA convened the hearing after the IAOMT and other antiamalgam groups and individuals petitioned the agency to reconsider its 2009 decision to reclassify the material from a lower-risk class I device to a moderate-risk class II device. That reclassification entailed revising product instructions to state in part that

* clinical studies have not established a causal link between dental amalgam and health problems for adults and children aged 6 years and older,
* the developing nervous systems of fetuses and young children "may be more sensitive to the neurotoxic effects of mercury vapour," and
* little or no clinical data are available regarding long-term health outcomes for fetuses, children younger than 6 years, and breast-fed infants.

The petitioners urged the agency to either ban dental amalgam, as Norway, Sweden, and Denmark already have done, or else reclassify it as a high-risk class III device with more restrictions on its use.

"Industry Will Go Crazy if That Reference Level Gets Moved"

By weight, dental amalgam is composed of roughly 40% to 50% liquid elemental mercury and a powdered alloy of mostly silver, copper, and tin. Much of the 2-day hearing focused on how much mercury is absorbed by people with these fillings, and what should be the reference exposure level (REL), or safety threshold, for the mercury vapor that the fillings release. Because mercury doses can be calculated from vapor exposure levels, an REL can establish a permissible dose. At the end, the advisory panel recommended that the agency take a second look at its positions on these issues.

The FDA currently holds that an individual with 7 to 10 amalgam fillings absorbs 1 to 5 μg of mercury per day. Amalgam opponents say this dose can be 4 times as high, meaning that tens of millions of people with these fillings are at risk for health problems, based on the current REL in place. The advisory panel's advice to the FDA is to study mercury doses for various population categories.

"We have virtually no data on fetuses," panel chairwoman Marjorie Jeffcoat, DMD, a professor at the University of Pennsylvania School of Dental Medicine, told Medscape Medical News. "It's important to subset out the different populations."

Also in dispute is the REL for mercury vapor. The FDA uses an REL of 0.3 μg/m3, set by the US Environmental Protection Agency (EPA). The EPA refers to this safety threshold as a "reference concentration" (RfC), which is an REL for inhaled, as opposed to swallowed, chemicals. This REL or RfC of 0.3 μg/m3 translates into a permissible dose that lies in the same range as the actual amalgam-derived dose assumed by the FDA.

The IAOMT told the panel that the REL for elemental mercury should be lower than 0.1 μg/m3 and cited a study it commissioned as proof. That study, whose lead author is Canadian biologist G. Mark Richardson, PhD, states that the EPA based its REL in part on studies of industrial workers exposed simultaneously to mercury and chlorine gas, with the gas acting to reduce mercury exposure, thus skewing the numbers. He notes that Health Canada, the Canadian equivalent of the US Department of Health and Human Services (and his former employer), set an REL of 0.06 μg/m3 by relying on studies free of this distortion.

The panel did not fully agree with Dr. Richardson's critique and called his chlorine gas argument a "red herring." Nevertheless, it advised the FDA to reexamine the scientific literature to reassess the REL and develop its own, noting that "the EPA RfC needs to be updated with the latest studies," according to an FDA hearing summary.

In essence, the panel wants the FDA to determine whether the REL really protects vulnerable populations, Dr. Jeffcoat told Medscape Medical News. "Tiny children can't speak for themselves," she said.

However, any lowering of the REL for elemental mercury has enormous consequences that extend far beyond the dentist's office, IAOMT attorney Jim Love told Medscape Medical News. The EPA, he said, uses this REL to regulate how much mercury that heavy industry can put into air and water, as well as to designate waste sites for its Superfund clean-up program. A lower REL means higher environmental protection costs — think billions of dollars — all around.

"Industry will go crazy if that reference level gets moved," said Love.

Need to Acknowledge Amalgam Benefits

The panel also revisited the question — raised in the FDA's 2009 deliberations — of whether clinical studies point to a causal relationship between dental amalgam and adverse health events. The panel reaffirmed that the literature at that time failed to do so, but only in terms of the general population. Again, it recommended that the agency continue to study the issue, particularly in terms of "susceptible subpopulations."

The panel grappled with how to best spell out the possible health risks of dental amalgam in the product instructions that dentists receive. It finally suggested adding warnings for young children, pregnant women, and individuals with metal allergies, and making the reference to limited scientific data about such individuals more explicit.

Panel members also stressed the need for dentists to discuss this information with patients. A number of individuals who spoke at the hearing complained that their dentists never mentioned mercury-associated risks for amalgam fillings, which they blamed for serious illnesses.

A model for warning language, incidentally, lies north of the border. Health Canada states on its Web site that although dental amalgam generally does not pose a health threat, the primary teeth of children should be filled with a nonmercury material when feasible. Pregnant women, individuals allergic to mercury, and those with impaired kidney function should avoid mercury-based fillings, according to Health Canada.

Tempering the panel's recommendations on Wednesday was an acknowledgment that amalgam's risks must be weighed against its benefits — namely, its superiority over tooth-colored composite fillings for restoring multiple surfaces, and its greater durability. In addition, although the use of amalgam has drastically declined during the last few decades as a result of patients choosing more cosmetically attractive alternatives, its lower price has made it the default material for poorer patients, who might not be able to afford more expensive fillings if amalgam were banned.

"It's nice for us to talk about risk and benefit and choice," said panel member Thomas Burbacher, PhD, a professor of environmental and occupational health sciences at the University of Washington in Seattle. "But if you don't have a choice, that discussion is meaningless."

Tuesday, October 5, 2010

Probiotics for Gastroenteritis and Allergies -- A Double Benefit?: Commentary

What Are Probiotics?

by Diseree lie MD

Probiotics are defined by the World Health Organization (WHO) as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host."
Probiotics are found in the gastrointestinal tract or as components of foods and beverages.
They are different from prebiotics, which are complex carbohydrates (nondigestable, fermentable polysaccharides) that stimulate the growth and/or activity of beneficial bacteria already in the colon. Prebiotics may be considered precursors to probiotics, and their role has yet to be defined in larger clinical studies.

Probiotics and prebiotics may be combined in a single product called synbiotics.
Most probiotics are either Lactobacillus or Bifidobacterium and their various species and strains (for example, Lactobacillus acidophilus and Bifidobacterium bifidus).
Other common probiotics are yeasts -- for example, Saccharomyces boulardii.

Probiotics are believed to reinforce the integrity of the intestinal lining as a protective barrier to prevent invasion by pathogenic organisms, and they are purported to prevent harmful bacteria or yeast from breaching the gastrointestinal mucosa.
They have an effect on priming immunophysiologic regulation in the intestinal mucosal barrier and may exert clinical effects beyond the nutritional value of food.
This effect is the rationale for their efficacy in preventing infectious or other forms of diarrhea and for the treatment of allergic conditions.

Formulations of Probiotics

Probiotics are available as tablets, powder, capsules and can also be mixed into beverages such as yogurt, milk, or juice.
Many different forms are offered worldwide.
Bifidobacteria appear to be safe when used orally, including in those under 2 years and ill neonates.
For example, a combination probiotic consisting of Lactobacillus, Bifidobacteria, and Streptococcus salivarius, known as VSL#3, was used in children ages 1 to 16 years for up to a year.
For preventing diarrhea in children, 5-10 billion live Lactobacillus GG have been used twice daily as tablets. Doses of 10-100 billion live organisms are available in tablet form, and capsules of 3 grams are also available.

Clinical Evidence

Diarrhea-associated illness.
There is a body of evidence supporting the benefit of probiotics in diarrhea-associated diseases. Several probiotics (Saccharomyces boulardii and a mixture of L acidophilus and B bifidum) have shown efficacy for preventing traveler's diarrhea with a relative risk (RR) reduction of 15% (RR=0.85, P < .001).[8,9]

Probiotics have also been shown to benefit antibiotic-associated and pediatric infectious diarrhea, especially rotavirus-related diarrhea. Probiotics have been used for a variety of gastrointestinal disorders as well, including these clinically successful applications for conditions related to inflammatory bowel disease:

•Lactobacillus GG to maintain remission in those with ulcerative colitis;
•S boulardii in combination with mesalamine to prevent clinical relapse of Crohn's disease (it should be noted that a Cochrane review concluded that studies to date have been too small to draw conclusions about use of probiotics for Crohn's disease prophylaxis);
•VSL#3 for prophylaxis of pouchitis and improved quality of life following ileal pouch-anal anastomosis; and
•VSL #3 for prevention of recurrent pouchitis after antibiotic-induced remission in patients with a refractory form of this condition.
Probiotics have also been found to be helpful in diarrhea-predominant irritable bowel syndrome. For example, in a meta-analysis, the odds ratio (OR) in favor of active probiotic treatment over placebo in children for diarrhea was 0.39 (P < .001) for yeast and 0.34 (P < .01) for Lactobacilli.

