Tuesday, August 31, 2010

SSRIs Not Recommended for Autism in Children or Adults Based on Current Evidence

From MedscapeCME Clinical Briefs

News Author: Pauline Anderson
CME Author: Charles P. Vega, MD

CME/CE Released: 08/17/2010;

Clinical Context

Estimates of the prevalence of ASD vary from study to study, according to the authors of the current systematic review. However, it appears that these estimates have been increasing during the last several years, with rates as high as 116 per 10,000 individuals.
ASD affects boys approximately 4 times more often than girls, and symptoms of ASD usually begin in early childhood.
ASD promotes chronic disability for many patients;
only 3% to 10% of adults with autism are able to live independently.

SSRIs are the most frequently prescribed psychotropic medications for patients with ASD, and they may help to reduce anxiety and obsessive-compulsive symptoms common to ASD.
The current systematic review examines the efficacy and safety of SSRI treatment among patients with ASD.

Study Highlights

•Researchers examined randomized, placebo-controlled trials of SSRIs for patients with ASD. Study outcomes could include core features of ASD or other aspects of behavior, function, or quality of life.
•Included studies were published before December 2009.
•46 studies were found on the original search. These titles were pared to 5 studies of children and 2 studies of adults for the final data analysis. The total number of patients in these 7 studies was 271.
•The 5 studies of children included participants between the ages of 3 and 17 years. These protocols tested fenfluramine, fluoxetine, fluvoxamine, and citalopram. 2 studies focused exclusively on children with autism and intellectual impairment, and the others included children with ASD.
•None of the included research in children suggested that SSRIs could significantly improve core features of ASD in this population. Likewise, SSRIs did not appear to significantly reduce the clinical global impression or obsessive-compulsive symptoms.
•There were only minor improvements in children's behavior with SSRIs vs placebo.
•Citalopram was associated with a higher rate of adverse events vs placebo among children. In 1 child, prolonged seizures developed from use of citalopram. However, in another study, fluoxetine was not associated with a higher rate of adverse events vs placebo among children.
•Among adults, a study of 30 patients focused on fluvoxamine, and another study examined fluoxetine among 6 patients.
•There was some suggestion of global clinical improvement with SSRIs vs placebo in adults. Fluoxetine improved a measure of anxiety, but not depression. Fluvoxamine improved a measure of aggression.
•Fluvoxamine was associated with a significant improvement in obsessive-compulsive behaviors vs placebo, whereas fluoxetine was not.
•SSRIs were not associated with significant adverse events among adults.
•The reviewers conclude that SSRIs appear not to be beneficial and, in fact, may be harmful to children with ASD. Small studies among adults with ASD have indicated some efficacy and better tolerability of SSRI.

Clinical Implications

•The prevalence of ASD appears to have increased during the last several years. ASD affects boys approximately 4 times more often than girls, and symptoms of ASD usually begin in early childhood. Only 3% to 10% of adults with autism are able to live independently.
•The current systematic review finds that SSRIs are not helpful for children with ASD but may have more efficacy among adults with ASD.

Sunday, August 29, 2010

Metabolic Syndrome in Children and Adolescents

From U.S. Pharmacist
Kirandeep Panesar, BPharmS(Hons), MRPharmS, RPh, CPh

There has been a renewed interest in metabolic syndrome in children in recent years in association with increasing childhood obesity, and the origins of metabolic syndrome have been traced back to childhood.[1] This article attempts to collate the information available so far and to describe the challenges currently faced in diagnosing and treating metabolic syndrome in children.

Metabolic syndrome is a group of risk factors that increase a patient's chance of developing heart disease and diabetes, including abdominal obesity, dyslipidemia, glucose intolerance, and hypertension.[2] However, health care providers do not commonly recognize that these components may coexist in children and may lead to future atherosclerotic cardiovascular disease in young adults.[3]

Various attempts have been made to define metabolic syndrome in adults. Ford and Li describe metabolic syndrome as "a cluster of anthropometric, physiological, and biochemical abnormalities tied together by incompletely understood underlying mechanisms that predisposes those affected to development of diabetes and cardiovascular disease."[3] Washington defines metabolic syndrome as "a cluster of a variable number of risk factors that exceed criterion values. These risk factors include an increased waist circumference (central adiposity), systemic hypertension, elevated fasting plasma triglyceride, and an elevated fasting glucose or insulin resistance."[3] Metabolic syndrome is described by Zimmet et al as a "cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which include abdominal obesity, dyslipidaemia, glucose intolerance, and hypertension."[4] According to the Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATP III), metabolic (or insulin resistance) syndrome is "the presence in an individual of at least three of the following five risk factors: central or abdominal obesity, hypertriglyceridemia, hypertension, low HDL cholesterol, and high fasting glucose levels."[5]

There is currently no uniform definition for metabolic syndrome in children. This poses a challenge for measuring prevalence, setting up screening measures, and establishing treatment protocols.[6,7] Furthermore, it is not possible to accurately compare the results of different studies measuring prevalence in children since the studies' threshold values vary. What is known so far is that the prevalence of metabolic syndrome in children is much lower than in adults.[8]
In addition to helping patients and caregivers identify metabolic syndrome and understand the complex matrix of underlying issues, pharmacists can provide support and training for appropriate management. A number of approaches have been used to manage metabolic syndrome in children and reduce risks later in life; however, the primary focus is on lifestyle intervention. Specifically, lifestyle changes involving diet and physical activity are recommended by several expert authors as first-line therapy for overweight, hypertension, insulin resistance, and dyslipidemia.[5] One paper proposes that focusing treatment strategies on improving insulin sensitivity may be more beneficial than focusing on obesity reduction for preventing or delaying the onset of cardiovascular disease and type 2 diabetes in high-risk youths.[8] TABLE 2 lists American Academy of Pediatrics (AAP)–recommended target BMIs for determining which children need to reduce weight to be healthy.[5]

Since there is increasing evidence to support insulin resistance as the underlying cause of metabolic syndrome, treatment strategies are being developed to improve insulin sensitivity.[4] The cornerstones of treatment are diet and exercise intervention, nutritional intervention, and pharmacologic intervention.

Diet and Exercise Intervention
It is well established that lifestyle changes, such as diet and level of physical activity, are fundamental to prevention. Regular exercise not only improves response to a 2-hour glucose tolerance test, but also improves insulin sensitivity, even without weight loss.[5] It is thought that this action occurs through the activation of cellular glucose uptake independent of insulin.[5] Additionally, exercise is associated with lower blood pressure.

A recent study examining the effect of diet and exercise intervention on metabolic syndrome in overweight children indicated that metabolic syndrome can be reversed even with short-term lifestyle intervention.[16] The 16 study participants, aged 10 to 17 years, were given a complete physical examination and then underwent underwent a 14-day diet and exercise program. In addition to attending daily cooking classes and talks about nutrition, exercise, and general wellness, the subjects consumed a healthy, balanced diet containing less than 100 mg cholesterol and less than 1,600 mg sodium per day. Caffeinated beverages were not permitted. To meet the goal of increased physical activity and energy expenditure, the subjects engaged in 2 to 2.5 hours of supervised activity, including tennis, beach games, and gym-based exercises, each day. Before the intervention, seven subjects had metabolic syndrome based on parameters of insulin level, insulin resistance, body weight, cholesterol, and triglycerides, as well as blood pressure. In all subjects, all values except body weight were reduced post-intervention.

In an earlier study, high-intensity physical training for 8 months in overweight adolescents resulted in improvements in fasting plasma triglycerides, LDL particle size, and diastolic blood pressure, despite little change in body weight.[17] Non–weight-bearing activities, in particular, have been shown to be more acceptable to overweight children and to promote long-term health. Therefore, youthful patients should be directed to concentrate on cardiovascular training activities that are more enjoyable for children and adolescents.[18]

Similarly, a 12-week program based on the Kids N Fitness lifestyle intervention program had a positive effect on reducing risk factors for metabolic syndrome and insulin resistance in overweight children.[19] Parents and caregivers attended educational sessions about the comorbidities of obesity, and the children took part in an exercise program. The exercise sessions included cardiovascular training activities such as dodgeball, volleyball, jump rope, and running.[19] This was followed by family-centered educational sessions for both children and caregivers. Statistically significant improvements in BMI, systolic blood pressure, cholesterol and triglycerides, postprandial glucose, and leptin levels were seen in all children who completed the program.[19]

The CASPIAN study discovered an association between physical activity and metabolic syndrome in children that was independent of BMI and age.[1] The researchers used questionnaires to collect data regarding the children's level of physical activity.[1] The level of physical activity was assessed and categorized, and the measurements for metabolic syndrome were based on the criteria set forth by ATP III.[1]

In addition to providing advice on healthy eating and exercise, pharmacists can assist children and adolescents who need to lose weight by discouraging them from spending long periods of time in front of the television, supporting physical-education programs in schools, and helping create safe neighborhoods that promote physical activity.

Different authorities have proposed guidelines for healthy eating habits. The U.S. Department of Health and Human Services recommends that children and adolescents consume at least five fruits and vegetables a day and that no more than 30% of total calories per day comes from dietary fat. This program encourages increased consumption of whole grains and advises the avoidance of sweets, sodas, and other empty-calorie foods.[5]

The "stoplight diet," created by Epstein and Squires, divides foods into three categories: green (foods that can be eaten at any time), yellow (foods that are eaten within limits), and red (foods that should be avoided).[5] The AAP takes a slightly different approach, guiding parents and families to make lifestyle changes by teaching them strategies to promote and maintain healthy eating habits and physical activity.[20] While the majority of patients should be referred to a dietitian when making drastic changes to their diet, pharmacists should have a basic understanding of healthy eating habits to better guide their patients.

