From Medscape Medical News
American Academy of Pediatrics Updates Guidelines for Use of Rotavirus Vaccine
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD, FAAFP
04/30/2009
There are now 2 vaccines against rotavirus licensed in the United States: one derived from 5 human-bovine strains (RV5) and one from a single human strain (RV1). Although both vaccines are live, attenuated oral vaccines, the dosing schedule for the 2 vaccines differs.
RV5 should be administered in 3 doses at ages 2, 4, and 6 months, and RV1 is a 2-dose series delivered at ages 2 and 4 months.
The current policy statement from the AAP examines the efficacy and safety data for both vaccines.
Study Highlights
The AAP does not express a preference for the use of RV5 or RV1.
The vaccines have been evaluated in 11 randomized trials involving more than 146,000 infants worldwide.
Both vaccines are well tolerated. They do not appear to promote fever or severe fever more than placebo. RV5 is associated with a small increase in the incidence of vomiting and diarrhea vs placebo.
Intussusception has not been associated with either vaccine, whether in clinical trials or, in the case of RV5, postmarketing analysis.
Both vaccines result in viral shedding in the stool (9% of children receiving RV5 and 25% of children receiving RV1). However, this viral shedding has not been documented to promote any new infections with rotavirus.
Vaccine efficacy studies demonstrated protection rates of 74% to 87% against any rotavirus disease and 85% to 98% against severe rotavirus disease.
No studies have addressed the interchangeability of the 2 vaccines. Although children should ideally be continued to receive the rotavirus vaccine they began, clinicians should not delay dosing because a product is unavailable. The available vaccine should be used.
A cost-benefit analysis demonstrated that the estimated cost per case of rotavirus averted was $139.00 for RV5 and $94.00 for RV1. However, the researchers cautioned that this cost difference might not be reflected in clinical practice.
Because latex rubber is used in the RV1 applicator, children with severe latex allergy should not receive RV1.
Clinicians should use caution in administering the rotavirus vaccines to children with altered immunocompetence. However, preliminary data suggest that the vaccines may be safe in children with HIV infection in Africa.
Children with moderate to severe acute gastroenteritis or other moderate to severe acute illness may defer the vaccination until a later date. However, children with mild illness should receive the vaccine to avoid failing to complete the series.
No data are available regarding the administration of the vaccines to children with a history of intussusception.
Repeated dosing in children who immediately regurgitate or vomit their dose of rotavirus vaccine is not recommended.
Preterm infants should receive the rotavirus vaccine, and those who are age-eligible should receive the vaccine at the time of discharge from the hospital. This obviates the theoretic risk for transmission of rotavirus in the hospital because of asymptomatic viral shedding after the vaccine.
The maximal age at the first dose of either vaccine is 14 weeks and 6 days, and the maximal age for the last dose of the vaccine is 8 months. The minimal interval between rotavirus vaccines is 4 weeks.
Clinical Implications
RV5 and RV1 are both live, attenuated vaccines, but they are derived from different sources and have different schedules of administration.
The AAP does not recommend one rotavirus vaccine vs the other. Both vaccines are efficacious and do not promote fever more than placebo. Both vaccines may be administered during cases of mild gastroenteritis, but the vaccine should not be readministered when a child regurgitates the dose.
Thursday, December 31, 2009
Management of Common Childhood Poisonings Reviewed
From Medscape Medical News
News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD
03/11/2009;
In 2003, more than 2.4 million reports of toxin exposures were received by poison control centers in the United States. Children younger than 6 years accounted for 51% of exposures; of these, 38% involved children 3 years or younger.
Most exposures involved oral ingestion (76%), occurred in the home (93%), and were unintentional (> 80%).
In addition, most ingestions involved nontoxic substances and were managed at home.
The aim of this article was to review the evaluation and treatment of unintentional toxin ingestions in children younger than 12 years.
Study Highlights
The history of patients with suspected toxin ingestions should include age and sex, time and type of probable exposure, and all medications present in the home
Initial evaluation involves determining whether the patient is symptomatic; any patient who has ingested a toxin and who has respiratory, circulatory, or neurologic symptoms should be transported by ambulance to the nearest emergency department
If the ingestion was witnessed, a nontoxic substance was involved, and the patient appears asymptomatic, a prompt examination by the clinician in the office or a period of observation at home may be appropriate; otherwise, poison control should be consulted, and the patient should be evaluated in the clinician's office or in the emergency department.
In the emergency department, rapid triage is crucial, including airway, respiration, and circulation stabilization.
The most toxic substances to a child include iron, antidepressants, hypoglycemics, cardiovascular drugs, salicylates, anticonvulsants, and illicit drugs.
Iron poisoning is one of the most fatal in children younger than 6 years, especially because as few as 5 to 10 adult ferrous fumarate tablets can kill or seriously harm a child.
An asymptomatic child with suspected toxin ingestion may have ingested a delayed-action medication and should be monitored for a longer period
Identifying toxidromes or symptoms that point to toxin exposure is crucial; therefore, the patient's mental status, vital signs, pupil reactivity, skin moisture and color, bowel sounds, powder or vomit around the mouth, and any unusual breath odors should be noted.
Useful laboratory tests usually include bicarbonate levels, blood glucose levels, electrocardiography, electrolytes, prothrombin time, pulse oximetry, serum acetaminophen levels, and urine human chorionic gonadotropin levels in women of childbearing age.
Appropriate supportive or toxin-specific treatment should be initiated with all childhood poisonings.
Gastric decontamination, such as activated charcoal and gastric lavage, is no longer routinely recommended
It is only recommended when performed by a clinician with experience placing orogastric tubes and when administered within 1 hour of the ingestion.
Activated charcoal decreases the absorption of toxins in the stomach and intestinal tract.
It is most likely to help children who have ingested carbamazepine, dapsone, phenobarbital, quinine, theophylline, salicylates, phenytoin, or valproic acid.
The American Academy of Clinical Toxicology discourages the routine use of activated charcoal except within 1 hour of ingestion (
If used, a charcoal-to-drug ratio of 10:1 is recommended or a dose of 1 to 2 g/kg is recommended for children with ingestions of an unknown quantity. Sorbitol is used to improve taste and transit through the intestinal tract.
Syrup of ipecac is no longer recommended.
Hemodialysis may be appropriate for lithium, salicylate, theophylline, methanol, atenolol, phenobarbital, or valproic acid toxicity.
Psychiatric consultation is appropriate in the setting of intentional ingestion.
Pearls for Practice
In 2003, reports of toxin exposure usually involved children younger than 6 years, were unintentional, involved oral ingestion, and occurred in the home.
Gastric decontamination, such as activated charcoal and gastric lavage, is no longer routinely recommended and should be reserved for the most severe cases, with poison control center support.
Management options should consider the type and amount of substance ingested, potential toxicity, time elapsed since ingestion, and symptoms exhibited.
News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD
03/11/2009;
In 2003, more than 2.4 million reports of toxin exposures were received by poison control centers in the United States. Children younger than 6 years accounted for 51% of exposures; of these, 38% involved children 3 years or younger.
Most exposures involved oral ingestion (76%), occurred in the home (93%), and were unintentional (> 80%).
In addition, most ingestions involved nontoxic substances and were managed at home.
The aim of this article was to review the evaluation and treatment of unintentional toxin ingestions in children younger than 12 years.
Study Highlights
The history of patients with suspected toxin ingestions should include age and sex, time and type of probable exposure, and all medications present in the home
Initial evaluation involves determining whether the patient is symptomatic; any patient who has ingested a toxin and who has respiratory, circulatory, or neurologic symptoms should be transported by ambulance to the nearest emergency department
If the ingestion was witnessed, a nontoxic substance was involved, and the patient appears asymptomatic, a prompt examination by the clinician in the office or a period of observation at home may be appropriate; otherwise, poison control should be consulted, and the patient should be evaluated in the clinician's office or in the emergency department.
In the emergency department, rapid triage is crucial, including airway, respiration, and circulation stabilization.
The most toxic substances to a child include iron, antidepressants, hypoglycemics, cardiovascular drugs, salicylates, anticonvulsants, and illicit drugs.
Iron poisoning is one of the most fatal in children younger than 6 years, especially because as few as 5 to 10 adult ferrous fumarate tablets can kill or seriously harm a child.
An asymptomatic child with suspected toxin ingestion may have ingested a delayed-action medication and should be monitored for a longer period
Identifying toxidromes or symptoms that point to toxin exposure is crucial; therefore, the patient's mental status, vital signs, pupil reactivity, skin moisture and color, bowel sounds, powder or vomit around the mouth, and any unusual breath odors should be noted.
Useful laboratory tests usually include bicarbonate levels, blood glucose levels, electrocardiography, electrolytes, prothrombin time, pulse oximetry, serum acetaminophen levels, and urine human chorionic gonadotropin levels in women of childbearing age.
Appropriate supportive or toxin-specific treatment should be initiated with all childhood poisonings.
Gastric decontamination, such as activated charcoal and gastric lavage, is no longer routinely recommended
It is only recommended when performed by a clinician with experience placing orogastric tubes and when administered within 1 hour of the ingestion.
Activated charcoal decreases the absorption of toxins in the stomach and intestinal tract.
It is most likely to help children who have ingested carbamazepine, dapsone, phenobarbital, quinine, theophylline, salicylates, phenytoin, or valproic acid.
The American Academy of Clinical Toxicology discourages the routine use of activated charcoal except within 1 hour of ingestion (
If used, a charcoal-to-drug ratio of 10:1 is recommended or a dose of 1 to 2 g/kg is recommended for children with ingestions of an unknown quantity. Sorbitol is used to improve taste and transit through the intestinal tract.
Syrup of ipecac is no longer recommended.
Hemodialysis may be appropriate for lithium, salicylate, theophylline, methanol, atenolol, phenobarbital, or valproic acid toxicity.
Psychiatric consultation is appropriate in the setting of intentional ingestion.
Pearls for Practice
In 2003, reports of toxin exposure usually involved children younger than 6 years, were unintentional, involved oral ingestion, and occurred in the home.
Gastric decontamination, such as activated charcoal and gastric lavage, is no longer routinely recommended and should be reserved for the most severe cases, with poison control center support.
Management options should consider the type and amount of substance ingested, potential toxicity, time elapsed since ingestion, and symptoms exhibited.
Saturday, December 26, 2009
Enemas, Oral Laxatives Equally Effective for Childhood Fecal Impaction
MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
December 22, 2009 — Enemas and orally administered laxatives are equally effective in treating rectal fecal impaction (RFI) in functional childhood constipation, according to the results of a randomized controlled trial reported in the December issue of Pediatrics.
