Sunday, February 28, 2010

CDC Advisory Panel Recommends Use of Newly Approved Pneumococcal Vaccine

From Medscape Medical News
Kathleen Louden

February 25, 2010 — The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) voted yesterday to recommend the use of a 13-valent pneumococcal conjugate vaccine (PCV13), which provides broader protection for young children against pneumococcal diseases.

The vote, at a meeting in Atlanta, Georgia, came after an announcement that the US Food and Drug Administration had approved the vaccine, marketed as Prevnar 13. The agency approved the vaccine for active immunization of infants and children aged 6 weeks through 5 years against Streptococcus pneumonia–caused invasive pneumococcal diseases, such as pneumonia and meningitis, and against otitis media.

Manufactured by Pfizer subsidiary Wyeth Pharmaceuticals of Collegeville, Pennsylvania, Prevnar 13 will succeed Prevnar, a 7-valent PCV (PCV7). The new version of the vaccine protects against 6 more serotypes of S pneumonia than the original version. Unlike Prevnar, Prevnar 13 includes serotype 19A, which is the most common serotype causing invasive pneumococcal infections in children, according to a study published online February 22 in Pediatrics. In addition to serotype 19A, Prevnar 13 also contains conjugated antigens representing serotypes 1, 3, 4, 5, 6A and B, 7F, 9V, 14, 18C, 19F, and 23F.

"PCV13 will be replacing PCV7," said Jeanne Santoli, MD, MPH, from the Vaccine Supply and Assurance Branch of the CDC's National Center for HIV, Hepatitis, STD, and TB Prevention (NCIRD), after the vote.


The advisory committee approved 5 recommendations that the pneumococcal vaccines work group proposed. The recommendations, presented by Pekka Nuorti, MD, DSc, an epidemiologist with the NCIRD, were as follows:

Unvaccinated infants and children: PCV13 is recommended for all children aged 2 through 59 months. In the United States, infants receive a "3 plus 1" dosing schedule, with doses at 2, 4, and 6 months and a booster dose at 12 to 15 months. Older children will follow the schedule currently recommended for PCV7.
Children incompletely vaccinated with PCV7: Children aged 24 to 59 months who received 1 or more doses of PCV7 should complete their vaccine series with PCV13. The age may be extended to 71 months for children with an underlying medical condition, such as sickle cell disease, HIV, or asplenia.
Children completely vaccinated with PCV7: Those children 14 to 59 months of age who have received all 4 doses of PCV7 should receive a single supplemental dose of PCV13. The age may be extended to 71 months for children with an underlying medical condition.
High-risk children aged 6 years and older: This permissive recommendation for an off-label use states: "Vaccination with a single dose of PCV13 may be appropriate for children 6 through 18 years of age who are at increased risk for pneumococcal disease." Healthy older children should not receive the vaccine.
Additional vaccine for children with underlying medical conditions: Children aged 2 years and older who are at increased risk for invasive pneumococcal disease should receive a 23-valent pneumococcal polysaccharide vaccine after vaccination with PCV13.
The final recommendation is new since the draft recommendations that ACIP made in October 2009, according to Dr. Nuorti.

In discussing the third recommendation, Dr. Nuorti said a supplemental (formerly called catch-up) dose of PCV13 "appears safe, has been shown to elicit antibodies against 6 additional serotypes in children older than 12 months, and has been found to be cost saving."


The manufacturer expects to start shipping PCV13 the week of March 15 to private buyers. Each dose will cost $108, a company representative said at the meeting.

Once providers have PCV13 in their offices, they should give the new version, not PCV7, to unvaccinated or incompletely vaccinated children, Dr. Santoli stated.

"Pfizer is offering credit for returned unused PCV7" from private stock, she said. Providers with stock through the publicly funded Vaccines for Children Program should use up their PCV7 supplies, she added.

The ACIP recommendations will become official CDC recommendations once the CDC director and the US secretary of health and human services accept them.

Meeting of the Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention, Atlanta, Georgia. Presented February 24, 2010.

Lactose Intolerance Management Guidelines Issued by NIH Panel

From Medscape Medical News
Emma Hitt, PhD

February 25, 2010 — Many lactose-intolerant individuals can tolerate up to 24 g lactose daily (the amount in 2 cups of milk) if it is ingested throughout the day, according to a National Institutes of Health (NIH) Consensus Development Conference Statement on Lactose Intolerance and Health.

"A lot of people who think they have lactose intolerance don't," noted panel and conference chairperson Frederick J. Suchy, MD, chief of pediatric hepatology at Mount Sinai School of Medicine, New York City, in a news release. "They may have other conditions, or they may just need to consume smaller amounts of dairy products."

The 14-member consensus development panel was convened earlier this week by the NIH's Office of Medical Applications of Research for 3 days. The panel addressed several issues regarding lactose intolerance, including the prevalence, health outcomes, amount of lactose likely to be tolerable, and strategies for managing lactose-intolerant individuals.

"The prevalence of lactose intolerance in the United States cannot be estimated," according to a draft statement from the conference.

A systematic review of all studies on lactose intolerance published in English from 1967 to November 2009 was conducted. Despite the identification of 54 articles, including 15 studies in the United States involving 4817 participants, evidence was insufficient to accurately assess prevalence in the US population. However, the authors did confirm that race and age differences exist in the prevalence of lactose intolerance.

The panelists also concluded that children with low lactose intake have worse bone outcomes compared with children assigned to receive supplemental dairy interventions.

"Research is needed to evaluate lactose intolerance prevalence, bone outcomes in adults in association with lactose intake, genetic predisposition, lactose malabsorption, and intolerance," the panelists say.

According to the draft statement, healthcare providers should offer "personalized, culturally-sensitive management strategies to lactose intolerant individuals to ensure that they ingest calcium, vitamin D, and other nutrients found in dairy products." An overall nutritional eating plan should be emphasized, focusing on nutrients potentially reduced by a dairy-free diet while maintaining appropriate caloric intake. Patients can be referred to for nutritional guidance. Lactose-reduced milk may be an effective strategy for preventing symptoms.

"Whether [patients] are truly lactose intolerant or not, it is important that they meet recommended intakes of calcium and other essential nutrients," Dr. Suchy pointed out.

A draft statement from the conference is available on the NIH Web site.

A summary of the systematic evidence review is available on the Agency for Healthcare Research and Quality Web site.

The full report, "Lactose Intolerance and Health," is also available on the agency's Web site.

Tuesday, February 23, 2010

Best Evidence Review: Ibuprofen or Acetaminophen With Codeine -- Which Is Better for Acute Pain in Children?

From Medscape Family Medicine > Best Evidence Review
Charles P. Vega, MD

Clinical Pearls
Forearm fracture is most common among children between the ages of 10 and 14, and there is evidence that the prevalence of pediatric forearm fracture is increasing.
Many children do not receive adequate analgesia in the acute care setting.
Adverse events related to analgesics are common in children and frequently are preventable.
The current study found that ibuprofen and acetaminophen with codeine provide similar levels of effective acute analgesia in children with injury to an extremity.
Adverse events were rare with both ibuprofen and acetaminophen with codeine in the current study.
The precise analgesic regimen for children is not as critical as adherence to a protocol of regular assessment and treatment of pain, both in the clinical setting and at home.

Review Found No Link Between Pediatric Abdominal Pain and H pylori Infection

From Medscape Medical News
Laurie Barclay, MD

February 19, 2010 — A systematic review found no link between pediatric abdominal pain and Helicobacter pylori infection, as reported online in the February 15 issue of Pediatrics.

"Recurrent abdominal pain (RAP) and other gastrointestinal (GI) symptoms are common complaints among children," write Leo A. A. Spee, MD, from Erasmus Medical Center–University Medical Center in Rotterdam, the Netherlands, and colleagues. "The role of [H pylori] in the cause of these complaints remains controversial. Nevertheless, there is an increasing pressure on primary care clinicians to screen for H pylori infection in symptomatic children. "

The reviewers searched Medline and Embase databases up to July 2009 for studies examining the association between H pylori and GI symptoms in children through 18 years of age. Studies reporting on abdominal pain without any further definition, and therefore not fulfilling Apley's criteria, were grouped as unspecified abdominal pain (UAP). Using a standardized list of criteria, the reviewers scored methodologic quality, and they also calculated and pooled crude odds ratios (ORs).

Of 38 studies meeting inclusion criteria, 23 were case-control studies, 14 were cross-sectional studies, and there was 1 prospective cohort study, with low methodologic quality overall.

For the association between RAP and H pylori infection in children, pooled ORs were 1.21 (95% confidence interval [CI], 0.82 - 1.78) in 12 case-control studies and 1.00 (95% CI, 0.76 - 1.31) in 7 cross-sectional studies. Meta-analysis of the association between UAP and H pylori infection yielded a pooled OR of 2.87 (95% CI, 1.62 - 5.09) in 6 hospital-based studies vs 0.99 (95% CI, 0.46 - 2.11) in 5 population-based studies. There was a statistically significant positive association of epigastric pain with H pylori infection in 2 of 3 studies reporting this outcome.

"We found no association between RAP and H. pylori infection in children and conflicting evidence for an association between epigastric pain and H. pylori infection," the study authors write. "We found evidence for an association between UAP but could not confirm this finding in children seen in primary care."

Limitations of this study include the possibility that some published and unpublished studies may have been missed, and that some information collected by the reviewers may not have been provided in the journal article. Overall methodologic quality was poor, and there was a large statistical and clinical heterogeneity between studies.

"There is no association between RAP and H. pylori infection in children; therefore, screening children with this classical symptom is not warranted, regardless of setting and geographic location," the study authors conclude. "Furthermore, all other GI symptoms investigated in primary care–based or population-based studies, except for epigastric pain, were not associated with H. pylori infection in children; therefore, we postulate that as long as no typical clinical picture of a child with H. pylori infection has been established and treatment effectiveness is not known, referral to a subspecialist for this matter is not recommended."

The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online February 15, 2010.

Monday, February 22, 2010

Assessment and Management of Hypertension in Children and Adolescents

From Nature Reviews Cardiology

Brian W. McCrindle, MD, MPH

The epidemic of overweight and obesity in youth is increasing the prevalence of prehypertension and hypertension among children and adolescents.
The younger the child is at presentation and the more severe the blood pressure abnormality, the more likely a secondary cause of hypertension is to be present. Measurement of blood pressure in children requires adaptation to the age and size of the child.
Interpretation must be related to normative values specific for age, sex, and height.
Evaluation is primarily aimed at identifying secondary causes of hypertension, associated comorbidities, additional risk factors, and evidence of target-organ damage.
Ambulatory blood pressure monitoring is emerging as a useful tool for evaluation of some patients, particularly for those with suspected 'white coat' hypertension.