Nutritional Intervention
Grains, fiber, and phytoestrogens are the primary nutrients that have beneficial effects on insulin sensitivity.[8] Pharmacists and dietitians should encourage patients to regularly consume foods such as soy, flaxseed, whole-grain cereals, fruits, and vegetables, which contain high levels of these nutrients.

Pharmacologic Intervention
Drug therapy with insulin sensitizers, including metformin and thiazolidinediones (TZDs), has shown positive effects. A recent systemic review showed that individually tailored lifestyle interventions, when combined with metformin, demonstrated a reduction in fasting insulin and BMI in children and adolescents with insulin resistance.[21] TZDs are useful insulin sensitizers that enhance glucose uptake via their activation of peroxisome proliferator-activated receptor gamma.[13] The primary effect of TZDs is on the adipose tissue, where they favorably alter the production of inflammatory molecules that contribute to the many components of metabolic syndrome.[4]

In addition to the above, some patients may require drug therapy for hypertension and/or hypercholesterolemia, since at present each component of the syndrome is treated separately.[4]

Since a large percentage of youths with metabolic syndrome probably will develop type 2 diabetes and cardiovascular disorders later in life, it is important that health care providers develop and test primary prevention strategies to manage childhood metabolic syndrome.[3] By building close relationships with their patients and opening up communication, pharmacists can help identify candidates for diagnosis, provide support for patients and their families in making lifestyle changes, and advise patients on the correct use of their medications.

Giving Influenza Vaccine to Egg-Allergic Patients

From Medscape Pediatrics > Viewpoints

William T. Basco, Jr., MD

Pediatrics. 2010;125:e1024-e1030

Study Summary
In this article, Chung, Huang, and Schneider review the conflicted state of affairs with respect to giving influenza vaccine to patients with egg allergy. Given that many patients with egg allergy also have asthma, which places them at high risk for morbidity from influenza illness, the patients who might benefit most from influenza vaccination have difficulty getting it.

The current approach for administration of influenza vaccine to patients with egg allergy involves 3 steps:
(1) skin prick testing with the vaccine;
(2) administration of a low dose of vaccine; and
(3) administration of the remainder of the vaccine. The sequence is completed only if the patient does not react at each successive stage.

The aim of this study was to determine the safety of skipping the first stage, skin prick testing.
The investigators reviewed the outcomes of patients with egg allergy who were immunized against influenza at 1 institution from the 2002/2003 influenza season to the 2008/2009 season.
The participants were 6 months to 18 years old; all had egg allergy as determined by a series of criteria that included skin test results, RAST test results, and history of clinical allergic reaction to egg.
During the first 5 influenza seasons studied, the institution followed the 3-step protocol of skin testing, followed by administration of 10% of the vaccine dose (followed by 30 minutes of observation), followed by administration of the remaining 90% of the vaccine dose.

During the last 3 seasons evaluated, the investigators eliminated the skin-testing step and gave the influenza vaccine in the graded fashion. The clinical notes included data about both local and systemic reactions (urticaria, wheezing, or exacerbation of eczema). They skin-tested 146 participants before influenza vaccination during the first 5 influenza seasons. Ninety-one (62.3%) had a positive skin-prick test, and 55 had negative skin tests (53 of whom received influenza vaccine). Three subjects with a positive skin-prick test still received the influenza vaccine. Therefore, 56 participants received influenza vaccine under the 3-step protocol compared with 115 who received the vaccine later under the 2-step protocol.

A large majority of participants in both the 3-step group and the 2-step group had allergies to more than 1 food (91% and 84%, respectively) and had atopic dermatitis (71% and 64%, respectively). The groups were slightly different in other ways; specifically, the 3-step group had a higher mean age (6.2 years vs 3.9 years), a higher frequency of asthma (76.8% vs 49.6%), and higher rates of allergic rhinitis. Many of the differences were a result of a change in influenza vaccine recommendations during the study period such that the later period included more patients without asthma and younger children who had egg allergy. The study authors attempted to adjust for these between-group differences by using propensity scores in their regression analyses. No differences were seen in the percentages of participants who tolerated influenza vaccine without any reaction (78.6% in the 3-step group and 79.1% in the 2-step group). The frequency of tolerating vaccine without a systemic reaction was 94.6% and 96.5%, respectively, in the 3-step and 2-step groups. Seven subjects (3 in the 3-step group and 4 in the 2-step group) had systemic adverse reactions, and another 29 experienced localized adverse reactions. None of the participants experienced anaphylaxis. The investigators concluded that the influenza vaccine can be administered safely to patients with egg allergy in a graded approach, without first conducting skin prick testing.

Although propensity scores can eliminate bias, they do not eliminate all bias. It is difficult to know how much the differences between groups might have affected the outcomes, but the raw percentages for adverse reactions are similar despite the differences in the patient populations. The investigators reviewed several advantages of skipping the skin-testing step, including the time required to administer and observe the test, the fact that patients must discontinue antihistamines prior to skin testing, and the fact that false-positive skin-testing results can occur from local irritation reactions. It is also important to remember that none of these subjects had a history of anaphylactic reaction to eggs, so these results should not be extended to that high-risk group.


Headache in Teens Related to Lack of Exercise, Weight Gain, Smoking

From Medscape Medical News
Allison Gandey

August 19, 2010 — Teenagers who get little exercise, are overweight, or who smoke are more likely to have frequent headaches or migraines, report researchers.

"There was a significant trend for stronger associations between the number of negative lifestyle factors that were present and the different headache diagnoses and headache frequency," point out the investigators led by John-Anker Zwart, MD, from Oslo University in Norway. "We believe that the associations observed and the additive effect of these negative lifestyle factors on the prevalence of recurrent headache strongly indicates that these lifestyle factors are possible targets for headache preventive measures."

The new study appears in the August 18 issue of Neurology. As part of the cross-sectional study, researchers interviewed more than 5500 students about headache complaints. The adolescents also completed a questionnaire and underwent a clinical examination with height and weight measurements.

Investigators classified adolescents who were very physically fit and who were not current smokers as having a good lifestyle. Negative lifestyle factors were surprisingly common with low physical activity in 31%, smoking in 19%, and overweight in 16% of these teens.

In adjusted multivariate analyses, recurrent headache was associated with overweight (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2 – 1.6; P < .0001), low physical activity (OR, 1.2; 95% CI, 1.1 – 1.4; P = .002), and smoking (OR, 1.5; 95% CI, 1.3 – 1.7; P < .0001). The presence of more than 1 negative lifestyle factor heightened the risk of headache.

This study shows overweight, low physical activity, and smoking are independently and in combination associated with recurrent headache among adolescents, report the study authors.

In an accompanying editorial, Dr. Andrew Hershey and Dr. Richard Lipton say that "this study is a vital step toward a better understanding of lifestyle effects and the potential for behavioral interventions for adolescents with headache disorders."

Dr. Hershey is at the University of Cincinnati in Ohio and Dr. Lipton is at the Albert Einstein College of Medicine in the Bronx, New York. They point out the effects of each negative lifestyle factor were similar in magnitude for each headache type. "This lack of specificity for headache type raises the possibility that these factors may be associated not just with headache but with all-cause pain."

These results mirror those of another study published in June in the journal Headache. Investigators led by Rudiger von Kries, MD, from Ludwig-Maximilians-University in Munich, Germany, found that being physically active and abstaining from alcohol, caffeine, and tobacco could help prevent headaches in adolescents.

The study included 1260 students, and after controlling for socioeconomic variables, the prevalence of any headache was increased in teens who reported regularly drinking cocktails (OR, 2.0; 95% CI, 1.3 – 3.0), who drank at least 1 cup of coffee per day (OR, 2.0; 95% CI, 1.2 – 3.5), and who were physically less active (OR, 2.0; 95% CI, 1.3 – 3.1). Smoking daily had an OR of 1.8.

These findings, say editorialists, suggest that a better understanding of modifiable risk factors and trigger factors may lead to novel intervention strategies.

Neurology. 2010;75:712-717.

allergies - simple to severe slide show


Saturday, August 28, 2010

New 13-Valent Pneumococcal Vaccine Expands Protection in Young Children

From Reuters Health Information

NEW YORK (Reuters Health) Aug 23 - The 13-valent pneumococcal conjugate vaccine (PCV13) is as effective as the seven-valent vaccine against the original seven pneumococcal serotypes and should provide further protection against the six additional serotypes, a multicenter team reports.

PCV13, also known by the brand name Prevnar 13 (Wyeth), was approved by the US Food and Drug Administration in February 2010 for preventing invasive pneumococcal disease in children aged 6 weeks to 71 months.

One of the pivotal studies of the immunogenicity and safety of PCV13 in infants and toddlers appeared online today in Pediatrics.

Lead author Dr. Sylvia H. Yeh, at the UCLA-Kaiser Vaccine Research Center in Torrance, California, and colleagues explain that the 7-valent pneumococcal conjugate vaccine (PCV7) covers the serotypes that caused up to 90% of invasive disease in the U.S. before its introduction.

"The widespread use of PCV7 in the U.S. has dramatically reduced the burden of this disease in children, with herd immunity benefiting adults as well," she said in an e-mail. "However, pneumococcal disease still occurs in the U.S. due to replacement serotypes."

The six additional serotypes in PCV13 account for up to 92% of invasive cases worldwide in children under five. "Whereas the potential impact of PCV7 was limited in certain countries such as Africa and Asia, PCV13 potentially expands the impact of disease prevention through vaccine use in these countries," Dr. Yeh said.