"Despite a lack of scientific data, rectal enemas have long been advocated as the best first-line treatment for RFI," write Noor-L-Houda Bekkali, MD, from Academic Medical Centre in Amsterdam, Netherlands, and colleagues. "Two studies showed that oral [polyethylene glycol (PEG)] treatment yielded 95% successful disimpaction....This is the first prospective, randomized, controlled trial evaluating disimpaction with either rectal enemas or orally administered laxatives for children with severe RFI attributable to constipation."
The hypothesis tested by this study was that enemas and PEG would be equally effective in treating RFI but that enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction.
The study sample consisted of 90 children (from 95 who were eligible), aged 4 to 16 years, with functional constipation and RFI. Rectal examination and first CTT measurement were performed, and symptoms of constipation were recorded 1 week before disimpaction. Patients with RFI were randomly assigned to treatment with once-daily enemas or with PEG (1.5 g/kg per day) for 6 consecutive days.
A second CTT measurement was performed during this treatment, as well as a child's behavior questionnaire. Other outcomes included successful rectal disimpaction, frequencies of defecation and fecal incontinence, and presence of abdominal pain and watery stools.
Mean age was 7.5 ± 2.8 years. Of the 90 participants, 60 were boys; 46 were assigned to enema treatment and 44 to PEG, with 5 dropouts in each group. Disimpaction was successful in 80% of patients in the enema group and 68% of the PEG group (P = .28).
Although fecal incontinence and watery stools occurred more often in the PEG group (P < .01), both groups had similar frequency of defecation (P = .64), abdominal pain (P = .33), behavior scores, and CTT normalization (P = .85).
"Enemas and PEG were equally effective in treating RFI in children," the study authors write. "Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI."
Limitations of this study include possible confounding of findings regarding fearful behavior and evaluation of behavior scores only after the start of disimpaction.
"Given the comparable behavior in the 2 groups, disimpaction with enemas should not necessarily be withheld to prevent anxiety," the study authors conclude. "We did not find more fearful behavior in the enema group, which might be explained by the administration of enemas by parents at home instead of by nurses in an unfamiliar environment (hospital), which is more common in practice."
The study authors have disclosed no relevant financial relationships.
Pediatrics. 2009;124:e1108-e1115. Abstract
Clinical Context
The worldwide prevalence of functional constipation in children is 7% to 30%, according to van den Berg and colleagues in the October 2006 issue of the American Journal of Gastroenterology. RFI refers to a large fecal mass on abdominal palpation or rectal examination that is unlikely to be passed on demand, as reported by Benninga and colleagues in the March 2005 issue of the Journal of Pediatric Gastroenterology and Nutrition. Treatment options for RFI include enemas, manual evacuation, and PEG.
This randomized controlled trial assesses the efficacy, effect on CTT, and tolerability of enema vs PEG treatment of RFI in children with functional constipation.
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
December 22, 2009 — Enemas and orally administered laxatives are equally effective in treating rectal fecal impaction (RFI) in functional childhood constipation, according to the results of a randomized controlled trial reported in the December issue of Pediatrics.
"Despite a lack of scientific data, rectal enemas have long been advocated as the best first-line treatment for RFI," write Noor-L-Houda Bekkali, MD, from Academic Medical Centre in Amsterdam, Netherlands, and colleagues. "Two studies showed that oral [polyethylene glycol (PEG)] treatment yielded 95% successful disimpaction....This is the first prospective, randomized, controlled trial evaluating disimpaction with either rectal enemas or orally administered laxatives for children with severe RFI attributable to constipation."
The hypothesis tested by this study was that enemas and PEG would be equally effective in treating RFI but that enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction.
The study sample consisted of 90 children (from 95 who were eligible), aged 4 to 16 years, with functional constipation and RFI. Rectal examination and first CTT measurement were performed, and symptoms of constipation were recorded 1 week before disimpaction. Patients with RFI were randomly assigned to treatment with once-daily enemas or with PEG (1.5 g/kg per day) for 6 consecutive days.
A second CTT measurement was performed during this treatment, as well as a child's behavior questionnaire. Other outcomes included successful rectal disimpaction, frequencies of defecation and fecal incontinence, and presence of abdominal pain and watery stools.
Mean age was 7.5 ± 2.8 years. Of the 90 participants, 60 were boys; 46 were assigned to enema treatment and 44 to PEG, with 5 dropouts in each group. Disimpaction was successful in 80% of patients in the enema group and 68% of the PEG group (P = .28).
Although fecal incontinence and watery stools occurred more often in the PEG group (P < .01), both groups had similar frequency of defecation (P = .64), abdominal pain (P = .33), behavior scores, and CTT normalization (P = .85).
"Enemas and PEG were equally effective in treating RFI in children," the study authors write. "Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI."
Limitations of this study include possible confounding of findings regarding fearful behavior and evaluation of behavior scores only after the start of disimpaction.
"Given the comparable behavior in the 2 groups, disimpaction with enemas should not necessarily be withheld to prevent anxiety," the study authors conclude. "We did not find more fearful behavior in the enema group, which might be explained by the administration of enemas by parents at home instead of by nurses in an unfamiliar environment (hospital), which is more common in practice."
The study authors have disclosed no relevant financial relationships.
Pediatrics. 2009;124:e1108-e1115. Abstract
Clinical Context
The worldwide prevalence of functional constipation in children is 7% to 30%, according to van den Berg and colleagues in the October 2006 issue of the American Journal of Gastroenterology. RFI refers to a large fecal mass on abdominal palpation or rectal examination that is unlikely to be passed on demand, as reported by Benninga and colleagues in the March 2005 issue of the Journal of Pediatric Gastroenterology and Nutrition. Treatment options for RFI include enemas, manual evacuation, and PEG.
This randomized controlled trial assesses the efficacy, effect on CTT, and tolerability of enema vs PEG treatment of RFI in children with functional constipation.
Bruising on Torso and Other Sites Helps Identify Pediatric Trauma Due to Abuse
From Reuters Health Information
NEW YORK (Reuters Health) Dec 07 - In toddlers and small children, bruising on the torso, ear, or neck is suggestive of abuse, according to the developers of a new child abuse screening tool. In infants younger than 4 months, they say, bruising anywhere may be suspicious for abuse.
Dr. Mary Clyde Pierce, from Children's Memorial Hospital, Chicago, and her colleagues were able to create a decision rule that is 97% sensitive and 84% specific in identifying child abuse in bruised youngsters up to four years old.
The rule starts by asking if the bruise is on the torso, ear, or neck (TEN) regions. If so, then the suspicion for abuse is high, provided that an accident in a public setting could not be confirmed. If the bruise is not in a TEN region, then suspicion for abuse is only high if the child is younger than 4 months and an accident in a public setting could not be confirmed.
The findings, which are reported in the December 7th online issue of Pediatrics and will later appear in the January print issue, stem from a study of 95 children, 0 to 48 months of age, who were admitted to a pediatric intensive care unit for trauma. Forty-two of the children had been victims of physical abuse; the other 53 had accidental trauma and served as controls.
Using data on the 71 with bruises - 33 abused children and 38 trauma patients - the researchers derived their bruising clinical decision tool. Twenty-five abused children had bruises in a TEN region compared with just 6 control children.
Abused children also typically had more bruises than did controls. For instance, 18 abused children had more than 4 bruises, while no control children had this many. Among children under 4 months, there were 74 bruises in 14 abused children compared with 9 bruises in 7 controls.
The researchers say their tool correctly identified 32 of 33 abuse victims and 32 of 38 accident victims.
Further studies, the authors conclude, are needed to prospectively test and validate the bruising decision rule.
Pediatrics 2010;125:64-71.
NEW YORK (Reuters Health) Dec 07 - In toddlers and small children, bruising on the torso, ear, or neck is suggestive of abuse, according to the developers of a new child abuse screening tool. In infants younger than 4 months, they say, bruising anywhere may be suspicious for abuse.
Dr. Mary Clyde Pierce, from Children's Memorial Hospital, Chicago, and her colleagues were able to create a decision rule that is 97% sensitive and 84% specific in identifying child abuse in bruised youngsters up to four years old.
The rule starts by asking if the bruise is on the torso, ear, or neck (TEN) regions. If so, then the suspicion for abuse is high, provided that an accident in a public setting could not be confirmed. If the bruise is not in a TEN region, then suspicion for abuse is only high if the child is younger than 4 months and an accident in a public setting could not be confirmed.
The findings, which are reported in the December 7th online issue of Pediatrics and will later appear in the January print issue, stem from a study of 95 children, 0 to 48 months of age, who were admitted to a pediatric intensive care unit for trauma. Forty-two of the children had been victims of physical abuse; the other 53 had accidental trauma and served as controls.
Using data on the 71 with bruises - 33 abused children and 38 trauma patients - the researchers derived their bruising clinical decision tool. Twenty-five abused children had bruises in a TEN region compared with just 6 control children.
Abused children also typically had more bruises than did controls. For instance, 18 abused children had more than 4 bruises, while no control children had this many. Among children under 4 months, there were 74 bruises in 14 abused children compared with 9 bruises in 7 controls.
The researchers say their tool correctly identified 32 of 33 abuse victims and 32 of 38 accident victims.
Further studies, the authors conclude, are needed to prospectively test and validate the bruising decision rule.
Pediatrics 2010;125:64-71.
Monday, December 21, 2009
Inhaled Corticosteroids May Be Superior to Montelukast in Children With Asthma
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
December 9, 2009 — Inhaled corticosteroids (ICSs) may be superior to montelukast (MONT) in children and adolescents with asthma, according to the results of an extensive meta-analysis reported in the November 27 online issue of the Archives of Disease in Childhood.
"Asthma is one of the most common chronic diseases in children worldwide," write Jose A. Castro-Rodriguez, MD, PhD, from the School of Medicine, Pontificia Universidad Católica de Chile, and Gustavo J. Rodrigo, MD, from Hospital Central de las Fuerzas Armadas in Montevideo, Uruguay.
"All current international guidelines recommend the use of low-dose (200-400 mcg of beclomethasone [BDP] or equivalent) [ICS] as the preferred controller therapy, with leukotriene receptor antagonist (LTRA) as an alternative, for the management of persistent asthma in children (5-11 years of age) and adolescents....
The objective of this systematic review is to compare the efficacy of ICS vs. [MONT] (the most common LTRA use in children worldwide) and vs. MONT add-on to ICS in schoolchildren and adolescents with persistent asthma."
A search of Medline, Embase, and Central databases identified randomized, prospective, controlled trials published from January 1996 to November 2009. Inclusion criteria were a minimum of 4 weeks of ICS vs MONT and of ICS vs MONT+ICS, with primary outcome of asthma exacerbations requiring systemic corticosteroids. Secondary outcomes were pulmonary function, study withdrawal or hospitalization because of asthma exacerbations requiring systemic corticosteroids, change in symptoms score, rescue-medication-free days, albuterol use, adverse effects, and adherence.
