From the recent medical literature...
1. ACC/AHA Update Guidelines for Unstable Angina, NSTEMI
Shelley Wood. August 14, 2007 — The American College of Cardiology (ACC) and the American Heart Association (AHA) have updated their 2002 Guidelines for the Management of Patients with Unstable Angina (UA)/Non-ST-Elevation Myocardial Infarction (NSTEMI), introducing a number of recommendations for initial diagnostic tests, choice and duration of antiplatelet therapy, and new anticoagulants. The new document also highlights strategies and agents that are no longer considered valuable in the treatment or diagnosis of patients with unstable coronary artery disease (CAD). The guidelines are published online August 6, 2007 in the Journal of the American College of Cardiology and Circulation.
In an interview with heartwire, writing group chair Dr Jeffrey Anderson (University of Utah Hospital, Salt Lake City) highlighted some of the key changes in the updated guidelines. "There have been a lot of new trials, new drugs, new anticoagulants, and new issues, so there are a moderate number of changes," he said. "I don't think there are a lot of things that are completely reversed, but there's certainly been an evolution and fine-tuning of the 2002 guidelines."
One of the overarching themes, according to Anderson, is a slight pullback in terms of the emphasis on an initial invasive strategy for all UA/NSTEMI patients. "In these guidelines we've sort of swung the pendulum back a little bit from the initial invasive strategy from 2002," he said. Instead, the 2007 update urges physicians to first establish whether patients are high or low risk and then apply the guidelines according to that initial risk assessment. "In low-risk patients, particularly low-risk women, an initially conservative strategy is more appropriate.... Low-risk patients should first be noninvasively risk-stratified and treated medically, but not all sent to the lab." Based on the Invasive Versus Conservative Treatment in Unstable Coronary Syndome (ICTUS) trial, the guidelines also state that an initially conservative strategy can also be considered in stabilized patients, he said.
But Dr Eric Peterson (Duke University, Durham, NC), another member of the writing group, sees this slightly differently. "I take it almost the other way around," he told heartwire. "The guidelines give a 1a recommendation for use of an early invasive strategy in patients who match any of these risk factors, including those who have positive markers, but there is some latitude that's given to physicians — a 2b recommendation — that they can consider a conservative strategy if they initially stabilize the patient."
Peterson acknowledged there was "tension inside the guideline committee" about how to balance some of the conflicting trials in this area — for example, ICTUS vs [Intracoronary Stenting with Antithrombotic Regimen Cooling Off] ISAR-COOL or [Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction] TACTICS-TIMI 18. "When it comes to the issue of invasive vs conservative strategies, there is evidence that goes both ways, depending on which study you choose to look at.... Following that evidence, there are differences in clinician opinion as to what the right strategy would be, and I think in part the guidelines reflect that."
What the guidelines do urge, says Peterson, is for physicians to first make the decision as to what treatment strategy they're going to take, then follow the recommended pathways according to what they've decided. "These guidelines give clinicians the mandate to make that decision up front and then to tailor the therapy that would go along with that, depending on what strategy you choose."
In with the new, out with the old
As expected, bivalirudin and fondaparinux have made it into the 2007 update. Both agents have a class 1 indication for use on top of antiplatelet therapy for patients in whom an invasive strategy is selected. Unfractionated heparin (UFH) and enoxaparin are given class 1 indications in patients undergoing an invasive strategy or a conservative strategy, but fondaparinux is preferred over these other agents in patients at an increased risk of bleeding for whom a conservative strategy is selected. In UA/NSTEMI patients for whom an initial conservative strategy is selected (with the possibility of converting to an invasive strategy other than coronary artery bypass grafting [CABG]), enoxaparin or fondaparinux are recommended over UFH.
Also new to the guidelines are recommendations for the use of multislice computed tomographic (CT) angiography and cardiac MRI, reflecting other recent appropriateness criteria and scientific statements dealing with imaging. Brain-type natriuretic peptide (BNP) makes its debut in the updated guidelines as a biomarker test that can be considered to supplement global risk assessment in ACS patients. Otherwise, a cardiac-specific troponin is now recommended as the "preferred marker."
