pediatric immunisation n anaphylaxis

From Medscape Medical News

Anaphylaxis After Pediatric Immunization Rare

Troy Brown

January 26, 2012 — A recent study found that anaphylaxis occurred rarely after pediatric immunization, and not at all after routine infant and preschool immunization.

Michel Erlewyn-Lajeunesse, MD, from the Children's Allergy Clinic, University Hospital, Southampton, United Kingdom, and colleagues described their findings in an article published online January 23 in the Archives of Disease in Childhood.

Because it is so rare, "[e]ven the largest prelicensure vaccine trials are unlikely to detect a single case, let alone provide an estimate of incidence," write the authors. "The onus for detection of anaphylaxis falls to national post-marketing surveillance...systems, all of which rely upon passive reporting of cases."

For this reason, Dr. Erlewyn-Lajeunesse and colleagues conducted a study using prospective active surveillance to determine the incidence and clinical presentation of anaphylaxis as an adverse event after immunization (AEAI) in children younger than 16 years.

The British Paediatric Surveillance Unit (BPSU) sends an "orange card" with a list of rare disorders to consultant pediatricians in the United Kingdom and Ireland each month. Physicians note the presence or absence of these disorders on the card and return it to the BPSU. Reports were collected for 13 months, from September 1, 2008, to September 30, 2009, with more than 90% of participants returning the cards (93.2% in the United Kingdom and 91.8% in Ireland).

Clinicians were instructed to report actual cases of anaphylaxis, as well as cases in which anaphylaxis was only suspected but further immunization was contraindicated. The Brighton Collaboration Case Definition (BCCD) for anaphylaxis as an AEAI was used to identify cases of anaphylaxis.

During the 13 months, 15 reports of anaphylaxis as an AEAI were made to the BPSU. Of those, 7 cases met the BCCD criteria (3 were BCCD level 1, 3 were BCCD level 2, and 1 was BCCD level 3). The child whose symptoms met level 3 diagnostic criteria was treated with intramuscular adrenaline quickly, and this may have been the reason that case was less severe.

Of the other 8 cases, 3 were withdrawn by the reporting physician, and further information was unavailable from reporting clinicians for 3 others. One child experienced a hypotonic hyporesponsive episode, and the last case was not included because it occurred outside of the study period.

In 6 of the 7 cases, the reporter believed the episode was caused by the immunization, and in the other case, the reporter believed it was probably related.

All but 1 of the children were receiving the vaccination for the first time. One child had received the immunization before without incident, and 2 of the children were given several immunizations at the same appointment.

The study analyzed reports related to 3 human papilloma virus vaccines (Cervarix, GlaxoSmithKline), 2 single-component measles vaccines (Rouvax, Sanofi Pasteur MSD), a meningococcal C conjugate vaccine, a school leaver's booster (probably tetanus/inactivated polio virus), an inactivated typhoid vaccine (Typhim Vi, Sanofi Pasteur MSD), a quadrivalent meningococcal polysaccharide vaccine (ACWY Vax, GlaxoSmithKline), and a hepatitis A vaccine (Havrix Junior Monodose, GlaxoSmithKline).

Symptoms began within 15 minutes of administration in 3 children, and 30 minutes or later in the other 4 children. One of those 4 children experienced symptoms 120 minutes after immunization.

Intramuscular adrenaline was administered to 6 children, intravenous fluids were given to 3 children, and 1 child received salbutamol nebulization. Corticosteroids were given to 2 children, H₁ histamine receptor inverse agonists were given to 5 children, and 1 child improved without treatment.

No child required pediatric intensive care admission, but 3 required emergency department treatment, 4 needed acute pediatric treatment, and 2 received pediatric outpatient care after the occurrence. All children recovered completely with no sequelae.

Preexisting atopic disease made it necessary for 3 children to carry injectable adrenaline: 1 child had multiple food allergies, and 2 had idiopathic urticaria with anaphylaxis.

During the study period, 16,625 doses of single-component measles vaccine were ordered by United Kingdom and Ireland. There were 2 reports of anaphylaxis AEAI, amounting to an incidence of 12 cases per every 100,000 immunizations.

Of 2,081,272 vaccines given during the study period to children aged from 12 to 19 years (most younger than 16 years), there were 3 events, amounting to an incidence of 1.4 cases per million immunizations.

"The important thing for clinicians to remember is that vaccines are extremely safe," Vivian Hernandez-Trujillo, MD, director of the Division of Allergy and Immunology at Miami Children's Hospital in Florida, told Medscape Medical News in a telephone interview.

"Adverse reactions to vaccines may occur, [but] anaphylaxis is extraordinarily rare," she added.

"No events were related to routine infant and preschool immunizations despite over 5.5 million primary schedule vaccines being delivered in this time period. Some children had delayed onset of symptoms and this should be considered in those at higher risk of anaphylaxis," the authors conclude.