Similarly, probiotics offer a possible way to prevent antibiotic-associated diarrhea. A randomized study using 100g of a drink containing Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus taken twice daily for one week after a course of antibiotics reduced the incidence of antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea.[12]

Allergic diseases. Two Cochrane reviews looking at the prevention of allergic disease and food hypersensitivity in infants found positive evidence from studies using Lactobacillus rhamnosus in favor of eczema prevention but not treatment.

A few reviews found encouraging, but not strong, effects, for several species of Lactobacilli for atopic dermatitis; these reports were based on placebo-controlled, randomized studies, using the SCORing Atopic Dermatitis (SCORAD) index for assessment, with possibly greater effects in children who have cow's milk allergy.
As noted in other reviews, a benefit was more likely to be seen for the prevention of eczema than for improvement of existing eczema. Most of the studies showing benefit were small and limited in scope. Of interest, when mothers consumed probiotics during pregnancy (starting 2 to 4 weeks before delivery), the likelihood of atopic dermatitis in the child was reduced at 2 years by about 50% in one study, and the cumulative effect on prevention was still evident at 4 years.
However, there was no effect on respiratory allergy, immunoglobulin E (IgE) levels, or allergic sensitization in these children. When infants were given probiotics in the first 6 months of life, a similar reduction in incidence of atopic eczema at 2 and 4 years was noted in these 2 studies.

Another randomized controlled trial of infants 5 months and younger, however, showed no effect of probiotic supplementation with L rhamnosus compared with placebo in the form of a hydrolyzed whey-based formula on atopic dermatitis in children when given for 3 months.

Overall, while there is a sound theoretical basis for a benefit of using probiotics for allergic disease, there is currently insufficient data to recommend it for all allergic conditions. With that said, there is more evidence supporting its use in preventing atopic dermatitis in children than for other allergic or immune conditions.

Respiratory illnesses. Studies in teenagers and adults with established respiratory disease have failed to show symptom improvement in asthma or allergic rhinitis although quality of life was improved in 1 study.

Studies on the common cold in adults have shown a reduction in duration and severity but not the incidence of cold episodes with improved cytotoxic T and T- suppressor cell immune function.
When given in winter for at least 3 months, a combination of probiotics and vitamins and minerals reduced both the incidence and severity of common cold infections in adults with concomitant immune function improvement.

In children, a twice-daily dose of L acidophilus alone or in combination with Bifidobacterium compared with a placebo given over 6 months in winter was found to reduce:

•Antibiotic use by 68% (single strain) to 84% (strain combination);
•Absenteeism from day care due to respiratory infection by 32% (single strain) and 28% (strain combination); and
•Symptoms of cough, fever, and rhinorrhea by 28% to 60%.[38]
These observations were confirmed in another study of 571 children attending day care centers that provided cow's milk with or without Lactobacillus GG for 7 months, and found a relative reduction in:

•Incidence of respiratory infection (17% reduction);
•Antibiotic use for infection (19% reduction); and
•Absence from day care due to illness (16% or 1-day difference; P = .03).

Thursday, September 30, 2010

First Direct Genetic Evidence for ADHD Discovered

From Medscape Medical News

Caroline Cassels

September 29, 2010 — New research provides the first direct evidence that attention-deficit/hyperactivity disorder (ADHD) is genetic.

In a study published online September 30 in The Lancet, investigators from the University of Cardiff in the United Kingdom say their findings, which show that ADHD has a genetic basis, suggest it should be classified as a neurodevelopmental and not a behavioral disorder.

"We've known for many years that ADHD may well be genetic because it tends to run in families in many instances. What is really exciting now is that we've found the first direct genetic link to ADHD," principal investigator Anita Thapar, MD, told reporters attending a press conference to unveil the study results.

In the genomewide analysis, 366 children 5 to 17 years of age who met diagnostic criteria for ADHD but not schizophrenia or autism and 1047 matched controls without the condition were included. Researchers found that compared with the control group without ADHD, children with the disorder were twice as likely — approximately 15% vs 7% — to have copy number variants (CNVs).

CNVs, explained study investigator Nigel M. Williams, PhD, are sections of the genome in which there are variations from the usual 2 copies of each chromosome, such that some individuals will carry just 1 (a deletion) and others will have 3 or more (duplications).

"If a gene is included in one of these copy number variants, it can have deleterious consequences," said Dr. Williams.

Shared Biological Link

The study authors note that the increased rate of CNVs was particularly high among children with a combination of ADHD and learning disabilities but "there was also a significant excess in cases with no such disability."

The researchers also found that CNVs overlap with chromosomal regions that have previously been linked to autism and schizophrenia. Although these disorders are thought to be completely separate, there is some overlap between ADHD and autism in terms of symptoms and learning difficulties.

We've looked at only 1 class of variation, but it's an important one because it has been linked to other brain disorders.

This finding suggests there may be a shared biological basis for the 2 conditions and, according to investigators, provides the first direct evidence that ADHD is a neurodevelopmental condition.

"We found that the most significant excess of these types of copy number variants was on a specific region of chromosome 16. This chromosomal region includes a number of genes, including one that affects brain development," said Dr. Thapar.

The team's research marks the start of the "unraveling of the genetics" of ADHD, according to Dr. Thapar.

"We've looked at only 1 class of variation, but it's an important one because it has been linked to other brain disorders," she said.

Implications for DSM-5?

Dr. Thapar added that the study results also have direct implications for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is currently under development by the American Psychiatric Association.

A "huge debate" about whether ADHD should be classified as a behavioral or neurodevelopmental disorder is ongoing. However, she said, these findings should help put this controversy to rest.

"Our results clearly show that ADHD should be considered a neurodevelopmental disorder," she said.

In fact, Dr. Thapar noted that the study findings have been submitted to one of the DSM-5 work groups for consideration in the development of the new manual.

The investigators note that despite epidemiologic evidence derived from twin studies showing high heritability and the fact that ADHD is often accompanied by learning disabilities, there is still a great deal of public misunderstanding about the disorder.

Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma.

"Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma," said Dr. Thapar.

Although there are no immediate treatment implications, Dr. Thapar said she hopes the research will have an immediate impact in terms of shifting public perception about ADHD and fuel further research into the biological basis of the disorder with a view to developing better, more effective therapies for affected individuals.

In an accompanying editorial, Peter H. Burbach, PhD, from the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands, writes, "The first gains beyond today's study might be initial insights into the pathogenesis and neurobiology of brain development as influenced by these genetic variants. This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype."

The study authors and Dr. Burbach have disclosed no relevant financial relationships.

Lancet. Published online September 30, 2010.

Exclusive Breast-Feeding for 6 Months May Protect Infants Against Common Infections

From Medscape Medical News

Laurie Barclay, MD

September 28, 2010 — Exclusive breast-feeding for 6 months, as recommended by the World Health Organization, may protect infants against common infections, according to the results of a prospective study reported online September 28 in the Archives of Disease in Childhood.

"Breastfed infants are considered to be less prone to a variety of infections, including acute otitis media, and gastrointestinal and lower respiratory tract infections," write Fani Ladomenou, from the University of Crete in Heraklion, Greece, and colleagues.

The goal of the study was to determine the impact of breast-feeding on the frequency and severity of infections in a well-defined population of infants with adequate vaccination coverage and healthcare standards. The investigators recorded type of feeding and all infectious episodes, including acute otitis media (AOM), acute respiratory infection (ARI), gastroenteritis, urinary tract infection, conjunctivitis, and thrush, in a representative sample of 926 infants who were followed up at ages 1, 3, 6, 9, and 12 months.

Compared with partially breast-fed or non−breast-fed infants, those who were exclusively breast-fed for 6 months had fewer infectious episodes. Adjustment for potential confounders did not abolish this protective effect, with odds ratio (OR) of 0.58 for ARI (95% confidence interval [CI], 0.36 - 0.92), 0.37 for AOM (95% CI, 0.13 - 1.05), and 0.14 for thrush (95% CI, 0.02 - 1.02). Although partial breast-feeding was not associated with a reduced risk, prolonged exclusive breast-feeding was associated with fewer infectious episodes (Spearman's rs = −0.07; P = .019) through age 1 year, as well as with fewer hospitalizations for infection (Spearman's rs = −0.06; P = .037).