"Troponin has continued to rise and really everything else has fallen way behind," Anderson explained. "In 2002, there was more attention paid to alternative markers; now we've sort of pushed those down the list."
Other notable changes or tweaks in the 2007 update include a fresh emphasis on reducing delays to initial evaluation and facilitated emergency-department (ED) diagnosis and triage, including the use of a 12-lead ECG ideally within 10 minutes of ED arrival. For patients treated invasively, recommended duration of clopidogrel therapy has been extended. "The guidelines now recommend that clopidogrel therapy be continued for at least one year after drug-eluting stent placement and ideally up to one year with a bare-metal stent or even with medical therapy, because we think the additional antiplatelet therapy seems to be beneficial," Anderson commented.
The new guidelines also give the option of using a higher loading dose of clopidogrel. "A lot of the more recent studies use 600 mg, and even though we need more studies in terms of larger numbers and hard outcomes, those studies look very promising. So we offer that as an option," Anderson said.
According to Anderson, recommendations for glycoprotein (GP) IIb/IIIa inhibitors are largely unchanged from the 2002 guidelines. "The only thing that's come along is whether, with high-risk ACS patients, you can just give clopidogrel alone without adding a GP IIb/IIIa inhibitor," Anderson explained. "There's one study that has showed that adding on a GP IIb/IIIa inhibitor did seem to benefit patients, so in higher-risk patients we're still suggesting you use a GP IIb/IIIa inhibitor if you're doing an invasive strategy, even if you're using clopidogrel. In the lower-risk patients, you can use either one or the other; at least one and possibly both."
Finally, the guidelines also drive the final nail into the coffin for strategies that have proved nonbeneficial or harmful over the past five years, including the use of supplements such as beta-carotene, vitamins E and C, and folic acid. Also singled out as harmful in the new guidelines are hormone replacement therapy in postmenopausal women and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), except for aspirin, for UA/NSTEMI patients during hospitalization.
"If one looks at what has happened over the past five to 10 years, adverse outcomes in NSTEMI have really fallen dramatically," Anderson said. "The bottom line is, the guidelines seem to be working. In the past 10 years we've pushed the envelope in terms of evidence-based medicine for diagnostics and treatment, and we do seem to be having an impact on the risks associated with ACS. With that in mind, the message would be to push ahead and fine-tune what we do and hopefully get even better outcomes."
Full-text: http://content.onlinejacc.org/cgi/content/full/50/7/e1 and
Exec summary: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.185752
2. The Role of Post-Reduction Radiographs after Shoulder Dislocation
To determine whether post-reduction radiographs add clinically important information to what is seen on prereduction X-rays in ED patients with shoulder dislocation, a prospective observational study was conducted. Clinicians recorded pre-reduction and post-reduction X-ray readings, and the films were subsequently reviewed by a blinded attending radiologist. While the majority of fractures associated with shoulder dislocations were seen on pre-reduction radiographs, more than one-third of fractures were visible only on post-reduction X-rays.
Kahn JH, et al. J Emerg Med 2007;33:169-173.
3. Midazolam vs. Diphenhydramine for the Treatment of Metoclopramide-induced Akathisia: A Randomized Controlled Trial
Parlak I, et al. Acad Emerg Med. 2007;8:715-721.
Objectives: To compare the effects of midazolam, which is a fast and short-acting benzodiazepine, and diphenhydramine, which is a widely used anticholinergic agent, in clinical practice for the treatment of metoclopramide-induced akathisia.
Methods: All adults older than 17 years given metoclopramide for nausea and vomiting or for headache and who had akathisia were eligible for this clinical, randomized, double-blind trial. Patients were randomized to receive diphenhydramine or midazolam. Subjective, objective, and total akathisia scores and modified Ramsay Sedation Scale scores were recorded. Repeated-measures analysis of variance was used to compare the efficacy and side effects of the medications.