Management of prehypertension and hypertension is directed at the underlying cause, exacerbating factors, and the magnitude of the blood pressure abnormality.
Healthy behavioral changes are a primary management tool for treating hypertension and, more particularly, prehypertension and for addressing other cardiovascular risk factors, such as obesity.
Pharmacological management is reserved for patients with hypertension who do not respond to behavioral changes, have additional cardiovascular risk factors or diabetes, are symptomatic, or have developed target-organ damage.

Hypertension is a well-recognized cardiovascular risk factor in adults, contributing to morbidity and mortality from myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, retinopathy, and end-stage renal disease.
No study has been of sufficient duration to determine whether hypertension identified in youth is related to cardiovascular disease in adulthood.
In addition, manifest atherosclerotic cardiovascular disease is extremely rare in childhood. nonetheless, evidence to support an association between elevated blood pressure and atherosclerosis in youth is available from pathology studies and studies of noninvasive markers of atherosclerosis.

Blood pressure assessment in youth, either by direct measurement (Bogalusa Heart Study)[1] or by inference (Pathobiological Determinants of Atherosclerosis in Youth Study),[2,3] is independently correlated with the percentage of intimal surface in the coronary arteries and aorta that are affected by early atherosclerotic lesions, including fatty streaks and fibrous plaques.
In addition, clustering of elevated blood pressure and other cardiovascular risk factors, as seen with the epidemic of the metabolic syndrome and obesity, is associated with an exponential increase in atherosclerotic vascular involvement. These correlations are also evident when noninvasive measures of vascular involvement are used in children and young adults.

ultrasonography has shown that increased blood pressure in children and adolescents is associated with endothelial dysfunction in systemic arteries, increased thickness of the arterial intima-media complex, impaired arterial compliance and distensibility, and increased levels of inflammatory markers.

Research using ultrafast CT has shown a positive correlation between blood pressure and coronary artery calcification in adolescents and young adults. These studies provide consistent and compelling evidence that the atherosclerotic process begins in youth, and is accelerated by increased blood pressure.

In addition to accelerated atherosclerosis, there is also evidence of target-organ damage—primarily left ventricular hypertrophy (LVH). LVH has been reported in about one third of children and adolescents with mild, untreated hypertension and in a greater proportion of those with persistent hypertension.[4,8,9] LVH can be concentric or eccentric, with concentric being associated with a higher risk of cardiovascular outcomes.[8]

The risk of LVH increases with the severity of hypertension in adolescents, but the odds of LVH are also increased in those with masked and milder hypertension (but not with 'white coat' hypertension), compared with normotensive adolescents.[10]

Lande et al. showed that, after matching for BMI, children with 'white coat' hypertension had greater left ventricular mass index than normotensive controls, but less than patients with persistent hypertension (26% with LVH).[11]

Studies have also shown that the presence of concomitant obesity further increases the prevalence of LVH in youths with hypertension.[9] In addition, LVH has been shown to be correlated with increased carotid intima-media thickness—an early marker for atherosclerosis—and increasing adiposity in children and adolescents with hypertension.[4] The working group of the National High Blood Pressure Education Program on Children and Adolescents recommended that the presence of LVH be used to influence therapeutic decisions in patients with hypertension.[12] In this Review, I provide a general overview of hypertension, highlighting evaluation and management aspects of this condition that are specific to infants, children, and adolescents.

Diagnosis of Early-Onset Schizophrenia

From MedscapeCME Psychiatry & Mental Health

Linmarie Sikich, MD 02/10/2010

Although schizophrenia is generally thought of as an adult disorder, it can occur in children and adolescents.
Indeed, the majority of cases of schizophrenia emerge when patients are between 15 and 25 years of age.
Early-onset schizophrenia appears to have a worse prognosis than schizophrenia emerging during adult years.
Although families often seek medical advice pertaining to behavioral symptoms of the disorder or its prodrome, clinicians frequently fail to recognize the illness and misdiagnose it as a more prevalent childhood disorder such as attention-deficit/hyperactivity disorder or oppositional defiant disorder because of the nonspecificity of early symptoms and developmental differences in reporting psychotic phenomena.
In addition, differential diagnosis often depends on a longitudinal perspective of the disorder that may be lacking during early stages of treatment.
These difficulties often lead to prolonged periods without treatment or with inadequate treatment.

In addition, there may be cases in which clinicians suspect schizophrenia but are reluctant to diagnose it because of fears about stigmatizing the child or demoralizing the child and family.
However, affected individuals and their families often feel frustrated because the child is not responding to the treatments provided. Ineffective treatments may lead to hopelessness and problems with long-term treatment adherence.

Delays in effective treatment appear to lead to worse prognosis, with higher rates of treatment resistance and greater functional impairment.
Because reductions in the duration of untreated psychosis in adults with schizophrenia have been repeatedly demonstrated to improve outcomes, enhancing the ability of clinicians to recognize and diagnose early-onset schizophrenia spectrum disorders is expected to lead to better outcomes, improve the quality of life of affected individuals, and reduce the tremendous societal and personal costs associated with treatment-resistant illness.

This article will review the diagnostic criteria, prevalence, and typical course of early-onset schizophrenia spectrum disorders in children and adolescents and discuss typical developmental variations in the presentation of symptoms and specific approaches to eliciting symptoms in children and adolescents. The suggested workup, differential diagnosis, and frequent comorbidities will be reviewed. Vignettes will illustrate key points.

Diagnostic Criteria for Early-Onset Schizophrenia Spectrum Disorders
Schizophrenia and schizoaffective disorder are diagnosed using the same Diagnostic and Statistical Manual of Mental Disorders -- Fourth Edition (DSM-IV)[7] criteria in pediatric and adult populations.
These criteria require the presence of 2 or more "characteristic symptoms" including:

Positive psychotic symptoms, such as
Disorganized speech;
Grossly disorganized behavior or catatonia; or
Negative symptoms. These reflect the absence of behaviors that are present in healthy individuals and include
Poverty of speech;
Limited thought content;
Failure to make choices (avolition);
Reduced or absent facial expressions (flat affect); or
Poor attention to activities of daily living such as personal hygiene.

In addition, the diagnostic process must confirm social and occupational dysfunction and it must exclude mood disorders, substance abuse, and general medical conditions. If a primary diagnosis of autism spectrum disorder exists, the diagnosis of schizophrenia must include clear hallucinations or delusions.
Symptoms must persist for 6 months in DSM-IV criteria or 1 month in International Statistical Classification of Diseases and Related Health Problems -- Tenth Edition (ICD-10) criteria. However, both classification systems allow nonspecific prodromal and residual symptoms to be included in the duration of symptoms.
Schizophrenia also includes persistent neurocognitive impairments in executive function (particularly working memory, cognitive flexibility, and problem-solving), memory, and general cognition that are likely to be given greater prominence in DSM-V.[8-10]

Schizoaffective disorder is distinguished from schizophrenia by the presence of significant affective symptoms for a significant proportion of the time.
Many clinicians only include symptoms of mania, although depression is highly prevalent in schizophrenia.
The diagnostic criteria for depression and bipolar disorder are also consistent between pediatric and adult populations.
The criteria for obsessive-compulsive disorder (OCD) are largely the same in adults and children, although the obsessions and compulsions are not required to be egodystonic in youth, which may increase confusion with schizophrenia spectrum disorders.

In addition to these well-established diagnostic criteria, there is increasing awareness that some children suffer from severe psychiatric disturbances that often involve odd language and social behavior, distortions of reality in response to specific environmental events and unpredictable behaviors, but do not clearly meet criteria for diagnosis of schizophrenia.

Such children have been proposed to have a unique disorder that has been termed "Multidimensionally Impaired Disorder"or "Multiple Complex Developmental Disorder."
Both overlap with severe mood dysregulation, except that severe mood dysregulation specifically excludes any psychotic symptoms.
There have been limited follow-up studies of such children and these have yielded somewhat discrepant results. A National Institutes of Mental Health group led by Judith Rapoport evaluated 26 pediatric patients (mean age,11.6 ± 2.7 years) and found that half of subjects followed up at 2-8 years were diagnosed with psychosis NOS, 3%-12% had schizoaffective disorder, 38% had bipolar disorder, 12% had major depression, and 15% were symptom-free.[15] A European group found that 78% of children with multiple complex developmental disorder examined as adolescents had symptoms that appeared prodromal for schizophrenia although none had yet been diagnosed with a schizophrenia spectrum disorder.

Longer Needle May Be Preferred for HBV Vaccination of Obese Teens

From MedscapeCME Clinical Briefs
Laurie Barclay, MD

February 12, 2010 — Use of a longer needle results in significantly higher titers in response to hepatitis B virus (HBV) vaccine among obese adolescents, according to the results of a randomized study reported online in the February 8 issue of Pediatrics.

"Obese youth achieve lower titers than average-weight peers in response to hepatitis B vaccine when a 1-inch needle is used," write Amy B. Middleman, MD, MSEd, MPH, from Baylor College of Medicine in Houston, Texas, and colleagues.

The goal of the study was to evaluate whether using a longer (1.5-inch) vs a standard (1-inch) needle to penetrate the thicker deltoid fat pad among obese youth who had not previously received the HBV vaccine would achieve higher antibody titers after immunization against HBV. The investigators randomly assigned 65 obese adolescents from a large metropolitan area to be immunized with HBV vaccine using either a 1-inch or a 1.5-inch needle. Analyzable data were available for 10 adolescents in the 1-inch needle group and for 14 in the 1.5-inch needle group.

Compared with obese adolescents immunized with a 1-inch needle, those who were immunized with a 1.5-inch needle had significantly higher antibody titers to hepatitis B surface antigen (median titers 189.8 mIU/mL with the 1-inch needle; 345.4 mIU/mL with the 1.5-inch needle; P = .03).

"This finding supports the hypothesis that needle length accounts for a significant portion of the discrepancy in immune response to HBV vaccine that is seen among those with obesity," the study authors write.

Limitations of this study include sample size smaller than planned with loss of participants to follow-up, few male participants, limited ability to enroll patients who had not yet received HBV vaccine, and limited variability in race and ethnicity (most participants were Hispanic).

"As we continue to experience high rates of obesity in the United States and throughout the world, additional evidence-based research on optimizing the effective delivery of immunizations to adolescents and young adults will be critical," the study authors conclude. "Following updated needle length recommendations will be a first step toward improving the health of our youth and young adults by preventing vaccine-preventable diseases."

Pediatrics. Published online February 8, 2010.

Clinical Context

Previous evidence suggests that obese adolescents and adults tend to have lower antibody titers than their nonobese peers when immunized with HBV or other vaccines. Given the increasing number of vaccines targeting adolescents, and the rising rates of obesity in this population, this observation may be of some concern.