Arch Dis Child. Published online January 23, 2012. Abstract

Clarifying Meningococcal Booster Dose Recommendations

From CDC Expert Commentary Amanda Cohn, MD 01/17/2012 Hi, I am Dr. Amanda Cohn, a pediatrician and epidemiologist. Thanks for tuning in to this CDC Expert Video Commentary on Medscape. In January 2011, recommendations were made by the Advisory Committee on Immunization practices (ACIP) for adolescents to receive a booster dose of meningococcal conjugate vaccine. Today I am going to explain the rationale behind this recommendation and answer frequently asked questions about implementation. First, some background. When this vaccine was first recommended for adolescents in 2005, the expectation was that protection would last for 10 years. However, currently available data suggest that immunity wanes much earlier than 10 years. In fact, only about half of adolescents are still protected 5 years after administration of the initial dose. Based on that information, a single dose for all 11- to 18-year-olds, recommended to be given at age 11-12 years, may not offer continued protection through the period when risk for meningococcal infection is highest, 16-21 years of age. Therefore, ACIP voted to recommend a booster dose of meningococcal conjugate vaccine for adolescents. This booster dose is recommended to be given at 16 years of age, following the routine first dose at age 11-12 years. Unfortunately, not all adolescents receive these doses on time, so here are some key points about when to give the booster dose. For adolescents who receive the first dose at age 13-15 years, a 1-time booster dose should be administered, preferably between the ages of 16 and 18 years. There is no need to wait 5 years from the first dose before administering the booster. Rather, give the booster dose any time after the child's 16th birthday. Eight weeks is the minimum interval between doses. If the teen is younger than 16 years of age, but the clinician believes this is a situation where there may not be another opportunity to provide the booster dose, the second dose can be given prior to 16 years of age. The booster dose is not recommended for adolescents who receive their first dose of meningococcal conjugate vaccine after their 16th birthday. What about college requirements? Meningococcal vaccination is required to attend many colleges, but which kids going off to college still need the booster dose? You may have a patient going off to college who requires vaccination. Many colleges will consider any dose given within 5 years prior to matriculation as valid. However, the recommendation for providers is to still follow the new guidelines: Administer a dose (a booster dose or the first dose if the adolescent is unvaccinated) after the 16th birthday and prior to college. Ideally, we want kids to get the booster dose before they reach the age when they are at greatest risk. All college freshmen living in a dormitory are recommended to be fully vaccinated. The booster dose may still be given to college students not living in dorms but is not routinely recommended. Which vaccine should be used? Only the meningococcal conjugate vaccine is recommended for adolescents. However, if the first dose of meningococcal vaccine was administered as polysaccharide vaccine, it is still counted as valid in the adolescent schedule. The booster dose of meningococcal vaccine for adolescents should always be a conjugate vaccine. The 2 licensed products, Menactra® and Menveo®, are interchangeable. If polysaccharide vaccine is inadvertently administered as the booster dose, revaccination with conjugate vaccine is recommended 8 weeks later. We want to protect as many kids as possible from this rare but often devastating disease. For more information on meningococcal disease and vaccine recommendations, visit www.cdc.gov/meningococcal. Thanks for tuning in today.

HPV & Sex

From Medscape Infectious Diseases HPV & Sexual activity - any relationship? Paul A. Offit, MD 01/17/2012 Hi, my name is Paul Offit. I am talking to you today from the Vaccine Education Center at the Children's Hospital of Philadelphia. What I want to talk about is an article on the human papillomavirus (HPV) vaccine that recently appeared in American Journal of Preventive Medicine. The first HPV vaccine, called Gardasil®, contains serotypes 6, 11, 16, and 18 and came out in 2006. At that time, it was recommended for girls only. This past year, the vaccine was also recommended for boys. When the vaccine came out, there were a number of issues that were of concern to parents. People wondered whether the vaccine was really safe. There were questions about whether it caused blood clots, with consequent strokes and heart attacks. There were questions about whether it caused chronic fatigue syndrome. More recently, in September 2011, during the Republican national debates, Michele Bachmann raised the question of whether the HPV vaccine could cause severe developmental delays, which she referred to as "mental retardation." So, there has been a lot of fear surrounding this vaccine. In fact, none of those concerns are true. A number of studies have shown that the HPV vaccine does not cause chronic fatigue syndrome, blood clots, strokes, or heart attacks. But another issue was raised that really hasn't been addressed until this article was published, and that is the question of whether getting an HPV vaccine increases your desire for sexual activity -- or, said another way, promiscuity. The researchers at the Centers for Disease Control and Prevention, headed by Lauri Markowitz, looked at this. In their article titled "Human Papillomavirus Vaccine and Sexual Behavior Among Adolescent and Young Women," they looked at whether those who got the HPV vaccine were more likely to be promiscuous than those who did not. The answer was, not surprisingly, no. It doesn't make sense that that would have ever been true. First of all, no vaccine is 100% effective. Second, this particular vaccine protects against about 70% of strains that cause cervical cancer and 90% of strains that cause anal and genital warts. So, it's not even 100% effective against all strains of HPV. Obviously, the vaccine does not prevent other sexually transmitted diseases, such as syphilis, gonorrhea, chlamydia, or herpes. The concern never made sense. It's like making an argument that once I get a tetanus-containing vaccine, I can feel comfortable running through a bed of rusty nails. I don't think that is true either. I think we can now feel comfortable about the safety of this vaccine and also the notion of whether it increases sexual activity or promiscuity. The problem with HPV vaccine is that people haven't been very good about getting it. Only about one third of girls and young women for whom this vaccine is recommended get it. Hopefully, we can be better at encouraging vaccine use, and hopefully this study will make people feel more comfortable about the vaccine. Thank you. Related Resource Prevent HPV

