From Medscape Pediatrics > Viewpoints
Analgesic Effects of Sweet-Tasting Solutions for Infants: Current State of Equipoise
Harrison D, Bueno M, Yamada J, Adams-Webber T, Stevens B
Pediatrics. 2010;126:894-902
Study Summary
This article describes a meta-analysis of multiple randomized controlled trials that evaluated oral sucrose (or other sugar product) for acute, painful procedures in infants. Harrison and colleagues examined whether a state of equipoise (equilibrium about whether an intervention is likely to be helpful) still exists in regard to the use of oral sucrose for pain amelioration.
They noted that many randomized, placebo-controlled trials have been conducted despite the fact that reviews published throughout the 2000s demonstrated overwhelming evidence of clinical effectiveness. In addition to conducting a meta-analysis of the literature, this study sought to identify research questions or areas upon which future studies could focus.
The investigators reviewed 4 online literature databases and existing evidence-based reviews on the topic. They identified 125 primary research studies on the topic, with 49% using heel lance as the painful procedure, 14% using venipuncture or intramuscular injection, and 6% studying pain relief related to circumcision.
In 103 studies (93%), the use of sucrose or other sweet solution reduced pain response. One of 8 studies evaluating pain control with circumcision had negative results, but the other 7 (87.5%) demonstrated benefit. The solutions used in the trial varied greatly, but the most common was sucrose.
In general, sweeter solutions (higher concentrations) tended to have higher rates of success. The investigators concluded that there is no longer ethical justification for placebo groups in trials investigating the use of sweet solutions to limit short-term procedural pain. They pointed out the following knowledge gaps that could ethically be the focus of future investigation:
* Are sweet solutions effective in mitigating procedural pain for extremely premature infants?
* Are repeated administrations of the solution more effective than single administrations?
* Are sweet solutions effective over extended hospitalizations?
* How do sweet solutions compare with narcotic pain medications for short procedures?
* What is the effectiveness of sweet solutions for longer noxious procedures?
* Are sweet solutions effective in this setting for older children?
Harrison and coworkers suggested that these unanswered questions should be the focus of future research.
Wednesday, December 29, 2010
Tuesday, December 28, 2010
Complementary, Alternative Medicine Linked to Adverse Events in Children
From Medscape Medical News
Laurie Barclay, MD
December 27, 2010 — The use of complementary and alternative medicine (CAM) can be associated with serious, and even fatal, adverse events in children, according to the results of a monthly active surveillance study reported online December 22 in the Archives of Disease in Childhood.
"...CAM is commonly administered to children," write Dr. Alissa Lim, from Royal Children's Hospital in Melbourne, Australia, and colleagues. "As CAM is frequently regarded as natural and therefore safe, adverse events may go unreported."
The goal of the study was to assess the types of adverse events linked to use of CAM that came to the attention of Australian pediatricians. Between January 2001 and December 2003, a total of 39 cases of adverse events associated with CAM use were reported to the Australian Paediatric Surveillance Unit, and a physician completed the questionnaire.
Almost two thirds of the reported cases (64%) were considered to be severe, life threatening, or fatal. Reported adverse events included constipation, bleeding, pain, allergic reactions, mouth ulcers, seizures, vomiting, stunted growth, infections, and malnutrition.
Several areas of concern were apparent that posed significant risks, including those related to failure to use conventional medicine because CAM therapy was substituted, those associated with medication changes made by CAM practitioners, and those caused by dietary restriction in the belief that this would cure symptoms. There were 4 reported deaths associated with a failure to use conventional medicine because a CAM treatment was substituted.
"CAM use has the potential to cause significant morbidity and fatal adverse outcomes," the study authors write. "The diversity of CAM therapies and their associated adverse events demonstrate the difficulty addressing this area and the importance of establishing mechanisms by which adverse effects may be reported or monitored."