The reasons underlying the disparity in vaccine immune response based on body mass index are still unknown. One possibility is that use of the standard needle length does not penetrate the deltoid fat pad and into the muscle of obese adolescents and adults. The less abundant blood supply in adipose tissue may delay vaccine antigen presentation to the B and T cells involved in immune response.

Sunday, February 21, 2010

Secondhand Smoke Exposure Linked to Sleep Problems in Children With Asthma CME

From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

January 26, 2010 — Exposure to secondhand smoke (SHS) is associated with increased sleep problems among children with asthma, according to the results of a study reported online January 18 and to be published in the February print issue of Pediatrics.

"Adult and adolescent smokers report difficulties with sleep," write Kimberly Yolton, PhD, from Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, and colleagues. "Young children who are exposed to tobacco smoke have poorer sleep quality. Children with asthma report more sleep problems and are more sensitive to the respiratory effects of tobacco smoke."

The goal of this study was to analyze the association between exposure to SHS and child sleep patterns among a group of 219 children with asthma who were enrolled in an asthma intervention trial and who had regular exposure to tobacco smoke at home. SHS exposure was measured with serum cotinine levels, and the Children's Sleep Habits Questionnaire was used to evaluate sleep patterns based on parental reports.

Statistical analyses allowed adjustment for covariates of age, sex, race, maternal marital status, education, income, prenatal tobacco exposure, maternal depression, Home Observation for Measurement of the Environment total score, household density, asthma severity, and use of asthma medications.

SHS exposure was associated with longer sleep-onset delay (P = .004), sleep-disordered breathing (P = .02), parasomnias (P = .002), daytime sleepiness (P = .022), and overall sleep disturbance (P = .0002).

"We conclude that exposure to SHS is associated with increased sleep problems among children with asthma," the study authors write. "As SHS exposure increased, parents reported that their children had longer delays in sleep onset, more-frequent parasomnias and sleep-disordered breathing, increased daytime sleepiness, and greater overall sleep disturbance."

Limitations of this study include lack of generalizability to children without asthma; wide variance of the degree of SHS exposure; sleep data based only on parental reports; and lack of information on prematurity, which could be an important contributor to sleep problems.

"We report significant associations between SHS exposure, as measured with a biological marker (serum cotinine levels), and sleep problems in children with asthma," the study authors conclude. "Reduction in SHS exposure is an area with the potential for significant impact in the pediatric population."

The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online January 18, 2010. Abstract

Clinical Context

Sleep problems are very common during childhood, with a prevalence exceeding 25%. Children with asthma experience an even higher prevalence of sleep problems during childhood, with up to 60% of these children reporting sleep problems. Fortunately, appropriate treatment of asthma can improve sleep efficiency.

Sleep problems in childhood are more than just an annoyance. Inadequate sleep in this population is associated with poor school performance, somatic complaints, and behavioral problems. Children with sleep problems are also at higher risk for obesity.

Smoking has been associated with sleep problems, and there is some suggestion that SHS can negatively affect sleep in children. The current study tests this hypothesis among children with asthma.

Study Highlights

•Study participants were between the ages of 6 and 12 years and had received treatment of physician-diagnosed asthma in the past year. All participants were exposed to at least 5 cigarettes' worth of SHS per day at home.
•Children with other respiratory tract diseases and heart disease were excluded from study participation.
•Researchers collected detailed information regarding the volume and location of SHS exposure. Children provided baseline serum cotinine levels to corroborate SHS exposure.
•Sleep patterns were measured with the Children's Sleep Habits Questionnaire, which measures sleep quality within the previous 2 weeks.
•The main outcome of the study was the interaction between SHS and sleep quality. This result was adjusted to account for asthma severity, demographic data, and social factors.
•219 children with a mean age of 9.4 years provided data for study analysis. 61% of participants were boys, and 56% were black.
•The median amount of daily cigarette exposure at home was 13 cigarettes.
•The mean sleep time was 9.6 hours per night, and 93% of children had a sleep disturbance score that was considered clinically relevant.
•On multivariate analysis, higher levels of SHS exposure were associated with increased rates of sleep-onset delay, parasomnias, daytime sleepiness, sleep-disordered breathing, and total sleep disturbance scales.
•SHS had no significant overall effect on sleep duration, sleep anxiety, or night wakings.
•Boys were particularly sensitive to the effects of SHS in increasing sleep anxiety, whereas SHS promoted higher levels of sleep-onset delay among girls.

Clinical Implications

•More than one quarter of all children have sleep problems, and the prevalence of sleep problems can increase to 60% among children with asthma. The treatment of asthma can reduce sleep problems. Inadequate sleep in children is associated with poor school performance, somatic complaints, obesity, and behavioral problems.
•The current study demonstrates that SHS can promote increased rates of sleep-onset delay, parasomnias, daytime sleepiness, sleep-disordered breathing, and total sleep disturbance among children with asthma. SHS had no significant overall effect on sleep duration, sleep anxiety, or night wakings.

Saturday, February 20, 2010

Pediatric Respiratory Emergencies: An Expert Interview with Karen Santucci,

From Medscape Medical News
Daniel Keller, PhD

February 18, 2010 —
In this interview, Medscape Emergency Medicine discussed the topic with Karen Santucci, MD. Dr. Santucci is medical director and section chief of pediatric emergency medicine at Yale-New Haven Children's Hospital and is associate professor of pediatrics at the Yale University School of Medicine in New Haven, Connecticut.

Medscape: What do you look for first when a pediatric patient presents to you in respiratory distress?

Dr. Santucci: The first thing I do is a very careful physical exam. Oddly enough, sometimes you can do your best physical starting outside the exam room. Pediatric emergency medicine is a little bit different from adult emergency medicine, in that there's a huge anxiety component, particularly in older infants and younger toddlers. Sometimes I pause outside the exam room for 5 or 6 seconds just to get a look at the status of the child in terms of increased work of breathing, because once you walk into the room, you introduce a new variable in terms of frightening the kid to death.

You can get a good sense of their baseline respiratory rate and what their affect looks like. Are they frightened because they have a partial airway obstruction or because they are really having a lot of difficulty breathing, or are they frightened because you just walked in the room and they associate any of us in healthcare with an immunization, a needle? There's a huge fear factor.

So standing outside the room, getting a sense of how they're interacting in their comfort zone with their family member and whether or not they're manifesting any head bobbing, which would be movement of their head with every respiration, which would be an indication of increased work of breathing and accessory muscle use, and if they might even have nasal flaring, which is also evidence of severe respiratory distress. The physical exam is certainly critical, but I think it starts outside the exam room.

And then doing a good lung exam and observing how they're moving air, using all your senses in terms of whether you hear stridor. Is there evidence of congestion? Is there audible wheezing? Feeling them in terms of their capillary refill, tapping on their nail bed, seeing how long it takes to refill, feeling their distal extremities, whether or not they're warm and well perfused or cool, because children are at increased risk of becoming dehydrated with respiratory distress because of insensible losses. Certainly, if they're manifesting with a fever, they'll also have increased insensible losses, and they're more at increased risk of dehydration.

Medscape: Once you've gone through the physical exam findings, are there any questions or particular areas you focus on when taking the history of a pediatric patient?

Dr. Santucci: One of the major things that tends to be missed in pediatrics is asking about potential risk for a foreign-body exposure, and I probably spend half of the talk on that because it is so pediatric-specific in terms of occult exposure to a foreign body that could have been missed.

Medscape: Is there a risk of clinicians becoming complacent and missing the less common causes of obstruction?

Dr. Santucci: A lot of what we see in terms of respiratory distress is associated with more common things; for example, at this time of year — January, February — we're seeing a lot of [respiratory syncytial virus]–related bronchiolitis, particularly in children less than 2 years of age. What I would caution the clinician about is tending to think, it's bronchiolitis season, so if an infant or toddler is presenting with respiratory distress, it's probably bronchiolitis. I think maintaining the possibility of it being something else is so critically important.

Increased work of breathing and some congestion, and a little bit of a wheeze . . . could also be something like an inborn error of metabolism, and the child is actually presenting with what appears to be increased work of breathing because they're developing increased respiratory drive to compensate for a metabolic acidosis.

In one case we had, what was felt to be bronchiolitis in a 10-month old was actually a salicylate overdose secondary to a mother giving increased amounts of Maalox Extra Strength for gastroesophageal reflux. We discovered that this baby had an increased anion gap . . . and, had we not erred on the side of sending a tox screen and had not this been recognized in real time, this child would have died. . . . Ask about over-the-counter meds and ointments and preparations because they can kill an individual — so [that is] very significant information.

One of the hugest points that I've learned over the years is maintaining a differential diagnosis when the points don't seem to fit, delving and asking some questions, maybe sending a few extra labs to err on the side of being overly cautious and not just accepting things at face value. Even if you can't figure things out in the emergency department, sharing that you're really perplexed by a patient with the accepting team upstairs when you're admitting a patient and making sure that they follow up on the lab tests as quickly as possible and initiate a pretty comprehensive work-up can absolutely be life saving.

Medscape: What are some of the tools that physicians can use to work through and manage respiratory distress in children?

Dr. Santucci: One specific case was a case of a 4-year-old girl presenting in the winter with some stridor, and she had some tripodding, which means she was leaning forward because she was trying to maximize airflow through the upper airway, and she was febrile to 104 degrees. This was a little girl who presented with all the classic signs and symptoms of epiglottitis. Even at a major tertiary-care center, there were specialists who just didn't believe in epiglottitis any more. Ever since we've introduced Haemophilus influenzae type B vaccination, and this has become routine, we have reduced the incidence of epiglottitis so immensely that many people in healthcare don't believe that it exists anymore.

The [attending ENT] was able to successfully intubate her in the operating room, but she clearly had epiglottitis and a near-complete airway obstruction, because the epiglottis was so inflamed and swollen, so edematous. The only way they were able to secure her airway on direct laryngoscopy was to squeeze her thorax and create a small air bubble. This could be a life-saving technique if you can't get the child to the operating room, to squeeze the chest. While you're doing direct laryngoscopy, there can be an air bubble, which will delineate where to pass the endotracheal tube.

Medscape: Besides H influenzae type B, are there other organisms that can cause epiglottitis?

Dr. Santucci: We almost always attribute it to H influenzae type B, but there are other types of bacteria — Staphylococcus, Streptococcus, and other serotypes of H influenzae — that can cause epiglottitis. Quite amazingly, there are other etiologies for epiglottitis — inhalational if someone is inhaling different types of illicit drugs. We've had a couple of cases associated with cold weather where people will take a gulp of some hot chocolate while they're outside, and this thermal injury to the epiglottis will cause inflammation of the epiglottis.

So epiglottitis is still out there. We still need to maintain an index of suspicion for this, just like with foreign bodies. If you don't think about it, you're going to miss it, and someone's going to die.