The current study compared PCV13 with PCV7 in terms of immunogenicity and safety in toddlers and infants. Ultimately, the authors report, "The evaluable immunogenicity populations consisted of 504 infants (PCV13: 252; PCV7: 252) and 462 toddlers (PCV13: 239; PCV7: 223)."

The immunoglobulin G titers elicited by PCV13 for the original seven serotypes were noninferior but somewhat lower than those elicited by PCV7. The PCV13 toddler dose produced higher immune responses than the infant-series doses, according to the authors.

Local and systemic reactions were mild for the most part and much the same in both vaccine groups. "For specific reactions, the only statistical difference was in the incidence of moderate fever after dose 1 (2.8% vs 0.0% for PCV13 and PCV7, respectively; p=0.026)," the report states.

"Data from this study support that PCV13 will be as effective as PCV7 in preventing disease caused by serotypes common to both vaccines," the authors conclude. "In addition, PCV13 should mediate protection against the 6 additional serotypes, all of which are important worldwide causes of severe pneumococcal disease."

Pediatrics. Posted online August 23, 2010. Abstract

Prepubertal Overweight Children With Prediabetes May Have Lower Bone Mass

From Medscape Medical News

Laurie Barclay, 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."

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

Friday, August 27, 2010

An Update on Autism -- Perspectives and Treatment

From Medscape Neurology & Neurosurgery

Andrew N. Wilner, MD

An Autism Update: Introduction

Autism is a common disorder of children that presents with a spectrum of neurobehavioral and cognitive disorders, particularly problems with socialization, communication, and repetitive behaviors. There are no biologic markers for autism. The diagnosis is clinical, based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV).[1] Lack of timely development of language, or regression in communication skills, are indications for an evaluation for autism (Table 1). Multiple diagnostic tools are available to assist clinicians in the assessment of a child with suspected autism (Table 2).

Table 1. Absolute Indications for Autism Evaluation
No babbling, pointing, or other gesture by 12 months
No single words by 16 months
No 2-word spontaneous (not echolalic) phrases by 24 months
Any loss of any language or social skills at any age

Data from the American Psychiatric Association.[1]

Table 2. Diagnostic Tools
Diagnostic Parental Interviews
The Gilliam Autism Rating Scale
The Parent Interview for Autism
The Pervasive Developmental Disorders Screening Test-Stage 3
The Autism Diagnostic Interview-Revised
Diagnostic Observation Instruments
The Childhood Autism Rating Scale
The Screening Tool for Autism in 2-Year-Olds
The Autism Diagnostic Observation Schedule-Generic

Data from the American Psychiatric Association.[1]

Like epilepsy, autism is a not a single syndrome. There is no cure, but early intervention can improve quality of life. The devastating nature of the disorder has attracted many unproven approaches, providing many opportunities for misguided, expensive, and potentially harmful "alternative" treatments.

An Update on Treatment

Medscape: What is the treatment for autism?

Dr. Goldstein: There are very little data concerning efficacy of behavioral treatments for autism. Most rely on close personal interactions between therapists/teachers and the children. Medications may be used to treat abnormal behaviors, but there are no medications that address the underlying disorder.

Dr. Chez: Treatment is purely symptomatic. For example, I sometimes use risperidone, which is US Food and Drug Administration approved for children with autism with aggressive behavior. We need more controlled studies of treatments. Clinical trials are now ongoing for memantine, an N-methyl-D-aspartic acid and glutamate antagonist that plays a role in brain neurogenesis, epilepsy, learning, and neuroglial inflammation, all of which may be important in autism. Designer drugs based on single gene defects, and stem cells are some other possibilities for the future.

Dr. Pellock: Autism has many faces and treatment must be individualized to each child. When children are referred with autism, they need a comprehensive evaluation to identify symptoms and developmental delays that may accompany autism. Treatment goals need to be identified. For example, is the therapy to decrease impulsiveness, hyperactivity, improve sleep, or treat seizures? The biggest issue is usually behavior. Children need behavioral controls throughout the day to learn which behaviors are acceptable and which are not to allow them to achieve to the best of their ability within the school system. A comprehensive, multimodal approach is necessary. Educational and environmental treatments are frequently at least as important, if not more important, than medications.

Autism remains a frustrating and challenging problem for many children and their families. While the experts do not agree on all of the details regarding management, all children with symptoms suggestive of autism should receive a comprehensive evaluation by a pediatric neurologist or other expert to determine whether the child has autism or another developmental disorder. If autism is diagnosed, the child’s behavioral, communication, and cognitive problems should be identified, as well as comorbidities such as epilepsy, sleep disorders, and gastrointestinal problems, so that a comprehensive treatment plan can be implemented. Early diagnosis and intervention offer children with autism the best opportunity to improve their social integration and quality of life.


Friday, August 20, 2010

The Clinicians Approach to Genetic Testing for Autistic Children

Bruce Buehler, MD, Pediatrics, General, 07:43PM Jul 25, 2010

The incidence of Autism is estimated at 1/100 children by the CDC. Often, families with children who are speech delayed, inattentive, or motorically delayed will search the internet or ask teachers about what might be wrong. Autism is often considered. The family usually seeks a diagnosis from their clinician, asking whether it is Autism.

The broad criteria are:
1. qualitative impairment in social interaction
2. qualitative impairments in communication
3. restricted repetitive and stereotyped patterns of behavior,interests, and activities ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). Washington DC: American Psychiatric Association; 2000:75.)

If the clinician feels the child fits criteria for Autism Spectrum Disorder (ASD), or the child has had psychological testing suggesting Autism, should there be further work up before referral to the schools for interventions? This is an individual decision by the clinician. If testing is indicated, a basic guideline for laboratory studies was proposed by Mendelsohn and Schaefer, Genetic Evaluation of Autism, Seminars in Pediatric Neurology, Volume 15, Issue 1, March 2008, Pages 27-31, Advances in Clinical Genetics (Part III).

In our clinic we have developed a limited approach for initial screening of children with ASD that can be used by the clinician prior to referral for a more extensive developmental or genetic evaluation.
It is our experience that this approach will identify a specific genetic syndrome or abnormality in a percentage of patients brought in by the family for Autism. After initial examination, the child with dysmorphic features or neurologic findings who meets the criteria for Autism Spectrum Disorder will yield the highest percentage, approximately 20% positive tests. Whereas the child without any physical anomalies or neurologic findings will rarely show positive results on this screen.

The tests recommended are Microarray, Fragile X, methylation of Chromosome 15, and MECP2 in females. Microarray will identify small deletions or duplications including Chromosome 16 that cause a condition with Autistic behavior. Fragile X accounts for approximately 10% of males and females with Autistic behavior. Methylation of Chromosome 15 will identify Angelman's Syndrome. MECP2 will diagnose approximately 50% of girls with Retts Syndrome. MRI can be considered if there are significant neurologic findings, including a history of unexplained seizures. If these tests are negative then it is appropriate to refer to a Developmental Pediatrician or Geneticist for further evaluation. Metabolic testing and specific gene tests are very complicated and have a lower yield. Having a specific syndrome or laboratory diagnosis aids in intervention and type of treatment for that child. It also provides information necessary to families for support, prognosis, and risk to future children.

If the evaluation suggests Autism Spectrum Disorder or Autistic behaviors, referral to the schools should be initiated for further educational testing and services. School referral should be made even if the laboratory testing is negative. Early intervention and treatment programs for Autism are most successful when initiated before 2 years of age. .

Wednesday, August 18, 2010

Obesity Linked to Lower Sperm Count in Young Men

From Reuters Health Information

NEW YORK (Reuters Health) Aug 12 - Young men who are obese may have a lower sperm count than normal-weight young men, a new study suggests.

The findings, reported online July 29th in Fertility and Sterility, add to evidence tying obesity to relatively poorer quality sperm.

A number of recent studies have found that compared with leaner men, obese men tend to have lower sperm counts, fewer rapidly mobile sperm and fewer progressively motile sperm.

But age is a confounding factor in examining the relationship between obesity and sperm quality. Older men tend to have lower sperm quality than younger men, and they also tend to have more body fat.

However, among the more than 2,000 men in the current study, obese men between the ages of 20 and 30 generally had a lower sperm count than normal-weight men in the same age group.

What all of this might mean for an obese younger man's chances of becoming a father is unclear. Studies have so far come to conflicting conclusions as to whether obesity actually impairs a man's fertility.

And these latest findings do not reveal whether the difference in sperm count between obese and normal-weight men would be enough to also make a difference in their fertility, according to lead researcher Dr. Uwe Paasch, of the University of Leipzig in Germany.

For their study, Dr. Paasch and colleagues looked at data on 2157 men who had come to their fertility clinic for a semen analysis between 1999 and 2005. They were 30 years old, on average, and had no known fertility problems.

Overall, obese men had a relatively lower average sperm count than normal-weight men, but were still within what's considered the normal range (20 to 150 million per milliliter of semen).

In e-mail, Dr. Paasch told Reuters Health that "we do not know in detail" whether the difference in sperm count between obese and lean men would affect their fertility. But, he added that the relationship between weight and sperm count offers young men another reason to try to maintain a normal weight.

It is not entirely clear why obesity is related to sperm quality. Some studies have found that obese men tend to have altered levels of testosterone and other reproductive hormones compared with thinner men. In this study, though, hormone levels correlated with age, but not with body weight.

In other research, Dr. Paasch and his colleagues have found that high levels of body fat are associated with changes in the proteins that allow sperm to survive and function.

The current study had a number of limitations, including the fact that the men were patients at a fertility clinic rather than a sample from the general population.

The researchers also point out that weight categories were based on body mass index, which does not precisely reflect body fat level.

Other studies have suggested that body fat, and abdominal fat in particular, is more closely related to sex-hormone levels than is BMI.