Inclusion criteria were met in 18 of 124 studies identified. Of these 18 studies, which enrolled a total of 3757 patients, 13 compared ICS vs MONT, 3 compared ICS vs MONT+ICS, and 2 compared ICS vs MONT vs ICS+MONT.
Compared with patients receiving MONT, those receiving an ICS had a significantly decreased risk for asthma exacerbations requiring systemic corticosteroids (relative risk [RR], .83; 95% confidence interval [CI], .72 - .96; P = .01). This finding appeared to be independent of study quality, sponsorship, and study duration, based on post hoc analysis.
Children treated with an ICS also fared better than those treated with MONT in terms of pulmonary function (final forced expiratory volume in 1 second [FEV1] percentage predicted, change from baseline FEV1 percentage, final morning PEF) and clinical parameters (albuterol use, symptom score, rescue medication-free days, and study withdrawals resulting from asthma exacerbations requiring systemic corticosteroids).
In 2 studies comparing MONT as add-on therapy to ICS vs ICS alone, there was no significant difference in primary or secondary outcomes.
"Schoolchildren and adolescents with mild-persistent asthma treated with ICS had less ... [asthma exacerbations requiring systemic corticosteroids] and better lung function and asthma control than with MONT," the review authors write. "There is insufficient data to determine if the addition of MONT to ICS improves outcome."
Limitations of this review are that the analysis of the main outcome was based on only 7 studies (representing 65% of the total sample) and that stratification of studies based on different relevant factors was not always possible.
Arch Dis Child. Published online November 27, 2009.
Clinical Context
According to the 2007 Guidelines for the Diagnosis and Management of Asthma from the National Heart, Lung, and Blood Institute, the preferred controller treatment for persistent asthma in children aged 5 to 11 years and adolescents is an ICS, whereas the alternative treatment is leukotriene receptor antagonist.
A meta-analysis by Ducharme and di Salvio, published online July 24, 2004, in the Cochrane Database of Systematic Reviews, found that an ICS vs leukotriene receptor antagonist was more effective in decreasing the number of asthma exacerbations requiring systemic corticosteroids. A meta-analysis by Ducharme, published online July 23, 2001, in the Cochrane Database of Systematic Reviews, noted that adding leukotriene receptor antagonist treatment to ICS treatment vs ICS treatment alone did not reduce the exacerbations requiring systemic corticosteroids.
This systematic review includes subsequent studies in children with mild to moderate persistent asthma to compare treatment with ICS vs leukotriene receptor antagonist (MONT) vs MONT added to ICSs for the prevention of severe asthma exacerbation requiring systemic corticosteroids, improvement in lung function, and improvement in asthma control.
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
December 9, 2009 — Inhaled corticosteroids (ICSs) may be superior to montelukast (MONT) in children and adolescents with asthma, according to the results of an extensive meta-analysis reported in the November 27 online issue of the Archives of Disease in Childhood.
"Asthma is one of the most common chronic diseases in children worldwide," write Jose A. Castro-Rodriguez, MD, PhD, from the School of Medicine, Pontificia Universidad Católica de Chile, and Gustavo J. Rodrigo, MD, from Hospital Central de las Fuerzas Armadas in Montevideo, Uruguay.
"All current international guidelines recommend the use of low-dose (200-400 mcg of beclomethasone [BDP] or equivalent) [ICS] as the preferred controller therapy, with leukotriene receptor antagonist (LTRA) as an alternative, for the management of persistent asthma in children (5-11 years of age) and adolescents....
The objective of this systematic review is to compare the efficacy of ICS vs. [MONT] (the most common LTRA use in children worldwide) and vs. MONT add-on to ICS in schoolchildren and adolescents with persistent asthma."
A search of Medline, Embase, and Central databases identified randomized, prospective, controlled trials published from January 1996 to November 2009. Inclusion criteria were a minimum of 4 weeks of ICS vs MONT and of ICS vs MONT+ICS, with primary outcome of asthma exacerbations requiring systemic corticosteroids. Secondary outcomes were pulmonary function, study withdrawal or hospitalization because of asthma exacerbations requiring systemic corticosteroids, change in symptoms score, rescue-medication-free days, albuterol use, adverse effects, and adherence.
Inclusion criteria were met in 18 of 124 studies identified. Of these 18 studies, which enrolled a total of 3757 patients, 13 compared ICS vs MONT, 3 compared ICS vs MONT+ICS, and 2 compared ICS vs MONT vs ICS+MONT.
Compared with patients receiving MONT, those receiving an ICS had a significantly decreased risk for asthma exacerbations requiring systemic corticosteroids (relative risk [RR], .83; 95% confidence interval [CI], .72 - .96; P = .01). This finding appeared to be independent of study quality, sponsorship, and study duration, based on post hoc analysis.
Children treated with an ICS also fared better than those treated with MONT in terms of pulmonary function (final forced expiratory volume in 1 second [FEV1] percentage predicted, change from baseline FEV1 percentage, final morning PEF) and clinical parameters (albuterol use, symptom score, rescue medication-free days, and study withdrawals resulting from asthma exacerbations requiring systemic corticosteroids).
In 2 studies comparing MONT as add-on therapy to ICS vs ICS alone, there was no significant difference in primary or secondary outcomes.
"Schoolchildren and adolescents with mild-persistent asthma treated with ICS had less ... [asthma exacerbations requiring systemic corticosteroids] and better lung function and asthma control than with MONT," the review authors write. "There is insufficient data to determine if the addition of MONT to ICS improves outcome."
Limitations of this review are that the analysis of the main outcome was based on only 7 studies (representing 65% of the total sample) and that stratification of studies based on different relevant factors was not always possible.
Arch Dis Child. Published online November 27, 2009.
Clinical Context
According to the 2007 Guidelines for the Diagnosis and Management of Asthma from the National Heart, Lung, and Blood Institute, the preferred controller treatment for persistent asthma in children aged 5 to 11 years and adolescents is an ICS, whereas the alternative treatment is leukotriene receptor antagonist.
A meta-analysis by Ducharme and di Salvio, published online July 24, 2004, in the Cochrane Database of Systematic Reviews, found that an ICS vs leukotriene receptor antagonist was more effective in decreasing the number of asthma exacerbations requiring systemic corticosteroids. A meta-analysis by Ducharme, published online July 23, 2001, in the Cochrane Database of Systematic Reviews, noted that adding leukotriene receptor antagonist treatment to ICS treatment vs ICS treatment alone did not reduce the exacerbations requiring systemic corticosteroids.
This systematic review includes subsequent studies in children with mild to moderate persistent asthma to compare treatment with ICS vs leukotriene receptor antagonist (MONT) vs MONT added to ICSs for the prevention of severe asthma exacerbation requiring systemic corticosteroids, improvement in lung function, and improvement in asthma control.
Friday, December 18, 2009
Delaying Solid Foods in Infant Diet May Increase Later Risk for Allergies
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
December 17, 2009 — Late introduction of solid foods into the infant diet is associated with an increased risk for allergic sensitization to food and inhalant allergens at age 5 years, according to the results of a prospective, birth cohort study reported online in the December 7 issue of Pediatrics.
"The recommendation of exclusive breastfeeding for the first 6 months for the prevention of allergic diseases may lack strong scientific evidence," write Bright I. Nwaru, MPhil, MSc, from University of Tampere in Tampere, Finland, and colleagues.
"Conversely, increased risk for atopic dermatitis, eczema, and allergic sensitization (with or without symptoms) has been associated with delayed introduction of egg, milk, cereals, and other solids....In the present study, we aimed to assess the association between age at the introduction of different solid foods during the first year of life and food and inhalant allergic sensitizations in a cohort of 5-year-old children with HLA [human leukocyte antigen]-conferred susceptibility to type 1 diabetes, taking into account reverse causality."
The investigators analyzed data regarding breast-feeding, age when solid foods were introduced, and allergen-specific immunoglobulin E (IgE) levels at 5 years from 994 children with HLA-conferred susceptibility to type 1 diabetes mellitus who were enrolled in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) nutrition study. Logistic regression allowed analysis of the association between age at the introduction of solid foods and allergic sensitization.
Median duration of exclusive breast-feeding was 1.8 months (range, 0 -10 months). Late dietary introduction of potatoes (> 4 months), oats (> 5 months), rye (> 7 months), wheat (> 6 months), meat (> 5.5 months), fish (> 8.2 months), and eggs (> 10.5 months) was directly and significantly associated with sensitization to food allergens, after adjustment for potential confounders.
Late introduction of potatoes, rye, meat, and fish was significantly associated with sensitization to any inhalant allergen.
Eggs, oats, and wheat were the most important foods related to sensitization to food allergens, in models that included all solid foods that were significantly related to the endpoints. For sensitization to inhalant allergens, potatoes and fish were the most important foods. When parental allergic rhinitis and asthma were considered, the investigators found no evidence of reverse causality.
"Late introduction of solid foods was associated with increased risk of allergic sensitization to food and inhalant allergens," the study authors write. "Our observations in the present study are in accordance with reports showing that delayed introduction of solid foods may not prevent the development of allergic diseases in children."
Limitations of this study include short median duration of exclusive breast-feeding in the study population and selection of birth cohort based on HLA-conferred susceptibility to type 1 diabetes, limiting generalizability. In addition, the endpoints were sensitization against food and inhalant allergens, so these results may not indicate the effects of timing of the introduction of solid foods on actual asthma, atopic eczema, or other clinical allergic outcomes. The number of these endpoints was small, resulting in insufficient statistical power for any meaningful analysis.
"Extended follow-up monitoring of our study cohort will clarify whether our present observations can be translated into clinical allergic outcomes," the study authors conclude. "These findings challenge the current recommendations regarding infant feeding for the prevention of allergic diseases."
Pediatrics. Published online December 7, 2009. Abstract
Clinical Context
Although exclusive breast-feeding for the first 6 months of life and introduction of solid foods thereafter are currently recommended to prevent allergic diseases in children, evidence to support this advice is limited. Among the few studies that have attempted to address this issue, the results are inconsistent.
Reverse causality must also be considered in assessing the relationship between the timing of the introduction of solid foods and the development of allergic diseases. Families in which there is positive family history of allergic diseases, or in whom infants have early signs of allergy, may delay introducing solids into the infant diet, thereby masking any temporal relationship between the introduction of solid foods and the development of allergies.