Results: Forty-one (73.3%) of the 56 enrolled patients were women. The mean (±SD) age was 39.9 (±15.7) years in the diphenhydramine group and 40.9 (±16.2) years in the midazolam group. Mean subjective, objective, and total akathisia scores in the first 5 minutes declined considerably in the midazolam group compared with the diphenhydramine group (p less than 0.001). However, the mean Ramsay Sedation Scale score in the first 15 minutes increased significantly in the midazolam group compared with the diphenhydramine group (p less than 0.001).
Conclusions: Midazolam can correct the symptoms of metoclopramide-induced akathisia faster than diphenhydramine, but it causes more sedation.
4. Epilepsy Can Cause Isolated Transient Amnesia
Consider the diagnosis of nonconvulsive epilepsy in patients with unexplained episodic memory loss.
When a patient presents with an episode of transient memory loss without other neurologic symptoms, the diagnosis "transient global amnesia" (TGA) is often made, but the etiology is often unclear. Researchers in the U.K. describe 50 patients, recruited over 18 months, in whom epilepsy was thought to be the cause of otherwise unexplained transient amnesia, resulting in the more specific diagnosis of "transient epileptic amnesia" (TEA).
All patients had recurrent episodes of amnesia in which other cognitive functions were judged by witnesses to have remained intact. Diagnostic criteria for epilepsy were presence of at least one of these conditions: (1) epileptiform abnormalities on electroencephalogram (EEG), (2) presence of other clinical features of epilepsy such as lip-smacking or olfactory hallucinations, and (3) clear response to anticonvulsant therapy. Each of the three conditions was met by 18, 36, and 48 patients, respectively. Mean age at onset was 62, median attack frequency was 12 per year, and median duration of amnestic episodes was 30 to 60 minutes. Compared with age-matched controls, patients had subtle long-term memory problems on standardized tests. A diagnosis of epilepsy was initially considered in only 12 of these patients.
Comment: This is the largest published case series to date of patients with TEA. Because only 18 of the patients had documented epileptiform activity on EEG, one might challenge whether the diagnosis of TEA was certain in all cases. Nevertheless, this report demonstrates that clinicians should consider the diagnosis of nonconvulsive epilepsy in patients with unexplained episodic memory loss.
— Allan S. Brett, MD. Published in JW Gen Med July 24, 2007. Citation: Butler CR et al. Ann Neurol 2007 Jun; 61:587-98.
5. Average patient spends 4 hours in ED
The average time spent in emergency departments rose in 2006, but so did patient satisfaction, according to a new report by Press Ganey Associates. Based on the firm’s patient surveys in 1,500 hospitals, patients spent an average of 4 hours in the ED, 18 minutes more than in 2005. The more patients an ED saw over the year, the longer the average visit, which increased by 30 minutes for every additional 10,000 patients annually. Patient satisfaction dropped as time in the ED increased, with the lowest satisfaction reported from 3-11 p.m. and highest from 7 a.m.-3 p.m.
To view the report, go to: http://www.pressganey.com/ER-report.pdf
6. In the Elderly A Fibber, Warfarin Superior to Aspirin for Preventing Stroke
Warfarin is more effective than aspirin in preventing stroke, intracranial hemorrhage, and arterial embolism among elderly patients with atrial fibrillation, the Lancet reports.
Researchers randomized 973 patients over 75 years of age with atrial fibrillation either to warfarin (target INR, 2 to 3) or to 75 mg of aspirin daily. After an average follow-up of 2.7 years, the warfarin group had an annual relative risk of 0.48 for stroke, intracranial hemorrhage, or embolism. The number needed to treat for 1 year to prevent a primary event was 50. There was no difference between the groups in the risk for major hemorrhage — a result the authors called "surprising."
Editorialists, citing the study's "unprecedented number of patients in an age group that has been largely under-represented in randomised trials," say it "firmly establishes the superior efficacy of warfarin as a stroke-prevention strategy in elderly patients with atrial fibrillation."