Fertil Steril. Posted online July 29, 2010. Abstract

Sugary Drinks Linked to Metabolic Syndrome, Diabetes

From Medscape Medical News
Emma Hitt, PhD

August 16, 2010 — Consumption of sugar-sweetened drinks, at least 1 drink per day, is significantly associated with the development of metabolic syndrome and type 2 diabetes mellitus vs consumption of less than 1 sugar-sweetened drink per month, and these effects do not appear to result entirely from an association with weight gain, new research findings suggest.

Vasanti S. Malik, ScD, with the Harvard School of Public Health, Boston, Massachusetts, and colleagues reported their findings in Diabetes Care, published online August 6, 2010.

Although consumption of sugar-sweetened drinks has been associated with weight gain, their role in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed, Dr. Malik and colleagues note.

According to the researchers, the high content of rapidly absorbable carbohydrates in sugar-sweetened drinks and the large volumes consumed may "increase risk of metabolic syndrome and type 2 diabetes mellitus not only through obesity but also by increasing dietary glycemic load, leading to insulin resistance, beta-cell dysfunction, and inflammation."

To evaluate this association, the researchers conducted a MEDLINE database search, selecting 11 prospective cohort studies assessing sugar-sweetened drink intake and the risk for type 2 diabetes (8 studies) or the risk for metabolic syndrome (3 studies).

Sugar-sweetened beverages were defined as soft drinks, fruit drinks, sports drinks, energy and vitamin waters, sweetened iced tea, punch, cordial, squashes, and lemonade. Not included were 100% fruit juices without added sweeteners.

The 8 studies assessing type 2 diabetes included 310,819 participants and 15,043 case patients with diabetes. The highest quantile of consumption was most often 1 to 2 servings per day vs the lowest quantile (0 or < 1 serving per month).

The risk for type 2 diabetes in the highest quantile was increased by 26% (relative risk [RR], 1.26; 95% confidence interval [CI], 1.12 - 1.41). Likewise, among studies evaluating metabolic syndrome, including 19,431 participants and 5803 case patients, the risk was increased by 20% (RR, 1.20; 95% CI, 1.02 - 1.42).

The authors point out in their discussion that fructose, present in large quantities in sugar-sweetened drinks, may promote accumulation of visceral adiposity and ectopic fat deposition, both of which create a dysmetabolic state, increasing the risk for type 2 diabetes and cardiovascular disease.

"This meta-analysis has demonstrated that higher consumption of [sugar-sweetened drinks] is significantly associated with development of metabolic syndrome, and type 2 diabetes mellitus," the study authors conclude.

The study "provides further support to limit consumption of these beverages in place of healthy alternatives such as water, to reduce obesity-related chronic disease risk," they add.

The study was not commercially supported. The study authors have disclosed no relevant financial relationships.

Diabetes Care. Published online August 6, 2010.

Probiotic Improves Symptoms of Infantile Colic

From Medscape Medical News
Fran Lowry

August 16, 2010 — Supplementation with the probiotic Lactobacillus reuteri DSM 17 938, at a dose of 108 colony-forming units per day, improved the symptoms of infantile colic in breastfed infants and was well-tolerated and safe, according to a new study published online August 16 in Pediatrics.

"Colic affects 3% to 28% of infants, causing considerable stress and concern for parents, and the pathogenesis of the condition remains elusive, although evidence suggests multiple independent causes," write Francesco Savino, MD, PhD, from the University of Turin, Italy, and colleagues. "Recently, coliform bacteria, particularly Escherichia coli, were found to be more abundant in the feces of colicky infants, suggesting a role for coliform colonic fermentation and consequent excessive intraintestinal air production, aerohagia, and pain, typical in crying infants."

The aim of this study was to test the efficacy of L reuteri on infantile colic and to evaluate its relationship to the gut microbiota.

The study randomly assigned 50 colicky exclusively breastfed infants aged 2 to 16 weeks to receive either L reuteri or placebo daily for 21 days. Colic was defined according to modified Wessel's criteria as episodes of fussy crying that lasted 3 or more hours a day and episodes that lasted for 3 or more days in the week before enrollment in the study.

Both L reuteri and placebo formulations were given in 5 drops, once a day, 30 minutes before the infants' daily morning feed. The parents filled out a structured diary to record daily crying time in minutes, stool characteristics and frequency, and any adverse effects, such as constipation, vomiting, and skin reactions. Forty-six infants completed the study — 25 in the L reuteri group and 21 in the placebo group.

At the start of the study, daily crying times were similar in both groups. The median crying time in the L reuteri group was 370 minutes per day (interquartile range [IQR], 120 minutes) and 300 minutes per day (IQR, 150 minutes) in the placebo group (P = .127).

At the end of the study, the median daily crying times were 35.0 minutes per day (IQR, 85 minutes) in the L reuteri group vs 90.0 minutes per day (IQR, 148 minutes) in the placebo group (P = .022).

The authors also report that the number of responders, defined as having a 50% reduction in crying time from baseline, were significantly higher in the L reuteri group than in the placebo group on days 7 (20 vs 8; P = .006), 14 (24 vs 13; P = .007), and 21 (24 vs 15; P = .036).

The study also found a significant increase in fecal lactobacilli (P = .002) and a reduction in fecal E coli and ammonia in the L reuteri group only (P ≤ .001).

There were no differences in weight gain, stooling frequency, or incidence of constipation or regurgitation between groups, and no adverse events associated with supplementation with L reuteri were observed.

"Possible mechanisms of the action of L reuteri include an improvement in gut motility and function and direct effects on visceral pain, both of which may induce a calming effect and reduced crying in infants," the authors write.

They address the fact that infants assigned to the placebo group of the study also had reduced crying time by day 21. They suggest that this response could be a result of the mother's cow's-milk-free diet or of physiologic maturation that ultimately resolves colic during normal development.

The authors note that they recently reported a higher prevalence of coliform bacteria, particularly E coli, in colicky infants compared with healthy counterparts. The present finding, that fecal E coli levels were significantly reduced with L reuteri supplementation, but not with placebo, suggests that L reuteri promotes gut health through a reduction of E coli colonization, they write.

"Administration of L reuteri DSM 17 938 to colicky infants is well tolerated and improves symptoms of infantile colic compared with placebo, and this effect may be related to induced changes in the fecal microbiota, particularly E coli," they conclude. "These findings provide important insights into the role of an aberrant bacterial flora in the pathogenesis of infantile colic and the potential to overcome this with probiotic supplementation."

The study was supported by BioGaia AB. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online August 16, 2010.

Friday, August 13, 2010

SSRIs Not Recommended for Autism in Children or Adults Based on Current Evidence

From Medscape Medical News
Pauline Anderson

August 12, 2010 — Based on the research to date, selective serotonin reuptake inhibitors (SSRIs) cannot be recommended for treating autism in children or adults, the results of a new Cochrane review of the literature show.

The analysis found no evidence that SSRIs are effective in children with autism and may even be harmful, and although there is limited evidence that SSRIs are effective in adults, the sample size of the trials is small and there is a risk of bias.

Decisions about treating conditions that might accompany autism spectrum disorder (ASD), for example, obsessive-compulsive disorder (OCD) or depression, should be made on an individual basis, said the study authors.

"It's not surprising that clinicians and parents have hoped that SSRIs will help core features of autism as well as associated problems, but there is no strong evidence that they do," said lead study author Katrina Williams, PhD, School of Women's and Children's Health, University of New South Wales & Sydney Children's Hospital, Australia, in email correspondence with Medscape Medical News.

"So when trying to balance benefit and harm from existing evidence, clinicians and families are still in a situation where decisions will need to take into account the severity of the problem, the type of problem, and the potential risks."

The study was published online August 8 in The Cochrane Library, issue 8.

Most Studies Small

For this report, researchers searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycINFO for randomized controlled trials of an oral SSRI compared with placebo in participants with an ASD. Characterized by impairment in social interaction and communications skills, stereotypic behaviors, and limited activities and interests, ASDs include autism, pervasive developmental disorder–not otherwise specified, and Asperger syndrome.

The analysis included 7 studies that evaluated 4 SSRIs: fluoxetine, fluvoxamine, fenfluramine, and citalopram. The studies included a total of 271 subjects and were performed in the United States (5 studies), France (1), and Japan (1). Five of the studies included only children, and 2 included only adults.

The studies, which continued for a maximum of 12 weeks, reported 17 different outcome measures. Most of the studies were small; although 1 multicenter trial included a sample size of over 100, the next largest study recruited 39 participants. For these and other reasons, the reviewers found that meta-analyses were not possible.

None of the studies assessed sleep disturbance, self-mutilation, attention and concentration problems, gastrointestinal function, or quality of life.

In the 5 studies of children, including 1 large good quality study of citalopram and 4 smaller studies of fluoxetine, fluvoxamine, and fenfluramine, there was no evidence of benefit. The study of citalopram reported significantly more adverse events in children taking this drug compared with placebo, including 1 serious adverse event, a prolonged seizure.

Different Adverse Effects in Children

Dr. Williams pointed out that children with autism may experience different side effects of SSRIs than adults with autism or other children without autism. "It's important that parents embark on SSRI treatment aware that, as yet, there are few proven benefits and some known harms. That's different from making a decision about commencing a treatment with likely benefit and no known harms."

With monitoring, dose adjustment, and time, all but one of the adverse effects in these studies were resolved, said the study authors.

Although none of the trials assessing "core features" of autism in children — communication, social interaction, and behavior problems — showed improvement, it is possible that SSRIs may still be effective in treating autism in children.