Ages at which dietary introduction was considered to be late was older than 4 months for potatoes, older than 5 months for oats, older than 7 months for rye, older than 6months for wheat, older than 5.5 months for meat, older than 8.2 months for fish, and older than 10.5 months for eggs.
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
December 17, 2009 — Late introduction of solid foods into the infant diet is associated with an increased risk for allergic sensitization to food and inhalant allergens at age 5 years, according to the results of a prospective, birth cohort study reported online in the December 7 issue of Pediatrics.
"The recommendation of exclusive breastfeeding for the first 6 months for the prevention of allergic diseases may lack strong scientific evidence," write Bright I. Nwaru, MPhil, MSc, from University of Tampere in Tampere, Finland, and colleagues.
"Conversely, increased risk for atopic dermatitis, eczema, and allergic sensitization (with or without symptoms) has been associated with delayed introduction of egg, milk, cereals, and other solids....In the present study, we aimed to assess the association between age at the introduction of different solid foods during the first year of life and food and inhalant allergic sensitizations in a cohort of 5-year-old children with HLA [human leukocyte antigen]-conferred susceptibility to type 1 diabetes, taking into account reverse causality."
The investigators analyzed data regarding breast-feeding, age when solid foods were introduced, and allergen-specific immunoglobulin E (IgE) levels at 5 years from 994 children with HLA-conferred susceptibility to type 1 diabetes mellitus who were enrolled in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) nutrition study. Logistic regression allowed analysis of the association between age at the introduction of solid foods and allergic sensitization.
Median duration of exclusive breast-feeding was 1.8 months (range, 0 -10 months). Late dietary introduction of potatoes (> 4 months), oats (> 5 months), rye (> 7 months), wheat (> 6 months), meat (> 5.5 months), fish (> 8.2 months), and eggs (> 10.5 months) was directly and significantly associated with sensitization to food allergens, after adjustment for potential confounders.
Late introduction of potatoes, rye, meat, and fish was significantly associated with sensitization to any inhalant allergen.
Eggs, oats, and wheat were the most important foods related to sensitization to food allergens, in models that included all solid foods that were significantly related to the endpoints. For sensitization to inhalant allergens, potatoes and fish were the most important foods. When parental allergic rhinitis and asthma were considered, the investigators found no evidence of reverse causality.
"Late introduction of solid foods was associated with increased risk of allergic sensitization to food and inhalant allergens," the study authors write. "Our observations in the present study are in accordance with reports showing that delayed introduction of solid foods may not prevent the development of allergic diseases in children."
Limitations of this study include short median duration of exclusive breast-feeding in the study population and selection of birth cohort based on HLA-conferred susceptibility to type 1 diabetes, limiting generalizability. In addition, the endpoints were sensitization against food and inhalant allergens, so these results may not indicate the effects of timing of the introduction of solid foods on actual asthma, atopic eczema, or other clinical allergic outcomes. The number of these endpoints was small, resulting in insufficient statistical power for any meaningful analysis.
"Extended follow-up monitoring of our study cohort will clarify whether our present observations can be translated into clinical allergic outcomes," the study authors conclude. "These findings challenge the current recommendations regarding infant feeding for the prevention of allergic diseases."
Pediatrics. Published online December 7, 2009. Abstract
Clinical Context
Although exclusive breast-feeding for the first 6 months of life and introduction of solid foods thereafter are currently recommended to prevent allergic diseases in children, evidence to support this advice is limited. Among the few studies that have attempted to address this issue, the results are inconsistent.
Reverse causality must also be considered in assessing the relationship between the timing of the introduction of solid foods and the development of allergic diseases. Families in which there is positive family history of allergic diseases, or in whom infants have early signs of allergy, may delay introducing solids into the infant diet, thereby masking any temporal relationship between the introduction of solid foods and the development of allergies.
Ages at which dietary introduction was considered to be late was older than 4 months for potatoes, older than 5 months for oats, older than 7 months for rye, older than 6months for wheat, older than 5.5 months for meat, older than 8.2 months for fish, and older than 10.5 months for eggs.
Most Patients With Vaccine Allergy May Be Safely Vaccinated
From Medscape
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
Adverse events associated with vaccines are rare and are frequently transient. For example, transient rash may occur in 3% to 5% of persons receiving the measles and varicella vaccines, and these rashes can resemble those of clinical measles or varicella. The MMR vaccine can also promote thrombocytopenia, which does not usually lead to clinical consequences. The rubella vaccine causes acute arthritis among approximately 15% of women.
Other adverse events, such as encephalopathy with pertussis vaccination or Guillain-Barré syndrome after influenza vaccine, are quite serious but are also so rare that an exact estimate regarding their prevalence is difficult. Allergic reactions to vaccination could also be included in this rare-but-serious category, and the current practice parameter suggests the best strategy in caring for a patient with suspected allergy to a vaccine.
October 20, 2009 — Most patients with vaccine allergy may be safely vaccinated, according to a practice parameter published in the October issue of the Annals of Allergy, Asthma & Immunology. However, the new guidelines also recommend that patients with suspected allergy to vaccines or vaccine components be evaluated by an allergist or immunologist vs simply avoiding future immunizations, which could leave patients at higher risk for infectious disease.
The new recommendations were issued by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.
"Local, injection site reactions and constitutional symptoms, especially fever, are common after vaccinations and do not contraindicate future doses," chief editor John M. Kelso, MD, from the Division of Allergy, Asthma & Immunology at Scripps Clinic in San Diego, California, said in a news release.
Guidelines Not Provided in Other Reviews
The practice parameter contains detailed and specific guidelines not contained in previously published reviews. It offers a practical, peer-reviewed, evidence-based guide to assist primary care clinicians as well as specialists in allergy and immunology in assessing and treating patients with suspected allergy to vaccines.
The guidelines provide general and vaccine-specific recommendations for skin testing to vaccines and components, serum-specific immunoglobulin E (IgE) in vitro antibody testing, serologic testing for protective antibody responses to vaccines, vaccine administration, and avoidance. If this practice parameter is implemented, most patients who avoid vaccination because of allergy concerns will be able to be vaccinated appropriately.
Of approximately 235 million doses of vaccines given annually in the United States, only 1 dose per million causes anaphylaxis. Furthermore, death caused by vaccine-induced anaphylaxis is extremely uncommon.
The guidelines recommend reporting all serious events after vaccination to the Vaccine Adverse Event Reporting System of the Centers for Disease Control and Prevention and US Food and Drug Administration.
Responsible Allergens
Patients with suspected anaphylactic reactions to vaccines should be examined by an allergist to identify the allergen responsible for IgE-mediated reaction and to recommend optimal treatment. Typically, the responsible allergen is one of the vaccine components vs the specific antigen needed for immunization. Potentially allergenic vaccine components may include gelatin, egg protein, rarely yeast, latex from the vial stopper or syringe plungers, neomycin, or thimerosal.
"Gelatin, which is added to many vaccines as a stabilizer, is either bovine or porcine, which are extensively cross-reactive," Dr. Kelso said. "We recommend that a history of allergy to the ingestion of gelatin should be sought before administering a gelatin-containing vaccine....However rare, if a patient gives a history of an immediate-type reaction to yeast, latex, neomycin or thimerosal, we recommend that it be investigated with skin testing before immunization with a vaccine containing these constituents."
Skin testing may include prick test with full-strength vaccine (or diluted vaccine if there is a history of life-threatening reaction). If results of the prick test with full strength vaccine are negative, intradermal testing can be performed with 0.02-mL vaccine 1:100. Skin tests to vaccine components may include prick tests with commercial extracts of whole egg or egg white (influenza and yellow fever vaccines), chicken (yellow fever vaccine), or Saccharomyces cerevisiae yeast (hepatitis B vaccine and human papillomavirus vaccine).
"The MMR (measles and mumps vaccines) and one type of rabies vaccine contain negligible or no egg protein, and can be administered to egg allergic children without prior skin testing," Dr. Kelso said. "Egg protein is present in higher amounts in yellow fever and influenza vaccines and may cause reactions in egg-allergic patients, who should be evaluated by an allergist prior to receiving these vaccines."
A prick test with sugared gelatin may be useful if allergic reactions develop after administration of vaccines that contain gelatin, including some brands of diphtheria and tetanus toxoids and acellular pertussis (DTaP), rabies or influenza, Japanese encephalitis, measles, mumps, rubella, varicella, yellow fever, and zoster.
"Persons with a history of allergy to egg or a past reaction to an influenza vaccine may still be able to receive the H1N1 vaccine or the seasonal flu vaccine safely," said co-chief editor James T. Li, MD, Mayo Clinic professor of medicine and chair, Division of Allergy and Immunology. "I believe that anyone with this concern should check with their doctor and consult with an allergist."
Summary Statements in the Parameter
Specific summary statements in the parameter include the following:
Mild local reactions, fever, and other constitutional symptoms after vaccinations occur often and are not a contraindication to subsequent doses.
Anaphylactic reactions after vaccination are rare, with incidence of approximately 1 per million doses.
Even if the vaccine is not clearly the cause, all serious events occurring after vaccine administration should be reported to the Vaccine Adverse Event Reporting System.
Measurement of IgG antibody levels to the immunizing antigen in a vaccine suspected of causing a serious adverse reaction can determine if levels are protective and whether subsequent doses are needed.
Ideally, all suspected anaphylactic reactions to vaccines should be evaluated so that the responsible allergen may be identified.
Gelatin, egg protein, or other vaccine components are more likely than the immunizing agent itself to cause IgE-mediated reactions to vaccines.
Immediate-type allergy skin testing should be performed in patients who appear to have had an anaphylactic reaction after vaccination. This testing should help confirm that the reaction was IgE mediated and identify the responsible vaccine component.
If the intradermal skin test result is negative, it is extremely unlikely that the patient has IgE antibody to any vaccine component, and the patient can be vaccinated in the usual manner. In a patient with a history suggesting anaphylactic reaction, however, it is prudent to vaccinate with the patient under observation and to have epinephrine and other emergency treatment available.
In patients with history and skin tests results suggesting an IgE-mediated reaction to a vaccine but who need additional doses of the suspected vaccine or other vaccines with shared ingredients, the clinician can consider administering the vaccine in graded doses while observing the patient.
There are other less common but more serious reactions to vaccines, but only a few represent absolute contraindications to future doses.
Pregnant women should not be given live vaccines.
Live vaccines should generally not be given to immunocompromised persons.
Epidemiologic studies have not supported associations between specific vaccines or vaccination in general with long-term sequelae such as atopy, autism, and multiple sclerosis.
"The 2 key points of the practice parameter are that (1) patients with suspected allergy to vaccines or vaccine components should be evaluated by an allergist/immunologist and (2) most patients with suspected allergy to vaccines can receive vaccination safely," the guidelines authors conclude.