Parental age and education, ethnicity, having siblings, secondhand smoke exposure, season of birth, and other confounding factors also affected the frequency of infections during infancy.

"Findings from this large-scale prospective study in a well-defined infant population with adequate healthcare standards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes," the study authors write. "Partial breastfeeding did not seem to provide this protective effect."

Limitations of this study include reliance on maternal recall, possible detection bias, nonspecific definition of diarrhea, and possible confounding factors.

"Despite limitations, our results suggest breastfeeding has beneficial effects against common infections in infancy," the study authors conclude. "This protection seems to be related to the exclusive breastfeeding and its duration. Therefore, mothers should be advised by health professionals that, in addition to all the other benefits, exclusive breastfeeding helps prevent infections in babies and lessens the frequency and severity of infectious episodes."

The study authors have disclosed no relevant financial relationships.

Arch Dis Child. Published online September 28, 2010.

Rotarix Label Has New Warning About Risk for Bowel Abnormality

Medscape Alerts

Robert Lowes

September 23, 2010 — The US Food and Drug Administration (FDA) has revised the label of the rotavirus vaccine Rotarix (GlaxoSmithKline) to warn of a small increased risk for intussusception that was reported in a Mexican study, the agency announced yesterday.

A potentially life-threatening condition, intussusception occurs when 1 portion of the intestine telescopes into another. This anomaly, which can develop in the absence of vaccination, may lead to internal bleeding, an intestinal hole, and abdominal infection.
The annual rate of spontaneous intussusception — and subsequent hospitalization — is roughly 34 in 100,000 healthy young infants and children, the FDA stated.

Symptoms, which usually develop suddenly, include fussiness, frequent vomiting, diarrhea or stools containing blood or mucus, and severe belly pain, cramping, and swelling.

Preliminary results from a postmarketing study of Rotarix in Mexico suggest that there is an increased risk for intussusception in the 31 days after the first dose, with a relative risk of 1.8, according to the agency. Most cases occurred during the first 7 days after the first dose.

Extrapolated to the United States, these results would represent up to 4 additional hospitalizations due to intussusception per 100,000 infants within 31 days of the first Rotarix dose. The agency noted that the annual background rate of intussusception in Mexico — between 60 and 90 per 100,000 children — is higher than that in the United States.

The FDA said it would review the final results from the Mexican study when they become available in 2011. It noted that GlaxoSmithKline is conducting a postmarketing study of Rotarix and intussusception in the United States.

In 1999, the rotavirus vaccine RotaShield was withdrawn from the market after studies suggested an elevated risk for intussusception on the order of 9 additional cases per 100,000 infants.
No increased risk for this bowel condition emerged in clinical trials for both Rotarix and another rotavirus vaccine, RotaTeq (Merck), but the agency nevertheless has monitored the 2 vaccines for this potential problem.

The postmarketing study in Mexico did not examine RotaTeq, and it is not undergoing a label revision.
The FDA said it has uncovered no evidence of an increased risk for intussusception with RotaTeq, but it will continue to study the issue.

More information about yesterday's FDA announcement is available on the agency's Web site.

The FDA and the US Centers for Disease Control and Prevention encourage clinicians to report intussusception or any adverse event after vaccination to the Vaccine Adverse Event Reporting System.

Disclosure: Robert L. Lowes has disclosed no relevant financial relationships.

Improve Brain Health Now: Easy Steps

Apr 11, 2007
By: Caroline Latham

We can sum­ma­rize a lot of research by say­ing that there are four essen­tial pil­lars to main­tain­ing a healthy brain that func­tions bet­ter now and lasts longer. Those pil­lars are:

◦1) Phys­i­cal Exercise
◦2) Men­tal Exercise
◦3) Good Nutrition
◦4) Stress Management

Great … now what?! How do you develop a healthy lifestyle that includes all four pil­lars? Let’s look at each one.

1.1. Phys­i­cal Exer­cise
◦- Start by talk­ing to your doc­tor, espe­cially if you are not cur­rently phys­i­cally active, have spe­cial health con­cerns, or are mak­ing sig­nif­i­cant changes to your cur­rent program.
◦- Set a goal that you can achieve. Do some­thing you enjoy for even just 15 min­utes a day. You can always add more time and activ­i­ties later.
◦- Sched­ule exer­cise into your daily rou­tine. It will be become a habit faster if you do.
◦- If you can only do one thing, do some­thing car­dio­vas­cu­lar, mean­ing some­thing that gets your heart beat­ing faster. This includes walk­ing, run­ning, ski­ing, swim­ming, bik­ing, hik­ing, ten­nis, bas­ket­ball, play­ing tag, ulti­mate Fris­bee, and other sim­i­lar sports/activities.

2.2. Men­tal Exer­cise
◦- Be curi­ous! Get to know your local library and com­mu­nity col­lege, look for local orga­ni­za­tions or churches that offer classes or workshops
◦- Do a vari­ety of things, includ­ing things you aren’t good at (if you like to sing, try paint­ing too)
◦- Work puz­zles like cross­words and sudoku or play games like chess and bridge
◦- Try a com­put­er­ized brain fit­ness pro­gram for a cus­tomized workout
◦- If you can only do one thing, learn some­thing new every day

3.3. Good Nutri­tion
◦- Eat a vari­ety of foods of dif­fer­ent col­ors with­out a lot of added ingre­di­ents or processes
◦- Plan your meals around your veg­eta­bles, and then add fruit, pro­tein, dairy, and/or grains
◦- Add some cold-water fish to your diet (tuna, salmon, mack­erel, hal­ibut, sar­dines, and her­ring) which con­tain omega-3 fatty acids
◦- Learn what a portion-size is, so you don’t overeat
◦- Try to eat more foods low on the Glycemic Index
◦- If you can only do one thing, eat more veg­eta­bles, par­tic­u­larly leafy green ones

4.Stress Man­age­ment
◦- Get reg­u­lar car­dio­vas­cu­lar exercise
◦- Try to get enough sleep each night
◦- Keep con­nected with your friends and family
◦- Prac­tice med­i­ta­tion, yoga, or some other calm­ing activ­ity as way to take a relax­ing time-out (maybe a bath)
◦- Try train­ing with a heart rate vari­abil­ity sen­sor, like the one in emWave (for­merly known as Freeze-Framer)
◦- If you can only do one thing, set aside 5–10 min­utes to just breathe deeply and recharge

Tuesday, September 28, 2010

Sleep Disorder: Nightmares

Pediatrics: Developmental and Behavioral > Medical Topics

Author: Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program
Updated: Feb 25, 2008

Sleep disorders occur in 35-45% of children aged 2-18 years. Nightmares are frightening events for a child and may cause the entire family distress; however, they are sporadic in most children. Nightmare disorder is characterized by repeated episodes of a frightening or unpleasant dream that disrupts the child's sleep. The child's reaction often interrupts the parents' sleep. Upon awakening from a nightmare, the child is alert and aware of the present surroundings, but the sleep disturbance causes distress and impairment in everyday functioning.

Nightmares are often confused with the parasomnia known as night terrors, which are episodes of extreme panic and confusion associated with vocalization, movement, and autonomic discharge. Children with night terrors are difficult to arouse and console and do not remember a dream or nightmare.

Sleep is divided into 2 distinct states: rapid eye movement (REM) and nonrapid eye movement (non-REM).
REM and non-REM sleep alternate in 90- to 100-minute cycles.
In older children and adults, 75% of sleep is non-REM sleep, which consists of 4 stages. Most dreaming occurs during REM sleep.
REM sleep is characterized by EEG activity similar to a wakeful pattern.

United States
Prevalence varies because of different diagnostic criteria and different study populations. Some studies estimate as many as 50% of children aged 3-6 years have nightmares that disturb both their sleep and the parents' sleep.

Nightmares occur in all races and cultures.

Both sexes are equally affected.