Lack of evidence is not the same as evidence that SSRIs don't work.
"This is a complex area because there are many SSRIs available — and not all have been studied in large well-conducted trials," said Dr. Williams. "Lack of evidence is not the same as evidence that SSRIs don't work."

According to the study authors, replication of the citalopram study will provide further information about the effectiveness and safety of SSRIs for childhood autism. "For completeness, an adequately powered [randomized controlled trial] should be conducted on at least 1 other SSRI," the study authors note, and recommend this SSRI be fluoxetine because of its favorable safety profile.

Studies in Adults

The studies that included adults reported significant improvements in clinical global impression (fluvoxamine and fluoxetine), OCD behaviors (fluvoxamine), anxiety (fluoxetine), and aggression (fluvoxamine). However, the 2 relevant studies were small (1 had only 6 subjects, the other 30 subjects). and the quality of the trials was uncertain, said Dr. Williams. Both adult studies reported that treatment was well tolerated.

As well as covering a wide age range, the studies in the analysis included subjects whose conditions were diagnosed using different classification systems and assessment procedures. The studies also varied in terms of the subjects' IQ, severity of their problems, and whether they had the problems that the treatment is suggested to ameliorate.

Despite such differences, there is consistency of findings for the studies conducted in both children and adults, said the study authors.

None of the studies evaluated sertraline, paroxetine, or escitalopram — drugs used in clinical practice to treat problems associated with ASD, for example, OCD and depression. "When conducting a review of a drug class, it's important for prescribers to know what has and has not been examined," commented Dr. Williams. "It's also important for those planning future research."

Prevalence of autism varies between 1 and 40 per 10,000, and for ASD it is between 3 and 82 per 10,000. Males are affected about 4 times more frequently than females.

Antidepressants, most of which are SSRIS, are the most commonly prescribed psychotropic medication for ASD, but the number of SSRI prescriptions for children have decreased because concerns have been raised about increased risk of suicide-related behaviors.

Off-Label Use

SSRIs are not approved for treatment of autism, so use of these drugs in children with this condition is either off-label or used to treat depression or OCD. The US Food and Drug Administration (FDA) has approved sertraline in children 6 years and older, fluoxetine in children 7 years and older, and fluvoxamine in children 8 years and older for the treatment of OCD. The FDA has also approved fluoxetine in children 8 years and older and escitalopram in adolescents 12 to 17 years for the treatment of depression.

In autism, there's a "fundamental difference" between treating a co-occurring problem and treating the underlying disorder, explained Dr. Williams. "If SSRIs were useful in treating core features of autism, their use would become widespread, and it's likely they would be used in younger age groups. That would require much more rigorous review and monitoring — especially with regard to side effects."

The thinking is different when it comes to treating co-occurring problems, said Dr. Williams. "Trials are building on existing evidence about effectiveness for that problem in individuals who don't have autism. The treatment would only need to be long enough to address the problem, if it were short term, or to allow receptiveness to other proven nonmedication therapies."

Not a Single Condition

Commenting on the findings, Isabelle Rapin, MD, professor of neurology and pediatric neurology at Albert Einstein College of Medicine, New York City, emphasized how extremely difficult it is to perform studies of autism.

"We know that autism is not a single condition; we know that it has multiple causes, marked differences in symptomatology, and marked differences in severity," she said.

Some children with autism might respond well to an SSRI "if they were properly classified," but because these patients are a heterogenous group, it is important to make decisions subject by subject, said Dr. Rapin.

She said there are "hundreds and hundreds" of children with autism who are prescribed an SSRI to treat symptoms such as self-injury, irritability, or repetitive movements.

Cochrane Database Syst Rev. 2010;8.

Wednesday, August 11, 2010

Early Evidence of Brain Complications With Type 2 Diabetes in Obese Adolescents

From Medscape Medical News

Megan Brooks

August 10, 2010 — In a small study of obese adolescents, those with type 2 diabetes performed worse on several cognitive function tests than their equally obese peers without diabetes or prediabetes. Subtle brain abnormalities on magnetic resonance imaging (MRI) were also seen only in the type 2 diabetes group.

"This is the first report of brain and cognitive abnormalities among obese adolescents with type 2 diabetes," the study team notes in the journal Diabetologia, published online July 30. "We demonstrate that, in the absence of clinically significant vascular disease, there may be clear brain complications among adolescents with type 2 diabetes.

"There is good evidence to believe that it is the insulin resistance itself that causes the cognitive dysfunction," study author Antonio Convit, MD, professor of psychiatry and medicine at New York University Langone Medical Center and the Nathan S. Kline Institute for Psychiatric Research in New York City noted in a telephone interview with Medscape Medical News.

The study included 18 obese adolescents with type 2 diabetes (mean age, 16.4 years) and 18 obese adolescents without type 2 diabetes or marked insulin resistance (mean age, 17.1 years). In addition to age, the 2 groups were "very well matched," Dr. Convit said; they were comparable in sex, school grade, ethnicity, socioeconomic status, body mass index, waist circumference, and ratings of sleep apnea. During 2 clinic visits, all of the subjects underwent comprehensive medical, endocrine, psychiatric, neuropsychological, and brain MRI assessments.

Consistently Worse Cognitive Function

According to Dr. Convit and colleagues, the adolescents who had been diagnosed as having type 2 diabetes for 2.61 years on average (range, 5 months to 7.50 years) consistently scored lower than obese nondiabetic controls on all cognitive tests administered. "They scored significantly lower in 6 of 13 cognitive tests and we had trends in others, so this is not a type 1 error," Dr. Convit said.

More specifically, the adolescents with type 2 diabetes had significantly lower overall intellectual functioning, lower verbal memory scores, and lower psychomotor efficiency (all P < .05) and tended to have lower executive function ability (P = .06). All of these measures showed "medium-large to large effect sizes," the study authors note.

Despite being in the same grade and socioeconomic status, the adolescents with type 2 diabetes also posted lower scores on standard reading (P = .09) and spelling (P = .07) tests, "both trending toward significance and with medium effect sizes."

The difference in estimated full-scale IQ between the diabetic and nondiabetic teens (87.8 vs 103.6; P < .001) "could be a hot button," Dr. Convit noted. "But it's not that they are less smart than the other kids, it's just that they are not performing as well on the tasks and therefore their measured IQ is going to be lower."

IQ Difference Potentially Concerning

In an email to Medscape Medical News, Claude Messier, MD, PhD, who was not involved in the study, noted that the IQ difference of roughly 15 points "would suggest a significant intellectual impairment.

"A larger study will be needed to confirm this observation, particularly one with enough participants to allow to verify developmental delay as a possible explanation for the results. It will also help to determine if the reduction is equal at all IQ levels," said Dr. Messier, who is with the School of Psychology and Behavioral Neuroscience Specialization Coordinator at University of Ottawa in Ontario, Canada.

Prior studies by Dr. Messier and colleagues, and others, have documented significant cognitive slowing and learning and memory deficits in older adults with type 2 diabetes.

The findings in the current study of obese adolescents with type 2 diabetes were "not really expected since otherwise healthy type 2 diabetes patients (with no important cerebrovascular disease or hypertension) only have very mild cognitive changes before the age of 70," Dr. Messier added.

Subtle but Significant Differences on MRI

MRI-based automated brain structural analyses showed reduced white matter volume and enlarged cerebrospinal fluid space in the whole brain and the frontal lobe in particular but no obvious reduction in the volume of gray matter.

Diffusion-tensor imaging revealed reduced white and gray matter microstructural integrity.

"Particularly worrisome," Dr. Messier said, "is the cerebral ventricle enlargement, which is usually associated with many brain diseases. If ventricular enlargement was not present, the other reductions in brain volume or density could still be explained by development delay, particularly since anatomical changes in the frontal cortex (a late-developing region) and functional changes associated with the frontal cortex were prominent in the study. The presence of ventricular enlargement makes this possibility less likely," he said.

"The fact that large IQ differences and anatomical changes were found in the Convit study," Dr. Messier said, "suggest that type 2 diabetes is more damaging to the brain during development possibly with the combination of obesity (and associated health problems such as sleep apnea and depression, which may also be associated with brain anatomical and functional changes)."

This study, Dr. Messier added, "suggests that brain-related impairments are yet another reason to change the societal conditions that lead to obesity and type 2 diabetes. Although reduced intelligence and brain functions may pale in comparison to heart attacks and limb amputation as a consequence of early type 2 diabetes, as a society, a reduction in the intellectual abilities of significant proportion of its youth is definitely not a good trend," he said.

Strengths, Shortcomings and a Cautionary Note

Roger A. Dixon, MD, professor of psychology and Canada Research Chair in Cognition and Aging at the University of Alberta in Canada, told Medscape Medical News this new study provides "preliminary evidence for brain complications that could be associated with type 2 diabetes in adolescents.

"It is preliminary for methodological reasons," Dr. Dixon noted, "in that the study has a very small sample size and only 1 wave of measurement." Still, it is a very promising direction of research, because it examines markers of both brain and cognitive functioning, and such findings can help researchers and clinicians link the better-known effects of type 2 diabetes in older adults with those of the growing population of children and younger adults acquiring this disease, he said.

"The inclusion of a measure of depression," added Dr. Messier, "could have been informative since obesity is associated with a higher risk of depression and depression is associated with anatomical changes and cognitive deficits, although most studies linking depression and brain anatomical or functional changes have been done in adults."

Future Directions

Dr. Convit and colleagues say studies are needed to determine the underlying pathophysiologic mechanisms of cognitive impairment and brain changes in obese adolescents with type 2 diabetes. They propose that the negative impact of type 2 diabetes on the adolescent brain "may result from a combination of functional vascular changes and glucose and lipid metabolism abnormalities in the absence of overt vascular disease."