Mant J, et al. The Lancet 2007; 370:493-503.
7. Antibiotic Prophylaxis Does Not Lower Rate of Recurrent UTI in Children
Conway PH, et al. JAMA. 2007;298:179-186.
Context: The evidence regarding risk factors for recurrent urinary tract infection (UTI) and the risks and benefits of antimicrobial prophylaxis in children is scant.
Objectives: To identify risk factors for recurrent UTI in a pediatric primary care cohort, to determine the association between antimicrobial prophylaxis and recurrent UTI, and to identify the risk factors for resistance among recurrent UTIs.
Design, Patients, and Setting: From a network of 27 primary care pediatric practices in urban, suburban, and semirural areas spanning 3 states, a cohort of children aged 6 years or younger who were diagnosed with first UTI between July 1, 2001, and May 31, 2006, was assembled. Time-to-event analysis was used to determine risk factors for recurrent UTI and the association between antimicrobial prophylaxis and recurrent UTI, and a nested case-control study was performed among children with recurrent UTI to identify risk factors for resistant infections.
Main Outcome Measures: Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens.
Results: Among 74 974 children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22-3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37-5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19-5.12), and grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; 95% CI, 1.26-15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.50-2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antibimicrobial resistance among children with recurrent UTI (HR, 7.50; 95% CI, 1.60-35.17).
Conclusion: Among the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections.
8. Cognitive Impairment from H2 Blockers for 1 in 5 Older Patients
INDIANAPOLIS, IN -- August 2, 2007 -- Long-term use of histamine2 receptor antagonists (H2A), one class of drugs that blocks stomach acid, may be associated with cognitive impairment in older African-American adults. According to an Indiana University School of Medicine and Regenstrief Institute study published in August issue of the Journal of the American Geriatrics Society, the risk for showing signs of cognitive impairment is 2.5 times greater for patients using these medications long-term.
These acid blockers, including ranitidine and famotidine, are among the most popular medications prescribed in the United States. More than 16 million prescriptions were dispensed in 2005 and several of these medications are also available over-the-counter. The drugs are sold under brand names such as Axid, Pepcid, Tagamet and Zantac, and are used to treat ulcers, acid reflux and other gastrointestinal disorders.
The 5-year observational study included 1,558 cognitively normal African-Americans aged 65 and older. After controlling for other possible factors, nearly 18% of H2A users studied exhibited signs of cognitive impairment.
"Taking these medications continuously appears to put older African-Americans at greater risk for the development of cognitive impairment," said Malaz Boustani, MD, MPH, lead author of the study. "We need to study this further to determine how acid blockers might be causing or creating this effect and if it occurs only in African-Americans."
9. Emergency Angioplasty Use Rises, But Some Patients Still Miss Out
NEW HAVEN, CT -- August 3, 2007 -- Compared with their counterparts a decade ago, today's heart attack patients are receiving emergency angioplasty or clot-busting drugs to re-open clogged arteries at a far greater rate, but 10% of patients who could benefit from this life-saving treatment still do not receive it, according to a study published in The American Journal of Medicine by Yale and University of Michigan researchers.
The results also showed that the chance of missing out on lifesaving emergency treatment was highest among patients without typical symptoms like chest pain, patients who did not arrive at the hospital until 6 or more hours after the heart attack began, female patients, those over age 75 and non-whites.
The 10-year study was based on data from 238,291 heart attack patients between 1994 and 2003 who were listed in the National Registry of Myocardial Infarction. The patients had a particular kind of heart attack called ST-elevated myocardial infarction (STEMI). It is the most current and comprehensive look at the use of emergency reperfusion, a treatment that can restore blood flow to the heart muscle. To track the changes in emergency reperfusion therapy over time, the researchers divided the study data into three time periods: June 1994 through May 1997, June 1997 through May 2000, and June 2000 through May 2003.