Limitations of this study include lack of information about the products used, information collected only from pediatricians, and underreporting by families and also by clinicians because of time pressures and uncertainly about causality and severity of outcome. Although 46 instances of adverse events associated with CAM were reported during the study period, only 40 questionnaires were completed, and one of these was a duplicate, leaving 39 cases for analysis.
"Discussions with families about CAM use may empower them to talk about any medication changes suggested by a CAM practitioner before altering or ceasing the medication," the study authors conclude. "However, many of the adverse events associated with failure to use conventional medicine resulted from the family's belief in CAM and determination to use it despite medical advice."
The study authors have disclosed no relevant financial relationships.
Arch Dis Child. Published online December 22, 2010. Abstract
Laurie Barclay, MD
December 27, 2010 — The use of complementary and alternative medicine (CAM) can be associated with serious, and even fatal, adverse events in children, according to the results of a monthly active surveillance study reported online December 22 in the Archives of Disease in Childhood.
"...CAM is commonly administered to children," write Dr. Alissa Lim, from Royal Children's Hospital in Melbourne, Australia, and colleagues. "As CAM is frequently regarded as natural and therefore safe, adverse events may go unreported."
The goal of the study was to assess the types of adverse events linked to use of CAM that came to the attention of Australian pediatricians. Between January 2001 and December 2003, a total of 39 cases of adverse events associated with CAM use were reported to the Australian Paediatric Surveillance Unit, and a physician completed the questionnaire.
Almost two thirds of the reported cases (64%) were considered to be severe, life threatening, or fatal. Reported adverse events included constipation, bleeding, pain, allergic reactions, mouth ulcers, seizures, vomiting, stunted growth, infections, and malnutrition.
Several areas of concern were apparent that posed significant risks, including those related to failure to use conventional medicine because CAM therapy was substituted, those associated with medication changes made by CAM practitioners, and those caused by dietary restriction in the belief that this would cure symptoms. There were 4 reported deaths associated with a failure to use conventional medicine because a CAM treatment was substituted.
"CAM use has the potential to cause significant morbidity and fatal adverse outcomes," the study authors write. "The diversity of CAM therapies and their associated adverse events demonstrate the difficulty addressing this area and the importance of establishing mechanisms by which adverse effects may be reported or monitored."
Limitations of this study include lack of information about the products used, information collected only from pediatricians, and underreporting by families and also by clinicians because of time pressures and uncertainly about causality and severity of outcome. Although 46 instances of adverse events associated with CAM were reported during the study period, only 40 questionnaires were completed, and one of these was a duplicate, leaving 39 cases for analysis.
"Discussions with families about CAM use may empower them to talk about any medication changes suggested by a CAM practitioner before altering or ceasing the medication," the study authors conclude. "However, many of the adverse events associated with failure to use conventional medicine resulted from the family's belief in CAM and determination to use it despite medical advice."
The study authors have disclosed no relevant financial relationships.
Arch Dis Child. Published online December 22, 2010. Abstract
Monday, December 20, 2010
Moderate vs Low ICS Doses May Not Give Added Benefit in Childhood Asthma
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
December 8, 2010 — Compared with low doses, moderate doses of inhaled corticosteroids (ICSs) may not give an added benefit to children with mild to moderate persistent asthma, according to the results of a systematic review and meta-analysis reported online December 6 in Pediatrics.
"...ICSs are currently considered the first-line treatment for persistent childhood asthma; however, uncertainty remains regarding the optimal dose," write Linjie Zhang, MD, PhD, from the Maternal and Child Health Unit, Faculty of Medicine, Federal University of Rio Grande in Rio Grande, Brazil, and colleagues.
"The most recent asthma guidelines recommend a dose of up to 400 μg/day beclomethasone dipropionate (BDP)-hydrofluoroalkane equivalent for children with mild-to-moderate persistent asthma, but these recommendations are generally based on results from individual randomized trials rather than a body of evidence that has been critically appraised by a systematic review."