Have an index of suspicion for things like foreign bodies, and what kids are doing. They like to put stuff in their mouths, and so that's a huge risk factor for morbidity and mortality if it's not recognized early.

Medscape: Can a child's activities before coming to the emergency department raise your suspicion of a foreign body?

Dr. Santucci: When you have a really sick kid, a lot of people mobilize, and they want to be at the bedside, but one thing that I've learned over the last couple of decades is that having a person break off from the bedside to talk to the family . . . it can be life-saving just to take a moment to go back and do a really thorough history.

Medscape: To wrap things up, can you give me a couple of bullet points that a physician should keep in mind when seeing a child in respiratory distress?

Dr. Santucci: An increased respiratory rate is not always a respiratory problem, so remember that tachypnea is not always a respiratory etiology and that sometimes that increase in respiratory rate is because of a compensatory mechanism for a metabolic problem. Propionic acidemia [propionyl-CoA carboxylase deficiency] is one example, and another would be diabetic ketoacidosis.
Another thing is to remember the developmental status of children, particularly older infants and toddlers, and that whole foreign-body spectrum.

With regard to increased respiratory rate and increased work of breathing, when someone is presenting with acute anaphylaxis and severe allergic reaction, all the studies support getting epinephrine in within the first 30 minutes — it can absolutely save a life.
If you delay that intramuscular injection of epinephrine, the cascade has already taken place in terms of what's going on chemically, and you may have irreversible anaphylaxis. If you're thinking about epinephrine, it would be better to give the epinephrine than to delay it.

We do not give the epinephrine intravenously. We give it intramuscularly. It's going to be absorbed very nicely from an [intramuscular] route, and it's extremely safe to give it intramuscularly.

Even in adults, giving intramuscular epinephrine is really quite safe. Anaphylaxis absolutely affects the heart as well, and if you don't treat the anaphylaxis, someone might actually develop an acute myocardial infarct because of the anaphylaxis and the strain on the myocardium. So when you weigh all the pros and cons, you're better off erring on the side of giving the epinephrine intramuscularly. That's a huge critical life-saving point.

Friday, February 19, 2010

More Than 1,500 Affected in NY, NJ Mumps Outbreak

From Reuters Health Information

By Julie Steenhuysen

CHICAGO (Reuters) Feb 11 - An outbreak of mumps that started in a summer camp last June has sickened more than 1,500 people in New York and New Jersey, state and federal health officials said on Thursday.

The outbreak is the biggest in the United States since 2006, when more than 6,000 people became infected, the U.S. Centers for Disease Control and Prevention said in its weekly report on death and disease.

School-age children in orthodox Jewish communities in New York have been hard hit. Officials said the group had high vaccination rates, but some had not been vaccinated or had only received one dose of the mumps vaccine.

The New York City Department of Health this week urged young Jewish adults to get vaccinated unless they knew they had been fully vaccinated in the past.

"Mumps can lead to serious complications in people who are not vaccinated, especially adults," said Dr. Jane Zucker, assistant commissioner for immunization.

Widespread vaccination with the measles, mumps and rubella vaccine vastly cut the number of U.S. mumps cases to fewer than 500 in the early 2000s.

But concerns that the vaccine could cause autism, based on a discredited study that was retracted this month, prompted some parents not to protect their children.

Mumps made a resurgence in parts of Europe last year with outbreaks in Britain, the Balkans and Moldova.

The current outbreak appears to have started with an 11-year-old boy who returned from a trip to Britain in June and then attended a summer camp where he infected others. The illness spread as campers returned home.

As of January 29, 1,521 cases had been reported, almost two thirds among people aged 7 to 18. Nineteen people needed hospitalization, but none had died. Three quarters of those infected were male.

About 88% of those who reported their vaccination status had received at least one dose of vaccine, and three quarters of those infected had been given two doses.

The mumps virus can mutate, so people who have had only one or even two doses of vaccine remain vulnerable.

Brain Care 101

Jan 11, 2008

It is Not Only Cars That Deserve Good Maintenance: Brain Care 101
By: Alvaro Fernandez

Last week, the US Car Care Council released a list of tips on how to take care of your car and “save big money at the pump in 2008.”

You may not have paid much attention to this announcement. Yes, it’s important to save gas these days; but, it’s not big news that good maintenance habits will improve the performance of a car, and extend its life.

If we can all agree on the importance of maintaining our cars that get us around town, what about maintaining our brains sitting behind the wheel?

A spate of recent news coverage on brain fitness and “brain training” has missed an important constituency: younger people.
Recent advancements in brain science have as tremendous implications for teenagers and adults of all ages as they do for seniors.

In a recent conversation with neuroscientist Yaakov Stern of Columbia University, he related how surprised he was when, years ago, a reporter from Seventeen magazine requested an interview.
The reporter told Dr. Stern that he wanted to write an article to motivate kids to stay in school and not to drop out, in order to start building their Cognitive Reserve early and age more gracefully.

What is the Cognitive Reserve?

Emerging research since the 90s from the past decade shows that individuals who lead mentally stimulating lives, through their education, their jobs, and also their hobbies, build a “Cognitive Reserve” in their brains.
Only a few weeks ago another study reinforced the value of intellectualy demanding jobs.

Stimulating the brain can literally generate new neurons and strengthen their connections which results in better brain performance and in having a lower risk of developing Alzheimer’s symptoms.
Studies suggest that people who exercise their mental muscles throughout their lives have a 35-40% less risk of manifesting Alzheimer’s.

As astounding as these insights may be, most Americans still devote more time to changing the oil, taking a car to a mechanic, or washing it, than thinking about how to maintain, if not improve, their brain performance.

Further, better brain scanning techniques like fMRI (glossary) are allowing scientists to investigate healthy live brains for the first time in history.
Two of the most important findings from this research are that our brains are plastic (meaning they not only create new neurons but also can change their structure) throughout a lifetime and that frontal lobes are the most plastic area. Frontal lobes, the part of our brains right behind the forehead, controls “executive functions” — which determine our ability to pay attention, plan for the future and direct behavior toward achieving goals. They are critical for adapting to new situations.

We exercise them best by learning and mastering new skills.

This part of the brain is delicate: our frontal lobes wait until our mid to late 20s to fully mature.
They are also the first part of our brain to start to decline, usually by middle age.

In my view, not enough young and middle-aged people are benefiting from this emerging research, since it has been perceived as something “for seniors.” Granted, there are still many unknowns in the world of brain fitness and cognitive training, we need more research, better assessments and tools. But, this does not mean we cannot start caring for our brains today.

Recent studies have shown a tremendous variability in how well people age and how, to a large extent, our actions influence our rate of brain improvement and/or decline. The earlier we begin the better. And it is never too late.

What can we do to maintain our brain, especially the frontal lobes?

Focus on four pillars of brain health: physical exercise, a balanced diet, stress management, and brain exercise.
Stress management is important since stress has been shown to actually kill neurons and reduce the rate of creation of new ones.
Brain exercises range from low-tech (i.e. meditation, mastering new complex skills, lifelong learning and engagement) to high-tech (i.e. using the growing number of brain fitness software programs).

I know, this is starting to sound like those lists we all know are good for us but we actually don’t do. Let me make it easier by proposing a new New Year Resolution for 2008: every time you wash your car or have it washed in 2008, ask yourself, “What have I done lately to maintain my brain?”

Related blog posts and resources

Monday, February 15, 2010

Longer Needle May Be Preferred for HBV Vaccination of Obese Teens

From Medscape Medical News
Laurie Barclay, MD

February 8, 2010 — Use of a longer needle results in significantly higher titers in response to hepatitis B virus (HBV) vaccine among obese adolescents, according to the results of a randomized study reported online in the February 8 issue of Pediatrics.

"Obese youth achieve lower titers than average-weight peers in response to hepatitis B vaccine when a 1-inch needle is used," write Amy B. Middleman, MD, MSEd, MPH, from Baylor College of Medicine in Houston, Texas, and colleagues.

The goal of the study was to evaluate whether using a longer (1.5-inch) vs a standard (1-inch) needle to penetrate the thicker deltoid fat pad among obese youth who had not previously received the HBV vaccine would achieve higher antibody titers after immunization against HBV. The investigators randomly assigned 65 obese adolescents from a large metropolitan area to be immunized with HBV vaccine using either a 1-inch or a 1.5-inch needle. Analyzable data were available for 10 adolescents in the 1-inch needle group and for 14 in the 1.5-inch needle group.

Compared with obese adolescents immunized with a 1-inch needle, those who were immunized with a 1.5-inch needle had significantly higher antibody titers to hepatitis B surface antigen (median titers 189.8 mIU/mL with the 1-inch needle; 345.4 mIU/mL with the 1.5-inch needle; P = .03).

"This finding supports the hypothesis that needle length accounts for a significant portion of the discrepancy in immune response to HBV vaccine that is seen among those with obesity," the study authors write.

Limitations of this study include sample size smaller than planned with loss of participants to follow-up, few male participants, limited ability to enroll patients who had not yet received HBV vaccine, and limited variability in race and ethnicity (most participants were Hispanic).

"As we continue to experience high rates of obesity in the United States and throughout the world, additional evidence-based research on optimizing the effective delivery of immunizations to adolescents and young adults will be critical," the study authors conclude. "Following updated needle length recommendations will be a first step toward improving the health of our youth and young adults by preventing vaccine-preventable diseases."

This project was funded by the SAM/APA/CDC Adolescent Special Immunization Projects Award, 2001, and, in part, by the Maternal and Child Health Bureau (Title V, Social Security Act), Health Resources and Services Administration, Department of Health and Human Services. GlaxoSmithKline donated all vaccine doses. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online February 8, 2010.

Sunday, February 14, 2010

HPV Vaccine Reduces Rates of Genital Diseases in Young Women

From Medscape Medical News

Nick Mulcahy

February 11, 2010 — The quadrivalent vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (Gardasil, Merck & Co) results in statistically significant reductions of HPV-associated genital diseases, such as warts and cervical dysplasia, in young women who receive it, according to the final analysis of 2 randomized placebo-controlled efficacy trials.

The HPV vaccine also statistically significantly reduces Pap test abnormalities, procedures such as colposcopy, and definitive cervical therapy, compared with placebo, report the study authors, led by Nubia Muñoz, MD, from the National Institute of Cancer, in Bogota, Colombia.

The study, which was sponsored by Merck, was published online February 5 in the Journal of National Cancer Institute. The average follow-up was 3.6 years for the 17,622 young women (aged 16–26 years) in the trials.

The prophylactic efficacy of the vaccine was best when the genital lesions and diseases being evaluated were related to HPV 6, 11, 16, and 18. When the researchers considered lesions caused by all types of HPV, the efficacy rate fell.