"By conducting longitudinal studies, we need to see whether some of these deficits are reversible on reversal of insulin resistance," Dr. Convit said. The diabetes study participants had a mean hemoglobin A1c of 8.3%, indicating intermediate glycemic control.

In just completed (unpublished) research, Dr. Convit's team found that obese kids who have insulin resistance short of diabetes also have cognitive impairment relative to lean kids. "So there is a stepwise function with higher levels of insulin resistance leading to greater and greater cognitive dysfunction," he noted.

The study was supported by grants from the National Institutes of Health and the National Center for Research Resources and the Pollock-Nguyen Charitable Fund. The study authors, as well as Dr. Messier and Dr. Dixon, have disclosed no relevant financial relationships.

Diabetologia. Published online July 30, 2010.

Study: Girls Entering Puberty Earlier

From WebMD Health News

Kathleen Doheny

August 10, 2010 — The age of puberty is declining for girls, with more girls developing breasts by age 7 than in years past, according to a new study.

Ethnicity plays a role in earlier puberty, says researcher Frank M. Biro, MD, director of the division of adolescent medicine at Cincinnati Children's Hospital Medical Center, Cincinnati. So does body composition.

"We found that girls who are African-American matured before whites, and that's been shown in several studies," Biro tells WebMD. "White girls are maturing earlier than they had before, compared to 20 years earlier."

In his study of 1,239 girls, 10% of whites, 23% of African-Americans, and 15% of Hispanic girls had breast development indicating onset of puberty by age 7, Biro found.

Biro can't give an average age of puberty at this time, he says, because many girls in the study have not yet developed breasts. Over time, further analysis is expected to provide that and other information.

The study is published online in the journal Pediatrics.

Age of Puberty Study: Details

Biro and his colleagues took a ''snapshot in time'' or cross-sectional look at girls who were recruited at three sites when they were aged 6 to 8 in 2004-2006. They lived in East Harlem, New York, Cincinnati, or the San Francisco Bay area.

The researchers assessed the onset of puberty by a standard measurement of breast development.

They compared the findings to a 1997 study of age of puberty. They found that:

* 10.4% of white girls in the current study had breast development, compared to 5% in the 1997 study.
* 23.4% of African-American girls had beat development, compared to 15.4% in the 1997 study.

Besides ethnicity, body mass index or BMI was found to play a role in onset of puberty, Biro's team found. Girls who had breast development at age 7 were more likely to have a higher BMI. Body fatness has been linked with onset of puberty in girls, other research by Biro and others has shown.

The study was conducted within the Breast Cancer and the Environment Research Centers (BCERC), established in late 2003 as a partnership with the National Institute of Environmental Health Science and National Cancer Institute, which funded the research. Research suggests that women with breast cancer started their periods earlier, and that those with earlier onset of periods have an increased breast cancer risk.

Earlier Puberty: Explaining the Findings

The researchers also collected urine and blood specimens from the girls to look at levels of compounds called endocrine-disrupting chemicals, Biro says, to see what role these environmental exposures might play in early puberty.

''It appears that some of the endocrine-disrupting chemicals are interacting with body composition and this may be the reason some girls are going into puberty earlier and others later," Biro tells WebMD. "That would have to be speculation," he says of the interaction idea. "But we do know BMI is doing it."

Among 6- to 11-year-olds, obesity has increased from 6.5% in 1976-1980 to 19.6% in 2007-2008, according to the CDC.

Endocrine-disrupting compounds or EDCs are found in a host of consumer products, ranging from personal care products such as antibacterial soaps to furniture and anti-stain fabrics.

Earlier Puberty Study: Other Thoughts

Although further research is likely to pinpoint the cause of earlier puberty in girls, the focus now should be on more practical matters, says Warren Seigel, MD, a member of the American Academy of Pediatrics' Committee on Adolescence and chair of the department of pediatrics at Coney Island Hospital in Brooklyn.

"Instead of debating the cause only, let's talk about what we can do right now, and [that is], we have to be on guard," Seigel tells WebMD.

Pediatricians as well as parents should be talking to children earlier than they previously have thought necessary, discussing sex as well as substance abuse, Seigel says.

Earlier Puberty: Tips for Parents

Until more is known about what drives earlier puberty in girls, Biro suggests families try ''living greener, trying to minimize exposure to chemicals in the environment, and part of that might be using safer personal care products."

He suggests choosing products that are free of the chemical phthalates. And to control weight, he says families can participate in physical activity together.


More Than a Third of Kids With Sore Throat Likely Have Strep A

From Reuters Health Information

By Robert Saunders

NEW YORK (Reuters Health) Aug 09 - A substantial proportion of children with pharyngitis probably have group A streptococcal infection, a new meta-analysis shows. Furthermore, about one in every eight healthy kids is a carrier.

Those numbers are drawn from 29 studies with data on the prevalence of group A Streptococcus (GAS) in pharyngeal specimens in children younger than 18 years.

Writing online today in Pediatrics, lead author Dr. Nader Shaikh of Children's Hospital of Pittsburgh, Pennsylvania, and colleagues report that the prevalence of GAS in children presenting with sore throat is 37% overall and 24% in children younger than five.

In other words, Dr. Shaikh told Reuters Health, "Of school-aged children who present to their physicians with a sore throat, more than one third will have strep throat (which is much much higher than the rate in adult patients)."

The implications? "The relatively high probability of GAS disease and acute rheumatic fever in school-aged children, as compared with adults and children who are younger than 5 years, suggests that testing of school-aged children who present with sore throat is beneficial," the authors advise.

Twelve percent of asymptomatic kids over five carry GAS. "So it is probably not wise to test children who have absolutely no signs or symptoms of pharyngitis. This will lead to unnecessary antibiotic use," Dr. Shaikh said.

Posttreatment cultures are unnecessary in the majority of patients with GAS pharyngitis, the authors suggest. However, "In selected children with recurrent pharyngitis, posttreatment testing may help to differentiate children with true recurrent GAS pharyngitis from carriers; children who are carriers are likely to have persistent GAS even after being treated with appropriate antimicrobial agents."

SOURCE: Abstract

Pediatrics 2010.

AUA Says When to Screen Families for Vesicoureteral Reflux

From Reuters Health Information
David Douglas

August 6, 2010 — Siblings and offspring of patients with vesicoureteral reflux (VUR), and infants with prenatal hydronephrosis, also have high prevalences of VUR – but it's not clear how much they'll gain from having the condition diagnosed, the American Urological Association says.

On July 21st in the Journal of Urology, the Association issued updated guidelines to help physicians decide who to screen, and when.

But due to a lack of randomized clinical trials, the Association's update panel found it difficult to make evidence-based recommendations. When necessary, the panel members based the guidelines on current practice, risk assessment, meta-analysis results and consensus.

Led by Dr. Steven J. Skoog of the Oregon Health & Sciences University in Portland, the panel issued seven "summary guidelines," with two labeled "recommendations" (the first two, below) and the others labeled "options."

•In siblings of children with VUR, a voiding cystourethrogram (VCUG) or radionuclide cystogram is recommended if ultrasound shows renal corticoid abnormalities or renal size asymmetry, or if the sibling has a history of urinary tract infections (UTI).
•VCUG is recommended for infants with high-grade hydronephrosis (Society for Fetal Urology grades 3-4), hydroureter or abnormal bladder, or UTI.
•Given the unclear benefit of finding and treating VUR, siblings of children with VUR can be observed without screening, as long as any acute UTI is promptly followed by evaluation for VUR.
•Older siblings who are toilet trained may be screened, although the value of detecting VUR is unclear.
•Siblings of children with VUR can have renal ultrasound studies to identify significant renal scarring and to focus attention on the presence and potential further risk of VUR.
•Screening offspring of patients with VUR can be considered as similar to screening of siblings.
•Children with prenatal hydronephrosis (SFU grades 1-2) can be observed without screening as long as any UTI is promptly treated, given the unproven value of identifying and treating VUR. VCUG in these patients is optional.
In developing these guidelines, the panel analyzed pooled data from 22 sibling screening studies involving more than 3200 children, as well as 43 studies of more than 6500 infants with prenatal hydronephrosis.

Overall in the meta-analysis, the prevalence of VUR was 27.4% in siblings and 35.7% in offspring. The prevalence decreased as the age of the screened cohort increased, and the annual resolution rate of 4% "can aid in assessing the need for screening based on patient age," the authors note.

Infants with prenatal hydronephrosis had a 16.2% prevalence of VUR.

Overall, the panel concludes that despite absence of clear-cut benefit, "identification of VUR may increase the awareness of parents and health providers to the potentially increased risk of pyelonephritis and renal scarring."

J Urol. 2010;184:1145-1151.

Reuters Health Information 2010. © 2010 Reuters Ltd.

Intranasal Medication Delivery for Children Reviewed

From Medscape Medical News

Laurie Barclay, MD

August 9, 2010 — The most frequent pediatric indications for intranasal medication delivery are pain control, anxiolysis, and seizure control, according to a review published online August 9 in Pediatrics. Other potential indications for intranasal medication delivery not reviewed in this article include the treatment of epistaxis, pretreatment before nasogastric tube insertion, and administration of naloxone for reversal of narcotic overdose.

"Intranasal delivery offers unique advantages that may allow more efficient use of resources, more rapid patient care, and higher patient and provider satisfaction," write Timothy R. Wolfe, MD, from University of Utah School of Medicine in Salt Lake City, and Darren A. Braude, MD, from the University of New Mexico School of Medicine in Albuquerque. "The highly vascularized nasal mucosa and the olfactory tissue in direct contact with the central nervous system allow nasally administered drugs to be rapidly transported into the bloodstream and brain, with onsets of action approaching that of intravenous therapy. First-pass drug metabolism via the liver is also avoided, resulting in high bioavailability of many medications."