Ann Allergy Asthma Immunol. 2009;103:S1-14.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
Adverse events associated with vaccines are rare and are frequently transient. For example, transient rash may occur in 3% to 5% of persons receiving the measles and varicella vaccines, and these rashes can resemble those of clinical measles or varicella. The MMR vaccine can also promote thrombocytopenia, which does not usually lead to clinical consequences. The rubella vaccine causes acute arthritis among approximately 15% of women.
Other adverse events, such as encephalopathy with pertussis vaccination or Guillain-Barré syndrome after influenza vaccine, are quite serious but are also so rare that an exact estimate regarding their prevalence is difficult. Allergic reactions to vaccination could also be included in this rare-but-serious category, and the current practice parameter suggests the best strategy in caring for a patient with suspected allergy to a vaccine.
October 20, 2009 — Most patients with vaccine allergy may be safely vaccinated, according to a practice parameter published in the October issue of the Annals of Allergy, Asthma & Immunology. However, the new guidelines also recommend that patients with suspected allergy to vaccines or vaccine components be evaluated by an allergist or immunologist vs simply avoiding future immunizations, which could leave patients at higher risk for infectious disease.
The new recommendations were issued by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.
"Local, injection site reactions and constitutional symptoms, especially fever, are common after vaccinations and do not contraindicate future doses," chief editor John M. Kelso, MD, from the Division of Allergy, Asthma & Immunology at Scripps Clinic in San Diego, California, said in a news release.
Guidelines Not Provided in Other Reviews
The practice parameter contains detailed and specific guidelines not contained in previously published reviews. It offers a practical, peer-reviewed, evidence-based guide to assist primary care clinicians as well as specialists in allergy and immunology in assessing and treating patients with suspected allergy to vaccines.
The guidelines provide general and vaccine-specific recommendations for skin testing to vaccines and components, serum-specific immunoglobulin E (IgE) in vitro antibody testing, serologic testing for protective antibody responses to vaccines, vaccine administration, and avoidance. If this practice parameter is implemented, most patients who avoid vaccination because of allergy concerns will be able to be vaccinated appropriately.
Of approximately 235 million doses of vaccines given annually in the United States, only 1 dose per million causes anaphylaxis. Furthermore, death caused by vaccine-induced anaphylaxis is extremely uncommon.
The guidelines recommend reporting all serious events after vaccination to the Vaccine Adverse Event Reporting System of the Centers for Disease Control and Prevention and US Food and Drug Administration.
Responsible Allergens
Patients with suspected anaphylactic reactions to vaccines should be examined by an allergist to identify the allergen responsible for IgE-mediated reaction and to recommend optimal treatment. Typically, the responsible allergen is one of the vaccine components vs the specific antigen needed for immunization. Potentially allergenic vaccine components may include gelatin, egg protein, rarely yeast, latex from the vial stopper or syringe plungers, neomycin, or thimerosal.
"Gelatin, which is added to many vaccines as a stabilizer, is either bovine or porcine, which are extensively cross-reactive," Dr. Kelso said. "We recommend that a history of allergy to the ingestion of gelatin should be sought before administering a gelatin-containing vaccine....However rare, if a patient gives a history of an immediate-type reaction to yeast, latex, neomycin or thimerosal, we recommend that it be investigated with skin testing before immunization with a vaccine containing these constituents."
Skin testing may include prick test with full-strength vaccine (or diluted vaccine if there is a history of life-threatening reaction). If results of the prick test with full strength vaccine are negative, intradermal testing can be performed with 0.02-mL vaccine 1:100. Skin tests to vaccine components may include prick tests with commercial extracts of whole egg or egg white (influenza and yellow fever vaccines), chicken (yellow fever vaccine), or Saccharomyces cerevisiae yeast (hepatitis B vaccine and human papillomavirus vaccine).
"The MMR (measles and mumps vaccines) and one type of rabies vaccine contain negligible or no egg protein, and can be administered to egg allergic children without prior skin testing," Dr. Kelso said. "Egg protein is present in higher amounts in yellow fever and influenza vaccines and may cause reactions in egg-allergic patients, who should be evaluated by an allergist prior to receiving these vaccines."
A prick test with sugared gelatin may be useful if allergic reactions develop after administration of vaccines that contain gelatin, including some brands of diphtheria and tetanus toxoids and acellular pertussis (DTaP), rabies or influenza, Japanese encephalitis, measles, mumps, rubella, varicella, yellow fever, and zoster.
"Persons with a history of allergy to egg or a past reaction to an influenza vaccine may still be able to receive the H1N1 vaccine or the seasonal flu vaccine safely," said co-chief editor James T. Li, MD, Mayo Clinic professor of medicine and chair, Division of Allergy and Immunology. "I believe that anyone with this concern should check with their doctor and consult with an allergist."
Summary Statements in the Parameter
Specific summary statements in the parameter include the following:
Mild local reactions, fever, and other constitutional symptoms after vaccinations occur often and are not a contraindication to subsequent doses.
Anaphylactic reactions after vaccination are rare, with incidence of approximately 1 per million doses.
Even if the vaccine is not clearly the cause, all serious events occurring after vaccine administration should be reported to the Vaccine Adverse Event Reporting System.
Measurement of IgG antibody levels to the immunizing antigen in a vaccine suspected of causing a serious adverse reaction can determine if levels are protective and whether subsequent doses are needed.
Ideally, all suspected anaphylactic reactions to vaccines should be evaluated so that the responsible allergen may be identified.
Gelatin, egg protein, or other vaccine components are more likely than the immunizing agent itself to cause IgE-mediated reactions to vaccines.
Immediate-type allergy skin testing should be performed in patients who appear to have had an anaphylactic reaction after vaccination. This testing should help confirm that the reaction was IgE mediated and identify the responsible vaccine component.
If the intradermal skin test result is negative, it is extremely unlikely that the patient has IgE antibody to any vaccine component, and the patient can be vaccinated in the usual manner. In a patient with a history suggesting anaphylactic reaction, however, it is prudent to vaccinate with the patient under observation and to have epinephrine and other emergency treatment available.
In patients with history and skin tests results suggesting an IgE-mediated reaction to a vaccine but who need additional doses of the suspected vaccine or other vaccines with shared ingredients, the clinician can consider administering the vaccine in graded doses while observing the patient.
There are other less common but more serious reactions to vaccines, but only a few represent absolute contraindications to future doses.
Pregnant women should not be given live vaccines.
Live vaccines should generally not be given to immunocompromised persons.
Epidemiologic studies have not supported associations between specific vaccines or vaccination in general with long-term sequelae such as atopy, autism, and multiple sclerosis.
"The 2 key points of the practice parameter are that (1) patients with suspected allergy to vaccines or vaccine components should be evaluated by an allergist/immunologist and (2) most patients with suspected allergy to vaccines can receive vaccination safely," the guidelines authors conclude.
Ann Allergy Asthma Immunol. 2009;103:S1-14.
Daily Consumption of Diet Soda Linked to Metabolic Syndrome, Type 2 Diabetes
From Medscape Medical News
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Diet soda and other artificially sweetened beverages were originally considered "benign" because they contribute no calories and few nutrients to the diet. Previously reported links between intake of diet soda and MetSyn were therefore thought to result from residual confounding by other dietary, lifestyle, or demographic factors.
However, biological mechanisms possibly underlying these associations may be plausible, such as artificial sweeteners increasing the desire for and consumption of energy-dense foods or interfering with the ability to accurately estimate energy intake and remaining energy needs. Better understanding of these associations has important implications for nutritional counseling.
February 11, 2009 — Drinking diet soda at least daily is associated with significantly greater risks for select incident components of the metabolic syndrome (MetSyn) and type 2 diabetes, according to the results of an observational study reported in the January 16 Online First issue of Diabetes Care.
"Two longitudinal cohort studies have shown positive associations between diet soda consumption and incident MetSyn independent of baseline measures of adiposity," write Jennifer A. Nettleton, PhD, from the University of Texas Health Sciences Center in Houston, and colleagues. "Replication of previously observed diet soda-MetSyn associations in a distinct cohort would bolster their credibility and provide further insight into the nature of the relationship. Previous studies have not addressed associations between diet soda and individual MetSyn components or risk of type 2 diabetes nor have they fully addressed potential longitudinal mediators of these relationships, i.e., changes in adiposity status."
The goal of this study was to evaluate associations between diet soda consumption and the risk for incident MetSyn, its components, and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA).
Initial evaluation was performed from 2000 to 2002, at which time baseline food frequency questionnaires measured diet soda consumption. Three follow-up evaluations were performed from 2002 to 2003, 2004 to 2005, and 2005 to 2007. Incident type 2 diabetes was defined as fasting glucose levels of more than 126 mg/dL, self-reported type 2 diabetes, or use of diabetes medication. National Cholesterol Education Program Adult Treatment Panel 3 criteria were used to define MetSyn and its components. After adjustment for demographic, lifestyle, and dietary confounders, hazard ratios (HRs) were estimated for type 2 diabetes, MetSyn, and MetSyn components.
Compared with participants who did not drink diet soda, those who drank diet soda at least daily had a 36% greater relative risk for incident MetSyn (HR, 1.36; 95% confidence interval [CI], 1.11 - 1.66) and a 67% greater relative risk for incident type 2 diabetes (HR, 1.67; 95% CI, 1.27 - 2.20).
Of the individual components of MetSyn, only high waist circumference (men: ≥ 102 cm; women: ≥ 88 cm) and high fasting glucose levels (≥ 100 mg/dL) were prospectively associated with consumption of diet soda. Associations between diet soda intake and type 2 diabetes were independent of baseline measures of adiposity or changes in these measures. In contrast, associations between diet soda and MetSyn were not independent of these factors.
"Although these observational data cannot establish causality, consumption of diet soda at least daily was associated with significantly greater risks of select incident MetSyn components and type 2 diabetes," the study authors write.
Limitations of this study include observational design, precluding determination of causality; possible confounding by other dietary and lifestyle/behavioral factors; and difficulties in estimating intake of diet soda or artificial sweetener.
"These results corroborate findings from the ARIC [Atherosclerosis Risk in Communities] and Framingham studies and show stronger adverse associations exist between diet soda and type 2 diabetes," the study authors conclude. "Diet soda consumption, either independently or in conjunction with other dietary and lifestyle behaviors, may lead to weight gain, impaired glucose control, and eventual diabetes."
The National Heart, Lung, and Blood Institute supported this study. The study authors have disclosed no relevant financial relationships.
Diabetes Care. Published online January 16, 2009.
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Diet soda and other artificially sweetened beverages were originally considered "benign" because they contribute no calories and few nutrients to the diet. Previously reported links between intake of diet soda and MetSyn were therefore thought to result from residual confounding by other dietary, lifestyle, or demographic factors.