The efficacy was also better when the population being evaluated was that of young women who tested negative for a range of HPV types before vaccination, and thus approximated women who were "sexually naïve" — compared with a "mixed" population of HPV-exposed and -unexposed women that approximated sexually active women.

Impact on Everyday Clinical Practice

For clinicians who regularly take care of women, the results mean that everyday practice will eventually be affected in countries where the vaccine has been widely administered, suggested a study coauthor.

The most important thing in these results is the reduction in the number of abnormal Pap smears, related biopsies and colposcopies, and follow-up visits.
"I'm a gynecologist and, to me, the most important thing in these results is the reduction in the number of abnormal Pap smears, related biopsies and colposcopies, and follow-up visits," said Kevin Ault, MD, associate professor of obstetrics and gynecology at Emory University in Atlanta, Georgia.

"Most gynecologists spend a lot of time counseling women about minor abnormalities," continued Dr. Ault in an interview with Medscape Oncology.

Before this current study was published, another expert in HPV vaccination made similar comments, albeit from a patient perspective.

"In developed countries where Pap screening systems have been effective for decades, the biggest value of the HPV vaccine will not be in preventing deaths from cervical cancer. The true value of the HPV vaccine will be to provide women with a greater reassurance that their future Pap screens will more likely be normal," Diane Harper, MD, from the University of Missouri–Kansas City School of Medicine, previously told Medscape Oncology.

At the time, Dr. Harper also reminded clinicians that ongoing Pap testing was needed for all women, whether they receive the vaccine or not, because the vaccine does not protect against all types of HPV infection that cause cervical cancer.

Dr. Ault suggested that healthcare systems should see a return on their investment in the vaccination in the coming years. In the United States, for example, there are annually "several hundred thousand cases of cervical dysplasia" and "millions of abnormal Pap smears," he said.

We should see a big reduction in these costly items.
"We should see a big reduction in these costly items in the next few years," Dr. Ault argued, referring to diagnostic and therapeutic care related to such clinical events.

Dr. Ault noted that so far "about 40%" of American teenaged girls have received 1 or more vaccine shots. The uptake of the vaccine in the United States has been comparable to that of the booster for pertussis, tetanus, and diphtheria, he observed.

Eventually, the reductions seen in HPV-related genital diseases in young women in this new study should affect cervical cancer incidence, note the authors. "It is anticipated that these reductions will eventually translate into lower rates of cancer of the cervix, vulva, and vagina," they write.

The authors highlighted several important limitations of the study.

Only 14 of the 40 HPV types that infect the genital tract were assessed; thus, 26 types of HPV were not assessed. As a result, "there may have been prevalent HPV infections or disease that were not detected," concede the authors.

The mixed or intention-to-treat population was not entirely representative of the general population because of inclusion/exclusion criteria, say the authors. Study participants were required to have had no more than 4 sex partners and no previous abnormal Pap test or external genital abnormality.

Results for the Sexually Naïve Population

The women in the current study were enrolled in 1 of 2 randomized double-blind placebo-controlled trials: Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I and II.

In FUTURE, the impact of the HPV 6/11/16/18 vaccine was investigated in 2 different populations of women.

In one population, the women were described by the investigators as approximating sexually naïve women because they tested negative for 14 HPV types (sexually naïve group) before vaccination.

The other was a mixed population of HPV-exposed and -unexposed women (mixed group) that approximated sexually active women, said the investigators.

All women underwent cervicovaginal sampling and Pap testing on day 1 and every 6 to 12 months thereafter. They were administered either placebo or vaccine on day 1, month 2, and month 6.

In the sexually naïve group, vaccination was up to 100% effective in reducing the risk for HPV 16/18–related high-grade cervical, vulvar, and vaginal lesions and for HPV 6/11–related genital warts.

For example, in the sexually naïve group, only 5 of 4689 vaccinated women eventually tested positive for genital warts related to HPV 6, 11, 16, and/or 18, whereas 140 of 4735 women who received placebo did. Thus, the vaccine reduced the risk for these specific types of genital warts by 96.4% (95% confidence interval [CI], 91.4% - 98.9%).

Prophylactic vaccination resulted in a 92% reduction in HPV 16–related Pap test abnormalities and a 97% reduction in HPV 18–related Pap test abnormalities.

But, as expected, the impact on Pap test abnormalities, irrespective of causal HPV type, was less, with an overall reduction of only 17.1%; however, the reduction was still statistically significant, report the investigators.

Prophylactic vaccination in this sexually naïve population also statistically significantly reduced the risk for any colposcopy by 19.8%, any cervical biopsy examination by 22.0%, and any cervical definitive therapy by 42.3%, write the investigators.

Results for the Mixed Population

In the mixed population, vaccination was, predictably, not as powerful because of individuals' varying exposures to different types of HPV. The efficacy, as noted above, dropped further when lesions caused by all types of HPV were considered.

Still, in this population, statistically significant reductions were observed for all disease end points, irrespective of causal HPV type, with the exception of adenocarcinoma in situ.

The end points that were statistically significantly reduced include any high-grade cervical lesions (19%), vulvar and vaginal lesions (50.7%), genital warts (62.0%), Pap test abnormalities (11.3%), and cervical definitive therapy (23.0%).

With this 4-year study now complete, the researchers are looking at the possibility of second-generation vaccinations that protect against types of HPV not currently covered by the quadrivalent vaccine, said Dr. Ault.

Dr. Muñoz reports receiving lecture fees, advisory-board fees, and consultancy fees from Merck and Sanofi Pasteur. Dr. Ault reports receiving consultancy and advisory-board fees from Merck during the study, and previously receiving funding from his former institution to conduct HPV vaccine studies for GlaxoSmithKline. He reports currently receiving funding from Merck and Co. for another HPV vaccine trial.

J Natl Cancer Inst. Published online February 5, 2010. Abstract

Childhood Obesity and Glucose Intolerance Linked With Premature Death

From Heartwire
Michael O'Riordan

February 10, 2010 (Umeå, Sweden) – Obesity, glucose intolerance, and hypertension in childhood are strongly linked with premature death from endogenous causes in young adulthood and middle age, according to the results of a new epidemiological study in a cohort of American Indian children.
Elevated cholesterol levels, on the other hand, were not associated with early mortality, although investigators caution against concluding that hypercholesterolemia in childhood is not harmful.

"The linking factor here is almost certainly the obesity," lead investigator Dr Paul Franks (Umeå University Hospital, Sweden) told heartwire .
"When we adjusted the risk associated with glucose levels and blood pressure for obesity, the effect of those risk factors substantially diminished.
We also know the causal mechanisms with blood pressure, glucose, and obesity suggest that obesity is probably the primary metabolic derangement that causes hyperglycemia and high blood pressure, and not the other way around."

The results of the study are published in the February 11, 2010 issue of the New England Journal of Medicine.

BMI Associated With Increased Risk of Premature Death From Endogenous Causes

Speaking with heartwire , Franks noted that his group previously published studies examining the association between glucose levels during pregnancy and the risk of obesity and diabetes in the offspring, as well as studies linking clinical risk factors in children with diabetes in adulthood. The purpose of this study was to study the effect of childhood risk factors for cardiovascular disease on adult mortality.

In a cohort of 4857 American Indian children aged five to 19 years without diabetes, body-mass index (BMI), glucose tolerance, blood pressure, and cholesterol levels were assessed to determine the extent to which they predicted premature death. The analyses included data from the date of the baseline examination until the person's death, their 55th birthday, or the end of 2003. During a median follow-up of 24 years, there were 166 deaths, 3.4% of the cohort, from endogenous causes. Of these deaths, 59 were attributed to alcoholic liver disease, 22 to cardiovascular disease, 21 to infections, 12 to cancer, 10 to diabetes or diabetic nephropathy, nine to alcoholic poisoning or drug overdose, and 33 to other causes.

BMI was associated with a significantly increased risk of premature death from endogenous causes, with those in the highest quartile having a mortality rate 230% greater than those in the lowest BMI quartile.
The two-hour plasma glucose level assessed during an oral glucose-tolerance test was not associated with premature death, but children with elevated blood glucose, those in the highest quartile, had a 73% greater risk of premature death than those in the lowest quartile.

Incidence-Rate Ratios for Premature Death (Quartile 4 vs Quartile 1) Variable Premature death from endogenous causes, incidence-rate ratio (95% CI)
BMI 2.30 (1.46–3.62)
2-h glucose 1.73 (1.09–2.74)
Total cholesterol 1.28 (0.81–2.02)
Systolic blood pressure 1.34 (0.83–2.15)
Diastolic blood pressure1 1.40 (0.89–2.19)

In models looking only at children with impaired glucose tolerance, there was no significant association with premature death.

"That might sound slightly counterintuitive, that these children with impaired glucose tolerance, those at the top end, are not the ones really driving mortality," explained Franks. "My feeling is that this is a population with a well-known risk for diabetes, so children diagnosed with the highest glucose levels, even though they are not diabetic, might have been picked up by the medical services early on and treated, which would make them less prone to the consequences of hyperglycemia. The children just below that level, they still have high glucose, they're the ones really driving the mortality rate in this study. The take-home message from this is that having a threshold for high glucose and saying that we're only going to intervene when it is above that threshold might not be good enough."

There was no significant association observed between systolic and diastolic blood pressure and premature death, but when investigators used a childhood definition of hypertension, one that takes three measurements and is standardized for height, there was a 57% increase in the risk of premature death among hypertensive children.

Regarding the absence of an association between childhood hypercholesterolemia and premature mortality, Franks told heartwire that only total-cholesterol levels were measured and that they did not have access to a full lipid profile. Moreover, a limited number of cardiovascular events might have influenced this finding, and as a result clinicians should err on the side of caution about concluding that there is no risk associated with elevated cholesterol levels.

"I would say that the absence of a statistically significant effect does not mean that high cholesterol levels in childhood are not harmful," he said. "It could mean that we did not observe enough events related to cardiovascular death to produce a statistically significant association between cholesterol in childhood and early death. Possibly, if this cohort is followed until later in life and more cardiovascular deaths occur, it's possible that one would observe an association between childhood cholesterol and mortality rates."

How Should the Findings Be Put Into Practice?

In an editorial accompanying the study [2], Dr Edward Gregg (Centers for Disease Control, Atlanta, GA) notes that the causes of obesity and diabetes appear to be rooted in culture--inactivity and large portion sizes of calorie-dense fast food--and that fighting these diseases with "clinical and adult-based approaches" is akin to "pasting a small bandage on a gaping wound."

While future approaches might target young people as a means of preventing these metabolic disorders, it should not be assumed that targeting youths will be effective for reducing their prevalence. "Bridging the wide gap between risk factors in youth and the prevention of illness in adults needs not only evidence that risk factors track strongly from childhood to adulthood but also efficient interventions with sustainable effects across different life stages," he writes.

Franks agrees.