Except for orally and intranasally administered medications, most formulations require a needle injection, which may be painful, anxiety-provoking, and time-consuming for staff, who must be trained in proper injection technique and who are exposed to the risks for needle stick injury. In comparison, intranasal delivery of medication is relatively painless, inexpensive, and easy to administer with minimal training.

Specific uses of intranasally delivered medications include the following:

•For pain control, fentanyl 1.5 to 2.0 μg/kg. This may be titrated every 15 minutes as needed. Patients should be monitored for respiratory depression. It may be appropriate to administer oral medications concurrently so that they take effect as the intranasal fentanyl effect wears off.
•For anxiolysis, midazolam 0.4 to 0.5 mg/kg. The concentrated form (5 mg/mL) should be used, because other concentrations may be ineffective when administered intranasally. The patient and family should be advised that a burning sensation may last for 30 seconds.
•For seizures, midazolam 0.2 mg/kg. As for anxiolysis, the concentrated form (5 mg/mL) should be used for intranasal delivery.
Intranasal opiates may be especially useful for minor fractures, large abrasions, burns, wound-dressing changes, extremity fractures, and other acutely painful conditions in children. For treatment of acute pain, intranasal opiates have been shown to be as effective as intravenous morphine and faster than intramuscular morphine.

Procedures in which light procedural sedation and anxiolysis may be achieved with intranasal medications include laceration repair, magnetic resonance imaging and computed tomography scans, burn-dressing changes, dental extractions, endoscopies, and central venous port access. Although intranasal midazolam is the most commonly studied drug in these settings, other options may include intranasal fentanyl, ketamine, sufentanil, dexmedetomidine, and combinations of these drugs.

Intranasal midazolam is effective for prolonged seizures because it easily and rapidly crosses the nasal mucosa and the blood-brain barrier, with similar efficacy to intravenous diazepam but faster onset because of the lack of need to start an intravenous line. Intranasal midazolam and lorazepam are also safe for treating seizures outside of the hospital setting, and intranasal midazolam may be a useful option for treating status epilepticus when intravenous access is not immediately available.

Specific considerations for administering intranasally delivered medications include the following:

•Deliver immediately to allow absorption while the airway is being supported.
•The nostril should be inspected for significant amounts of blood or mucous discharge that could limit absorption of a nasal medication. When these are present, alternative delivery options should be considered, or it may be appropriate to suction the nasal passage before medication delivery.
•Deliver half of the medication dose up each nostril, which doubles the available mucosal surface area (vs a single nostril) for drug absorption and increases the rate and amount of absorption.
•The most concentrated form available of the medication should be used, because dilute forms are less effective for intranasal delivery.
•The ideal volume for intranasal medication delivery is 0.2 to 0.3 mL of medication per nostril, and volume per nostril should not exceed 0.5 to 1.0 mL. Two separate doses may be used when a higher volume is needed, with a few minutes between doses to allow the first dose to absorb.
Adverse effects of nasal medications seldom occur. The most common adverse effect is transient nasal burning and irritation with midazolam. Except with high doses of intranasal sufentanil for induction during surgery, oversedation has not been reported for intranasal medications, including fentanyl or midazolam.

"Intranasal medication delivery is an effective method of delivering analgesia, anxiolysis, and anticonvulsants to pediatric patients," the review authors conclude. "In the properly selected patient, nasal administration can reduce time to medication delivery and onset, reduce medical staff resource use, eliminate needle-stick exposure risk, and eliminate pain from the injection, thereby leading to improved patient and parent satisfaction. Pediatricians, pediatric emergency physicians, and emergency medical services medical directors should consider adopting this delivery method for medications and indications that are appropriate to their practice setting."

Dr. Wolfe is affiliated with Wolfe Tory Medical, Inc, the maker of the MAD nasal drug delivery device. Dr. Braude has disclosed no relevant financial relationships.

Pediatrics. Published online August 9, 2010.

Iron-Deficiency Anemia Linked to Memory Deficits in Children

From Medscape Medical News

Laurie Barclay, MD

August 6, 2010 — Iron-deficiency anemia (IDA) is linked to memory deficits in children, according to the results of a study reported online July 26 in Pediatrics.

"IDA in infancy is associated with cognitive deficits, which may persist later in life," write R. Colin Carter, MD, from Children's Hospital Boston and Harvard Medical School in Boston, Massachusetts, and colleagues. "Socioemotional deficits are also consistently observed in infants with IDA, but it is not known whether these deficits affect cognitive function."

The goal of the study was to determine effects of IDA on specific functions involved in infant cognition, as well as the effect of socioemotional deficits related to IDA in modulating these effects. During routine 9-month visits to an inner-city clinic, infants were recruited into the study. Criteria for IDA were hemoglobin levels of less than 110 g/L with abnormal values for at least 2 of the following iron deficiency indicators: mean corpuscular volume, red cell distribution width, zinc protoporphyrin-heme ratio, transferrin saturation, and ferritin.

Cognitive testing at 9 and 12 months included the Fagan Test of Infant Intelligence; A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale. The investigators adjusted the analyses for age, sociodemographic variables, and other potential confounders.

Study participants were 28 infants with IDA, 28 with nonanemic iron deficiency, and 21 with iron sufficiency. At 9 months, infants with IDA were least likely to demonstrate object permanence, iron sufficiency most likely, and nonanemic iron deficiency intermediate, suggesting a linear effect.

Compared with infants without IDA, those with IDA and those with hemoglobin level of 105 g/L or less had worse recognition memory on the Fagan Test of Infant Intelligence, but these effects were partially mediated by the Behavior Rating Scale orientation/engagement measure. Infants with poorer scores on the socioemotional measures had stronger effects of IDA on these outcomes.

"These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months," the study authors write. "These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function."

Limitations of this study include small sample size, inability to supervise iron administration, and inability to determine response to iron for infants who did not come for a subsequent blood test. In addition, the degree of IDA in this sample was relatively mild and duration probably quite short, limiting generalizability to more severe cases.

"Our findings provide evidence of specific deficits in cognitive processing (attention and memory) with IDA during an important period of infant development before the usual age for IDA screening in the primary care setting," the study authors conclude. "Deficits in these processes, which have demonstrated predictive validity for later cognitive function, have implications for intellectual function in childhood. Furthermore, these early cognitive deficits seem to be mediated, in part, by the effects of IDA on the infant's ability to engage affectively with the environment, and socioemotional deficits seem to increase the infant's vulnerability to the cognitive effects of early IDA."

Pediatrics. Published online July 26, 2010.

Early Cholesterol Predicts Later Coronary Calcium

From Heartwire
Reed Miller

August 3, 2010 (San Francisco, California) — A new prospective cohort study suggests younger people will pay for high cholesterol in the present with coronary calcium in the future, according to results of a study published in the August 3, 2010 issue of the Annals of Internal Medicine [1].

In the latest study from the ongoing Coronary Artery Risk Development in Young Adults (CARDIA) trial, Dr Mark Pletcher (University of California, San Francisco) and colleagues measured low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium in 3258 subjects age 18 to 20 in 1985 and 1986. They estimated time-averaged cumulative exposures to lipids between age 20 and 35 with repeated serum lipid measurements over 20 years and then related these data to coronary calcium scores acquired with computed tomography at years 15 and 20.

Nonoptimal levels of LDL cholesterol (>100 mg/dL), HDL cholesterol (<60 mg/dL), or triglycerides >150 mg/dL were found in 87% of young adults in the study. Coronary calcium prevalence 20 years later was 8% in participants who maintained optimal LDL levels <70 mg/dL and 44% in participants with LDL-cholesterol levels of >160 mg/dL (p<0.001). The same association was found in all races and genders.

The odds of finding coronary calcium increased as LDL increased. For example, compared with people with LDL levels less than 70 mg/dL, the odds ratio for coronary calcium later in life for patients with 70 to 99 mg/dL in their early adulthood was 1.5. For people with LDL of 100 to 129 mg/dL, the odds ratio was 2.4, and for people with LDL of 160 mg/dL or greater, the odds ratio was 5.6.

The results show that nonoptimal LDL-cholesterol levels during young adulthood are linked to coronary calcification down the road and that accounting for later-life lipid exposure does not explain the association of young adult LDL-cholesterol levels with later calcification. After the authors adjusted their analysis for "the potentially obscuring influences" of subjects' medication and clinically abnormal levels of other lipids, they observed an inverse association with HDL-cholesterol levels but no association with triglyceride levels.

Pletcher et al acknowledge that coronary calcium is a "subclinical end point," because the cohort is still too young to have enough MIs or deaths to study the connection between early lipid levels and those clinical outcomes. However, they point out that coronary calcium has been shown to be a strong independent predictor of coronary heart disease events and that the absence of coronary calcium is a strongly protective factor.

The authors recall previous studies that have found associations between lipid levels and atherosclerosis in children and young adults, demonstrated by autopsy, carotid intima–media thickness, and coronary calcium. But this CARDIA analysis is the first with adequate sample size, repeated measurements of the three major lipids, and sufficient follow-up to isolate the link between lipid levels during young adulthood with atherosclerosis during middle age while controlling for confounders, they claim.

"Our results suggest that atherosclerotic changes begin during young adulthood as a result of commonly observed nonoptimal lipid levels, that these changes persist into middle age, and that maintaining optimal levels of lipids--particularly LDL cholesterol--throughout young adulthood could provide substantial benefits in terms of lifetime coronary heart disease prevention," Pletcher et al conclude. "These findings reinforce the importance of a heart-healthy diet, exercise, and maintenance of normal weight beginning in young adulthood."