Hair Loss and its Management in Children

From Expert Review of Dermatology Vibhu Mendiratta; Masarat Jabeen 01/15/2012; Expert Rev Dermatol. 2011;6(6):581-590. © 2011 Expert Reviews Ltd. Abstract Hair loss in children can cause psychological stress to the parent and patient alike. Alopecia can be classified into congenital and acquired. Commonly encountered causes of pediatric alopecia (tinea capitis, alopecia areata, traction alopecia and trichotillomania) are reversible if diagnosed early. Special note should be made of the extent and type of alopecia (scarring or nonscarring), any hair shaft anomalies and signs of inflammation. Diagnostic evaluation includes a bewildering array of age-old simple bedside tests (e.g., potassium hydroxide preparation) to state-of-the art accurate instruments (e.g., trichoscan). Systemic antifungal therapy is required for tinea capitis. Topical and systemic immunomodulators are currently being employed for treating alopecia areata. A holistic approach would include not just therapeutic intervention but also an active search for associated nutritional deficits, underlying psychosocial disturbances and behavioral problems, the latter two requiring counseling and behavior therapy. Children with permanent hair loss can be offered surgical hair transplantation or camouflage devices, such as wigs. Introduction Though losing hair is not usually health threatening, it can scar a young child's vulnerable self esteem by causing immense psychological and emotional stress; not just to the patient, but also to the concerned parents and siblings. Thus, management of hair disorders can be quite a daunting task for the attending physician and mandates a holistic approach to the patient. Nevertheless, an organized diagnostic and management strategy can turn this challenging task into an interesting and fruitful exercise. To fully understand hair loss in childhood, a basic knowledge of normal hair growth is necessary. The normal hair cycle is divided into four phases: the active growth anagen phase, followed by a brief catagen phase, the resting telogen phase and finally the shedding exogen phase. Typically, 85–95% of hairs are in the anagen phase, which lasts approximately 3 years. Less than 1% of hairs are in catagen, the transitional phase, which lasts from a few days to weeks. The telogen phase (which accounts for 5–15% of hairs and lasts about 3 months) ends when the new anagen hair emerges from the follicle. For the classification of pathological hair loss in children, two major groups should be differentiated: congenital and acquired hair loss. This distinction is the first step in diagnosis (Box 1 & Figure 1). Pathological hair loss, although rare in the first year of life, may be a symptom of an underlying congenital syndrome or clue to an underlying metabolic disorder which may have a bearing on the mental and physical development of a child. Hair loss on the scalp can also be classified as focal or diffuse (Box 2). Focal hair loss is secondary to an underlying disorder that may cause nonscarring or scarring alopecia. Patient's personal and family history, a thorough clinical examination, as well as general and specific diagnostic procedures aid in correct diagnosis and early treatment. The key points in a patient's history are: Age of onset of the patient: congenital or acquired; Onset of hair loss: sudden or insidious; Extent of alopecia: localized or diffuse; Subsequent development of the disease and associated symptoms; Physical and mental development (may be affected as a part of a genotrichosis); Psychological problems of the child; Obvious physical or emotional triggers in the previous 2–5 months, and any accompanying complaints (e.g., fatigue, weight changes, and nail or skin abnormalities); Past medical history including chronic illnesses, surgeries, medication, autoimmune, dermatologic and psychiatric disorders (e.g., anxiety and obsessive–compulsive tendencies); Family history of alopecia, autoimmune disease, dermatologic or psychiatric disorders; Hair grooming practices (chemicals, tight braiding). Examination should have the following components: Sparsing of hair (hypotrichosis) or loss of hair (alopecia); Thorough examination of scalp as well as the other hair-bearing areas of the body, especially loss of axillary and pubic hair, eyelashes, eyebrows and body hair; Type of alopecia: localized or diffuse, scarring or nonscarring; Any hair shaft anomalies, hair quality, color, roughness and tendency to breakage, 'exclamation-point' hairs; Presence of erythema, edema, papules, pustules, scaling, atrophy, telangiectasias, follicular hyperkeratosis, ulceration and scarring; Hair pull test: Approximately 20 hairs are grasped and firmly tugged away from the scalp; The number of extracted hairs is counted; >10% of grasped hairs or two hairs suggests positive pull test and active hair shedding. The skin, nails, oral or genital mucous membranes (e.g., for evidence of associated dermatoses, such as lichen planus); Thorough clinical examination of the entire head and body is necessary in order to evaluate impaired vision, defective hearing, dysmorphic features, clues to autoimmune or metabolic diseases, or ectodermal anomalies. for rest of article go to: http://www.medscape.com/viewarticle/753720?src=mp&spon=9

PPIs Not Helpful in Children With Poor Asthma Control

From Medscape Medical News Jennifer Garcia January 24, 2012 — Use of proton pump inhibitors (PPIs) in children with poorly controlled asthma who were using inhaled corticosteroids and who had no symptoms of gastroesophageal reflux (GER) was not found to improve asthma control and was, in fact, associated with an increase in adverse effects, according to results of a study published in the January 25 issue of JAMA. PPIs "are often prescribed for poorly controlled asthma regardless of reflux symptoms, and there have been large increases in the use of PPIs among children between 2000 and 2005.... Hence, it is of clinical importance to determine whether antireflux therapy, the most common of which are PPIs, improves control of asthma in children," write Janet T. Holbrook, MPH, PhD, from the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers. The goal of this placebo-controlled, double-masked, randomized study was to determine whether the PPI lansoprazole was effective in controlling asthma symptoms in children with asthma, but no overt GER. The researchers also investigated whether pH testing would identify children with GER who responded to PPI therapy. Between April 2007 and September 2010, the Study of Acid Reflux in Children With Asthma enrolled 306 children at 19 US academic clinical trial centers. The children had physician-diagnosed asthma that was poorly controlled and were receiving inhaled corticosteroids (≥176 μg/day of fluticasone equivalents) for at least 8 weeks before enrollment. Participants were excluded if they had any symptoms of GER, were receiving any PPI or other reflux medications, or had any history of esophageal disease or other major illness. Participants were evaluated over the course of 24 weeks and ranged in age from 6 to 17 years (mean, 11 years of age). The children were randomly assigned to receive either lansoprazole (15 mg/day for those weighing <30 kg; 30 mg/day for those weighing ≥30 kg; n = 149) or a matching placebo (n = 157). The researchers found that the mean difference in the Asthma Control Questionnaire (ACQ) score between the 2 groups was 0.2 units (95% confidence interval [CI], 0.0 - 0.3 units), which was not statistically significant (P = .12). There also was no significant difference in the forced expiratory volume in the first second (0.0 L; 95% CI, −0.1 to 0.1 L), and no change in the rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9 - 1.5) or asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1). In addition, children treated with lansoprazole developed more respiratory infections (relative risk, 1.3; 95% CI, 1.1 - 1.6; P = .02) than those in the placebo group. A subgroup of children in the study (n = 115) underwent esophageal pH studies before randomization; the prevalence of GER among this group was found to be 43%. In those children with a positive pH study, there was no positive treatment effect with lansoprazole vs placebo for any asthma outcome. The researchers evaluated a change in the ACQ score between case and control participants as their primary outcome. The questionnaire was administered at enrollment, and again at the 24-week follow-up visit. Secondary outcomes included the rate of acute episodes of poor asthma control, the Asthma Symptom Utility Index, the Asthma Control Test for adolescents (aged 12 - 17 years)/children (aged 6 - 11 years), asthma-specific quality of life score, methacholine provocative concentration, spirometry, exhaled nitric oxide, gastrointestinal symptoms, and nocturnal awakenings. The authors also required the children to maintain a journal at home to record any asthma exacerbations, rescue treatments, morning peak expiratory flow, nocturnal awakenings, oral corticosteroid use, and unscheduled healthcare visits for asthma symptoms. The most common adverse event reported among both groups was asthma exacerbation. A higher prevalence of upper respiratory tract infections, sore throats, and episodes of bronchitis was noted among patients in the lansoprazole group. The study authors speculate that this may be a result of loss of host defense against bacterial colonization as a result of higher gastric pH levels. Activity-related bone fractures were not statistically different between the 2 groups (6/149 in the lansoprazole group vs 1/157 in the placebo group; P = .06). "The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airway reactivity, or quality of life," write the authors. The results also "indicate that PPI therapy for poorly controlled asthma is not warranted." In an accompanying editorial, Fernando Martinez, MD, from the Arizona Respiratory Center, University of Arizona, Tucson, notes that although it is not a statistically significant difference, the increase in activity-related bone fractures in the lansoprazole group also raises concerns. This potential complication has prompted an advisory from the US Food and Drug Administration about the risk for fractures in adults receiving chronic PPI therapy. "In this context, a less conservative test assessing if the odds ratio was significantly greater than 1.0 (not just different from 1 in any direction) might have been more appropriate and may have yielded a statistically significant result," writes Dr. Martinez. Overall, however, Dr. Martinez praises the work of Dr. Holbrook and colleagues and concludes that "[g]iven their potential adverse effects, these medications should thus be used with great restraint for treatment of GER/[gastroesophageal reflux disease] during childhood. The substantial increase in use of PPIs in children during the last decade is worrisome and unwarranted." Support for this study was provided by the American Lung Association Asthma Clinical Research Centers Infrastructure Award and National Institutes of Health/National Heart, Lung, and Blood Institute grants. Dr. Holbrook and colleagues have disclosed no relevant financial relationships. Dr. Martinez has served as a consultant to MedImmune and has presented at an Abbott-sponsored seminar. JAMA. 2012;307:373-381.