The reviewers searched MEDLINE for articles published between 1950 and August 2009 describing randomized controlled trials that compared 2 or more different ICS doses in children aged 3 to 18 years with persistent asthma.
The analyses focused on study endpoints of morning and evening peak expiratory flow, forced expiratory volume in 1 second, asthma symptom score, use of β2-agonists, withdrawal for lack of efficacy, and adverse events.
The investigators used meta-analyses to compare moderate doses of ICSs (300 - 400 μg/day) vs low doses of ICSs (≤ 200 μg/day beclomethasone equivalent).
The 14 included randomized controlled trials enrolled a total of 5768 asthmatic children and evaluated 5 ICSs. Moderate vs low doses were slightly but statistically significantly more effective in improving forced expiratory volume in 1 second among children with mild to moderate asthma, based on the pooled standardized mean difference from 6 trials (standardized mean difference, 0.11; 95% confidence interval, 0.01 - 0.21). However, other efficacy outcomes were not significantly different between the 2 doses, and there was no evidence of a dose-response relationship at low to moderate doses. Local adverse events were uncommon.
"Compared with low doses, moderate doses of ICSs may not provide clinically relevant therapeutic advantage in children with mild-to-moderate persistent asthma," the study authors write. "Additional RCTs [randomized controlled trials] are needed to clarify the dose-response relationship of ICSs in persistent childhood asthma."
Limitations of this study include an unclear risk for bias in the included trials, as well as nonuniform reporting of continuous efficacy outcome results and incomplete reporting of data collection and adverse events. Because of the language limitation, 1 small randomized trial conducted in Germany was not included.
"Although ICSs are generally considered safe treatment for children with asthma, the potential systemic adverse effects such as adrenal suppression, linear growth retardation, and effects on bone mass, are still of concern," the study authors conclude. "A limited number of studies included in this review assessed adverse effects of ICSs given at different doses on linear growth and on hypothalamic-pituitary-adrenal function, and their findings were inconsistent. There are no suitable data for investigating dose-response relationship of systemic adverse effects of ICSs."
Dr. Zhang has received grants from the Brazilian government agency CAPES for postdoctoral training in the Institute for Clinical Research and Health Policy Studies (Tufts Medical Center, Boston, Massachusetts).
Pediatrics. Published online December 6, 2010.
Clinical Context
ICSs are first-line therapy for children with persistent asthma, but the long-term use of these medications among children raises concerns regarding significant long-term adverse effects. This issue was addressed in a review by Allen, which was published in Advances in Pediatrics in 2006. He notes that the use of ICSs alone at small doses does not appear to be associated with any significant systemic adverse events. Although ICSs can retard vertical linear growth when given at high doses, ICS use alone does not appear to affect final adult height. Routine ICS use also should not lead to significant adrenal suppression or bone loss.
Although ICSs at low doses may be safe for children, are they effective enough? The current study examines the dose response to ICSs among children with persistent asthma.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
December 8, 2010 — Compared with low doses, moderate doses of inhaled corticosteroids (ICSs) may not give an added benefit to children with mild to moderate persistent asthma, according to the results of a systematic review and meta-analysis reported online December 6 in Pediatrics.
"...ICSs are currently considered the first-line treatment for persistent childhood asthma; however, uncertainty remains regarding the optimal dose," write Linjie Zhang, MD, PhD, from the Maternal and Child Health Unit, Faculty of Medicine, Federal University of Rio Grande in Rio Grande, Brazil, and colleagues.
"The most recent asthma guidelines recommend a dose of up to 400 μg/day beclomethasone dipropionate (BDP)-hydrofluoroalkane equivalent for children with mild-to-moderate persistent asthma, but these recommendations are generally based on results from individual randomized trials rather than a body of evidence that has been critically appraised by a systematic review."