Peak incidence occurs in children aged 3-6 years.1,2
•Sporadic nightmares are common in children and usually occur in the middle of the night or early morning, when REM sleep is more common.
•The dream typically involves some danger or threat to the child.
◦The child may dream about physical danger (eg, being chased).
◦A nightmare may also involve psychological threat (eg, being teased).
◦Nightmares may involve a monster, ghost, fierce animal, or bad individual.
◦Loss of control and fear of injury are common themes.
•Vocalizations, movement, and autonomic symptoms are minimal.
•When awakened, the child becomes oriented, can be calmed, and usually recalls the details of the dream.
•Nightmares are not associated with specific physical findings.
•Heart rate and respiratory rate may increase or show increased variability before the child awakens from a nightmare. Mild autonomic arousal, including tachycardia, tachypnea, and sweating, may occur transiently upon awakening.
•Developmental, genetic, psychological, and organic factors can contribute to occurrence.
•Approximately 7% of individuals who have frequent nightmares have family history of nightmares.
•Nightmares are more common in children with mental retardation, depression, and CNS diseases; an association has also been reported with febrile illnesses.
•Medications may induce frightening dreams, either during treatment or following withdrawal. Withdrawal of medications that suppress REM sleep can lead to an REM rebound effect that is accompanied by nightmares.
•Daytime emotional conflicts and psychological stress often contaminate sleep and predispose the child to nightmares.
•Nightmares may result from a severe traumatic event and may indicate posttraumatic stress disorder

Medical Care
◦Reassurance is the only treatment required for sporadic nightmares. Although all stressors cannot be removed from a child's life, parents can attempt to make bedtime a safe and comfortable time.
◦Encourage parents to spend time reading, relaxing, and talking with the child.
◦If the child has a recurring nightmare, instructing parents to encourage the child to imagine a good ending may help.
Psychological evaluation is indicated for patients whose nightmares occur more than twice a week over a period of several months.

Medications are neither helpful nor indicated.

Friday, September 17, 2010

Further Evidence Shows No Link Between Thimerosal and Increased Autism Risk

From Medscape Medical News
Emma Hitt, PhD

September 16, 2010 — Prenatal and infant exposure to thimerosal, a mercury-containing preservative used in some vaccines, does not increase risk of autism spectrum disorder (ASD), new research findings from the Centers for Disease Control and Prevention (CDC) and others suggest.

Frank DeStefano, MD, MPH, the CDC's director of immunization safety, and colleagues reported the findings in the September 16 issue of the New England Journal of Medicine.

According to the researchers, in 1999, the US Food and Drug Administration estimated that infants who were immunized according to the recommended schedule might have received amounts of ethylmercury in excess of Environmental Protection Agency limits for exposure to methylmercury. As a result, vaccine manufacturers were urged to remove thimerosal from all infant vaccines and to investigate any potential risks.

In the current study, Dr. DeStefano, in collaboration with researchers from Kaiser Permanente; Harvard Medical School, in Boston, Massachusetts; Stanford University, in Palo Alto, California; and others reviewed records from a managed care organization. They also interviewed the parents of 256 children verified to have ASD according to a standardized personal evaluation.

Children with ASD were further classified into having autistic disorder or ASD with regression. The children with autism were matched by age, sex, and managed care organization to children without autism.

None of the autism outcomes were associated with prenatal or early-life receipt of thimerosal-containing vaccines and immunoglobulins, and the receipt of vaccines was comparable between patients with ASD and control patients.

The adjusted odds ratios for ASD associated with a 2–standard deviation increase in ethylmercury exposure were 1.12 (95% confidence interval [CI], 0.83 - 1.51) for prenatal exposure, 0.88 (95% CI, 0.62 - 1.26) for exposure from birth to 1 month, 0.60 (95% CI, 0.36 - 0.99) for exposure from birth to 7 months, and 0.60 (95% CI, 0.32 - 0.97) for exposure from birth to 20 months, thus representing a decrease in risk for some time periods.

The researchers note that they are "not aware of a biological mechanism that would lead to this result."

Parents, Physicians Should Be Reassured

Dr. DeStefano told Medscape Medical News that this study adds stronger evidence regarding exposure during pregnancy and is the first study to evaluate subtypes of ASD, including ASD with regression.

"These findings add to the evidence that thimerosal-containing injections during pregnancy or infancy do not increase a child's risk of developing autism," he added. "In my opinion, further studies are not warranted," he said.

According to Dr. DeStefano, the Institute of Medicine has also reviewed the evidence regarding thimerosal and autism and concluded that it did not support such an association, and "the results of our study add further support to this conclusion."

"Clinicians can feel confident in counseling parents that the scientific evidence does not support a link between thimerosal in vaccines and autism," Dr. DeStefano said. "Currently, this should not be much of an issue because thimerosal is no longer included in most routinely used in infant and childhood vaccines in the United States."

According to Dr. DeStefano, the single exception is in some influenza vaccines, but "thimerosal-free preparations of influenza vaccines are available for parents who are more comfortable with thimerosal-free products."

Independent commentator Meg Fisher, MD, chair of the Department of Pediatrics and Medical Director with the Children's Hospital at Monmouth Medical Center, in Long Branch, New Jersey, noted that this study confirms previous findings that show no association of autism and thimerosal.

"It was a well-done study using information from 3 managed care organizations," she told Medscape Medical News. "Exposure to thimerosal through vaccines and immunoglobulin was determined both after birth and prenatally, and there was no increased risk of ASD associated with exposure to ethylmercury — prenatally or postnatally."

Dr. Fisher concurs with Dr. DeStefano that additional studies on this issue are not needed. "Parents and physicians should be reassured by this additional, well-designed study — there is no association of thimerosal and autism."

She added that the CDC's Vaccine Safety Datalink system provides a wealth of clinical data that can be used to test hypotheses about vaccine adverse events.

Dr. Marcy received honoraria for speaking for Merck and GlaxoSmithKline within the last 5 years and grant support for studies on Gardasil and ProQuad from Merck within the last 5 years; Mr. Lewis received grant support from Medimmune, Sanofi Pasteur, Chiron, Wyeth, Merck, and GlaxoSmithKline; and Dr Bernal received research funding from the CDC, the National Institute of Mental Health, Health Resources and Service Administration, and Autism Speaks. The other authors have disclosed no relevant financial relationships.

Pediatrics. 2010;126:656-664.

Disclosure: Emma Hitt, PhD, has disclosed no relevant financial relationships.

Tuesday, September 7, 2010

Guidelines Updated for Influenza Vaccination and Antiviral Therapy in Children

Pediatrics. Published online August 30, 2010.
From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD


Clinical Context

During the 2010-2011 influenza season, the AAP recommends annual trivalent seasonal influenza immunization for all children and adolescents who are at least 6 months old.

Special outreach efforts should target all children 6 months or older, including healthy children and those with conditions increasing the risk for complications from influenza. Other groups to be targeted include household contacts and out-of-home care providers of children with high-risk conditions or of healthy children younger than 5 years, healthcare personnel, and pregnant women.
Study Highlights

* Children younger than 6 months are too young to receive influenza vaccine.
* Children 9 years or older need only 1 dose.
* Children younger than 9 years require the following vaccination schedules:
o They need at least 2 doses of 2009 pandemic H1N1 vaccine.
o They require 2 doses of seasonal influenza vaccine this year if they did not receive the H1N1 vaccine last year.
o They need 2 doses if they have never before received seasonal influenza vaccine.
o If they received seasonal influenza vaccine before the 2009-2010 season, they need only 1 dose this year if they received at least 1 dose H1N1 vaccine last year, but they need 2 doses this year if they did not receive at least 1 dose H1N1 vaccine last year.
o If they received seasonal influenza vaccine for the first time last year but only received 1 dose, they require 2 doses this year.
o Those who received influenza vaccine last year should get 2 doses this year if it cannot be determined whether it was a seasonal influenza vaccine or the H1N1 influenza vaccine.
* For all children who need 2 doses, the second dose should be given at least 4 weeks after the first dose.
* All children 6 months or older, especially those at high risk for influenza complications, should receive trivalent seasonal influenza vaccine each year.
* Immunizing close contacts of children at high risk should lower the risk for influenza exposure for these children.
* Annual trivalent seasonal influenza vaccine is important for household members and out-of-home care providers of children and adolescents at high risk, healthy children younger than 5 years, and infants younger than 6 months.
* Only 1 trivalent seasonal influenza vaccine is being made for the current 2010-2011 seasonal influenza vaccine schedule, with the 2009 pandemic influenza A (H1N1) strain replacing the 2009 seasonal influenza A (H1N1) strain.
* The recommended trivalent vaccine for 2010-2011 contains A/California/7/2009 (H1N1)-like antigen (derived from 2009 pandemic influenza A [H1N1] virus); A/Perth/16/2009 (H3N2)-like antigen; and B/Brisbane/60/2008-like antigen.
* During the 2010-2011 season, the only antiviral medications routinely recommended for chemoprophylaxis or treatment are the neuraminidase inhibitors oseltamivir and zanamivir.