Delayed Introduction of Solid Foods

From Medscape Pediatrics > Viewpoints William T. Basco, Jr., MD 01/10/2012 The Introduction of Allergenic Foods and the Development of Reported Wheezing and Eczema in Childhood: The Generation R Study Tromp II, Kiefte-de Jong JC, Lebon A, et al Arch Pediatr Adolesc Med. 2011;165: 933-938 Study Summary Background. Parents give many reasons for delaying the introduction of complementary foods to a diet of breast milk or infant formula, including concerns about increased risk for early excessive weight gain, development of allergic sensitivity to the foods, and autoimmune diseases such as diabetes or celiac disease. Pediatric professional organizations generally recommend delaying the introduction of solid foods until the child is at least 4 months of age, with some recommending delaying these foods until the child is 6 months of age. Data about whether the early introduction of solid foods elevates the risk for allergies or other food sensitivities are conflicting. Methods. This study evaluated the results of a generational cohort study from The Netherlands that followed more than 7000 infants and mothers who delivered their infants between 2002 and 2006. The goal was to determine whether the timing of introduction of allergenic foods such as cow's milk, eggs, peanuts, tree nuts, soy, and gluten was associated with eczema and wheezing through the fourth year of life. The investigators also conducted subgroup analysis looking at children with and without a history of allergy to cow's milk demonstrated during the first year of life and subgroup analysis comparing children with and without a parental history of atopic disease. The outcomes were assessed when the children were ages 2, 3, and 4 years, using questionnaires completed by their parents. Approximately two thirds of the cohort parents responded at each of the survey points. Data on food introduction was obtained during visits when the child was between 6 and 12 months old, again collected by parental report on a questionnaire. Parents were asked about the age when they first introduced each of the allergenic foods. When children were between 6 and 12 months of age, parents again completed a short food frequency questionnaire. The analyses controlled for appropriate covariates including gender, gestational age, maternal sociodemographic factors, and family history of allergic diseases. The investigators were also able to control for illnesses experienced by the child. Finally, breastfeeding was divided into 6 different categories ranging from children who were "never" breastfed to children who were "exclusively breastfed" through at least 4 months of age. Data were obtained on whether the child had ever been seen by a physician for cow's milk allergy. The 2 main outcomes of interest were whether the child experienced eczema or wheezing, and the authors created prediction models for children experiencing either of those at age 2, 3, or 4 years. Findings. The investigators stratified analyses by both cow's milk allergy and parental history of allergic disease. There were 6905 children in the analysis cohort. At 2 years of age, 31% of the children had experienced wheezing and 38% had experienced eczema. At 3 years of age, 14% of the children reported wheezing and 20% reported eczema. At 4 years of age, 14% of the children had experienced wheezing and 18% had experienced eczema. Almost half (47%) of the children had a parent with a history of atopic disease. With respect to breastfeeding, 11% of the children had never been breastfed, whereas approximately 24% had been exclusively breastfed to at least 4 months. No respiratory illnesses at 12-24 months of life were reported by 48%. Three quarters of the children were in daycare during the second year of life. When looking at the outcomes of wheezing and eczema, the introduction of allergenic foods at ≤ 6 months of age was not associated with the likelihood of wheezing or experiencing eczema at either 2, 3, or 4 years of life. Wheezing and eczema were both more likely in children who experienced cow's milk allergy or who had a parental history of atopic disease, but introduction of allergenic foods before 6 months of life was not associated with either outcome in the stratified analyses. The investigators concluded that their data do not support delayed introduction of allergenic foods until after 6 months of age for the prevention of either wheezing or eczema. Viewpoint The discussion section of this article reviews additional cohort studies that had very similar findings. It appears that the bulk of evidence suggests that delayed introduction of allergenic foods, even among those felt to be atopic prone, does not provide protection against the development of atopic illness. It will be interesting to see how long it takes for general practice to evolve, but the building data suggest that we should reconsider feeding recommendations, at least as they pertain to allergy. Abstract