The reviewers searched MEDLINE for articles published between 1950 and August 2009 describing randomized controlled trials that compared 2 or more different ICS doses in children aged 3 to 18 years with persistent asthma.
The analyses focused on study endpoints of morning and evening peak expiratory flow, forced expiratory volume in 1 second, asthma symptom score, use of β2-agonists, withdrawal for lack of efficacy, and adverse events.
The investigators used meta-analyses to compare moderate doses of ICSs (300 - 400 μg/day) vs low doses of ICSs (≤ 200 μg/day beclomethasone equivalent).
The 14 included randomized controlled trials enrolled a total of 5768 asthmatic children and evaluated 5 ICSs. Moderate vs low doses were slightly but statistically significantly more effective in improving forced expiratory volume in 1 second among children with mild to moderate asthma, based on the pooled standardized mean difference from 6 trials (standardized mean difference, 0.11; 95% confidence interval, 0.01 - 0.21). However, other efficacy outcomes were not significantly different between the 2 doses, and there was no evidence of a dose-response relationship at low to moderate doses. Local adverse events were uncommon.
"Compared with low doses, moderate doses of ICSs may not provide clinically relevant therapeutic advantage in children with mild-to-moderate persistent asthma," the study authors write. "Additional RCTs [randomized controlled trials] are needed to clarify the dose-response relationship of ICSs in persistent childhood asthma."
Limitations of this study include an unclear risk for bias in the included trials, as well as nonuniform reporting of continuous efficacy outcome results and incomplete reporting of data collection and adverse events. Because of the language limitation, 1 small randomized trial conducted in Germany was not included.
"Although ICSs are generally considered safe treatment for children with asthma, the potential systemic adverse effects such as adrenal suppression, linear growth retardation, and effects on bone mass, are still of concern," the study authors conclude. "A limited number of studies included in this review assessed adverse effects of ICSs given at different doses on linear growth and on hypothalamic-pituitary-adrenal function, and their findings were inconsistent. There are no suitable data for investigating dose-response relationship of systemic adverse effects of ICSs."
Dr. Zhang has received grants from the Brazilian government agency CAPES for postdoctoral training in the Institute for Clinical Research and Health Policy Studies (Tufts Medical Center, Boston, Massachusetts).
Pediatrics. Published online December 6, 2010.
Clinical Context
ICSs are first-line therapy for children with persistent asthma, but the long-term use of these medications among children raises concerns regarding significant long-term adverse effects. This issue was addressed in a review by Allen, which was published in Advances in Pediatrics in 2006. He notes that the use of ICSs alone at small doses does not appear to be associated with any significant systemic adverse events. Although ICSs can retard vertical linear growth when given at high doses, ICS use alone does not appear to affect final adult height. Routine ICS use also should not lead to significant adrenal suppression or bone loss.
Although ICSs at low doses may be safe for children, are they effective enough? The current study examines the dose response to ICSs among children with persistent asthma.