However, biological mechanisms possibly underlying these associations may be plausible, such as artificial sweeteners increasing the desire for and consumption of energy-dense foods or interfering with the ability to accurately estimate energy intake and remaining energy needs. Better understanding of these associations has important implications for nutritional counseling.
February 11, 2009 — Drinking diet soda at least daily is associated with significantly greater risks for select incident components of the metabolic syndrome (MetSyn) and type 2 diabetes, according to the results of an observational study reported in the January 16 Online First issue of Diabetes Care.
"Two longitudinal cohort studies have shown positive associations between diet soda consumption and incident MetSyn independent of baseline measures of adiposity," write Jennifer A. Nettleton, PhD, from the University of Texas Health Sciences Center in Houston, and colleagues. "Replication of previously observed diet soda-MetSyn associations in a distinct cohort would bolster their credibility and provide further insight into the nature of the relationship. Previous studies have not addressed associations between diet soda and individual MetSyn components or risk of type 2 diabetes nor have they fully addressed potential longitudinal mediators of these relationships, i.e., changes in adiposity status."
The goal of this study was to evaluate associations between diet soda consumption and the risk for incident MetSyn, its components, and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA).
Initial evaluation was performed from 2000 to 2002, at which time baseline food frequency questionnaires measured diet soda consumption. Three follow-up evaluations were performed from 2002 to 2003, 2004 to 2005, and 2005 to 2007. Incident type 2 diabetes was defined as fasting glucose levels of more than 126 mg/dL, self-reported type 2 diabetes, or use of diabetes medication. National Cholesterol Education Program Adult Treatment Panel 3 criteria were used to define MetSyn and its components. After adjustment for demographic, lifestyle, and dietary confounders, hazard ratios (HRs) were estimated for type 2 diabetes, MetSyn, and MetSyn components.
Compared with participants who did not drink diet soda, those who drank diet soda at least daily had a 36% greater relative risk for incident MetSyn (HR, 1.36; 95% confidence interval [CI], 1.11 - 1.66) and a 67% greater relative risk for incident type 2 diabetes (HR, 1.67; 95% CI, 1.27 - 2.20).
Of the individual components of MetSyn, only high waist circumference (men: ≥ 102 cm; women: ≥ 88 cm) and high fasting glucose levels (≥ 100 mg/dL) were prospectively associated with consumption of diet soda. Associations between diet soda intake and type 2 diabetes were independent of baseline measures of adiposity or changes in these measures. In contrast, associations between diet soda and MetSyn were not independent of these factors.
"Although these observational data cannot establish causality, consumption of diet soda at least daily was associated with significantly greater risks of select incident MetSyn components and type 2 diabetes," the study authors write.
Limitations of this study include observational design, precluding determination of causality; possible confounding by other dietary and lifestyle/behavioral factors; and difficulties in estimating intake of diet soda or artificial sweetener.
"These results corroborate findings from the ARIC [Atherosclerosis Risk in Communities] and Framingham studies and show stronger adverse associations exist between diet soda and type 2 diabetes," the study authors conclude. "Diet soda consumption, either independently or in conjunction with other dietary and lifestyle behaviors, may lead to weight gain, impaired glucose control, and eventual diabetes."
The National Heart, Lung, and Blood Institute supported this study. The study authors have disclosed no relevant financial relationships.
Diabetes Care. Published online January 16, 2009.
Monday, December 14, 2009
Fat intake and health
FATS
Question 1: What Are the Relationships Between Total Fat Intake and Health?
At low intakes of fat (< 20 percent of energy) and high intakes of carbohydrates (>65 percent of energy), risk increases for inadequate intakes of vitamin E, α linolenic acid, and linoleic acid and for adverse changes in high-density lipoprotein (HDL) cholesterol and triglycerides. At high intakes of fat (> 35 percent of energy), the risk increases for obesity and coronary heart disease (CHD). This is because fat intakes that exceed 35 percent of energy are associated with both increased calorie and saturated fat intakes. Total fat intake of 20 to 35 percent of calories is recommended for adults and 25 to 35 percent for children age 4 to 18 years. A fat intake of 30 to 35 percent of calories is recommended for children age 2 to 3 years.
Question 2: What Are the Relationships Between Saturated Fat Intake and Health?
The relationship between saturated fat intake and low-density lipoprotein (LDL) cholesterol is direct and progressive, increasing the risk of cardiovascular disease (CVD). Thus, saturated fat consumption by adults should be as low as possible while consuming a diet that provides 20 to 35 percent calories from fat and meets recommendations for α linolenic acid and linoleic acid. In particular,
For adults with LDL cholesterol below 130 mg/dL, less than 10 percent of calories from saturated fatty acids is recommended.
For adults with an elevated LDL cholesterol (>130 mg/dL), less than 7 percent of calories from saturated fatty acids is recommended.2
Question 3: What Are the Relationships Between Trans Fat Intake and Health?
Conclusion
The relationship between trans fatty acid intake and LDL cholesterol is direct and progressive, increasing the risk of CHD. Trans fatty acid consumption by all population groups should be kept as low as possible, which is about 1 percent of energy intake or less.
Question 4: What Is the Relationships Between Cholesterol Intake and CVD?
Conclusion
The relationship between cholesterol intake and LDL cholesterol concentrations is direct and progressive, increasing the risk of CHD. Thus, cholesterol intake should be kept as low as possible within a nutritionally adequate diet. In particular,
For adults with an LDL cholesterol < 130 mg/dL, less than 300 mg of dietary cholesterol per day is recommended.
For adults with an elevated LDL cholesterol (≥130 mg/dL), less than 200 mg of dietary cholesterol per day is recommended.
Question 5: What Are the Relationships Between n-6 PUFA Intake and Health?
Conclusion
An n-6 PUFA intake between 5 to 10 percent of energy may confer beneficial effects on coronary artery disease mortality.
Question 6: What Are the Relationships Between n-3 Fatty Acid Intake and Health?
Conclusion
An α-linolenic acid intake between 0.6 to 1.2 percent of calories will meet requirements for this fatty acid and may afford some protection against CVD outcomes.
The consumption of two servings per week of fish high in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with reduced risk of both sudden death and CHD death in adults. To benefit from the potential cardioprotective effects of EPA and DHA, the weekly consumption of two servings (approximately 8 ounces) of fish, particularly fish rich in EPA and DHA is suggested. Other sources of EPA and DHA may provide similar benefits; however, further research is warranted.
Question 7: What Are the Relationships Between MUFA Intake and Health?
Conclusion
There is an inverse relationship between the intake of monounsaturated fatty acids (MUFAs) and the total cholesterol (TC):HDL cholesterol concentration ratio. If equal amounts of MUFAs are substituted for saturated fatty acids, LDL cholesterol decreases.
http://www.health.gov/dietaryguidelines/dga2005/report/HTML/D10_Conclusions.htm
Question 1: What Are the Relationships Between Total Fat Intake and Health?
At low intakes of fat (< 20 percent of energy) and high intakes of carbohydrates (>65 percent of energy), risk increases for inadequate intakes of vitamin E, α linolenic acid, and linoleic acid and for adverse changes in high-density lipoprotein (HDL) cholesterol and triglycerides. At high intakes of fat (> 35 percent of energy), the risk increases for obesity and coronary heart disease (CHD). This is because fat intakes that exceed 35 percent of energy are associated with both increased calorie and saturated fat intakes. Total fat intake of 20 to 35 percent of calories is recommended for adults and 25 to 35 percent for children age 4 to 18 years. A fat intake of 30 to 35 percent of calories is recommended for children age 2 to 3 years.
Question 2: What Are the Relationships Between Saturated Fat Intake and Health?
The relationship between saturated fat intake and low-density lipoprotein (LDL) cholesterol is direct and progressive, increasing the risk of cardiovascular disease (CVD). Thus, saturated fat consumption by adults should be as low as possible while consuming a diet that provides 20 to 35 percent calories from fat and meets recommendations for α linolenic acid and linoleic acid. In particular,
For adults with LDL cholesterol below 130 mg/dL, less than 10 percent of calories from saturated fatty acids is recommended.
For adults with an elevated LDL cholesterol (>130 mg/dL), less than 7 percent of calories from saturated fatty acids is recommended.2
Question 3: What Are the Relationships Between Trans Fat Intake and Health?
Conclusion
The relationship between trans fatty acid intake and LDL cholesterol is direct and progressive, increasing the risk of CHD. Trans fatty acid consumption by all population groups should be kept as low as possible, which is about 1 percent of energy intake or less.
Question 4: What Is the Relationships Between Cholesterol Intake and CVD?
Conclusion
The relationship between cholesterol intake and LDL cholesterol concentrations is direct and progressive, increasing the risk of CHD. Thus, cholesterol intake should be kept as low as possible within a nutritionally adequate diet. In particular,
For adults with an LDL cholesterol < 130 mg/dL, less than 300 mg of dietary cholesterol per day is recommended.
For adults with an elevated LDL cholesterol (≥130 mg/dL), less than 200 mg of dietary cholesterol per day is recommended.
Question 5: What Are the Relationships Between n-6 PUFA Intake and Health?
Conclusion
An n-6 PUFA intake between 5 to 10 percent of energy may confer beneficial effects on coronary artery disease mortality.
Question 6: What Are the Relationships Between n-3 Fatty Acid Intake and Health?
Conclusion
An α-linolenic acid intake between 0.6 to 1.2 percent of calories will meet requirements for this fatty acid and may afford some protection against CVD outcomes.
The consumption of two servings per week of fish high in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with reduced risk of both sudden death and CHD death in adults. To benefit from the potential cardioprotective effects of EPA and DHA, the weekly consumption of two servings (approximately 8 ounces) of fish, particularly fish rich in EPA and DHA is suggested. Other sources of EPA and DHA may provide similar benefits; however, further research is warranted.
Question 7: What Are the Relationships Between MUFA Intake and Health?
Conclusion
There is an inverse relationship between the intake of monounsaturated fatty acids (MUFAs) and the total cholesterol (TC):HDL cholesterol concentration ratio. If equal amounts of MUFAs are substituted for saturated fatty acids, LDL cholesterol decreases.
http://www.health.gov/dietaryguidelines/dga2005/report/HTML/D10_Conclusions.htm
Tamiflu - Oseltamivir Efficacy Questioned in Preventing Influenza Complications
Fran Lowry
December 9, 2009 — An updated Cochrane review has called into question the efficacy of neuraminidase inhibitors, including the most commonly used oral agent oseltamivir (Tamiflu, Roche Laboratories Inc), in preventing influenza complications in healthy adults.