"This study has good and bad news," said senior author Harlan M. Krumholz, MD, the Harold H. Hines, Jr. Professor of Medicine at Yale School of Medicine. "We have definitely made progress in treating appropriate patients, but our findings indicate that we need to improve further to be sure that no patient who could benefit from treatment is missed."
"We may never be able to get to 100%, but 10% of eligible patients going untreated is still too many," said first author Brahmajee Nallamothu, MD, assistant professor of cardiovascular medicine at the University of Michigan Medical School. "We hope our study highlights the opportunities to improve care and particularly some of the "at risk" subgroups still less likely to receive reperfusion therapy despite eligibility, so that we can focus our clinical efforts on them."
Hospitals around the nation, including Yale-New Haven and University of Michigan, are taking part in a national campaign to reduce "door-to-balloon" times -- the time from when a STEMI patient enters hospital doors to the time blood flow is restored to the heart by opening a blockage with angioplasty.
The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study. Genentech, Inc. provided researchers with access to the registry.
10. U.S. Life Expectancy Ranking Is Falling
Although Americans are living longer than ever, U.S. life expectancy ranks 42nd in the world — down from 11th two decades ago — according to an Associated Press story.
The report, based on data from the U.S. Census Bureau and National Center for Health Statistics, says the U.S. is now surpassed by most of Europe, Jordan, Guam, the Cayman Islands, and Japan, among other countries.
The article cites lack of health insurance, high obesity rates, and racial disparities among the reasons for the country's falling ranking. Many more countries are included in the standings now than 20 years ago, which also contributes to the U.S.'s lower placement.
11. Seldinger Cricothyrotomy Kit Slower, but Preferred, Compared to New Tube-over-Needle Device
Assmann HM, et al. Anesth Anal 2007; 105:148-154.
BACKGROUND: Percutaneous cricothyroidotomy may be a life-saving procedure in cannot intubate–cannot ventilate situations. In this study we compared the insertion times of a new indicator-guided cricothyroidotomy device and a wire-guided device in mannequins.
METHODS: This study was a crossover trial comparing the insertion times and success rates of an indicator-guided tube-over-needle device and a wire-guided cricothyroidotomy device in a mannequin. After an audiovisual training session, 64 anesthesiologists performed five cricothyroidotomies with each of the two devices. Successful insertion was defined as insertion of a device into the correct anatomic location. The insertion times and success rates between the two techniques for the five attempts were compared using repeated measures ANOVA, paired t-test, and 2 analyses.
RESULTS: Insertion times were faster (32.6 ± 14.9 s vs 42.3 ± 12.5 s, P less than 0.001) while success rates were similar (95% vs 93.1%) with the indicator-guided device when compared with the wire-guided device. For both devices, performance improved with repeated attempts. Four insertion attempts (1.3%) were positioned anterior or posterior to the trachea lumen with the indicator-guided device compared to none with the wire-guided device (P = 0.12) Subjectively, more participants chose to use the wire-guided than the indicator-guided device (59% vs 31%, P less than 0.001) in a clinical emergency situation.
CONCLUSION: In a mannequin model, cricothyroidotomy insertion times were faster for the indicator-guided technique than for the wire-guided technique, but success rates were similar. Subjectively, more participants chose to use the wire-guided device in a clinical emergency situation.
12. Cannabis Use Linked to Later Psychosis
A Lancet meta-analysis on the late effects of cannabis use finds that the drug is associated with a 40% increase in the risk for psychotic symptoms, with more use leading to greater risk.
The authors assessed the studies with particular attention to bias and confounding factors, such as intoxication effects and subjects' having experienced psychosis at baseline. In the seven studies evaluated for a link with psychosis, the odds ratio for psychosis in those who had ever used cannabis versus nonusers was 1.41. Among the most frequent users, the odds ratio was 2.09.
The authors say the question is not so much whether cannabis causes psychosis as it is "whether the evidence ... now available can justify policy implications, such as public education campaigns to alert people to the possible risks."