Clinical Implications

* The number of influenza vaccine doses each child requires is based on the child's age when receiving the first influenza vaccine dose and vaccination history.
* Only a single trivalent seasonal influenza vaccine is being made for the current 2010-2011 seasonal influenza vaccine schedule, with the 2009 pandemic influenza A (H1N1) strain replacing the 2009 seasonal influenza A (H1N1) strain. The recommended trivalent vaccine for 2010-2011 contains A/California/7/2009 (H1N1)-like antigen (derived from 2009 pandemic influenza A [H1N1] virus); A/Perth/16/2009 (H3N2)-like antigen; and B/Brisbane/60/2008-like antigen.

Monday, September 6, 2010

Prepubertal Overweight Children With Prediabetes May Have Lower Bone Mass CME

From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

August 24, 2010 — Prepubertal overweight children with prediabetes may have lower bone mass and an increased risk for poor skeletal development, according to the results of a study reported online July 16 in the Journal of Bone and Mineral Research.

"Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children," write Norman K. Pollock, from Medical College of Georgia's Prevention Institute in Augusta, and colleagues.

The investigators compared bone mass in 41 prepubertal overweight children with prediabetes with that in 99 prepubertal overweight children without prediabetes. The study authors also evaluated associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, markers of systemic inflammation, and osteocalcin. Age range of the children was 7 to 11 years.

Prediabetes was identified from an oral glucose tolerance test, which also allowed measurement of glucose, 2-hour glucose, glucose area under the curve (AUC), insulin, 2-hour insulin, and insulin AUC. Blood levels of lipids, C-reactive protein, and osteocalcin were also measured. Using dual-energy x-ray absorptiometry, the investigators measured total body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM), whereas visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were evaluated with magnetic resonance imaging scans.

After adjustment for sex, race, height, and weight, overweight children with prediabetes had a total body BMC 4% lower than those without prediabetes (P = .03). FM correlated directly with BMC in the total sample (β = .16; P = .01), after adjustment for sex, race, height, and FFST.

"This finding provides the first clue linking childhood obesity to skeletal fractures," Dr. Pollock said in a news release.
"While overweight children may have more bone mass than normal-weight kids, it may not be big or strong enough to compensate for their larger size."

After controlling for sex, race, height, FFST, FM, and SAAT or VAT, however, VAT (β = -.13; P = .03) and SAAT (β = -0.34; P = .02) were inversely associated with BMC. BMC was not significantly associated with any of the biochemical measurements.

"Taken together, it seems that excessive abdominal fat may play a key role linking pre-diabetes to lower bone mass," Dr. Pollock said.
"Our greatest window of opportunity to enhance bone strength and ultimately reduce the risk of osteoporosis is during childhood, before the capacity to build bone diminishes. One of the best things you can do for bone development and general health is exercise."

Limitations of this study include bone measurements derived only from dual-energy x-ray absorptiometry of the total body; and small sample size, precluding separate analysis of data by boys and girls or by white and black race.

"Children have a lot of potential and a whole lot of time to make positive changes," said coauthor Catherine Davis, also from the Prevention Institute. "If you could patent exercise as a drug, somebody would be really, really rich."

The National Institute of Diabetes and Digestive and Kidney Diseases supported this study. The study authors have disclosed no relevant financial relationships.

J Bone Mineral Res. Published online July 16, 2010. Abstract

Clinical Context

In the August 2004 issue of the American Journal of Clinical Nutrition, Leonard and colleagues reported that overweight vs healthy-weight children had greater bone mass, but in the November 2007 issue of the American Journal of Clinical Nutrition, Pollock and colleagues found that overweight children had relatively decreased bone mass. In the February 2005 issue of Diabetes Care, Afghani and colleagues noted that impaired glucose tolerance was associated with lower total body BMC.

This study uses data from a study of overweight children reported by Davis and colleagues in the December 2007 issue of Research Quarterly for Exercise and Sport to evaluate whether total body BMC differs between those with and without prediabetes.

Vaccination as a Tool for Cancer Prevention

From MedscapeCME Public Health & Prevention > Perspectives in Prevention From the American College of Preventive Medicine
Eric H. Raabe, MD, PhD; Julia M. Kim, MD, MPH; Miriam Alexander, MD, MPH


Infectious agents, such as viruses and bacteria, are the causes of several common cancers.
Infection with the bacterium Helicobacter pylori predisposes to gastric cancer.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with liver cancer, and Epstein-Barr virus (EBV) is associated with lymphoma and nasopharyngeal cancer.
Human papillomavirus (HPV) is a major cause of cervical, anal, penile, and oropharyngeal cancer.
Together, infection-associated tumors make up nearly 20% of all cases of cancer worldwide, causing more than 2 million malignancies per year. Most of these cases occur in developing countries. Under normal circumstances, immune surveillance helps to keep many of these virus-associated cancers in check, but in immunocompromised persons, such as those with late-stage HIV infection, the incidence and aggressiveness of these cancers increase. HBV and HPV vaccines are effective and in use, and vaccines against other cancer-causing agents are in development. Because many virus-associated cancers occur in the developing world (such as EBV-associated Burkitt's lymphoma in Africa and HBV-associated hepatocellular carcinoma [HCC] in Asia), the development and deployment of vaccines to prevent infection with HPV, HBV, HCV, and EBV can serve as effective preventative tools to reduce the burden of cancer morbidity and mortality worldwide.

Introduction: Cancer-Causing Infections

In the developing world, cancer is estimated to afflict 10 million people per year. Worldwide efforts to prevent cancer have generally focused on behavioral changes, such as smoking cessation. Because infectious agents cause some of the more common human cancers, understanding the role of the immune system is necessary to maximize cancer prevention strategies. The immune system has an endogenous role in preventing some cancers and can be stimulated with vaccines to prevent infection with cancer-causing viruses.

One of the paradoxes of cancer biology is that a lack of immune surveillance (such as in HIV-infected individuals or immunosuppressed organ transplant recipients) can lead to cancer, and chronic inflammation due to persistent infection can also do so. Chronic inflammation as a result of HBV or HCV infection leads to HCC, usually after the patient progresses to cirrhosis. In gastric cancer, nearly 60% of all cases in developed countries and 75% of cases in developing countries are attributable to chronic infection with H pylori. It is likely that chronic inflammation due to H pylori leads to intestinal metaplasia of the gastric epithelium and eventually to gastric cancer. Long-term infection with HPV and EBV leads to transfer of oncogenes present in the viral genome to human cells, thereby promoting cancer development.

Harnessing the immune system to prevent or clear cancer is a major goal of cancer research. Vaccination campaigns have been enormously successful in reducing the global burden of infectious diseases. A worldwide infrastructure exists for the manufacture, distribution, and administration of vaccines in urban, suburban, and rural areas.
The use of vaccines to prevent cancer caused by chronic infection with oncogenic agents has had a substantial benefit in the developed world and could have a major effect on cancer incidence in the developing world. This article will review the most common infection-related cancers and the role of vaccines for cancer prevention worldwide.

HPV and Cancers of the Anogenital Tract and Oropharynx

HPVs are commonly spread through sexual contact. These viruses are the cause of genital warts, and subtypes 16, 18, 31, 33, and 35 are the major subtypes that cause cervical, anal, and head and neck cancer. HPV infection is associated with 100% of cases of cervical cancer. The incidence of infection with HPV is far higher than the incidence of cancer, because the immune system clears most infections.However, more than 500,000 new cases of cervical cancer are estimated to occur worldwide in 2010. Routine Papanicolaou smears can monitor for early signs of cervical cancer, but many at-risk women in the United States and elsewhere do not receive appropriate gynecologic care. These women are more likely to be from nonwhite, lower-income, and immigrant groups, and they are more likely to develop and die of cervical cancer.

During the past 30 years, the incidence of aggressive serotype HPV-associated squamous-cell carcinoma of the anus has increased. This increase largely began in men who have sex with men, but increases in women have also been observed. HPV is also associated with cancer of the vagina, vulva, and penis, although these are much less common than cervical cancer.

Squamous-cell carcinoma of the oropharynx and head and neck is associated with tobacco and alcohol use, but HPV serotypes 16 and 18 are commonly observed in a subset of persons with this cancer. Of interest, the percentage of HPV-positive oral cancers is reported to be increasing in several countries. This increase is attributed to changing sexual practices, suggesting that HPV-associated oral cancer, like HPV-associated anal and cervical cancer, can be considered a sexually transmitted infection.