"What we don't know is, if we intervene in these children, would we decrease the mortality rates; and we don't yet know the best way to intervene," he told heartwire . "Weight loss is not normally considered an appropriate strategy in children; instead, we try to get them to migrate toward a healthy growth trajectory. The message for frontline therapists is healthy diet and physically active lifestyles."

In highlighting one of the limitations of the study, Gregg points out that many deaths occurred before individuals were 45 years of age and were influenced by a large number of deaths from liver disease, something that warrants further study. He said the clinicians should not assume that follow-up into later life, when people die of typical causes, would yield similar associations with impaired glucose, obesity, and death. Like Gregg, Franks noted the cohort is unique, but that trends with respect to obesity and diabetes have mirrored trends in the US population in the past few decades.

No conflicts of interest reported.
Cardiovascular risk management in Rheumatology (The EULAR recommendations)
Bruno Oliveira, MD, Rheumatology, 09:32AM Feb 1, 2010

Cardiovascular (CV) events are responsible for a significant proportion of morbidity and mortality in patients with Rheumatic Diseases.
In addition to traditional risk factors (age, gender, smoking, blood pressure, LDL and HDL levels), inflammation caused by some autoimmune states has been recognized as an independent risk factor for CV events.

Rheumatologists and other health care providers need to incorporate the notion of Rheumatic diseases as a CV risk factor into their practice. To that effect, The EULAR has released a list of 10 evidenced-based recommendations for cardiovascular risk management in rheumatic diseases:

1. RA should be regarded as a condition associated with higher risk for CV disease. This may also apply to AS and PsA, although the evidence base is less.
The increased risk appears to be due to both an increased prevalence of traditional risk factors and the inflammatory burden.

Comment: According to some publications, the CV mortality attributed to RA is as significant as diabetes. Inflammatory markers (at baseline and after treatment) are also independently linked to increased CV mortality.
Inflammation has been hypothesized to drive endothelial damage in autoimmune diseases.

2. Adequate control of disease activity is necessary to lower the CV risk (best evidence for anti-tumour necrosis factor treatment and methotrexate treatment)

Comment: Early and aggressive treatment with methotrexate and TNF alfa blockers lowers the added mortality from RA. When patients do not respond, this beneficial effect is less evident. Methotrexate may cause hyperhomocysteinemia by reducing folic acid levels and hyperhomocysteinemia has been regarded as a CV risk factor as well.
Folic acid supplementation is highly recommended to prevent this undesirable side effect.

3. CV risk assessment using national guidelines is recommended for all patients with RA and should be considered annually for all patients with AS and PsA. Risk assessments should be repeated when antirheumatic treatment has been changed (in absence of national guidelines the SCORE function model is recommended)

Comment (Not from EULAR):The American Heart Association online risk factor calculator is a very fast and easy to use tool. Link:

4. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor. This multiplication factor should be used when the patient with RA meets two of the following three criteria: ‣Disease duration of more than 10 years ‣RF or anti-CCP positivity ‣Presence of certain extra-articular manifestations

Comment: To factor in the added mortality caused by RA, the EULAR recommends multiplying the risk

assessment result by 1.5.

5. Total cholesterol/HDL cholesterol ratio should be used when the SCORE model is used

Comment: DMARDs, TNF blockers and even corticosteroid favorably affect lipid profiles in early RA treatment. Nevertheless, long term corticosteroids negatively affect metabolic profiles.

6. Intervention should be carried out according to national guidelines.
Comment: Thresholds to start treatment for hypertension and hyperlipidemia are similar to recommendations for the general population.

(Not from EULAR): RA patients typically present with atypical chest pain during coronary events. Having a lower lower threshold for ordering investigational studies (stress test, troponins, EKG and heart cath) is also recommended.

7. Statins, ACE-inhibitors and/or angiotensin II blockers are preferred treatment options due to their potential anti-inflammatory effects

8. The role of cyclo-oxygenase-2 inhibitors and most non-steroidal anti-inflammatory drugs in CV risk is not well established and needs further investigation. Hence, we should be very cautious about prescribing them, especially for patients with a documented CV disease or in the presence of CV risk factors

Comment: Most Rheumatologists already have this mindset due to the potential for life-threatening GI bleeds with long term NSAIDs and cox-2 inhibitors use

9. Corticosteroids: use the lowest dose possible

Comment: This is advisable not only for CV risk reduction but to prevent the myriad of side effects that corticosteroids may cause

10. Recommend smoking cessation

Comment: In addition to lowering CV risk, stop smoking may also increase the chances of achieving remission in RA.

Do you think it is realistic for Rheumatologists to take care of Internal Medicine problems in daily practice? Are these recommendations better accomplished by working in collaboration with Primary Care Physicians? Would Generalists like our interference in these areas?

Free Full Text Link:
EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010;69:325-331

Friday, February 12, 2010

New-Onset Afebrile Seizures in Infants Are Generally Brief, but Often Recurrent

From Reuters Health Information

NEW YORK (Reuters Health) Feb 02 - New-onset afebrile seizures in infants are usually brief, but they often recur, and babies who have them should probably be admitted for observation, according to an article in the January 12th issue of Neurology.

"Epilepsy in infants and young toddlers is not well characterized even though one third of all childhood epilepsy begins in this age group," senior author Dr. William Davis Gaillard, of Children's National Medical Center, Washington, DC, told Reuters Health by email.

Dr. Gaillard and his colleagues analyzed data on 317 infants (newborn to 24 months) with new-onset afebrile seizures, including results of CT scans that were done in 298 (94%) patients, EEGs from 286 (90.2%), and MRI in 182 (57.4%).

Nearly half of the infants were having partial seizures. Evidence for primary generalized seizures was rare. The researchers note that only 6 infants without partial features had generalized epileptiform discharges.

Overall, 71% of infants had more than one seizure upon presentation, and 38% presented with 5 or more.

Seizures tended to be brief, with 74% lasting no more than 5 minutes and 44% lasting less than 1 minute. Only 8.5% lasted more than 20 minutes.

Half of the EEGs were abnormal, as were a third of the CT scans and more than half of the MRIs. Nine percent of babies who had CT scans (26% of those with abnormal CT scans) required acute medical management.

One-third of normal CTs were associated with abnormal MRIs, but in only one case (a baby with postoperative seizures) was acute medical management altered.

The most common MRI abnormality was cerebral dysgenesis (p < 0.05).

"This study should provide necessary information for revising guidelines for care of infants with new-onset epilepsy," Dr. Gaillard noted.

"Based on our data all infants...with new-onset seizures should undergo acute neuroimaging, preferably with MRI (as nearly all infants will have focal onset seizures)," he said. "As a substantial proportion of children will have recurrent seizures close to presentation, a strong argument can be made for close observation (in hospital) for these infants."

Neurology 2010;74:150-156.

One in Five Kids With Abnormal Lipids

From Heartwire

Michael O'Riordan

February 3, 2010 (Atlanta, Georgia) — New data from the Centers for Disease Control and Prevention (CDC) shows that one in five youths aged 12 to 19 years has abnormal lipid levels [1]. Also, nearly one-third of these youths are obese or overweight and based on their body-mass index (BMI) are candidates for lipid screening, according to investigators.

In an editorial accompanying the new report [2], the CDC urges clinicians to be aware of the lipid screening guidelines so that interventions for overweight or obese children and youths can be recommended. "Healthcare providers can refer eligible youths to nutritional counseling, community fitness programs, and school-based lifestyle programs," writes the CDC.

The new report, from a combined sample of four National Health and Nutrition Examination Survey (NHANES) surveys taken from 1999 to 2006, includes data on 9187 youths, of which 3733 provided fasting blood samples for lipid testing.

Among the sample, 20% had at least one abnormal lipid measurement, such as elevated LDL cholesterol (>130 mg/dL), reduced HDL cholesterol (<35 mg/dL), or elevated triglyceride levels (>150 mg/dL). Researchers also showed that compared with normal-weight youths, those who were overweight or obese were significantly more likely to have at least one abnormal lipid measurement.

In addition to these findings, the CDC report also showed that boys were more likely than girls to have low HDL cholesterol, while older youths, those aged 18 to 19 years, were more likely to have low HDL and elevated triglyceride levels than kids aged 12 or 13 years.

The researchers point out that, based on the American Academy of Pediatrics (AAP) screening recommendations, 32% of youths would be eligible for lipid screening based solely on their BMI. The AAP recommends screening based on family history of high cholesterol or premature cardiovascular disease or an unknown family history of high cholesterol or premature disease, as well as the presence of at least one major cardiovascular disease risk factor, including overweight/obesity.

Flares in Childhood Eczema

From Skin Therapy Letter
S. M. Langan, MRCP, MSc, PhD

Eczema is a major public health problem affecting children worldwide. Few studies have directly assessed triggers for disease flares. This paper presents evidence from a published systematic review and a prospective cohort study looking at flare factors in eczema.

This systematic review suggested that foodstuffs in selected groups, dust exposure, unfamiliar pets, seasonal variation, stress, and irritants may be important in eczema flares.
We performed a prospective cohort study that focused on environmental factors and identified associations between exposure to nylon clothing, dust, unfamiliar pets, sweating, shampoo, and eczema flares.
Results from this study also demonstrated some new key findings. First, the effect of shampoo was found to increase in cold weather, and second, combinations of environmental factors were associated with disease exacerbation, supporting a multiple component disease model.
This information is likely to be useful to families and may lead to the ability to reduce disease flares in the future.

Eczema is an important condition that affects 2%-20% of children worldwide, and is associated with significant morbidity for children and their families.[1]
Although some progress has been made in understanding factors that are related to the occurrence of eczema, very little is known about factors associated with disease exacerbation. Most textbooks and review articles quote long lists of exacerbating factors, but we have found very little scientific data to support them.

Defining Flares of Eczema
In order to address the causes of flares, it is first important to define what is meant by an eczema flare. Langan et al. carried out a systematic review that assessed definitions of flare in the literature and sought parallels with definitions used in other relapsing and remitting diseases.[2]
The authors proposed that a flare could be defined as an episode requiring escalation of treatment or additional medical advice. This should be pre-defined by investigators at the onset of a study. For example, in studies of moderate or severe eczema, escalation to the use of topical corticosteroids might constitute a "flare". The need to use potent or super-potent topical corticosteroids, or to attend a primary care physician or dermatologist for disease exacerbation might be more appropriate. It is not possible to develop an entirely standardized definition for "flare", as the true meaning is related to the individual patient and his or her perception of disease worsening above baseline.

A Review of Evidence for Causes of Flares in Eczema

A systematic review was also carried out to assess the evidence for causes of eczema flares. This review highlighted the limited evidence for flare factors, but suggested that there may be a role for foodstuffs in selected groups, dust exposure, unfamiliar pets, seasonal variation, stress, and irritants in eczema flares.[3] However, scientific investigation was required to elucidate the relative impact of these factors in studies of longitudinal design over longer study periods. Another aspect requiring study was whether combinations of factors are more important than single factors, suggesting a complex disease model.