Allergy Tests Should Only Verify Diagnosis in Children

From Medscape Education Clinical Briefs News Author: Ricki Lewis, PhD CME Author: Désirée Lie, MD, MSEd 01/10/2012 Clinical Context According to the current study by Sicherer and Wood, most allergic responses are mediated by immunoglobulin E (IgE) antibodies specific to the trigger allergen, which can be detected with in vitro or skin tests. Quantification of in vitro allergen-specific IgE (sIgE) levels is becoming more common. The 3 detection systems approved by the US Food and Drug Administration have excellent performance characteristics to identify different IgE antibodies but do not measure IgE antibodies with similar efficiencies. Therefore, a test for an allergen in 1 of 3 test systems may not be equivalent to the same allergen test in a different system. This is a review of different tests available for allergen testing in children and indications for use. Study Synopsis and Perspective Allergy tests should be used only to confirm a diagnosis that has already been made on the basis of symptoms and medical history, advise 2 leading allergists in an article published in the January issue of Pediatrics. Scott Sicherer, MD, from Mount Sinai Hospital in New York City, and Robert Wood, MD, from the Johns Hopkins Children's Center in Baltimore, Maryland, reviewed the benefits and limitations of blood tests and skin-prick tests in the detection of allergic diseases. For blood tests, enzymatic assays for IgE antibodies (in vitro sIgE) tests have replaced radioallergosorbent tests, but the 3 products approved by the US Food and Drug Administration either detect different antibody populations or do not measure them with comparable efficiencies. Both the skin-prick test (SPT) and sIgE test detect a sensitized state. "However, detection of sensitization to an allergen is not equivalent to a clinical diagnosis. In fact, many children with positive tests have no clinical illness when exposed to the allergen," Dr. Sicherer and Dr. Wood write. They further point out that testing for allergens that do not make sense (because they would never be encountered in the patient's environment or because the patient is obviously not allergic to them) could lead to "detrimental actions of unnecessary allergen avoidance." They also warn against a false-negative on an SPT or sIgE test when a child is obviously allergic to a particular trigger. The allergists identify circumstances in which SPT and sIgE are warranted: to confirm a suspected allergic trigger after observing a child react, to monitor the course of a food allergy to detect when it might be waning or outgrown, to confirm allergy to an insect after an anaphylactic response, and to identify allergies to vaccines (SPT only). SPT and sIgE tests should not be used, Dr. Sicherer and Dr. Wood write, to screen for allergies in nonsymptomatic children or to diagnose food allergies or drug allergies. Food allergies should be assessed with food challenges, they write, and skin and blood tests do not detect antibodies to drugs. The tests might be useful for identifying the trigger of a respiratory allergy (allergic asthma or seasonal or perennial allergic rhinitis) that is ubiquitous but not obvious in the patient's environment: for example, SPT or sIgE can detect allergy to dust mites, animal dander, cockroaches, molds, or pollen. The authors have disclosed no relevant financial relationships. Pediatrics. 2012;129:193-97. Abstract

Antiretroviral Safe in Reducing HIV-1 Transmission via Breast-Feeding

m Medscape Education Clinical Briefs News Author: Laurie Barclay, MD CME Author: Hien T. Nghiem, MD 01/10/2012 Clinical Context Breast-feeding in sub-Saharan Africa is an important source of nutrition for infants between birth and age 24 months, leading to improved overall survival duration. However, breast-feeding for infants exposed to HIV can account for 30% to 40% of all mother-to-child transmissions. Strategies for prevention of mother-to-child transmission are needed. Guidelines from the World Health Organization recommend extended breast-feeding for infants exposed to HIV-1 until age 12 months, together with antiretroviral prophylaxis for the mother or infant for the duration of breast-feeding. Nevirapine given once daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breast-feeding reduces transmission through this route vs single-dose nevirapine at birth or neonatally. The aim of this study by Coovadia and colleagues was to assess the incremental safety and efficacy of extension of such prophylaxis to 6 months. Study Synopsis and Perspective A daily oral dose of nevirapine given to infants up to 6 months of age can safely reduce mother-to-child transmission of HIV-1 via breast-feeding, according to the results of a phase 3, double-blind, randomized, placebo-controlled trial published online December 23 in the Lancet. "Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally," write Professor Hoosen M. Coovadia, MD, from the University of Witwatersrand in Johannesburg and the Nelson Mandela School of Medicine at the University of Kwazulu-Natal in Durban, South Africa, and colleagues. "We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months." Within 7 days of birth, breast-feeding infants born to mothers with HIV-1 in 4 African countries were enrolled and given once-daily nevirapine from birth to 6 weeks. Using a computer-generated permuted block algorithm with random block sizes allowing stratification by site and maternal antiretroviral treatment status, 6-week-old infants without HIV infection were assigned to receive extended nevirapine prophylaxis or placebo either until 6 months or until breast-feeding stopped, whichever came first. Kaplan-Meier analyses allowed between-group comparison of the primary efficacy outcome of HIV-1 infection in infants at 6 months. Adverse reactions were also recorded in both groups as safety endpoints. Of 1527 infants randomly assigned between June 19, 2008, and March 12, 2010, 762 were assigned to receive nevirapine, and 765 to receive placebo. Five of these patients were excluded from the primary analyses because they had HIV-1 infection at randomization. HIV-1 infection occurred between 6 weeks and 6 months in 1.1% (95% confidence interval [CI], 0.3% - 1.8%) of infants who received extended nevirapine, and in 2.4% (95% CI, 1.3% - 3.6%) of those who received placebo. Reduction in transmission associated with extended nevirapine was 54% (difference, 1.3%; 95% CI, 0% - 2.6%; P = .049). At 6 months, both groups had similar mortality rates (1.2% with nevirapine vs 1.1% with placebo; P = .81) and combined HIV infection and mortality rates (2.3% vs 3.2%; P = .27). The treatment groups had no significant differences in frequency of adverse events, serious adverse events (16% vs 15%), and deaths. Limitations of this study include a lack of adjustment for multiple statistical tests, which could increase the risk for false-positive findings. "After 6 weeks of treatment with once-daily nevirapine, continued use of nevirapine to age 6 months in uninfected infants of breastfeeding mothers with HIV-1 is safe, and results in a greater than 50% reduction in mother-to-child transmission from breastfeeding compared with placebo," the study authors write. "No other study has directly assessed the incremental benefit of extension of nevirapine from age 6 weeks until 6 months to establish whether the extended period is more efficacious and whether there are increased safety issues associated with long-term treatment with nevirapine." The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships. Lancet. Published online December 23, 2011. Abstract