HPV Immunization for Male and Female Patients: Strategies to Reduce the Disease Burden
Kenneth A. Alexander, MD, PhD, Course Chair; Amanda Frisch Dempsey, MD, PhD, MPH; Maura L. Gillison, MD, PhD; Stephen E. Goldstone, MD
http://www.medscape.org/viewprogram/31840?src=cmemp
Contents of This CME Activity
1. Introduction
Kenneth A. Alexander, MD, PhD, Course Chair
Available As: Slides/Audio | Transcript
2. HPV Epidemiology: Infection to Genital Warts and Cancer
Maura L. Gillison, MD, PhD
Available As: Slides/Audio | Transcript
3. HPV Immunization: Making the Case for Males and Females
Stephen E. Goldstone, MD
Available As: Slides/Audio | Transcript
4. Incorporating HPV Into Adolescent Immunization
Amanda Frisch Dempsey, MD, PhD, MPH
Available As: Slides/Audio | Transcript
5. Talking to Patients and Parents
Faculty
Available As: Slides/Audio | Transcript
Earn CME Credit »
http://www.medscape.org/viewprogram/31840?src=cmemp
Contents of This CME Activity
1. Introduction
Kenneth A. Alexander, MD, PhD, Course Chair
Available As: Slides/Audio | Transcript
2. HPV Epidemiology: Infection to Genital Warts and Cancer
Maura L. Gillison, MD, PhD
Available As: Slides/Audio | Transcript
3. HPV Immunization: Making the Case for Males and Females
Stephen E. Goldstone, MD
Available As: Slides/Audio | Transcript
4. Incorporating HPV Into Adolescent Immunization
Amanda Frisch Dempsey, MD, PhD, MPH
Available As: Slides/Audio | Transcript
5. Talking to Patients and Parents
Faculty
Available As: Slides/Audio | Transcript
Earn CME Credit »
FDA Hearing on Mercury-Based Dental Fillings Pleases Both Sides of Debate
From Medscape Medical News
Robert Lowes
December 18, 2010 — An advisory panel to the US Food and Drug Administration (FDA) concluded this week that there are no huge scientific flaws in the agency's 2009 finding that mercury-based dental fillings, known as dental amalgam, are safe for adults and children aged 6 years and older.
However, at the end of its 2-day hearing, the agency's dental products panel recommended that the FDA look at more data — and the latest data — on the possible health risks that the filling material poses to pregnant women and their fetuses and to young children, particularly nursing infants whose mothers have these fillings. The panel also said the agency should consider adding warnings for these groups to the material's product instructions.
In one sense, the outcome of the hearing temporarily preserves the status quo for dental amalgam — so much so that the American Dental Association immediately issued a press release praising the expert panel's recommendations. The American Dental Association maintains that dental amalgam is safe and warrants no further regulation by the FDA as a medical device.
At the same time, the panel's quest for more scientific data about vulnerable populations acknowledged the concerns of dental amalgam opponents, who link mercury exposure to dozens of diseases ranging from autism to Alzheimer's disease. At high enough levels, mercury exposure can damage the brain and kidneys.
"We have to recognize that some patients should not have amalgam," said panel member Amid Ismail, BDS, DrPH, a professor and dean at the Kornberg School of Dentistry at Temple University in Philadelphia, Pennsylvania.
"There is really no place for mercury in children," added Suresh Kotagal, MD, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota. "The bottom line is, do no harm."
An attorney for the International Academy of Oral Medicine and Toxicology (IAOMT), which advocates mercury-free dentistry, told Medscape Medical News that he was encouraged by the consensus positions of the panel (no formal votes were taken).
"There was a lot of support that risk assessment needs to be done again," said Jim Love, the attorney for the group. "I thought it was a very constructive dialogue."
The FDA convened the hearing after the IAOMT and other antiamalgam groups and individuals petitioned the agency to reconsider its 2009 decision to reclassify the material from a lower-risk class I device to a moderate-risk class II device. That reclassification entailed revising product instructions to state in part that
* clinical studies have not established a causal link between dental amalgam and health problems for adults and children aged 6 years and older,
* the developing nervous systems of fetuses and young children "may be more sensitive to the neurotoxic effects of mercury vapour," and
* little or no clinical data are available regarding long-term health outcomes for fetuses, children younger than 6 years, and breast-fed infants.
The petitioners urged the agency to either ban dental amalgam, as Norway, Sweden, and Denmark already have done, or else reclassify it as a high-risk class III device with more restrictions on its use.
"Industry Will Go Crazy if That Reference Level Gets Moved"
By weight, dental amalgam is composed of roughly 40% to 50% liquid elemental mercury and a powdered alloy of mostly silver, copper, and tin. Much of the 2-day hearing focused on how much mercury is absorbed by people with these fillings, and what should be the reference exposure level (REL), or safety threshold, for the mercury vapor that the fillings release. Because mercury doses can be calculated from vapor exposure levels, an REL can establish a permissible dose. At the end, the advisory panel recommended that the agency take a second look at its positions on these issues.