Hepatitis B and C Viruses and HCC

Chronic HBV infection is highly prevalent throughout the developing world, particularly in Asia and Africa, where some countries have a prevalence rate as high as 12% of the total population. It is estimated to cause more than 1 million annual deaths worldwide, with one third of these deaths caused by HCC and the remainder by cirrhosis.
Chronic HBV infection confers a 20 times increased risk for HCC.
HBV vaccination is now included in the standard childhood vaccination series in the United States, but immigrant and older populations can have high HBV carrier rates.
Intrapartum transmission is a major cause of transmission of HBV to children. To prevent HBV infection, hepatitis B immune globulin, along with hepatitis B vaccine, must be given to neonates of HBV-positive mothers (see "Key Recommendations for Healthcare Providers to Prevent Cancers Caused by Infectious Disease").

HCV infection is another a major cause of HCC. Whereas the carrier rate of HCV in the United States was estimated at 1.6% in 2002, in Africa the prevalence ranged from more than 8% in Northern Africa to less than 2% in Southern Africa.Vaccines for HCV are in development, but for patients who have already contracted HCV, a regimen involving 6 months of pegylated interferon alpha and ribavirin can lead to eradication in up 60% to 80% of patients.Active surveillance for HCV and aggressive attempts at eradication can therefore reduce the subsequent risk for cancer in populations at risk.

EBV-Associated Cancers
EBV is the primary cause of infectious mononucleosis, a typically benign disease of adolescence and young adulthood. However, the virus is also a causative agent in many aggressive neoplasms, including 20% of cases of Hodgkin's lymphoma (one of the most common lymphomas of adolescence), nasopharyngeal carcinoma, and a subtype of Burkitt's lymphoma. Nasopharyngeal cancer affects approximately 80,000 people each year, predominantly in less developed countries. Most of these cases are attributable to EBV infection.[1] Although this cancer is curable with intensive chemotherapy and radiation therapy, most of the people affected by this cancer do not have access to these treatments.

More than 28,000 worldwide cases of Hodgkin's lymphoma are attributed to EBV infection. Like nasopharyngeal cancer, Hodgkin's lymphoma is highly treatable. More than half of Hodgkin's lymphoma cases occur in less developed countries, however, and curative treatment is often not available. The iconic image of a sub-Saharan African child with a very large facial or neck mass is an easily recognizable sign of endemic Burkitt's lymphoma caused by EBV infection. As many as 6800 cases of Burkitt's lymphoma caused by EBV occur every year, with more than 90% of these infections occurring in less developed countries. EBV-associated non-Hodgkin's lymphoma is particularly common in patients with advanced HIV infection. An estimated 68,000 cases of EBV-associated non-Hodgkin's lymphoma occur annually, and two thirds occur in developing countries.[1]

H Pylori-Associated Gastric Cancer and Mucosa-Associated Lymphoid Tissue Lymphoma
The causative infectious agent for peptic ulcer disease, H pylori, is also a known cancer-causing agent. Chronic infection with this pathogen predisposes to stomach cancer and to gut mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric cancer accounts for nearly 10% of all cases of cancer worldwide, and the causative agent in more than 60% of these cases is estimated to be H pylori (other risk factors include diet and excessive alcohol intake). In 2002, it was estimated that H pylori caused as many as 600,000 cases of gastric cancer per year worldwide.[1] Eradication of H pylori can be accomplished with antibiotic therapy; however, the very high burden of infection in many countries (for example, in sub-Saharan Africa, more than 75% of adults are infected with H pylori) and the relative ease of reinfection make treatment of asymptomatic carriers unfeasible. Because the infection first occurs in young children, H pylori seems to be an amenable target for vaccine development to prevent colonization and subsequent stomach cancer and gut-associated MALT lymphoma. Until a vaccine becomes available, healthcare providers should screen for dyspepsia and peptic ulcer disease and offer H pylori testing to affected patients. Healthcare providers should administer drug therapy for eradication of H pylori in those who are symptomatic and H pylori-positive.

Human Herpesvirus 8: Kaposi's Sarcoma
Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma, a once-rare sarcoma of blood vessels. Before the AIDS epidemic, Kaposi's sarcoma was primarily known to affect Mediterranean or eastern European men or immunosuppressed patients, such as organ transplant recipients. With the increasing worldwide prevalence of HIV infection, most cases of Kaposi's sarcoma are now associated with HIV or AIDS. In 2002, it was estimated that more than 60,000 cases of Kaposi's sarcoma occur yearly, and it is the most common type of cancer reported in some African countries highly affected by HIV, such as Zimbabwe. The best treatment for Kaposi's sarcoma in HIV-infected patients is initiation of antiretroviral agents to reduce HIV viral load and allow restoration of immune system function. Sometimes this is sufficient to cause regression of the cancer. In other cases, the cancer continues to spread and combination chemotherapy is required.

Role of Vaccines for Cancer Prevention in the United States
HBV vaccine. In 1991, the Centers for Disease Control and Prevention (CDC) recommended adoption of a comprehensive strategy for prevention of HBV infection, which included:

•Routine maternal prenatal testing for HBV;
•Immediate postpartum intervention to prevent maternal to child transmission;
•Universal vaccination of children for HBV;
•Vaccination of all adolescents who had not received HBV vaccine previously; and
•Vaccination of adults at risk for becoming infected with HBV.[10]
The childhood immunization schedule, a 3-vaccine series administered in the first year of life, confers long-term immunity to HBV. Infants born to HBV-positive mothers must receive both vaccination and hepatitis B immune globulin within the first 12 hours of life. This regimen is 85-95% effective in preventing transmission of HBV. Because children are at increased risk for becoming chronic carriers when infected with HBV, starting the vaccine at birth and completing the series during routine well-child visits during the first year of life decreases the risk for infection from HBV-positive household contacts. Analysis of immunization rates in newborns in the United States from 2003-2005 showed only a 50% vaccination rate, leaving many infants unprotected from HBV infection. Clearly, the United States needs to increase newborn vaccination rates for HBV.

HPV vaccine. Two HPV vaccines are approved for use in the United States: Gardasil® (Merck & Co., Inc., Whitehouse Station, New Jersey) and Cervarix® (GlaxoSmithKline, Philadelphia, Pennsylvania). Gardasil® targets the serotypes of the virus most associated with cervical cancer (16, 18) and genital warts (8, 11). Cervarix® also targets serotypes 16 and 18 and uses a different adjuvant than Gardasil® to boost immune response. Both vaccines are equally effective at preventing HPV infection caused by the serotypes contained in the vaccines, and both will prevent development of high-grade cervical lesions caused by the corresponding serotypes. These vaccines are most effective when given to women and girls who have not been exposed to HPV. However, in a mixed population of HPV-exposed and HPV-unexposed young women, compared with placebo, vaccination with Gardasil® led to a 60% reduction in genital warts and a nearly 20% reduction in the incidence of precancerous cervical lesions. A corresponding reduction in the number of women who required invasive surgical resection of their precancerous lesions suggests that even in older, HPV-exposed women, vaccination may be helpful in reducing cervical cancer rates. The follow-up timeframe for these vaccines is still short, so it is not clear how long the protective effect will last. Additional postapproval studies are ongoing to determine the duration of protection and to determine whether post exposure vaccination is warranted.

The availability of HPV vaccines against serotypes 16 and 18 gives healthcare providers the tools to prevent HPV infection and subsequent cervical cancer. The US Food and Drug Administration (FDA) approved Gardasil® for girls and young women from age 9 to 26 years and for boys and men in that same age group, on the basis of trials showing efficacy preventing cervical neoplasia and cancer in women and anogenital warts in both women and men.The FDA approved Cervarix® for girls and women ages 10 to 25 years for prevention of cervical neoplasia and cancer. These vaccines may also be effective in preventing cancer of the oropharynx and anus caused by HPV 16 and 18 in both men and women.

Whereas HPV vaccines have been approved and are being administered in the United States, the uptake of the vaccines has been uneven. A backlash against HPV vaccination has occurred in some communities. Further interventions are required to improve vaccination among those most at risk for invasive cervical neoplasia. Clinicians should offer HPV vaccination to all adolescent girls and young women who have not yet had their sexual debut, and they should consider giving the vaccine to young women after sexual debut, on the basis of the findings described above. These vaccines do not cover all of the subtypes of HPV that cause cervical cancer, and widespread vaccination does not replace the need for intermittent cervical cancer screening, although it is projected to reduce the number of invasive procedures.

Cancer Prevention Outside of the United States
Role of vaccines. The use of vaccines and eradication treatments to prevent infection-caused cancer in the United States and other developed countries will continue to reduce mortality and morbidity from these diseases. However, the major burden of disease and corresponding mortality lie in the developing world. Taken together, the number of infection-related cancers is estimated at nearly 2 million cases per year, accounting for almost 20% of all cancer cases.[1] Widespread application of vaccines for HBV and HPV could decrease the global burden of cancer by 900,000 cases per year, on the basis of 2002 estimates.