Bacterial Bronchitis Frequent in Children With Chronic Wet Cough

From Medscape Education Clinical Briefs News Author: Laura Newman, MA CME Author: Désirée Lie, MD, MSEd 01/11/2012 Clinical Context According to the current study by Zgherea and colleagues, chronic wet cough, defined as a wet cough that lasts for 4 weeks or more, is easily recognized by parents and pediatricians. Also, it is a major debilitating finding in children with pulmonary disorders such as cystic fibrosis or ciliary dyskinesia and immunodeficiency disorders. However, the diagnosis of chronic bronchitis is not easily accepted in pediatric practice as in adult practice, and it is uncertain what the prevalence of purulent and nonpurulent bronchitis is among children with wet cough. This retrospective study determines the frequency of bacterial infections among children with wet cough, using medical charts and bronchoscopic findings. Study Synopsis and Perspective Purulent bronchitis is common among children with chronic wet cough, according to a retrospective study published online January 9, 2012, in Pediatrics. In addition, 56% of the children in the study, all of whom had been referred to a pediatric pulmonary clinic because of an intractable wet cough, had bacterial infections of the lower airway. The investigators, led by Daniela Zgherea, MD, from the Department of Pediatrics, Maimonides Infants and Children's Hospital, Brooklyn, New York, also found that tracheomalacia was identified on bronchoscopy far more frequently in the 0- to 3-year-old children in their study (30.3%) than in the general pediatric population. The authors raise the need to better understand the etiology and best treatments for these lingering coughs (lasting 4 weeks or more). "The diagnosis of 'chronic bacterial bronchitis' is not readily accepted in the pediatric population, however, as many physicians assume that is an 'adult' respiratory illness associated with tobacco smoking," the authors write. In the study, investigators reviewed the charts and bronchoscopy findings of 197 children referred by their primary care physician to a pediatric pulmonary clinic at Maimonides Infants and Children's Hospital because of a persistent chronic wet cough. More than half of the study patients (55%) were aged 0 to 3 years, 36% were aged 3 to 7 years, and 9% were older than 7 years of age. One third of the children in the youngest group had bronchoscopy-confirmed laryngomalacia or tracheomalacia. However, the frequency of laryngomalacia and tracheomalacia did not appear to be associated with purulent or nonpurulent bronchitis. Bacterial cultures were positive in 91 children (46%). Of these, nontypable Haemophilus influenzae accounted for nearly half (49%) of the positive cultures, Streptococcus pneumoniae accounted for 20%, Moraxella catarrhalis accounted for 17%, and Staphylococcus aureus accounted for 12%. Bacterial infections were more frequently associated with purulent bronchitis (84%) than with nonpurulent bronchitis (16%; P < .001). Regarding the 16% of children with purulent bronchitis who had negative cultures, the authors hypothesize these may be false-negatives, in part resulting from the timing of sputum collection relative to antibiotics use. "The presence of a relatively large group of children with nonpurulent bronchitis and negative bacterial cultures among our study patients may point out the existing connection between chronic wet cough and asthma, which is also suggested by findings of [bronchoalveolar lavage] eosinophilia seen in some children in our study," the authors write. However, the study was unable to determine whether asthma contributed to the persistent cough. They recommend further prospective studies of the relationship between chronic wet cough, bacterial infections, and asthma in children. The authors have disclosed no relevant financial relationships. Pediatrics. Published online January 9, 2012. Abstract