The FDA currently holds that an individual with 7 to 10 amalgam fillings absorbs 1 to 5 μg of mercury per day. Amalgam opponents say this dose can be 4 times as high, meaning that tens of millions of people with these fillings are at risk for health problems, based on the current REL in place. The advisory panel's advice to the FDA is to study mercury doses for various population categories.
"We have virtually no data on fetuses," panel chairwoman Marjorie Jeffcoat, DMD, a professor at the University of Pennsylvania School of Dental Medicine, told Medscape Medical News. "It's important to subset out the different populations."
Also in dispute is the REL for mercury vapor. The FDA uses an REL of 0.3 μg/m3, set by the US Environmental Protection Agency (EPA). The EPA refers to this safety threshold as a "reference concentration" (RfC), which is an REL for inhaled, as opposed to swallowed, chemicals. This REL or RfC of 0.3 μg/m3 translates into a permissible dose that lies in the same range as the actual amalgam-derived dose assumed by the FDA.
The IAOMT told the panel that the REL for elemental mercury should be lower than 0.1 μg/m3 and cited a study it commissioned as proof. That study, whose lead author is Canadian biologist G. Mark Richardson, PhD, states that the EPA based its REL in part on studies of industrial workers exposed simultaneously to mercury and chlorine gas, with the gas acting to reduce mercury exposure, thus skewing the numbers. He notes that Health Canada, the Canadian equivalent of the US Department of Health and Human Services (and his former employer), set an REL of 0.06 μg/m3 by relying on studies free of this distortion.
The panel did not fully agree with Dr. Richardson's critique and called his chlorine gas argument a "red herring." Nevertheless, it advised the FDA to reexamine the scientific literature to reassess the REL and develop its own, noting that "the EPA RfC needs to be updated with the latest studies," according to an FDA hearing summary.
In essence, the panel wants the FDA to determine whether the REL really protects vulnerable populations, Dr. Jeffcoat told Medscape Medical News. "Tiny children can't speak for themselves," she said.
However, any lowering of the REL for elemental mercury has enormous consequences that extend far beyond the dentist's office, IAOMT attorney Jim Love told Medscape Medical News. The EPA, he said, uses this REL to regulate how much mercury that heavy industry can put into air and water, as well as to designate waste sites for its Superfund clean-up program. A lower REL means higher environmental protection costs — think billions of dollars — all around.
"Industry will go crazy if that reference level gets moved," said Love.
Need to Acknowledge Amalgam Benefits
The panel also revisited the question — raised in the FDA's 2009 deliberations — of whether clinical studies point to a causal relationship between dental amalgam and adverse health events. The panel reaffirmed that the literature at that time failed to do so, but only in terms of the general population. Again, it recommended that the agency continue to study the issue, particularly in terms of "susceptible subpopulations."
The panel grappled with how to best spell out the possible health risks of dental amalgam in the product instructions that dentists receive. It finally suggested adding warnings for young children, pregnant women, and individuals with metal allergies, and making the reference to limited scientific data about such individuals more explicit.
Panel members also stressed the need for dentists to discuss this information with patients. A number of individuals who spoke at the hearing complained that their dentists never mentioned mercury-associated risks for amalgam fillings, which they blamed for serious illnesses.
A model for warning language, incidentally, lies north of the border. Health Canada states on its Web site that although dental amalgam generally does not pose a health threat, the primary teeth of children should be filled with a nonmercury material when feasible. Pregnant women, individuals allergic to mercury, and those with impaired kidney function should avoid mercury-based fillings, according to Health Canada.