The HPV vaccine is approved for use in more than 60 countries. Widespread vaccination for HPV coupled with limited cervical cancer screening can be considered cost-effective in developing countries if a vaccine can be delivered for approximately $1 per dose (in a 3-dose regimen). The current course in the United States costs more than $300 USD. Improvements in HPV vaccines to make them more thermostable and efficacious, and less costly, will increase the feasibility of vaccinating adolescents in developing countries.

Drug treatment of HCV and H pylori infections to prevent cancer. Development of new vaccines or widespread identification and eradication efforts could further reduce the global cancer burden by reducing the carriage rate of H pylori, leading to fewer cases of gastric cancer (now estimated to be more than 500,000 cases per year).Eradication of HCV by use of ribavirin plus pegylated interferon, although expensive, could eliminate the nearly 200,000 cases per year of HCC that are attributed to HCV. To eliminate HCV in less developed countries successfully and cost-effectively, either a vaccine against HCV or a less burdensome eradication regimen is needed.

Burden of HIV as a cancer predisposition syndrome. The growing HIV epidemic is adding to the already substantial burden of cancer in lower-income countries (and in affected populations in the United States). Chronic HIV infection should be considered a cancer predisposition syndrome. Loss of immune surveillance as a result of HIV infection can lead, in HPV infection, to a rapid progression of precancerous lesions to cancer, and to increases in de novo cancer, particularly in HHV-8 and EBV-infected individuals. Restoration of immune function as evidenced by normalizing CD4 helper T-cell numbers after initiation of highly active antiretroviral therapy (HAART) can lead to stabilization or regression of cancer. However, in lower-income countries, initiation of HAART continues to encounter multiple barriers (lack of healthcare providers, lack of drug distribution infrastructure, and cultural barriers to testing and starting treatment).[18] Although initial trials of an HIV-prevention vaccine have not succeeded, additional trials of new strategies for an HIV vaccine are ongoing and under development.

Role of vaccines in immunocompromised hosts. For patients who are already HIV-infected, the ability to respond to an antiviral vaccine, such as the HBV vaccine, may be severely attenuated, depending on their CD4 count.Vaccination before HIV infection (such as in an HIV-negative child) may prevent subsequent infection with the target of the vaccine, even if the patient has become HIV-positive. Much depends on the degree of destruction of the immune system and the extent to which the immune system is reconstituted after starting antiretroviral therapy.

Future Directions
The current availability of vaccines against HPV and HBV cancer-causing viruses could prevent nearly 1,000,000 annual cases of cancer throughout the world. Barriers to widespread vaccination include expense, lack of sufficient healthcare personnel, problems with drug delivery and storage, and opposition of the local population. HPV and HBV vaccines are being deployed and improved, and an effort to develop vaccines against HCV and EBV continues. These new vaccines, along with those currently in use, have the promise of substantially reducing global morbidity and mortality from cancer. Finally, advances in immunobiology will further our understanding of the pathogenesis of cancer and may enable the development of vaccines to prevent other cancers not caused by infectious agents.

Key Recommendations for Healthcare Providers to Prevent Cancers Caused by Infectious Disease

1. Hepatitis B: Test for HBV in members of at-risk groups and offer vaccination to all adolescent and adult patients who are HBV negative. Begin HBV vaccinations in all neonates starting before discharge from the hospital and continuing through well-baby checks during the first year of life, according to Advisory Committee on Immunization Practices (ACIP) guidelines.[10] Consider treatment of HBV-positive patients to reduce the risk for progression to cirrhosis and HCC, according to National Institutes of Health Consensus Conference guidelines.

2. H pylori: Screen for dyspepsia and peptic ulcer disease and offer H pylori testing to affected patients. Administer drug therapy for eradication of H pylori in those who are symptomatic and positive for H pylori, according to American College of Gastroenterology guidelines.

3. HIV: Offer HIV testing to at-risk patients. In some areas with increasing prevalence of HIV, this would be considered all patients aged 13-64 years, according to CDC guidelines. In HIV-positive individuals, screen for HBV, HCV, and HPV, because HIV-positive patients are at increased risk for cancer caused by infectious agents .

4. HPV: Offer screening Papanicolaou smears for all women according to American Congress of Obstetricians and Gynecologists guidelines. Offer vaccination against HPV to adolescent girls and women up to age 26 years, according to ACIP guidelines.

5. Hepatitis C: Offer testing for HCV in all at-risk patients and offer eradication of HCV in patients who test positive, according to the National Institutes of Health Consensus Conference Statement on Hepatitis C.

Friday, September 3, 2010

New Guidance on Management of Increasing Problem of Sports-Related Concussions in Children

From Medscape Medical News
Pauline Anderson

September 2, 2010 — A new guidance document for the management of pediatric concussions recommends a more conservative approach to return to play policies for younger children with sports-related concussions.

Although there is little research on concussions in the pre–high school age group, there is evidence that high school athletes take longer to recover than college athletes, who take longer than professional athletes, said a lead author of the study, Mark Halstead, MD, assistant professor in the Departments of Pediatrics and Orthopedics at Washington University School of Medicine, St Louis, Missouri.

"We can only assume that if that trend continues, these younger children take even longer to recover, and my own personal experience is that this is the case," Dr. Halstead told Medscape Medical News.

The document, a clinical report from the American Academy of Pediatrics, is published in the September issue of Pediatrics.

A related paper in the same online issue shows that although participation in organized sports decreased by about 13% during a recent 10-year span, emergency department (ED) visits for concussions increased — by more than 50% in children 8 to 13 years old and by more than 200% in 14- to 19-year-olds — during the same period.

The study found that younger children accounted for about 35% of the 502,000 ED visits for concussions from 2001 to 2005. Overall, about half of these visits were sports related, but 58% were sports related among younger children.

Although it is important for children to play sports, these statistics underline the importance of ensuring they use proper prevention techniques while being physically active, lead study author Lisa L. Bakhos, MD, from the Department of Pediatric Emergency Medicine at Warren Alpert Medical School, Brown University, Rhode Island, told Medscape Medical News in an email.
"It's also important to make sure that if an injury does occur to seek medical attention and follow recommendations."

Conservative Approach Recommended

Young athletes whose brains are still developing pose a challenge because they may be more susceptible to the effects of a concussion, Dr. Halstead and colleagues write. Extensive research during the last 10 years has provided a better understanding of the course and potential long-term complications, resulting in an evolution in management, they note.
"Unfortunately, many parents, coaches, and young athletes still seem to believe that youth is a period of indestructibility."

This report, they write, "outlines the current state of knowledge on pediatric and adolescent sport-related concussions."

Other recommendations in the clinical report on concussion in children include the following:

•Athletes with concussion should rest not only physically but also cognitively until symptoms have resolved both at rest and with exertion. This may require modification of school plans and perhaps time away from school, said Dr. Halstead, who has seen student averages drop from A to C during recovery from a concussion.
•Any child who sustains a concussion should be evaluated by a healthcare professional and receive medical clearance before returning to play. The misconception that a concussion may be "toughed out" and does not require a visit to the doctor still persists, according to the study authors.
•Even if young athletes become asymptomatic, they should not return to play on the same day of a concussion. Just 10 years ago, a young athlete with a "ding" or low-grade concussion would have been allowed to return to sports as soon as 15 minutes after symptoms had cleared, said the study authors.
•Neuropsychological testing can be helpful but does not in itself make a diagnosis or determine when return to play is appropriate.
•Retirement from contact sports may be necessary for athletes with a history of multiple concussions. "We know that athletes who have had 3 concussions are 9 times more likely to have more severe symptoms than someone who has never had a concussion, and often their symptoms are more prolonged," said Dr. Halstead.
Symptom-Based Approach

Some diagnostic tools for concussions are now outdated, including the once widely used 3-tier grading system, the study authors add. "That system focused heavily on loss of consciousness, which is not a very prominent feature of sport concussions; only 10% will lose consciousness," said Dr. Halstead.

Instead, an individualized symptom-based approach is more advisable. Signs and symptoms of concussion, many of which overlap, fall into 4 categories: physical, cognitive, emotional, and sleep. Headache is the most frequently reported symptom. Although loss of consciousness occurs infrequently, it is an important sign that may herald the need for further intervention.

Concussions represent about 8.9% of all high school athletic injuries. It is difficult to determine the equivalent rate among children in grade school and middle school athletes because data are lacking, said Dr. Halstead.