"What we show here is that it matters what your cholesterol level is during young adulthood, and you should be thinking about it and trying to optimize it during young adulthood so that you have less built-up atherosclerosis later in life, and that will stand you in good stead for reducing your heart-attack risk later in life," Pletcher told heartwire. "We're not directly testing the hypothesis that modifying cholesterol with diet and exercise during young adulthood makes a difference later in life. But there's so much evidence that cholesterol really is a cause of heart disease that we think that it's reasonable that the same thing is going on here--that it's a treatable cause of disease that can be avoided."

He cautioned that the study does not address whether medication to lower cholesterol early in life will be beneficial, but Pletcher says these data support the AHA recommendation to begin cholesterol tests as early as 20. "I'm a general believer in the tenet that if you want to have an effect on some parameter, you have to measure it and watch it. It provides motivation."


Physicians Avoid Recommending HPV Vaccine in Girls Aged 11 to 12 Years

From Medscape Medical News
Fran Lowry

August 4, 2010 — The majority of pediatricians and family physicians in the United States are offering the human papillomavirus (HPV) vaccine to their older adolescent patients, but fewer are recommending the vaccine to their younger patients (those aged 11 to 12 years) — the age group that is particularly targeted for vaccination by national guidelines — according to a survey reported online August 2 and in the September print issue of Pediatrics.

"A HPV vaccine was licensed in 2006," write Matthew F. Daley, MD, from the University of Colorado School of Medicine and the Kaiser Permanente Institute for Health Research, Denver, and colleagues. "In surveys before vaccine licensure, physicians generally viewed HPV vaccines positively, but some expressed reservations about vaccinating young adolescents. Little is known about current HPV vaccination practices of US physicians."

The aims of this study were to assess HPV-related attitudes and vaccination practices, perceived barriers to vaccination, and factors associated with whether physicians strongly recommended HPV vaccine to 11- to 12-year-old female patients in a sample of US pediatricians and family physicians.

From January to March 2008, the researchers administered a survey through the Internet or by mail to a national network of 429 pediatricians and 419 family physicians recruited from the American Academy of Pediatrics and the American Academy of Family Physicians. Eighty-one percent of pediatricians and 79% of family physicians responded to the survey.

Virtually all pediatricians (98%) and 88% of family physicians reported administering HPV vaccine to female patients in their offices (P < .001). Female family physicians were more likely to give the vaccine than male family physicians (95% vs 83%; P = .001).

The survey also showed regional variation in vaccine administration among family physicians. In the South, 79% reported administering HPV vaccine in their offices, compared with 89% in the Northeast, 95% in the Midwest, and 92% in the West (P = .005). Comparisons of HPV vaccine administration rates by sex and region were not done for pediatricians because only 6 pediatricians reported they did not offer the vaccine.

Fewer respondents strongly recommended HPV vaccination for 11-to 12-year old girls than for older female patients. Among pediatricians, 57% said they recommended the vaccine for that age group, but 90% recommended the vaccine for their 13- to 15-year old patients (P < .001).

Among family physicians, 50% said they recommended the vaccine for 11- to 12-year-old girls, and 86% recommended the vaccine for their 13- 15-year-old patients (P < .001).

The survey also found that vaccine costs and insurance coverage were the main financial barriers to strongly recommending HPV vaccination. Another barrier was reluctance to discuss sexuality with 11- to 12-year-olds (risk ratio [RR], 1.27; 95% confidence interval, 1.07 - 1.51).

Parental concern about HPV vaccination was also a barrier, with 39% of pediatricians and 43% of family physicians reporting that parents of their adolescent patients worried that vaccination against a sexually transmitted infection may encourage earlier or riskier sexual behavior. The survey also found that 22% of pediatricians and 23% of family physicians reported that parents of their 11- to 12-year-old patients were upset that they were offering the vaccine to that age group. Eighteen percent of pediatricians and 29% of family physicians reported that at least one fourth of parents of 11- to 12-year-old patients refused HPV vaccine (P < .01). Common reasons for parent refusals were that the vaccine was too new, the child was too young, and lack of health insurance for HPV vaccination.

"These survey data indicate that there may be substantial challenges to timely initiation and completion of the 3-dose HPV vaccine series," the study authors write.

The possibility that attitudes of network physicians in the survey might differ from those of physicians outside of the network is one limitation of the study. Another is that only family physicians and pediatricians were surveyed. Finally, the study assessed physician-reported behavior but did not observe actual vaccination practices. "It is not known how physicians convey a 'strong vaccination recommendation' to patients and parents, and this may differ among physicians and between pediatricians and family physicians," the authors note.

Because physicians are more likely to recommend the HPV vaccine strongly at older ages, and because parents are more likely to refuse or defer vaccination at younger ages, vaccination may not occur at the age recommended by national guidelines. "It is also likely that proactive, innovative strategies will be needed to achieve high levels of 3-dose HPV vaccination coverage in the United States," the authors write in their conclusion.

"HPV vaccination is our best chance at preventing cervical cancer, so it's reassuring [that] doctors are using it. However, vaccination should ideally begin at 11 years of age, so that young women complete the 3-dose series and are protected," Dr. Daley added in a statement.

Pediatrics. Published online August 2, 2010.

Tuesday, August 10, 2010

Sucralose-Sweetened vs Rice-Based Oral Rehydration Solutions May Be More Palatable

From Medscape Medical News

Laurie Barclay, MD

August 6, 2010 — Sucralose-sweetened oral rehydration solutions may be more palatable than rice-based solutions, according to the results of a prospective, blinded, randomized 3-period, 3-treatment crossover trial reported in the August issue of the Archives of Pediatrics & Adolescent Medicine.

"Acute gastroenteritis accounted for more than 20 million episodes of diarrhea and 1.5 million outpatient visits annually in the United States by children younger than 5 years," write Stephen B. Freedman, MDCM, MSc, FRCPC, from The Hospital for Sick Children, University of Toronto in Ontario, Canada, and colleagues. "Therapy with oral rehydration solutions (ORSs) has reduced the mortality rates in underdeveloped countries, but its effect has been less dramatic in developed regions. Although this may be due to misperceptions regarding the need for extra time and effort to perform oral rehydration therapy, one possible explanation is that ORSs may not be appealing to children owing to their poor palatability."

The goal of this study was to compare the palatability of 3 oral rehydration solutions. The 2 solutions were sucralose sweetened (Pedialyte; Abbott Laboratories, Abbott Park, Illinois; and Pediatric Electrolyte; PendoPharm, Mont-Royal, Quebec, Canada), and 1 solution was rice based (Enfalyte; Mead Johnson Nutritionals, Evansville, Indiana).

At the emergency department of a tertiary care pediatric hospital, the investigators evaluated 66 children aged 5 to 10 years who presented with problems other than in the gastrointestinal tract. During a 15-minute period, the children were permitted to consume as much of each solution as they desired. Each child's taste rating on a 100-mm visual analog scale, where 0 mm was the worst taste and 100 mm was the best taste, was the main study endpoint. Volume consumed, willingness to drink each liquid again, and the most preferred liquid were secondary endpoints.

All participants completed all 3 study periods, with a carryover effect observed for taste scores (P = .03). These scores were significantly different with and without adjustment for the carryover effect (P < .001). Unadjusted taste scores were 65 mm for Pedialyte, 58 mm for Pediatric Electrolyte, and 23 mm for Enfalyte. Although differences in mean volume consumed were not significant (P = .44), the percentage of participants who said they would drink each beverage in the future was significantly different for Enfalyte vs Pediatric Electrolyte (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.11 - 0.46) and for Enfalyte vs Pedialyte (OR, 0.38; 95% CI, 0.25 - 0.57).

The best-tasting solution was identified as Pedialyte by 35 (53%) of 66 children, Pediatric Electrolyte by 26 (39%) of 66 children, and Enfalyte by 5 (8%) of 66 children (P < .001).

The OR of choosing Pedialyte vs Enfalyte was 12.3 (95% CI, 4.9 - 31.0) and vs Pediatric Electrolyte, 0.78 (95% CI, 0.44 - 1.4). Pediatric Electrolyte was preferred to Enfalyte (OR, 15.9; 95% CI, 6.0 - 41.7). No adverse effects were reported.

"Sucralose-sweetened oral rehydration solutions (Pedialyte and Pediatric Electrolyte) were significantly more palatable than was a comparable rice-based solution (Enfalyte)," the study authors write. "...Whether taste has a role in improving clinical outcomes remains unknown. Given the similar content of the solutions evaluated and that the sucralose solutions are less expensive, perhaps they should be recommended as initial therapy."

Limitations of this study include evaluation only of school-aged children without gastrointestinal tract complaints.

In an accompanying commentary, Peter Cummings, MD, MPH, from the University of Washington in Seattle, discusses the role of carryover bias as it affects this study.

"Despite the evidence of carryover bias reported by Freedman et al, their data still support their main findings," Dr. Cummings writes. "I doubt that carryover bias alone can explain the large taste score differences in their study; 2 sucralose solutions had tolerable flavor, while a rice-based solution tasted like dirt. But carryover bias could make it hard to interpret smaller taste score differences. Future studies of taste, and possibly other subjective outcomes, might be better conducted as parallel-group randomized studies."

The Paediatric Consultants Partnership's Grant for Creative Professional Activity supported this study. PendoPharm, a division of Pharmascience Inc, provided the Pediatric Electrolyte used in this study. The Hospital for Sick Children's Division of Nutrition Services provided the Enfalyte used in this study. The study authors and Dr. Cummings have disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. 2010;164:696-702, 703-705. Abstract