Tempering the panel's recommendations on Wednesday was an acknowledgment that amalgam's risks must be weighed against its benefits — namely, its superiority over tooth-colored composite fillings for restoring multiple surfaces, and its greater durability. In addition, although the use of amalgam has drastically declined during the last few decades as a result of patients choosing more cosmetically attractive alternatives, its lower price has made it the default material for poorer patients, who might not be able to afford more expensive fillings if amalgam were banned.
"It's nice for us to talk about risk and benefit and choice," said panel member Thomas Burbacher, PhD, a professor of environmental and occupational health sciences at the University of Washington in Seattle. "But if you don't have a choice, that discussion is meaningless."
Robert Lowes
December 18, 2010 — An advisory panel to the US Food and Drug Administration (FDA) concluded this week that there are no huge scientific flaws in the agency's 2009 finding that mercury-based dental fillings, known as dental amalgam, are safe for adults and children aged 6 years and older.
However, at the end of its 2-day hearing, the agency's dental products panel recommended that the FDA look at more data — and the latest data — on the possible health risks that the filling material poses to pregnant women and their fetuses and to young children, particularly nursing infants whose mothers have these fillings. The panel also said the agency should consider adding warnings for these groups to the material's product instructions.
In one sense, the outcome of the hearing temporarily preserves the status quo for dental amalgam — so much so that the American Dental Association immediately issued a press release praising the expert panel's recommendations. The American Dental Association maintains that dental amalgam is safe and warrants no further regulation by the FDA as a medical device.
At the same time, the panel's quest for more scientific data about vulnerable populations acknowledged the concerns of dental amalgam opponents, who link mercury exposure to dozens of diseases ranging from autism to Alzheimer's disease. At high enough levels, mercury exposure can damage the brain and kidneys.
"We have to recognize that some patients should not have amalgam," said panel member Amid Ismail, BDS, DrPH, a professor and dean at the Kornberg School of Dentistry at Temple University in Philadelphia, Pennsylvania.
"There is really no place for mercury in children," added Suresh Kotagal, MD, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota. "The bottom line is, do no harm."
An attorney for the International Academy of Oral Medicine and Toxicology (IAOMT), which advocates mercury-free dentistry, told Medscape Medical News that he was encouraged by the consensus positions of the panel (no formal votes were taken).
"There was a lot of support that risk assessment needs to be done again," said Jim Love, the attorney for the group. "I thought it was a very constructive dialogue."
The FDA convened the hearing after the IAOMT and other antiamalgam groups and individuals petitioned the agency to reconsider its 2009 decision to reclassify the material from a lower-risk class I device to a moderate-risk class II device. That reclassification entailed revising product instructions to state in part that
* clinical studies have not established a causal link between dental amalgam and health problems for adults and children aged 6 years and older,
* the developing nervous systems of fetuses and young children "may be more sensitive to the neurotoxic effects of mercury vapour," and
* little or no clinical data are available regarding long-term health outcomes for fetuses, children younger than 6 years, and breast-fed infants.
The petitioners urged the agency to either ban dental amalgam, as Norway, Sweden, and Denmark already have done, or else reclassify it as a high-risk class III device with more restrictions on its use.
"Industry Will Go Crazy if That Reference Level Gets Moved"
By weight, dental amalgam is composed of roughly 40% to 50% liquid elemental mercury and a powdered alloy of mostly silver, copper, and tin. Much of the 2-day hearing focused on how much mercury is absorbed by people with these fillings, and what should be the reference exposure level (REL), or safety threshold, for the mercury vapor that the fillings release. Because mercury doses can be calculated from vapor exposure levels, an REL can establish a permissible dose. At the end, the advisory panel recommended that the agency take a second look at its positions on these issues.
The FDA currently holds that an individual with 7 to 10 amalgam fillings absorbs 1 to 5 μg of mercury per day. Amalgam opponents say this dose can be 4 times as high, meaning that tens of millions of people with these fillings are at risk for health problems, based on the current REL in place. The advisory panel's advice to the FDA is to study mercury doses for various population categories.