Girls are reported to have a higher rate of concussion than boys in similar sports, but the reasons for this are unknown, according to the study authors. For boys, football carries the highest risk of concussion, whereas for girls, the rate of concussion is highest in soccer and basketball.

Organized Team Sports

For the study by Bakhhos and colleagues, the researchers used a retrospective review of the National Electronic Injury Surveillance System (NEISS) from January 1, 1997, to December 31, 2007, and the NEISS All Injury Program (NEISS-AIP) from January 1, 2001, to December 31, 2005.

The NEISS is a data collection system conducted by the US Consumer Product Safety Commission of a national probability sample of 100 hospitals with a minimum of 6 beds and a 24-hour ED. The NEISS-AIP includes 66 of 100 NEISS hospitals and collects data on the basis of type of injury.

Researchers divided children into pre–high school (8-13 years) and high school (14-19 years) and causes of concussions into all causes, all sports-related causes, those related to individual and leisure sports, and those linked to organized team sports.

To calculate injury rates they used population projections from the US Census Bureau and averaged population data during the 5-year study period. Sports participation data came from the National Sporting Goods Association, which conducts annual mail-based surveys of 30,000 US households.

The study found that 1 in 1000 children aged 8 to 13 years and 3 in 1000 aged 14 to 19 years visited a hospital for a concussion sustained during 1 of the top 5 organized team sports. Most concussions among younger kids were sustained during football (22.6% of all sports-related concussions), followed by basketball (9.2%), soccer (7.7%), ice hockey (3.8%), and baseball (3.5%). In older children, football accounted for 53% of all team sports–related concussions, whereas soccer accounted for 18%, basketball for 16%, hockey for 8%, and baseball for 5%.

As for rates of concussion, ice hockey came out on top for both age groups (10 and 29 per 10,000 in the younger and older ages, respectively) followed by football (8 and 27 per 10,000, respectively) and then soccer, basketball, and baseball.

"Although football had the greatest number of concussions, the highest rate was actually in ice hockey," noted Dr. Bakhos. "For both, we need to be sure that helmets fit properly and we are not encouraging children to be overly and unnecessarily aggressive."

Dr. Bakhos said hockey players should be a special target for information on concussion prevention and management because this sport "is one of the most contact sports there is in the country."

As for soccer, measures such as padding goal posts and making sure field conditions are safe could help reduce concussions, which are not usually caused by "head butting" the ball but by collisions between players, said Dr. Bakhos.

Increasing Awareness

Even though participation in organized sports decreased by 13% from 1997 to 2007, visits to the ED for team sports –related concussions increased significantly among all children, but the reasons for this are unknown. "It could be secondary to increasing awareness and reporting or it could be due to the increased competitiveness of sport or the fact that children are generally larger than they used to be," said Dr. Bakhos.

Although some people point to the increasing variety of sports being made available to young athletes, Dr. Bakhos pointed out that the highest concussion rates seem to be in sports that have been around for some time.

The increasing intensity of competition could also play a role by putting the drive to win ahead of safety concerns, said Dr. Bakhos. "Parents, coaches, and players just need to put things into perspective and realize that health is the number one priority."

As for leisure and individual sporting activities, biking resulted in the most hospital visits for concussions in all age groups (18,252 in younger and 11,031 in older children). Playground activities and skiing were the next most common causes of concussion in this category among younger children, whereas for the older age group, snow skiing and combative sports were the next most common.

Less overall head injury force is needed to produce clinical symptoms in children than in adults, according to background information included in the study. There is some suggestion that concussion among younger children, who are still developing their essential skills, may produce more severe long-term developmental and cognitive problems.

Dr. Halstead and his coauthors filed conflict of Interest statements with the American Academy of Pediatrics (AAP) and any conflicts have been resolved. The AAP has neither solicited nor accepted any commercial Involvement in the development of the content of the article. Dr. Bakhos and her coauthors have indicated they have no financial relationships relevant to their article.

Pediatrics. 2010;126:e449-e556, 596-615.

Wednesday, September 1, 2010

Guidelines Issued for Gynecologic Examination for Adolescents in the Pediatric Office Setting

From Medscape Medical News
Laurie Barclay, MD

August 31, 2010 — A clinical report from the American Academy of Pediatrics (AAP) offers recommendations for a gynecologic examination for adolescents in the pediatric office setting. The report, published in the September issue of Pediatrics, reviews indications for pelvic examination and gynecology referral and concludes that most adolescents do not need an internal examination, but when they do, the best setting is often in the primary care office with a pediatrician who has established trust and rapport with the patient.

"The ...AAP promotes the inclusion of the gynecologic examination in the primary care setting within the medical home," write Paula K. Braverman, MD, Lesley Breech, MD, and the Committee on Adolescence. "Gynecologic issues are commonly seen by clinicians who provide primary care to adolescents. Some of the most common concerns include questions related to pubertal development; menstrual disorders such as dysmenorrhea, amenorrhea, oligomenorrhea, and abnormal uterine bleeding; contraception; and sexually transmitted and non–sexually transmitted infections."

Because approximately half of high school students have been sexually active, they are at risk for sexually transmitted infections (STIs) and pregnancy. For younger adolescents, who often have questions about pubertal development, determining pubertal status and documenting physical findings are important objectives of the gynecologic examination.

For children and adolescents of all ages, the annual comprehensive physical examination should include, at a minimum, examination of the external genitalia. Routinely explaining and performing this examination normalizes the experience.

Indications for a pelvic examination include the following:

•Persistent vaginal discharge;
•Dysuria or other urinary symptoms in a sexually active adolescent girl;
•Dysmenorrhea unrelieved by treatment with nonsteroidal anti-inflammatory drugs;
•Abnormal vaginal bleeding;
•Lower abdominal pain;
•Contraceptive counseling regarding use of an intrauterine device or diaphragm;
•Performing a Papanicolaou test;
•Evaluating suspected or reported rape or sexual abuse; or
A speculum or bimanual examination is no longer required before prescribing most forms of contraception. A speculum examination is not needed to diagnose asymptomatic STIs, now that urine-based and vaginal-swab STI testing methods are available. A vaginal swab obtained by either the provider or the patient can also be used to diagnose nonsexually transmitted vaginal infections, such as bacterial vaginosis and yeast infections.

Current guidelines state that the first Papanicolaou test should be done at age 21 years, unless a patient has immune suppression or HIV infection, in which case annual Papanicolaou tests should begin with the onset of sexual activity.

"Most adolescents do not need an internal examination involving a speculum or bimanual examination," the authors of the clinical report write. "However, for cases in which more extensive examination is needed, the primary care office with the primary care clinician who has established rapport and trust with the patient is often the best setting for pelvic examination....The pelvic examination may be successfully completed when conducted without pressure and approached as a normal part of routine young women's health care."

The report reviews procedures and techniques for performing the gynecologic examination. The patient should be reassured and the examination done in the presence of a chaperone or a female relative.

Findings often encountered on gynecologic examination of the adolescent external genitalia may include abscess of the Bartholin glands, infection in the Skene glands, genital ulcers or fissures, genital warts (condyloma acuminata), papular lesions (condylomata lata from syphilis), molluscum contagiosum, urethral prolapse, folliculitis, hidradenitis suppurativa, vulvitis, pigmentary changes, or papillomatosis.

Cervical findings could include ectropion, strawberry cervix, human papillomavirus/condyloma, cervical polyp, or cervical ulcers. Examination of the vagina may reveal ulcers, white adherent plaques caused by Candida species, or condyloma acuminata.

Indications for gynecology referral include the following:

•Adnexal mass;
•Vulvar or cervical lesion with undetermined cause;
•Possible anomaly of the genital tract, such as imperforate hymen, duplicated upper tracts, or absent vagina or uterus;
•Abnormal Papanicolaou test result requiring colposcopy;
•Acute pelvic pain possibly resulting from ovarian torsion, ectopic pregnancy, tubo-ovarian abscess, or adnexal mass;
•Pelvic inflammatory disease when the primary care provider is not comfortable with management;
•Chronic pelvic pain;
•Dysmenorrhea unrelieved by pharmacotherapy;
•Abnormal vaginal bleeding unrelieved by pharmacotherapy or causing severe anemia;
•Intrauterine device insertion; or
"For conditions that require a complete pelvic examination, the patient may prefer to have it performed in a familiar setting rather than being referred to another provider," the report authors conclude. "There are instances in which the pelvic examination must be performed during a problem visit and cannot be deferred to a separate, dedicated appointment time slot. ...With appropriate backup from a gynecologist, most medical gynecologic issues can be managed by the clinician in the primary care office setting."

Pediatrics. 2010;126:583-590.