Acute Macular Degeneration

From Medscape Education Clinical Briefs Frequent Aspirin Use Linked With Early and Wet Late AMD CME/CE Daniel M. Keller, PhD CME Author: Laurie Barclay, MD 01/12/2012 Clinical Context Previous findings have been inconsistent regarding associations between aspirin use and age-related macular degeneration (AMD). Several studies suggested a harmful effect of aspirin on AMD, whereas other studies showed no evidence of an association, or possibly a nonsignificant benefit. Aspirin use is widespread and is often indicated for its antiplatelet activity as well as for its analgesic effect. The objectives of the European Eye Study by de Jong and colleagues were to estimate the prevalence of AMD across Europe and to investigate possible risk factors, particularly exposure to solar radiation and antioxidant vitamin use. This analysis aimed to study associations between aspirin use and early and late AMD. Study Synopsis and Perspective The risks for early AMD and wet late AMD are associated with frequent aspirin use, and the risk increases with greater aspirin consumption, European researchers reported in an article published in the January 2012 issue of Ophthalmology. The results, from the large, population-based, cross-sectional European Eye Study, suggest caution in recommending aspirin to patients with early or late AMD who may take it for other conditions, such as prevention of cardiovascular disease (CVD). When adjusted for all potential confounders of age, sex, education, smoking, body mass index, diabetes, CVD, angina, cholesterol, and systolic blood pressure, daily aspirin users had a greater than 2-fold increased risk for wet AMD when compared with participants who never consumed aspirin. The research, led by Paulus T.V.M. de Jong, MD, PhD, emeritus professor of ophthalmic epidemiology at the Academic Medical Center and a member of the Netherlands Institute of Neuroscience in Amsterdam involved 4691 participants aged 65 years or older who were chosen by taking a random sampling from population registers in 7 countries. Field workers interviewed the participants about sociodemographic, health, and lifestyle factors. Aspirin use was quantified as never (n = 2760), monthly or less (n = 766), weekly but not daily (n = 326), or daily (n = 839). Digitized color fundus images were recorded at each participating center and sent to Rotterdam, the Netherlands, where 2 staff members graded them according to the International Classification and Grading System for Age-Related Maculopathy and AMD. Grades 1, 2, and 3 corresponded to early AMD, and grade 4 corresponded to late AMD, which was subdivided into dry or wet AMD. Wet AMD was defined as serous or hemorrhagic detachment of the retinal pigment epithelium, a subretinal neovascular membrane, subretinal hemorrhage, or other signs. Participants with grade 0 (macula free of drusen or pigmentary irregularities or with hard drusen) were the control patients. The main outcome measure was the odds ratio (OR) for AMD in aspirin users. Daily aspirin users were older, were less likely to smoke, and had lower blood pressure and cholesterol levels, but more CVD and angina. Among all participants, 36.4% had early AMD, and 3.3% had late AMD, of whom about two thirds had wet and one third dry AMD. More frequent aspirin use was associated with higher grades of AMD. One third of the individuals with wet AMD consumed aspirin daily compared with only 16% of control participants. Similar trends in ORs were seen when investigators adjusted only for age and sex, or for age, sex, and CVD (both P < .001 for the trends). There was no significant association for aspirin with wet AMD according to the presence or absence of CVD or angina (ie, AMD was independent of CVD or angina). For the 42 cases of dry AMD with information on aspirin use and potential confounders, dry AMD was not associated with aspirin use after adjustment for age and sex. Limitations of the study include its cross-sectional and retrospective nature, with the possibility of recall error about aspirin use and possible confounders. In addition, there were no data on the doses of aspirin or the use of other antiplatelet or anticoagulant drugs. Dr. de Jong told Medscape Medical News that "people should be aware that aspirin, often just bought over the counter without prescription, may have adverse effects — apart from major gastrointestinal and other bleeds, also for AMD." He said future randomized trials will be necessary to find out whether there is a critical dose of aspirin in relation to the risk for AMD. On the basis of this study and the body of literature, he said, he would advise people who have early or late AMD not to take aspirin for pain, and if they are taking it for primary prevention of CVD to discuss with their physicians whether it is wise to continue doing so. "For secondary prevention...the benefits of daily aspirin outweigh the risks," Dr. de Jong said. George Williams, MD, chairman of the Department of Ophthalmology and director of the Beaumont Eye Institute at William Beaumont Hospital in Royal Oak, Michigan; clinical professor of ophthalmology and biomedical sciences at Oakland University William Beaumont School of Medicine; and an expert correspondent for the American Academy of Ophthalmology, commented to Medscape Medical News that the study "raises some interesting questions" but "does not provide a definitive answer on the role of aspirin in the development of AMD." There has not been a consistent trend among studies looking at this question, and differing inclusion criteria and definitions of AMD severity make it difficult to compare studies. "The strength of this study is that they have photographic documentation of the status of the macular degeneration," Dr. Williams said. "In some of the other studies, we know exactly how much aspirin people were on because they were randomized to aspirin. However, in those studies we are relying upon less robust data to determine the degree of macular degeneration." Another potential confounder is that aspirin is a component of many over-the-counter medications that people do not recognize as containing the drug. Dr. Williams said he is concerned that although the study started with almost 4700 patients, in the end there were only 36 patients in the wet AMD group who had been taking daily aspirin. He said he would want to see larger numbers before becoming more comfortable with an association of aspirin with wet AMD. He noted that the value of prophylactic aspirin for the prevention of CVD is coming under increasing scrutiny. "It's going to require physicians to take the time to talk to their patients about the possibility that there may be an association [of aspirin with the development of AMD]," he said. "So patients who are on aspirin should discuss with their prescribing physician the reasons why they're on aspirin, what the benefits are, and then make a decision as to whether they wish to continue. But at this point I certainly see no definitive reason for people to stop aspirin when it's indicated for their overall health." A disadvantage for primary care physicians is that most will not have a comprehensive knowledge of the status of their patients' macular degeneration, "so it will require communication between primary care providers and ophthalmologists to come up with the best solution for a specific patient," Dr. Williams advised. Dr. de Jong has disclosed no relevant financial relationships. Dr. Williams is a consultant/advisor to Alcon Laboratories, Allergan, Neurotech, OptiMedica, Pfizer, and Thrombogenics. He also has received grant support from Alcon Laboratories, Allergan, Genentech, and Neurotech, is an equity owner of Nu-Vue Technologies, OptiMedica, and Thrombogenics, and has patent/royalty income from Nu-Vue Technologies. Ophthalmology. 2012;119:112-118. Abstract

Most US Teenagers Lack Hepatitis A Immunization

From Medscape Medical News Daniel M. Keller, PhD January 23, 2012 — Most adolescents in the United States lacked immunization for hepatitis A in 2009, leaving them susceptible to hepatitis A infection going into adulthood. In the first study to evaluate hepatitis A vaccine (HepA) coverage in the United States, using data from healthcare providers, researchers from the US Centers for Disease Control and Prevention in Atlanta, Georgia, reported in an article published online January 23 and in the February print issue of Pediatrics that nationally, 1-dose coverage with HepA among adolescents was 42.0%. Of those teenagers who were vaccinated, approximately 70% completed the 2-dose series, which is equivalent to 29.5% of the entire cohort of adolescents surveyed. Using data from the 2009 National Immunization Survey-Teen (N = 20,066) to determine HepA coverage among 13- to 17-year-olds, Christina Dorell, MD, MPH, and coauthors found that among states in which the Advisory Committee on Immunization Practices (ACIP) has recommended universal child vaccination at 2 years since 1999 (group 1), 1-dose coverage was 74.3%. Among states with an ACIP recommendation for consideration for child vaccination at 2 years since 1999 (group 2), the rate was 54.0%, and among states with a recommendation of universal child vaccination at 1 year of age since 2006 (group 3), the rate was 27.8%. The researchers noted that 1 dose of vaccine induces protective levels of antibodies in more than 97% of infants and children, and a second dose is thought to confer long-lasting immunity. Because hepatitis A virus is highly infectious and will probably continue to be introduced to the United States through imported food, international travel, international adoption, and other means, the authors recommend continued vaccination of adolescents to protect them during this period, and as they mature into adults. In this way, the prevalence of significant hepatitis A disease may be minimized, lowering morbidity, hospitalizations, lost work, and the large expense of containment efforts. The authors have disclosed no relevant financial relationships. Pediatrics. 2012;129:213-221. Abstract