The results of the review, published online December 8 in the British Medical Journal, appear with other articles on oseltamivir that all come to the same conclusion: The evidence for the drug's efficacy in reducing complications in otherwise healthy individuals with pandemic influenza is now uncertain.
According to a statement by the BMJ, the results have led to a joint investigation into oseltamivir by BMJ and Channel 4 News, based in London, United Kingdom.
Tom Jefferson, MD, from the Acute Respiratory Infections Group, Cochrane Collaboration, Rome, Italy, and colleagues updated a 2005 Cochrane review published in the Cochrane Library.
The researchers selected 20 randomized, placebo-controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza to determine duration and incidence of symptoms, incidence of lower respiratory tract infections or their proxies, and adverse events.
They focused on oseltamivir because of the greater experience with the drug worldwide.
Few Trials Judged Adequate Also Had Shortcomings
Of the trials, only 5 were judged adequate by usual Cochrane Collaboration methods, Dr. Jefferson and colleagues write. Most of the trials were at risk for bias resulting from poor descriptions of the methods, no description of losses to follow-up, and blinding.
The authors write that their attempts to deal with these shortcomings failed. Only 3 of the 5 lead authors of the studies on oseltamivir replied to their request for more information. Of these authors, none possessed original data.
Instead, these authors referred them to Roche, oseltamivir's manufacturer. However, the company did not provide the information "as quickly as we needed it to update this review," Dr. Jefferson and colleagues write.
From their analysis, the reviewers found that oseltamivir did not reduce influenza-related lower respiratory tract complications (risk ratio, 0.55; 95% confidence interval, 0.22 - 1.35).
They also found that oseltamivir induced nausea (odds ratio, 1.79; 95% confidence interval, 1.10 - 2.93), that the evidence of rarer adverse events from pharmacovigilance studies was of poor quality, and that adverse events may have been underreported.
"Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective," Dr. Jefferson and colleagues conclude.
Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza.
Oseltamivir may be regarded as optional for reducing the symptoms of seasonal influenza, they add. "Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza. Independent randomized trials to resolve these uncertainties are needed."
In a related article, Peter Doshi, a doctoral student at Massachusetts Institute of Technology in Cambridge, and a coauthor of the updated Cochrane review, writes that his team of reviewers had been trying to obtain data to verify claims that oseltamivir lowers serious complications of influenza since August 2009.
Evidence Is Fragmented, Inconsistent, Contradictory
"We failed, but in failing discovered that the public evidence base for this global public health drug is fragmented, inconsistent, and contradictory. We are no longer sure that oseltamivir offers a therapeutic and public health policy advantage over cheap, over the counter drugs such as aspirin," he writes.
Mr. Doshi writes that the review team's suspicions were aroused after a Japanese pediatrician, Keiji Hayashi, MD, pointed out that their previous review, which had found that oseltamivir was effective in reducing pneumonia and other important complications of influenza, was based on a single peer-reviewed study by Kaiser and colleagues.
It turns out that the Kaiser study, which was a meta-analysis of 10 manufacturer-funded trials, included just 2 studies that were published in peer-reviewed journals. When the Cochrane reviewers tried to verify the data from the 8 unpublished trials, they found inconsistencies in the evidence for oseltamivir's effectiveness and safety.
Roche funded the Kaiser meta-analysis.
Mr. Doshi said the Kaiser paper was dropped from their new analysis. "The previous Cochrane review placed its trust in publications and included Kaiser's unpublished data, but to do so once again, despite our inability to obtain data sufficient to perform an independent analysis, would have shifted our position from that of trust in publication to that of trust in secrecy."
He also called into question US Food and Drug Administration's safety reporting rules. Manufacturers must report adverse events, but only if they occur in the United States. "In the case of oseltamivir, considering that 75% of global consumption has occurred in Japan, this has important implications for our knowledge of its safety," Mr. Doshi writes.
Treatment With Oseltamivir Unlikely to be Clinically Important
Nick Freemantle, PhD, and Melanie Calvert, MD, from the University of Birmingham, United Kingdom, were invited by BMJ to review the observational studies provided to the Cochrane reviewers by Roche. They said that in general, the studies support the conclusion that oseltamivir may reduce the incidence of complications of influenza in otherwise healthy adults, but as such events are rare, treatment with oseltamivir for most people is not likely to be clinically important.
They had several criticisms of the studies and said the studies were difficult to interpret. "Differences in baseline comorbidity or geographical distribution were present in several studies. It seems likely that some patients were included in more than one study, which undermines the ability of these studies to provide independent estimates," the authors write.
"We have remarkably few resources in this country to spend on pharmaceuticals on health and it's surprising to see such widespread use of oseltamivir. But I suppose that once you've gone and bought lots of doses then it's a bit like the situation with gun control in the US. If you have a gun in the house it's much easier to use it. But it does not mean it's the right thing to do," Dr. Freemantle said in a statement to BMJ.
Review Calls Entire Process Into Question
Fiona Godlee, MD, Editor-in-Chief of BMJ, and Mike Clarke, MD, Director of the UK Cochrane Centre, say the updated review is important because it calls into question "not only the effectiveness of oseltamivir but the whole system by which drugs are evaluated, regulated and promoted."
In her editorial, Dr. Godlee writes that the claims of the efficacy of oseltamivir, based on an analysis of 10 drug company trials, have formed a key part of decisions to stockpile the drug and made it widely available.
It was only after questions from the BMJ and Channel 4 News that Roche agreed to make full study reports available on a password-protected site, she writes.
It can't be right that the public should have to rely on this sort of detective work by academics and journalists to patch together the evidence for such a widely prescribed drug.
"It can't be right that the public should have to rely on this sort of detective work by academics and journalists to patch together the evidence for such a widely prescribed drug. Individual patient data from all trials of drugs should be readily available for scientific scrutiny," Dr. Godlee concludes.
In its reply, Roche says it has provided full responses to all questions from the BMJ and Channel 4, which "should leave no doubt about the high integrity of the data, publications, and interactions between Roche and independent investigators."
All reports were written to the standards of the regulatory authorities of Europe, the United States, and Japan, and have been accepted by all for licensing purposes. Roche has "willingly shared data and reports with numerous other eligible individuals and groups," writes James Smith, MD, International Medical Leader, Tamiflu, for Roche.
He voices concern that the Cochrane review team "chose to follow-up their inquiries through a television company rather than by approaching the manufacturer directly...it is unclear to us why Dr. Jefferson would adopt this approach, particularly given that he was a paid ad hoc consultant to Roche working on flu and oseltamivir between 1997 and 1999. During that period he worked closely with Roche experts, many of whom are still in the company, and he would therefore not have had difficulty in contacting them directly to discuss his requirements."
Dr. Smith ends by stating: "Why Dr. Jefferson and the BMJ chose to pursue their scientific enquiries through commercial television remains to be clarified."
Dr. Jefferson has reported he has received support from the UK National Institute for Health Research and the Australian National Health and Medical Research Council and that he was a paid ad hoc consultant to Roche from 1997 to 1999. Peter Doshi has reported he has no relevant financial relationships. Dr. Nick Freemantle and Dr. Melanie Calvert have reported that the BMJ helped them access 3 articles not available through their university library and that they supervise a PhD student who is supported and employed by Roche. Dr. Godlee has reported that she has published a number of articles critical of the drug industry and supports the idea that drugs should be evaluated by independent third parties rather than directly or indirectly by the drug's producers. As editor of the BMJ, she is a member of the International Committee of Medical Journal Editors and reports that the BMJ Group receives a proportion of its revenue from drug company advertising and sponsorship. Dr. Mike Clarke has reported that he is active in the Cochrane Collaboration and has a fixed-term contract with the National Institute for Health Research. Dr. Smith is international medical leader, Tamiflu, F Hofmann-La Roche.
BMJ. Published online December 8, 2009.
December 9, 2009 — An updated Cochrane review has called into question the efficacy of neuraminidase inhibitors, including the most commonly used oral agent oseltamivir (Tamiflu, Roche Laboratories Inc), in preventing influenza complications in healthy adults.
The results of the review, published online December 8 in the British Medical Journal, appear with other articles on oseltamivir that all come to the same conclusion: The evidence for the drug's efficacy in reducing complications in otherwise healthy individuals with pandemic influenza is now uncertain.
According to a statement by the BMJ, the results have led to a joint investigation into oseltamivir by BMJ and Channel 4 News, based in London, United Kingdom.
Tom Jefferson, MD, from the Acute Respiratory Infections Group, Cochrane Collaboration, Rome, Italy, and colleagues updated a 2005 Cochrane review published in the Cochrane Library.
The researchers selected 20 randomized, placebo-controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza to determine duration and incidence of symptoms, incidence of lower respiratory tract infections or their proxies, and adverse events.
They focused on oseltamivir because of the greater experience with the drug worldwide.
Few Trials Judged Adequate Also Had Shortcomings
Of the trials, only 5 were judged adequate by usual Cochrane Collaboration methods, Dr. Jefferson and colleagues write. Most of the trials were at risk for bias resulting from poor descriptions of the methods, no description of losses to follow-up, and blinding.
The authors write that their attempts to deal with these shortcomings failed. Only 3 of the 5 lead authors of the studies on oseltamivir replied to their request for more information. Of these authors, none possessed original data.
Instead, these authors referred them to Roche, oseltamivir's manufacturer. However, the company did not provide the information "as quickly as we needed it to update this review," Dr. Jefferson and colleagues write.
From their analysis, the reviewers found that oseltamivir did not reduce influenza-related lower respiratory tract complications (risk ratio, 0.55; 95% confidence interval, 0.22 - 1.35).
They also found that oseltamivir induced nausea (odds ratio, 1.79; 95% confidence interval, 1.10 - 2.93), that the evidence of rarer adverse events from pharmacovigilance studies was of poor quality, and that adverse events may have been underreported.
"Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective," Dr. Jefferson and colleagues conclude.
Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza.
Oseltamivir may be regarded as optional for reducing the symptoms of seasonal influenza, they add. "Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza. Independent randomized trials to resolve these uncertainties are needed."
In a related article, Peter Doshi, a doctoral student at Massachusetts Institute of Technology in Cambridge, and a coauthor of the updated Cochrane review, writes that his team of reviewers had been trying to obtain data to verify claims that oseltamivir lowers serious complications of influenza since August 2009.
Evidence Is Fragmented, Inconsistent, Contradictory
"We failed, but in failing discovered that the public evidence base for this global public health drug is fragmented, inconsistent, and contradictory. We are no longer sure that oseltamivir offers a therapeutic and public health policy advantage over cheap, over the counter drugs such as aspirin," he writes.