A commentator calls the study "the most comprehensive meta-analysis to date" and concludes that cannabis' "long-term hazardous effects ... with regard to psychosis seem to have been overlooked."
13. Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers
Pediatric ingestions of calcium channel blocking medications are becoming more frequent. A literature review revealed that although most accidental pediatric ingestions are asymptomatic, a small number do result in cardiovascular instability or even death. The dihydropyridines, particularly nifedipine, and the phenylalkylamine verapamil are most often implicated in symptomatic ingestions.
There are no adequate data to identify which children are predisposed to illness, or to determine cutoffs for toxic dosages. However, ingestions of only one pill have been documented to cause severe symptoms, including death. Thus, emergency evaluation to assess potential toxicity is necessary, and gastrointestinal decontamination and in-hospital observation of at least 6 h after toxic ingestion for regular release medications, and 12–24 h after toxic ingestion for sustained release medications is recommended for all cases of unintentional calcium channel blocker ingestion in children younger than 6 years of age.
Ranniger C, et al. J Emerg Med 2007;33:145-154.
14. Prognostic Factors in Heat Wave–Related Deaths: A Meta-analysis
Bouchama A, et al. Arch Intern Med. 2007;167:(doi:10.1001/archinte.167.20.ira70009).
Background: Although identifying individuals who are at increased risk of dying during heat waves and instituting protective measures represent an established strategy, the evidence supporting the components of this strategy and their strengths has yet to be evaluated. We conducted a meta-analysis of observational studies on risk and protective factors in heat wave–related deaths.
Methods: Using the OVID interface, we searched Medline (1966-2006) and CINHAL (1982-2006) databases. The Web sites of the World Health Organization, Institut National de Veille Sanitaire, and Centers for Disease Control and Prevention were also visited. The search terms included heat wave, heat stroke, heatstroke, sunstroke, and heat stress disorders. Eligible studies were case-control or cohort studies. Odds ratios (ORs) and information on study quality were abstracted by 2 investigators independently. Six case-control studies involving 1065 heat wave–related deaths were identified.
Results: Being confined to bed (OR, 6.44; 95% confidence interval [CI], 4.5-9.2), not leaving home daily (OR, 3.35; 95% CI, 1.6-6.9), and being unable to care for oneself (OR, 2.97; 95% CI, 1.8-4.8) were associated with the highest risk of death during heat waves. Preexisting psychiatric illness (OR, 3.61; 95% CI, 1.3-9.8) tripled the risk of death, followed by cardiovascular (OR, 2.48; 95% CI, 1.3-4.8) and pulmonary (OR, 1.61; 95% CI, 1.2-2.1) illness. Working home air-conditioning (OR, 0.23; 95% CI, 0.1-0.6), visiting cool environments (OR, 0.34; 95% CI, 0.2-0.5), and increasing social contact (OR, 0.40; 95% CI, 0.2-0.8) were strongly associated with better outcomes. Taking extra showers or baths (OR, 0.32; 95% CI, 0.1-1.1) and using fans (OR, 0.60; 95% CI, 0.4-1.1) were associated with a trend toward lower risk of death.
Conclusion: The present study identified several prognostic factors that could help to detect those individuals who are at highest risk during heat waves and to provide a basis for potential risk-reducing interventions in the setting of heat waves.
15. Diabetes Linked to Higher Mortality After Acute Coronary Syndromes
Patients with acute coronary syndromes experience higher mortality if they also have diabetes, according to a JAMA study.
Researchers pooled data on some 62,000 patients with acute coronary syndromes who were participants in 11 independent randomized trials from 1997 to 2006. About 17% of the patients had diabetes.
After controlling for other factors, the researchers found that diabetes was independently linked with higher mortality 30 days after ST-segment elevation myocardial infarction (odds ratio, 1.40) and after unstable angina/non-STEMI (OR, 1.78). After 1 year, the risk for death in patients with diabetes who had UA/NSTEMI approached that of patients without diabetes who had STEMI (7.2% vs. 8.1%).