A Study of Environmental Factors
Langan et al. addressed these issues in a prospective cohort study.[4] The objectives were to assess the role of various environmental factors on eczema severity in a cohort of eczematous children with the following identified hypotheses:

Hypothesis 1: In hot weather, the combination of heat, sweating, and grass pollen precipitates increased severity in children with eczema in the UK.

Hypothesis 2: The combination of cold weather, indoor aeroallergen exposure, and reduced relative humidity from central heating led to increased severity in children with eczema in the UK. These first 2 hypotheses were informed by previous research, which proposed "summer" and "winter" types of eczema.[5]

Hypothesis 3: Detergents (i.e., soap or shampoo) increase the propensity to disease flares triggered by other factors at all temperatures, but more so in cold weather due to impaired skin barrier function.

Hypothesis 4: Any combination of greater than or equal to 3 exposures at any time is associated with worsening of eczema. The exposures assessed included dust, pets, shampoo, sweating, swimming, nylon clothing next to the skin, and a change in mean temperature of more than 3°C from the previous weekly average.

Study Methods
A prospective cohort study (n=60) of children with moderate-to-severe eczema between 6 and 9 months of age and up to 15 years were enrolled with overlapping start dates to allow for the study of seasonal factors. The exposures studied included temperature, relative humidity, sun exposure, sweating, clothing, cleansing products/washing, outdoor pollen level, the extent and nature of exposure to household pets, dusty environments, and swimming. On a daily basis, children or their parents completed novel electronic diaries programmed for this study recording eczema severity and exposures. Portable dataloggers were used to record temperature and relative humidity. External meteorological data was obtained from a local monitoring center.

The primary outcome was measured as a daily "bother" score; the secondary outcomes were daily "scratch" scores and flares of eczema outcome measures. The daily bother score was determined in response to the question, "How much bother did your (your child's) eczema cause today?"

Global scores by the patients and their parents were rated on a scale from 0 to 10 (where 0=no bother at all and 10=the most bother you can imagine).

Binary outcomes were recorded with respect to the question, "Have you had to step up your treatment today because your (your child's) eczema was worse?" Stepping up treatment was defined at the outset and patient-specific for each child.

Statistical Methods
A time series method, autoregressive moving average models (ARMA), was used to model the impact of each exposure on eczema severity for each individual. This method was required to deal with the autocorrelation in the data, i.e., the severity of eczema on 1 day has a relationship with the severity of eczema on the next day and the day before. Standard random effects from meta-analysis techniques were used to pool estimated coefficients across participants. Heterogeneity of responses, as detected using Chi-squared tests, represented inter-individual variation. The body site specificity of reactions was also examined.

Primary Outcome: "Bother" Scores

Increased disease severity was associated with direct contact with nylon clothing (pooled regression coefficient 0.23, 95% confidence interval [CI] 0.03-0.43), increasing exposure to dust (pooled regression coefficient 0.53, 0.23-0.83), exposure to unfamiliar pets (pooled regression coefficient 0.22, 0.10-0.34), sweating (pooled regression coefficient 0.24, 0.09-0.39) and shampoo exposure (pooled regression coefficient 0.07, 0.01-0.13). The association between shampoo use and eczema exacerbation was enhanced in cold weather (pooled regression coefficient 0.30, 0.04-0.57). Body site specificity was observed for the reactions to nylon clothing, which was greater on covered sites [trunk (p=0.02), limbs (p=0.03)], and reactions to wool clothing on truncal covered sites (p=0.03), but not limbs (p=0.62), while exacerbation of hand eczema was associated with exposure to pets (p‹0.001). Significant heterogeneity of responses between individuals was observed for exposure to grass pollen and outdoor temperature. With regard to the final hypothesis, a combination of any 3 of 7 likely variables was associated with exacerbation of eczema (pooled regression coefficient 0.41, 0.20-0.63).

Secondary Outcome: "Scratch" Scores

Increased disease severity was seen associated with swimming (pooled regression coefficient 0.14, 95% CI 0.00-0.28), exposure to wool clothing (pooled regression coefficient 0.28, 0.11-0.45), sweating (pooled regression coefficient 0.15, 0.04-0.26), and shampoo (pooled regression coefficient 0.07, 0.01-0.13).

Secondary Outcome: Eczema Flares

Only swimming was clearly associated with eczema exacerbation using this outcome measure (pooled regression coefficient 0.42, 0.05-0.80).

A summary of exposure factors associated with exacerbation of eczema includes:

Shampoo + cold weather
Unfamiliar pets

Relative to the study hypotheses, the association between shampoo exposure and eczema exacerbation was shown to be increased in cold weather. There was also evidence showing an association between various combinations of exposures and disease worsening. There was insufficient evidence to support the other hypotheses tested in this study, but this may be explained by a low prevalence of these combinations of exposures. The implications of these study findings for clinical practice are that for the first time, it has been shown that shampoo exposure may be associated with eczema exacerbation and this effect is more pronounced in cold weather. This study also strengthens the systematic review findings that support disease worsening with dust, pet, and irritant exposure. Furthermore, this investigation suggests that eczema exacerbation may be more complicated in that multiple exposures acting in concert may be associated with worsening of the disease. The impact of food and stress were not examined in this prospective study.

Future research is required to specifically explore possible gene-environmental interactions with filaggrin mutations and their relevance in relation to disease flares, and to look at shampoo formulations in relation to eczema exacerbation.

Influenza Virus Infection in Infants Less than Three Months of Age

From The Pediatric Infectious Disease Journal®

Bender, Jeffrey M. MD; Ampofo, Krow MD; Gesteland, Per MD, MSc; Sheng, Xiaoming PhD; Korgenski, Kent MS; Raines, Bill; Daly, Judy A. PhD; Valentine, Karen MS; Srivastava, Rajendu MD, FRCP(C), MPH; Pavia, Andrew T. MD; Byington, Carrie L. MD

Objective: We evaluated the presentation, outcomes, and the risk of serious bacterial infection (SBI) in infants < 3 months old with influenza virus infection.

Patients and Methods: We identified demographic, hospitalization, and microbiologic data from computerized medical records for all infants and children < 24 months of age, with laboratory confirmed influenza infection cared for at a tertiary care children's hospital during 4 winter seasons (2004–2008). We compared those < 3 months of age with older groups.

Results: We identified 833 children < 24 months of age with laboratory-confirmed influenza. Of those, 218 were < 3 months old. Influenza accounted for 3.6% of all evaluations of febrile infants and 12% of febrile infant encounters during winter. Infants < 3 months of age were less likely to have a high risk chronic medical condition, but were more likely to be hospitalized than children 3 to < 24 months old (P < 0.005). Infants < 3 months with influenza had fewer prolonged hospital stays than those 3 to < 6 months old [P = 0.056; OR: 0.5 (0.24–1.0)] and 6 to < 12 months old [P = 0.011; OR: 0.43 (0.24–0.83)]. Five (2.3%) infants < 3 months old had SBI.

Conclusions: Infants < 3 months of age with influenza virus infection often present with fever alone. Although they are more likely to be hospitalized than those 3 to < 24 months old, hospital stays are short and outcomes generally good. Infants with influenza virus infection have a low risk of concomitant SBI.

Febrile infants younger than 3 months are often evaluated for serious bacterial infection (SBI). Approximately 8.5% to 9.5% of these infants have a SBI, with the remaining fevers presumably caused by viral illness.[1,2] Many studies have demonstrated that febrile infants with the clinical diagnosis of a specific viral illness such as bronchiolitis or a laboratory confirmed diagnosis of enterovirus or respiratory syncytial virus (RSV), are at lower risk for SBI than those with otherwise undifferentiated fever.[2–11] There are few data on the risk of SBI and outcomes of young infants with laboratory-confirmed influenza.

Influenza is a common viral cause of fever in young children during the winter.[12,13] Unlike other respiratory viruses, influenza frequently presents with high fever[14] that can be difficult to differentiate from SBI. In infants younger than 3 months, this often results in an evaluation for SBI and hospitalization.

Influenza vaccination is recommended for infants and children 6 months and older. Recent studies have demonstrated significant morbidity and mortality associated with influenza infection in infants younger than 6 months who are too young to be immunized.[15–17] Likewise, influenza infection in infants 6 months and younger may lead to high hospitalization rates and associated hospital costs.[17–19]

The objective of this study was to describe the outcomes, including rates of concomitant SBI, of a large cohort of infants younger than 3 months of age with laboratory confirmed influenza. We compare the outcomes of this group of infants with the outcomes among infants and children 3 to < 24 months old.

The Effect of Backpacks on the Lumbar Spine in Children: A Standing Magnetic Resonance Imaging Study

From Spine

Timothy B. Neuschwander, MD; John Cutrone, MD; Brandon R. Macias, BA; Samantha Cutrone; Gita Murthy, PhD; Henry Chambers, MD; Alan R. Hargens, MD

Study Design: This study is a repeated measures design to measure the lumbar spine response to typical school backpack loads in healthy children. The lumbar spine in this setting was measured for the first time by an upright magnetic resonance imaging (MRI) scanner.

Objective: The purpose of this study is to measure the lumbar spine response to typical school backpack loads in healthy children. We hypothesize that backpack loads significantly increase disc compression and lumbar curvature.
Summary of Background Data: Children commonly carry school backpacks of 10% to 22% bodyweight. Despite growing concern among parents about safety, there are no imaging studies which describe the effect of backpack loads on the spine in children.
Methods: Three boys and 5 girls, age 11 ± 2 years (mean ± SD) underwent T2 weighted sagittal and coronal MRI scans of the lumbar spine while standing. Scans were repeated with 4, 8, and 12 kg backpack loads, which represented approximately 10%, 20%, and 30% body weight for our sample. Main outcome measures were disc compression, defined as post- minus preloading disc height, and lumbar asymmetry, defined as the coronal Cobb angle between the superior endplates of S1 and L1.

Increasing backpack loads significantly compressed lumbar disc heights measured in the midline sagittal plane (P < 0.05, repeated-measures analysis of variance [ANOVA]). Lumbar asymmetry was: 2.23° ± 1.07° standing, 5.46° ± 2.50° with 4 kg, 9.18° ± 2.25° with 8 kg, and 5.68° ± 1.76° with 12 kg (mean ± SE).

Backpack loads significantly increased lumbar asymmetry (P < 0.03, one-way ANOVA). Four of the 8 subjects had Cobb angles greater than 10° during 8-kg backpack loads. Using a visual-analogue scale to rate their pain (0-no pain, 10-worst pain imaginable), subjects reported significant increases in back pain associated with backpack loads of 4, 8, and 12 kg (P < 0.001, 1-way ANOVA).