Mr. Doshi writes that the review team's suspicions were aroused after a Japanese pediatrician, Keiji Hayashi, MD, pointed out that their previous review, which had found that oseltamivir was effective in reducing pneumonia and other important complications of influenza, was based on a single peer-reviewed study by Kaiser and colleagues.
It turns out that the Kaiser study, which was a meta-analysis of 10 manufacturer-funded trials, included just 2 studies that were published in peer-reviewed journals. When the Cochrane reviewers tried to verify the data from the 8 unpublished trials, they found inconsistencies in the evidence for oseltamivir's effectiveness and safety.
Roche funded the Kaiser meta-analysis.
Mr. Doshi said the Kaiser paper was dropped from their new analysis. "The previous Cochrane review placed its trust in publications and included Kaiser's unpublished data, but to do so once again, despite our inability to obtain data sufficient to perform an independent analysis, would have shifted our position from that of trust in publication to that of trust in secrecy."
He also called into question US Food and Drug Administration's safety reporting rules. Manufacturers must report adverse events, but only if they occur in the United States. "In the case of oseltamivir, considering that 75% of global consumption has occurred in Japan, this has important implications for our knowledge of its safety," Mr. Doshi writes.
Treatment With Oseltamivir Unlikely to be Clinically Important
Nick Freemantle, PhD, and Melanie Calvert, MD, from the University of Birmingham, United Kingdom, were invited by BMJ to review the observational studies provided to the Cochrane reviewers by Roche. They said that in general, the studies support the conclusion that oseltamivir may reduce the incidence of complications of influenza in otherwise healthy adults, but as such events are rare, treatment with oseltamivir for most people is not likely to be clinically important.
They had several criticisms of the studies and said the studies were difficult to interpret. "Differences in baseline comorbidity or geographical distribution were present in several studies. It seems likely that some patients were included in more than one study, which undermines the ability of these studies to provide independent estimates," the authors write.
"We have remarkably few resources in this country to spend on pharmaceuticals on health and it's surprising to see such widespread use of oseltamivir. But I suppose that once you've gone and bought lots of doses then it's a bit like the situation with gun control in the US. If you have a gun in the house it's much easier to use it. But it does not mean it's the right thing to do," Dr. Freemantle said in a statement to BMJ.
Review Calls Entire Process Into Question
Fiona Godlee, MD, Editor-in-Chief of BMJ, and Mike Clarke, MD, Director of the UK Cochrane Centre, say the updated review is important because it calls into question "not only the effectiveness of oseltamivir but the whole system by which drugs are evaluated, regulated and promoted."
In her editorial, Dr. Godlee writes that the claims of the efficacy of oseltamivir, based on an analysis of 10 drug company trials, have formed a key part of decisions to stockpile the drug and made it widely available.
It was only after questions from the BMJ and Channel 4 News that Roche agreed to make full study reports available on a password-protected site, she writes.
It can't be right that the public should have to rely on this sort of detective work by academics and journalists to patch together the evidence for such a widely prescribed drug.
"It can't be right that the public should have to rely on this sort of detective work by academics and journalists to patch together the evidence for such a widely prescribed drug. Individual patient data from all trials of drugs should be readily available for scientific scrutiny," Dr. Godlee concludes.
In its reply, Roche says it has provided full responses to all questions from the BMJ and Channel 4, which "should leave no doubt about the high integrity of the data, publications, and interactions between Roche and independent investigators."
All reports were written to the standards of the regulatory authorities of Europe, the United States, and Japan, and have been accepted by all for licensing purposes. Roche has "willingly shared data and reports with numerous other eligible individuals and groups," writes James Smith, MD, International Medical Leader, Tamiflu, for Roche.
He voices concern that the Cochrane review team "chose to follow-up their inquiries through a television company rather than by approaching the manufacturer directly...it is unclear to us why Dr. Jefferson would adopt this approach, particularly given that he was a paid ad hoc consultant to Roche working on flu and oseltamivir between 1997 and 1999. During that period he worked closely with Roche experts, many of whom are still in the company, and he would therefore not have had difficulty in contacting them directly to discuss his requirements."
Dr. Smith ends by stating: "Why Dr. Jefferson and the BMJ chose to pursue their scientific enquiries through commercial television remains to be clarified."
Dr. Jefferson has reported he has received support from the UK National Institute for Health Research and the Australian National Health and Medical Research Council and that he was a paid ad hoc consultant to Roche from 1997 to 1999. Peter Doshi has reported he has no relevant financial relationships. Dr. Nick Freemantle and Dr. Melanie Calvert have reported that the BMJ helped them access 3 articles not available through their university library and that they supervise a PhD student who is supported and employed by Roche. Dr. Godlee has reported that she has published a number of articles critical of the drug industry and supports the idea that drugs should be evaluated by independent third parties rather than directly or indirectly by the drug's producers. As editor of the BMJ, she is a member of the International Committee of Medical Journal Editors and reports that the BMJ Group receives a proportion of its revenue from drug company advertising and sponsorship. Dr. Mike Clarke has reported that he is active in the Cochrane Collaboration and has a fixed-term contract with the National Institute for Health Research. Dr. Smith is international medical leader, Tamiflu, F Hofmann-La Roche.
BMJ. Published online December 8, 2009.
Tuesday, December 1, 2009
The Ten Habits of Highly Effective Brains
Start your kids young!
Aug 22, 2007
By: Alvaro Fernandez
The LA Times just completed a wonderful 4-part series on how learning and memory work.The NYT re-emphasized the importance of physical exercise for neurogenesis(the creation of new neurons).To put this news in better perspective, let’s review some good lifestyle options we can follow to maintain, and improve, our vibrant brains.
1. Learn what is the “It” in “Use It or Lose It”. A basic understanding will serve you well to appreciate your brain’s beauty as a living and constantly-developing dense forest with billions of neurons and synapses.
2. Take care of your nutrition. Did you know that the brain only weighs 2% of body mass but consumes over 20% of the oxygen and nutrients we intake? As a general rule, you don’t need expensive ultra-sophisticated nutritional supplements, just make sure you don’t stuff yourself with the “bad stuff”.
3. Remember that the brain is part of the body.Things that exercise your body can also help sharpen your brain: physical exercise enhances neurogenesis.
4. Practice positive, future-oriented thoughts until they become your default mindset and you look forward to every new day in a constructive way. Stress and anxiety, no matter whether induced by external events or by your own thoughts, actually kills neurons and prevent the creation of new ones. You can think of chronic stress as the opposite of exercise: it prevents the creation of new neurons.
5. Thrive on Learning and Mental Challenges. The point of having a brain is precisely to learn and to adapt to challenging new environments. Once new neurons appear in your brain, where they stay in your brain and how long they survive depends on how you use them. “Use It or Lose It” does not mean “do crossword puzzle number 1,234,567″. It means, “challenge your brain often with fundamentally new activities”.
We are (as far as we know) the only self-directed organisms in this planet. Aim high. Once you graduate from college, keep learning. The brain keeps developing, no matter your age, and it reflects what you do with it.
Explore, travel. Adapting to new locations forces you to pay more attention to your environment. Make new decisions, use your brain.
Don’t Outsource Your Brain. Not to media personalities, not to politicians, not to your smart neighbour… Make your own decisions, and mistakes. And learn from them. That way, you are training your brain, not your neighbour’s.
Develop and maintain stimulating friendships. We are “social animals”, and need social interaction. Which, by the way, is why ‘Baby Einstein’ has been shown not to be the panacea for children development.
Laugh. Often. Especially to cognitively complex humor, full of twists and surprises. Better, try to become the next Jon Stewart (Note: I just corrected his name from “John”…which may call for a #11: Spellcheck!)
Now, remember that what counts is not reading this article-or any other-, but practicing a bit every day until small steps snowball into unstoppable, internalized habits…so, pick your next battle and try to start improving at least one of these 10 habits today!
For more in-depth information on these topics, check our Brain Fitness Topics section.
http://www.sharpbrains.com/blog/2007/08/22/10-habits-of-highly-effective-brains/
Aug 22, 2007
By: Alvaro Fernandez
The LA Times just completed a wonderful 4-part series on how learning and memory work.The NYT re-emphasized the importance of physical exercise for neurogenesis(the creation of new neurons).To put this news in better perspective, let’s review some good lifestyle options we can follow to maintain, and improve, our vibrant brains.
1. Learn what is the “It” in “Use It or Lose It”. A basic understanding will serve you well to appreciate your brain’s beauty as a living and constantly-developing dense forest with billions of neurons and synapses.
2. Take care of your nutrition. Did you know that the brain only weighs 2% of body mass but consumes over 20% of the oxygen and nutrients we intake? As a general rule, you don’t need expensive ultra-sophisticated nutritional supplements, just make sure you don’t stuff yourself with the “bad stuff”.
3. Remember that the brain is part of the body.Things that exercise your body can also help sharpen your brain: physical exercise enhances neurogenesis.
4. Practice positive, future-oriented thoughts until they become your default mindset and you look forward to every new day in a constructive way. Stress and anxiety, no matter whether induced by external events or by your own thoughts, actually kills neurons and prevent the creation of new ones. You can think of chronic stress as the opposite of exercise: it prevents the creation of new neurons.
5. Thrive on Learning and Mental Challenges. The point of having a brain is precisely to learn and to adapt to challenging new environments. Once new neurons appear in your brain, where they stay in your brain and how long they survive depends on how you use them. “Use It or Lose It” does not mean “do crossword puzzle number 1,234,567″. It means, “challenge your brain often with fundamentally new activities”.
We are (as far as we know) the only self-directed organisms in this planet. Aim high. Once you graduate from college, keep learning. The brain keeps developing, no matter your age, and it reflects what you do with it.
Explore, travel. Adapting to new locations forces you to pay more attention to your environment. Make new decisions, use your brain.
Don’t Outsource Your Brain. Not to media personalities, not to politicians, not to your smart neighbour… Make your own decisions, and mistakes. And learn from them. That way, you are training your brain, not your neighbour’s.
Develop and maintain stimulating friendships. We are “social animals”, and need social interaction. Which, by the way, is why ‘Baby Einstein’ has been shown not to be the panacea for children development.
Laugh. Often. Especially to cognitively complex humor, full of twists and surprises. Better, try to become the next Jon Stewart (Note: I just corrected his name from “John”…which may call for a #11: Spellcheck!)
Now, remember that what counts is not reading this article-or any other-, but practicing a bit every day until small steps snowball into unstoppable, internalized habits…so, pick your next battle and try to start improving at least one of these 10 habits today!
For more in-depth information on these topics, check our Brain Fitness Topics section.
http://www.sharpbrains.com/blog/2007/08/22/10-habits-of-highly-effective-brains/
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