The authors conclude: "Despite modern therapies for [acute coronary syndromes], diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease."
JAMA article (Free abstract; full text requires subscription): http://jama.ama-assn.org/cgi/content/short/298/7/765
16. Parents Warned Cough Medicines Imperil Infants
By Gardiner Harris. NY Times. Published: August 16, 2007
WASHINGTON, Aug. 15 — Hoping to halt the growing number of injuries to infants and toddlers, the Food and Drug Administration issued an advisory Wednesday warning parents never to give cough and cold medicines to children under the age of 2 unless instructed to do so by a doctor.
The warning is part of a broad reassessment by the agency of the safety of the popular medicines, which have been blamed for hundreds of adverse reactions and a handful of deaths in children under the age of 2.
The F.D.A. will convene a panel of independent experts on Oct. 18 to discuss whether more prohibitions or warnings are warranted. Such meetings often signal that the agency is seriously concerned about the safety of the drugs under review. The drugs’ labels currently advise parents to see a doctor before giving the medicines if their child is under the age of 2, but too many parents are failing to heed this advice, the agency said. “We continue to see adverse effects associated with the medicines because people are not using them properly,” said Susan Cruzan, an F.D.A. spokeswoman.
If, despite label warnings, parents continue to use the drugs inappropriately in young children, the agency could take more serious action, like restricting the drugs’ wide availability.Most drugs that have been withdrawn in the past 15 years were taken off the market because doctors and patients failed to heed prominent warnings.
Some prominent pediatricians and public health experts said that the drug agency’s advisory did not go far enough. One group petitioned the agency to ban the marketing of the drugs for children under the age of 6, and some said that the medicines should no longer be sold over-the-counter for use in children at all.
“Unless convincing evidence shows that these medications are effective for children, their easy availability to families should be re-examined,” said Dr. Ian M. Paul, a pediatrician at Penn State Children’s Hospital in Hershey, Pa.
But the drugs’ makers say that the F.D.A. approved the drugs because they are safe and effective. Virginia Cox, a spokeswoman for the Consumer Healthcare Products Association, said that the drugs’ labels already advised against their use in children under the age of 2 unless a doctor approved. Ms. Cox said there was no need to raise this age limit to 6. Some of the drugs have drawings or pictures of infants in diapers on their labels.
The debate results because the standards for drug approvals have changed sharply in the decades since many of the medicines in children’s cough and cold products were approved. If those drugs were currently up for review, they would not be approved for use in children because the manufacturers never tested them thoroughly in children.
Instead, the drugs’ makers performed studies in adults and then simply assumed that they would work in children. Such assumptions, once common, are no longer acceptable. Indeed, a growing number of studies in children suggest that cough and cold medicines work no better than placebos. Among the ingredients that have caused concern are anticough medicines including dextromethorphan, which is the DM in many preparations. They can cause neurological problems, including abnormal movements and hallucinations, even in standard doses. Another is pseudoephedrine, which is a decongestant that has been associated with infant deaths, increased blood pressure and arrhythmias.
Some of the injuries and deaths associated with these products have resulted when parents gave two different products to their child, not realizing that both contained identical medicines, resulting in an overdose. In rare cases, children have been injured when given recommended doses.
Everyone agrees that more studies in children are needed, but companies have little incentive to undertake new trials because the medicines’ patents long ago expired. So the F.D.A. must decide how to regulate drugs that it knows very little about — a position in which it frequently finds itself. In such circumstances, it often turns to advisory boards.
Despite the growing worries, sales of the drugs are booming. Most major pharmacies carry a dozen or more brands. The medicines are popular largely because children have an average of 6 to 10 colds each year, far more than adults.
17. FDA Warns Nursing Mothers on Codeine-Containing Drugs
Mothers with a rare metabolic genotype may risk morphine overdose in themselves and their breastfeeding babies from prescription-strength doses of codeine, the FDA warns.