"We have virtually no data on fetuses," panel chairwoman Marjorie Jeffcoat, DMD, a professor at the University of Pennsylvania School of Dental Medicine, told Medscape Medical News. "It's important to subset out the different populations."
Also in dispute is the REL for mercury vapor. The FDA uses an REL of 0.3 μg/m3, set by the US Environmental Protection Agency (EPA). The EPA refers to this safety threshold as a "reference concentration" (RfC), which is an REL for inhaled, as opposed to swallowed, chemicals. This REL or RfC of 0.3 μg/m3 translates into a permissible dose that lies in the same range as the actual amalgam-derived dose assumed by the FDA.
The IAOMT told the panel that the REL for elemental mercury should be lower than 0.1 μg/m3 and cited a study it commissioned as proof. That study, whose lead author is Canadian biologist G. Mark Richardson, PhD, states that the EPA based its REL in part on studies of industrial workers exposed simultaneously to mercury and chlorine gas, with the gas acting to reduce mercury exposure, thus skewing the numbers. He notes that Health Canada, the Canadian equivalent of the US Department of Health and Human Services (and his former employer), set an REL of 0.06 μg/m3 by relying on studies free of this distortion.
The panel did not fully agree with Dr. Richardson's critique and called his chlorine gas argument a "red herring." Nevertheless, it advised the FDA to reexamine the scientific literature to reassess the REL and develop its own, noting that "the EPA RfC needs to be updated with the latest studies," according to an FDA hearing summary.
In essence, the panel wants the FDA to determine whether the REL really protects vulnerable populations, Dr. Jeffcoat told Medscape Medical News. "Tiny children can't speak for themselves," she said.
However, any lowering of the REL for elemental mercury has enormous consequences that extend far beyond the dentist's office, IAOMT attorney Jim Love told Medscape Medical News. The EPA, he said, uses this REL to regulate how much mercury that heavy industry can put into air and water, as well as to designate waste sites for its Superfund clean-up program. A lower REL means higher environmental protection costs — think billions of dollars — all around.
"Industry will go crazy if that reference level gets moved," said Love.
Need to Acknowledge Amalgam Benefits
The panel also revisited the question — raised in the FDA's 2009 deliberations — of whether clinical studies point to a causal relationship between dental amalgam and adverse health events. The panel reaffirmed that the literature at that time failed to do so, but only in terms of the general population. Again, it recommended that the agency continue to study the issue, particularly in terms of "susceptible subpopulations."
The panel grappled with how to best spell out the possible health risks of dental amalgam in the product instructions that dentists receive. It finally suggested adding warnings for young children, pregnant women, and individuals with metal allergies, and making the reference to limited scientific data about such individuals more explicit.
Panel members also stressed the need for dentists to discuss this information with patients. A number of individuals who spoke at the hearing complained that their dentists never mentioned mercury-associated risks for amalgam fillings, which they blamed for serious illnesses.
A model for warning language, incidentally, lies north of the border. Health Canada states on its Web site that although dental amalgam generally does not pose a health threat, the primary teeth of children should be filled with a nonmercury material when feasible. Pregnant women, individuals allergic to mercury, and those with impaired kidney function should avoid mercury-based fillings, according to Health Canada.
Tempering the panel's recommendations on Wednesday was an acknowledgment that amalgam's risks must be weighed against its benefits — namely, its superiority over tooth-colored composite fillings for restoring multiple surfaces, and its greater durability. In addition, although the use of amalgam has drastically declined during the last few decades as a result of patients choosing more cosmetically attractive alternatives, its lower price has made it the default material for poorer patients, who might not be able to afford more expensive fillings if amalgam were banned.
"It's nice for us to talk about risk and benefit and choice," said panel member Thomas Burbacher, PhD, a professor of environmental and occupational health sciences at the University of Washington in Seattle. "But if you don't have a choice, that discussion is meaningless."
Subscribe to:
Posts (Atom)