Conclusion: Backpack loads are responsible for a significant amount of back pain in children, which in part, may be due to changes in lumbar disc height or curvature. This is the first upright MRI study to document reduced disc height and greater lumbar asymmetry for common backpack loads in children.

Friday, February 5, 2010

Tylenol, Motrin, Benadryl, St. Joseph Aspirin, Rolaids Recall

From WebMD Health News > Alerts, Approvals and Safety Changes > Alerts

Daniel J. DeNoon

January 15, 2010 — Because of a sickening smell in some containers, 54 million packages of 27 different over-the-counter remedies now are being recalled.

Products include various types of child and/or adult Tylenol, Motrin, Benadryl, St. Joseph Aspirin, Rolaids, and Simply Sleep. This adds to the 6 million packages of Tylenol recalled late last year, bringing the total number of recalled products to 60 million.

A musty, moldy odor coming from the products has sickened at least 70 people with nausea, stomach pain, vomiting, and diarrhea. The symptoms go away by themselves and no one has been seriously injured.

The FDA says Johnson & Johnson's McNeil Consumer Health Care knew of the problem for more than a year. When the company did act in November and December 2008, it did too little too late, said Deborah M. Autor, director of the FDA's Office of Compliance.

"When something smells bad, literally or figuratively, companies must aggressively investigate and take all actions necessary to solve the problem," Autor said at a news conference. "McNeil should have acted faster."

The odor comes from a chemical, 2,4,6-tribromoanisole or TBA. TBA is produced when fungi break down a commonly used fungicide called 2,4,6-tribromophenol. The full health effects of TBA are not known.

Before being filled with product, product containers were stored on wooden pallets apparently treated with the fungicide. TBA seems to have infiltrated the product containers before they were filled.

The FDA inspected McNeil's main plant at Las Piedras, Puerto Rico, and was not happy with what it found. The FDA says McNeil began receiving complaints in May 2008, but failed to investigate fully or to warn consumers in a timely manner.

The FDA has given McNeil 15 days to respond to its seven-point warning letter. In addition to the contamination issue, the FDA says there are product-quality issues with some Motrin products.

Specific products included in the recall include:

Children's Motrin
Children's Tylenol
Extra Strength Tylenol
Regular Strength Tylenol
Tylenol 8 Hour
Tylenol Arthritis
Tylenol PM
Motrin IB
Simply Sleep
St. Joseph Aspirin
A complete list of the recalled products, including package sizes, product types, lot numbers, and UPC codes, can be seen at Consumers with question can call McNeil at 888-222-6036.

Consumers who think they may have suffered ill effects from the products should contact the FDA at


Cell Phones May Be Linked to Increase in Tumors, But Evidence Still Inconclusive

From Medscape Medical News
Roxanne Nelson

February 5, 2010 — Cell phones have become an integral part of everyday life, but concerns about their safety persist. A meta-analysis, published in the November 20 issue of the Journal of Clinical Oncology, which found evidence linking cell phone use to an increased risk for tumors has since attracted criticism.

The meta-analysis found that, overall, the use of cell phones was not significantly associated with the risk for tumors in a random-effects model meta-analysis. Compared with people who never or rarely used a cell phone, the odds ratio (OR) for the overall use of cell phones was 0.98 for malignant and benign tumors (95% confidence interval [CI], 0.89 - 1.07).

However, it also found that cell-phone use of 10 years or longer was associated with a risk for tumors in 13 studies that reported this association (OR, 1.18; 95% CI, 1.04 - 1.34).

The authors, led by Seung-Kwon Myung, MD, MS, from the National Cancer Center in Goyang, South Korea, write that the results of the studies included in their analysis varied widely, and appeared to depend on who conducted and funded the research and the controls used for bias and errors.

"We found a large discrepancy in the association between [cell] phone use and tumor risk by research group, which is confounded with the methodologic quality of the research," they noted.

However, in subsequent letters to the editor, published online January 25 in the journal, the meta-analysis was criticized for having methodologic flaws and issues and a number of limitations.

No Conclusive Evidence

A number of epidemiologic studies have reported associations between the use of cell phones and malignant or benign tumors of the brain and of the head and neck, non-Hodgkin's lymphoma, and testicular cancer. Results have been inconclusive or even contradictory. But as previously reported by Medscape Oncology, a report released in August 2009 by the International Electromagnetic Field Collaborative suggested that the regular use of cell phones can result in a "significant" risk for brain tumors.

Soon after the release of that report, a US Senate hearing on the health effects of cell-phone use was held; it concluded that more and better research is needed to determine if there is a risk to human health. Several nations have decided not to wait for additional data, have issued warnings about the use of cell phones, and advise taking precautionary measures. In the United States, the state of Maine is considering legislation that would require placing warnings on all cell phones.

Long-Term Use Associated With Benign Tumors

The meta-analysis was conducted to investigate the association between cell-phone use and the risk for malignant and benign conditions. It included 23 case–control studies, and involved 37,916 participants (12,344 patient cases and 25,572 control subjects).

They observed that the studies included in their meta-analysis varied in quality, and some that suggested there was little to no risk did not correct for bias. In 8 high-quality studies that used blinding, a significant positive association (harmful effect) was observed; in a fixed-effects analysis of 15 studies that did not use blinding, a significant negative association (protective effect) was observed.

A subgroup meta-analysis by methodologic quality showed a significant positive association in the high-quality studies (OR, 1.09; 95% CI, 1.01 - 1.18), whereas a negative association was observed in the low-quality studies. In that subgroup meta-analysis, cell-phone use of 10 years or longer was significantly positively associated with the risk for benign tumors but not for malignant tumors.

"Distinct Pattern" Seen

Another factor affecting the validity of the meta-analysis is the funding sources of each research group, "because it is possible that these may have influenced the respective study designs and results," the authors write. In subgroup meta-analyses by research group/funding source, they observed a "distinct pattern" in their findings. A positive association was seen in 7 studies, conducted by Swedish oncologist Lennart Hardell, MD, and colleagues, that were independent of industry funding. Conversely, a negative association was seen in the industry-funded INTERPHONE studies. No association was seen in studies conducted by other groups.

In an analysis of 15 studies involving brain tumors, a significant association was not observed. A preventive effect was observed for meningiomas, and the authors note that this effect was largely the result of a decreased OR in the INTERPHONE studies. A significant negative association was found when studies involving benign brain tumors were analyzed and, again, this was largely the result of a decreased OR in the INTERPHONE studies, report the authors.

They note that all of the studies conducted by Hardell et al used blinding to the status of patient cases or control subjects and were categorized as having a high methodologic quality, whereas most of the INTERPHONE studies and studies by other groups did not use blinding and were "thus categorized as having low methodologic quality."

The authors conclude that they "found a large discrepancy in the association between [cell] phone use and tumor risk by research group, which is confounded with the methodologic quality of the research," and that "our findings should be confirmed in prospective cohort studies to provide a higher level of evidence."

Critique and Response

In a letter to the editor, Andreas Stang, MD, Andrea Schmidt-Pokrzywniak, PhD, and Oliver Kuss, PhD, all from the Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany, expressed their concerns about some of the methodology in the meta-analysis. In particular, they point out that the study authors used the Newcastle-Ottawa Scale (NOS) to assess the quality of published case–control studies, but that "the validity of this checklist approach is at best unknown or doubtful."

Dr. Myung and colleagues, in their published response, "acknowledge that several methodologic issues raised by Stang et al are important for our main conclusions," and agree that the NOS is not an ideal quality-assessment tool for case–control studies because it has not yet been fully validated. However, they note that other checklists used to assess the quality of observational studies in systematic reviews have not been fully validated either. Of these tools, they considered the NOS to be comprehensive for case–control studies, and selected it for their quality assessment.

A second letter from Jack T. Rowley, PhD, from GSM Association in London, United Kingdom, and Michael J. Milligan, secretary general of Mobile Manufacturers Forum in Brussels, Belgium, rejected the "suggestion that there was any influence by our organizations on the scientific conduct of the INTERPHONE studies." They acknowledge that, in some cases, partial funding was provided by the GSM Association and Mobile Manufacturers Forum, but explain that funding was also received from noncommercial sources.

They also point out that a higher quality score was given to the Hardell group of studies, even though other analyses have raised methodologic questions about them.

Funding sources can influence research in subtle ways.
In response, the meta-analysis authors write that although they would prefer to believe that the design and conduct of the INTERPHONE studies were not influenced by the cell-phone industry, "nonetheless, we recommend that research on the topic of [cell]-phone use and health should not be funded by the industry because funding sources can influence research in subtle ways, and to preserve the credibility of the research it is important to avoid even the appearance of a conflict of interest."

However, they agree that the Hardell studies might have some methodologic limitations and acknowledge that they did not consider information and recall bias or validation of the self-reported indices of cell-phone use because the NOS does not include these items.

In a third letter, Florence Samkange-Zeeb, MPH, from the Universitätsmedizin der Johannes Gutenberg-Universität Mainz in Germany, and colleagues note that the authors "give no rationale" for pooling studies that cover a broad spectrum of heterogeneous and biologically diverse cancer sites, for which the localized exposure from the use of cell phones is completely different.

They also did not "understand why blinding is used as the major quality criteria," and found it surprising that there was no mention of the concerns that have been raised about the Hardell studies. As an example, they write, there have been questions about selection of the target population and the way the response rates were defined.

"In our opinion, this meta-analysis is an example of what happens when authors may have the technical skills [to perform] a meta-analysis, but are unfamiliar with the topic," they write.

The study authors responded by noting that there is "substantial precedent for pooling studies to examine the association of a potential risk factor with tumor risk in biologically diverse sites." They point out that researchers have pooled study results that reported the association between smoking and various heterogeneous diseases, including diabetes, cardiovascular disease, and cancers, to determine morbidity.

They reiterate the importance of blinding in this analysis, because "blinding and comparable response rates among case and control groups constituted the most important items in quality assessment using the NOS." These 2 items differentiated the 2 largest groups of studies in the meta-analysis, which were the Hardell and INTERPHONE studies.

"One of the problems in case–control studies is bias due to measurement error caused by the retrospective approach to measuring the predictor variable, and a recommended strategy for avoiding measurement error is blinding," they add.

Regarding the Hardell series, they agree with the critics that the differences in the methodologies, analyses, and presentation between the Hardell and other studies should have been explored. These issues and other potential confounding factors in the Hardell studies need to be explored in further studies, they write, and this issue was already discussed in their paper.

"We had no vested interest in the outcome of our meta-analysis" they point out.

The study was supported in part by the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

J Clin Oncol. 2009; 27:5565-5572. Abstract

J Clin Oncol. Published online January 25, 2010. Abstract, Abstract, Abstract, Abstract