Adopting a Healthy Diet May Help ADHD

From Medscape Medical News > Psychiatry Megan Brooks January 17, 2012 — When drug therapy fails to control attention-deficit/hyperactivity disorder (ADHD) or is unacceptable, adopting a "healthy" diet, eliminating items known to predispose to ADHD, and adding omega-3 fatty acid supplementation may be worth trying, new research suggests. "The recent increase of interest in this form of therapy for ADHD, and especially in the use of omega supplements, significance of iron deficiency, and the avoidance of the 'Western pattern' diet, make the discussion timely," the authors write. Many parents and physicians continue to be interested in how diet and dietary changes, particularly parents wanting to find an alternative to stimulant medication or a complementary therapy. Nevertheless, it remains a "controversial" topic, the authors note. For their review, J. Gordon Millichap, MD, and Michelle M. Yee, CPNP, from Children’s Memorial Hospital in Chicago, Illinois, searched PubMed for relevant studies on the role of diet and dietary supplements for the treatment of children with ADHD. They note that their recommendations on diet and dietary supplements are based on a critical review of the data and their own experience in a neurology clinic for children and adolescents with ADHD. The study was published on January 9 in Pediatrics. Elimination Diets Not Advisable Perhaps the "most promising and practical" complementary or alternative treatment, write Dr. Millichap and Ms. Yee, is adopting a "healthy" dietary pattern, omitting items shown to predispose to ADHD or to make the condition worse. These items include fast foods, red meat, processed meat, potato chips, high-fat dairy foods, and soft drinks. They point to a "provocative" study published last year, which found a link between ADHD in adolescents and a "Western-style" dietary pattern that was high in fat, refined sugars, and sodium and low in fiber, folate, and omega-3 fatty acids (Howard et al, J Atten Disord. 2011;15:403-411). ADHD was not associated with a "healthy" dietary pattern rich in fish, vegetables, fruit, legumes, and whole-grain foods. Adopting a healthy dietary pattern "may offer an alternative method of treatment of ADHD and less reliance on medications," the authors of the current study write. They also note that although many parents report worsening of hyperactivity symptoms after consumption of foods and drinks containing sugar or aspartame — and isolated reports support the parents' observations — most controlled studies have failed to find a significant harmful effect of sugar or aspartame, the authors note. Additionally, they say that the elimination of sugar and aspartame and adapting additive-free diets are complicated, disruptive, and often impractical; such measures are indicated only in select cases. Fatty Acid Supplements May Be Helpful Low levels of long-chain polyunsaturated fatty acids (PUFA) have been reported in the plasma and red cells of children with ADHD in comparison with their ADHD-free peers, Dr. Millichap and Ms. Yee note. Some studies have demonstrated a reduction in ADHD symptoms with PUFA supplementation, although no definitive conclusions can be drawn. However, the authors note that "on the basis of reports of efficacy and safety, we use doses of 300 to 600 mg/day of omega-3, and 30 to 60 mg/day of omega-6 fatty acids, continued for 2 or 3 months, or longer if indicated." "As initial or add-on therapy, we have occasional reports of improved school grades and lessening of symptoms of ADHD, without occurrence of adverse effects. Most parents are enthusiastic about trying the diet supplements, despite our explanation of only possible benefit and lack of proof of efficacy," they note. They also note that iron and zinc supplementation is advisable when there is a known deficiency in these minerals, and this may "enhance the effectiveness" of stimulant therapy. Dr. Millichap and Ms. Yee have disclosed no relevant financial relationships. Pediatrics. Published online January 9, 2012. Abstract

No Benefit of Additional Foods, Fluids in Breast-Fed Infants

From Medscape Education Clinical Briefs News Author: Lara C. Pullen, PhD CME Author: Laurie Barclay, MD 12/21/2011 Clinical Context Breast-feeding provides all of the nutritional, immunologic, and psychological requirements needed for a healthy, term infant to thrive, and it also benefits maternal health and well-being. Health organizations throughout the world recommend exclusive breast-feeding for 6 months. However, mothers in many countries and communities supplement breast-feeding with other fluids or foods before the infant is 6 months old, suggesting perceived benefits of early supplementation or lack of awareness of the possible risks. The objective of this Cochrane review by Becker and colleagues was to evaluate the benefits and harms of supplementation for full-term healthy breast-fed infants and to examine the timing and type of supplementation. Study Synopsis and Perspective Current research supports the World Health Organization's recommendation for exclusive breast feeding for the first 6 months after birth, according to a Cochrane review that was designed to assess the benefits and harms of supplementation for full-term healthy breast-fed infants up to 6 months of age. The systematic literature review included 6 trials (814 infants) and was published online December 7 and in the December issue of the Cochrane Library. The review included randomized or quasi-randomized controlled trials in infants younger than 6 months of age and compared exclusive breast-feeding vs breast-feeding with any additional food or fluids. All of the studies were conducted many years ago (1982 - 1999). There was a significant difference favoring exclusive breast-feeding over fluid supplementation up to and including week 20 (risk ratio, 1.45; 95% confidence interval [CI], 1.05 - 1.99). The review also raised concerns that the addition of glucose water at 70 mL/kg/day might displace nutrients provided by breast milk. Three trials examined infant morbidity and found a statistically, but not clinically, significant difference in temperature at 72 hours (mean difference [MD], 0.10°; 95% CI, 0.01° - 0.19°) in glucose-supplemented infants compared with exclusively breast-fed infants. In addition, serum glucose levels were higher in glucose-supplemented infants at 24 hours, but not at 48 hours (−0.24 mmol/L; 95% CI, −0.51 to 0.03). In addition to finding no benefit from fluid supplementation of newborns or infants (up to age 6 months), the review found possible negative effects on the duration of breast-feeding from the brief use of additional water or glucose water. The studies were independently selected for inclusion in the review by 2 authors, and 3 authors extracted the data and assessed the risk for bias. The review was performed because although the World Health Organization and other organizations recommend exclusive breast-feeding for 6 months, the addition of other fluids or foods is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. Although the review focused on the effects on the infant during the first 6 months of life, the authors noted that supplementation with nonhuman milk may have effects on the developing gastrointestinal, metabolic, and immune systems that persist through childhood and beyond. The review also did not include the effect of an artificial teat on infant sucking skills or its role as a potential source of infection. The review was also limited in that it only looked at effects on the infants and did not include the possible effects of supplementation on the mother. These could include engorgement, mastitis, earlier return to fertility, nutritional status, maternal use of time, and maternal mental health and financial effects. The authors have disclosed no relevant financial relationships. Cochrane Library. Published online December 7, 2011. Abstract Related Link Information about The Baby-Friendly Hospital Initiative, which discourages infant supplementation, was developed by WHO and UNICEF and is available online. Clinical Implications According to a Cochrane review of randomized controlled trials in healthy, breast-fed newborn infants, the benefits or harms of supplementation or the effect of timing and type of supplementation could not be determined. However, brief use of additional water or glucose water had no detectable benefit to newborn infants and possible negative effects on the duration of breast-feeding. For infants 4 to 6 months old, there was no detectable benefit from additional foods nor any detectable risks related to morbidity or weight change. This Cochrane review found no evidence to disagree with international health associations' recommendation for exclusive breast-feeding for healthy infants for the first 6 months.