The problem arises in people with duplications in the CYP2D6 gene, which allows unusually fast and complete metabolism of codeine into morphine, which can cause high levels of the metabolite in breast milk. The agency's alert cites a case of infant death thought to be due to ultrarapid metabolism.
The agency says that clinicians should warn nursing women to be watchful of signs of morphine overdose in themselves and their babies. Unusual sleepiness, difficulties in breathing, and decreased muscular tone in infants should prompt immediate medical attention.
There is a test for determining a patient's CYP2D6 genotype, although it is not frequently used clinically.
FDA alert (Free): http://www.fda.gov/cder/drug/infopage/codeine/default.htm
19. Emergency Physician Activation of the Cardiac Cath Lab: Door-to-balloon time decreased significantly, with few false positives.
Time from presentation to revascularization influences infarct size and mortality in ST-segment–elevation myocardial infarction (STEMI). These authors prospectively assessed door-to-balloon times before and after implementation of a protocol mandating that emergency physicians (EPs) activate the cath lab without cardiology consultation and that a team of three registered nurses immediately transfer each patient from the emergency department to the cath lab.
Sixty consecutive STEMI patients were catheterized during the 11 months before implementation of the protocol, and 86 were catheterized during the 10 months after. Median door-to-balloon time decreased significantly overall (113.5 vs. 75.5 minutes), during regular hours (83.5 vs. 64.5 minutes), during off-hours (123.5 vs. 77.5 minutes), and in cases transferred from an outside affiliated ED (147 vs. 85 minutes). Mean infarct size decreased significantly (peak creatinine kinase during first 24 hours, 2623 vs. 1517 IU/L), as did mean hospital stay (5 vs. 3 days) and total hospital costs per admission (US$26,826 vs. $18,280). Mortality rates did not differ significantly (7.4% vs. 5.2%). One patient was misrouted to the cath lab rather than to the critical care unit because of a communication error between the EP and the cardiologist.
Comment: This study is one of several demonstrating that door-to-balloon time is improved when EPs, not cardiologists, activate the cath lab (Journal Watch Emergency Medicine Nov 17 2006). The observed decreases in length of stay and cost seem too good to be true, and the authors provide insufficient detail to determine whether they fully accounted for the cost of the three nurses for patient transfer. Nonetheless, even if the authors overestimated the benefits, the only reason to require cardiologists to activate the lab would be if EPs did so unnecessarily, which didn’t happen in this study. If this finding is generalizable to other hospitals, we can conclude that qualified EPs, not cardiologists, should activate the cath lab for ED STEMI patients.
— Daniel J. Pallin, MD, MPH. Published in Journal Watch Emergency Medicine August 17, 2007. Citation: Khot UN, et al. Circulation 2007; 116:67-76.
20. FDA Announces Boxed Warnings on All Thiazolidinediones (TZDs)
The entire class of thiazolidinedione drugs used to treat type 2 diabetes must carry boxed warnings about the drugs' ability to cause or worsen heart failure, the FDA announced late yesterday.
The affected drugs are Avandia (rosiglitazone), Actos (pioglitazone), Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin), and Duetact (pioglitazone and glimepiride).
The action addresses the FDA's worry that "despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure," says the agency's chief of drug evaluation and research.
FDA announcement (Free): http://www.fda.gov/bbs/topics/NEWS/2007/NEW01683.html
21. Obesity Seems to Spread Through Social Networks
Obesity appears to spread from person to person through social ties, according to a New England Journal of Medicine study.
The research evaluated a network of about 12,000 people over 32 years. All were members of the Framingham Heart Study. Researchers found, for example, that a person's chances of becoming obese increased by 57% in a given period if a friend became obese, 40% if a sibling did, and 37% if a spouse did. The effects were seen even if the obese acquaintance lived far away.
The authors speculate that someone who sees a friend gain weight may regard putting on weight as more acceptable. An editorialist says the work suggests that "friends have an even more important effect on a person's risk of obesity than genes do."
NEJM article (Free): http://content.nejm.org/cgi/content/full/357/4/370