Lit Bits: January 18, 2006

From the recent medical literature...

1. Percutaneous Coronary Intervention May Be Beneficial After Failed Thrombolytic Therapy

Laurie Barclay, MD. Jan. 3, 2006 — Rescue percutaneous coronary intervention (PCI) may be beneficial after failed thrombolytic therapy, according to the results of a multicenter trial published in the December 29, 2005, issue of The New England Journal of Medicine.

"The appropriate treatment for patients in whom reperfusion fails to occur after thrombolytic therapy for acute myocardial infarction [MI] remains unclear," write Anthony H. Gershlick, MB, BS, from University Hospitals of Leicester, United Kingdom, and colleagues from the Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis (REACT) Trial Investigators. "There are few data comparing emergency percutaneous coronary intervention (rescue PCI) with conservative care in such patients, and none comparing rescue PCI with repeated thrombolysis."

In this multicenter trial, 427 patients with ST-segment elevation MI (STEMI) and failed reperfusion, defined as less than 50% ST-segment resolution within 90 minutes after thrombolytic treatment, were randomized to repeated thrombolysis (142 patients), conservative treatment (141 patients), or rescue PCI (144 patients). The main outcome measure was a composite of death, reinfarction, stroke, or severe heart failure within 6 months.

Rates of event-free survival were 84.6% for patients treated with rescue PCI, 70.1% for those receiving conservative therapy, and 68.7% for those undergoing repeated thrombolysis (overall P = .004). For repeated thrombolysis vs conservative therapy, the adjusted hazard ratio (HR) for the occurrence of the primary endpoint was 1.09 (95% confidence interval [CI], 0.71 - 1.67; P = .69) compared with adjusted HR of 0.43 (95% CI, 0.26 - 0.72; P = .001) for rescue PCI vs repeated thrombolysis and 0.47 (95% CI, 0.28 - 0.79; P = .004) for rescue PCI vs conservative therapy.

All-cause mortality was similar in all groups. Nonfatal bleeding, mostly at the sheath-insertion site, was more common in the rescue PCI group. Freedom from revascularization at 6 months was present in 86.2% of the rescue-PCI group, 77.6% of the conservative-therapy group, and 74.4% of the repeated-thrombolysis group (overall P = .05).

Study limitations include lack of data on myoglobin and other markers for detecting failed thrombolytic therapy; early trial termination; and possible selection bias.

"Event-free survival after failed thrombolytic therapy was significantly higher with rescue PCI than with repeated thrombolysis or conservative treatment," the investigators write. "Rescue PCI should be considered for patients in whom reperfusion fails to occur after thrombolytic therapy."

Four of the authors have disclosed various relevant financial relationships with Cordis, Boston Scientific, Medtronic, Guidant, Eli Lilly, and/or Conor Medsystems.

N Engl J Med. 2005;353:2758-2768

2. Two million Americans harbor MRSA, CDC estimates

[So what percentage is 2 million? Just how many Americans are there? According to the latest US Census data, as of July 1, 2005, the population hovered around 296,410,404. 2 million is less than 1%. --DRV]

January 4, 2006. NEW YORK (Reuters Health) - About 2 million people in the United States carry methicillin-resistant Staphylococcus aureus (MRSA) in their nasal passages, the US Centers for Disease Control and Prevention estimates.

Dr. Matthew J. Kuehnert and colleagues assessed S. aureus nasal carriage in 9,622 participants in the 2001-2002 National Health and Nutritional Examination Survey and found that 32.4% were colonized with S. aureus, of whom 0.8% harbored MRSA.

This translates into weighted population estimates of 89.4 and 2.3 million Americans colonized with S. aureus and MRSA, respectively, they report in the January 15th issue of The Journal of Infectious Diseases. S. aureus prevalence was highest among males and children between the ages of 6 and 11 years, whereas MRSA prevalence was highest among females and those older than age 60.

"In light of the increasing frequency of community-acquired MRSA infection," write the authors of a related editorial, "new antimicrobials are needed, particularly given the emergence of glycopeptides-resistant strains."

"Yet, new antimicrobials will remain fingers in the proverbial dike until a more-definitive solution can be found," contend Dr. Clarence Buddy Creech II and colleagues from Vanderbilt University in Nashville.

Stimulated by the development of effective vaccines against Haemophilus influenzae type b (Hib) and pneumococcus, several major pharmaceutical companies are working on staphylococcal vaccines, they also note. "The appropriate components of such a vaccine remain an area of active research, but early successes confirm that the vaccine-based approach is a viable undertaking," Dr. Creech and colleagues charge.

J Infect Dis 2006;193:169-179.

3. L-arginine may increase mortality risk after myocardial infarction
This explains why I’ve never noticed any improvement in the AMI patients to whom I’ve given L-arginine. Another drug bites the dust. But the concept is clever.

The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L-arginine has the potential to reduce vascular stiffness. Perhaps it might serve as an adjunctive intervention in patients with AMI. Below is a report of a recent RCT published this month in JAMA. [L-Arginine Therapy in Acute Myocardial Infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial. Schulman SP, et al. JAMA. 2006;295:58-64.]

NEW YORK (Reuters Health: January 4, 2006) - The amino acid L-arginine provides no benefit to patients who have experienced an ST-segment elevation myocardial infarction, and may even increase mortality in patients over the age of 60, Baltimore-based researchers report.

Based on the hypothesis that L-arginine can reduce vascular stiffness, Dr. Steven P. Schulman, from Johns Hopkins Hospital, and his associates initiated the prospective Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) clinical trial, in which 153 patients were randomly assigned to L-arginine (up to 3 grams three times daily) or placebo for 6 months after experiencing a first MI.

According to their report in the January 4th issue of The Journal of the American Medical Association, 6-month follow-up data were obtained for 55 subjects in the L-arginine group and 59 in the placebo group. There were no significant changes in either group in measures of ejection fraction, arterial elastance, arterial compliance, pulse pressure, or pulse wave velocity.

However, six deaths occurred in the L-arginine group, including five among patients age 60 years or older, and none in the control group (p = 0.01), which led to early termination of the study.

Dr. Schulman's team proposes several possible mechanisms by which L-arginine could cause post-MI damage, including increased generation of reactive oxygen species, homocysteine production, and increased activity of the inducible isoform of nitric oxide synthase.

"L-arginine therapy should not be given to patients following a myocardial infarction," they advise. Furthermore, they add, "L-arginine therapy in older patients with diffuse atherosclerosis may worsen clinical outcomes.

4. New Data on Treating Bronchiolitis in Kids

In two recent studies, researchers examined aspects of treatment for bronchiolitis, the most common lower respiratory tract infection in young children.

In recent studies, investigators have questioned whether bronchodilators (e.g., albuterol) are helpful for treating bronchiolitis, and whether very young infants might respond differently from older infants. To test this hypothesis, researchers in Austria gave inhaled salbutamol to 41 children (age range, 2 to 18 months) with mild-to-moderate respiratory syncytial virus–positive bronchiolitis. Pulmonary function studies that were conducted 15 minutes after inhalation demonstrated significant improvement in 11 children, worsening in 3 children, and no changes in 27 children. No correlation was observed between age and pulmonary response.

Medications to treat bronchiolitis usually are administered by face masks attached to nebulizers. This mode of delivery often is problematic, because many babies scream and squirm throughout treatment, which makes tight sealing of the masks difficult. In a randomized, controlled trial, Israeli investigators assigned 49 infants hospitalized with bronchiolitis to receive inhaled epinephrine either by conventional nebulizers with masks or passively in a hood. A statistically significant, but not dramatic, clinical improvement was noted in both groups during each of the 3 days of hospitalization, and no difference was observed between the groups. Parents strongly preferred the hood to the mask.

Comment: No medications consistently and effectively treat bronchiolitis in children. Therapeutic efficacy of agents such as bronchodilators and epinephrine should be assessed on an individual basis.

— Robert A. Dershewitz, MD, MSc. Published in Journal Watch January 3, 2006. Source: Modl M et al. Does bronchodilator responsiveness in infants with bronchiolitis depend on age? J Pediatr 2005 Nov; 147:617-21. Amirav I et al. Aerosol delivery in respiratory syncytial virus bronchiolitis: Hood or face mask? J Pediatr 2005 Nov; 147:627-31.

5. Children Fare Better Than Adults After In-Hospital Cardiac Arrest

Do kids and adults differ in their presenting rhythm? And how might this difference effect outcomes?

First Documented Rhythm and Clinical Outcome From In-Hospital Cardiac Arrest Among Children and Adults. Nadkarni VN, et al, for the National Registry of Cardiopulmonary Resuscitation Investigators. JAMA 2006;295:50-57,96-97.

By Anthony J. Brown, MD. NEW YORK (Reuters Health) Jan 04 - Contrary to what had been hypothesized, survival is better for children who experience in-hospital cardiac arrest than for adults, according to a report in the Journal of the American Medical Association for January 4. The results also suggest that CPR approaches for the two age groups should be more similar than different.

Previous reports have shown that cardiac arrests due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) have better outcomes than those due to asystole or pulseless electrical activity. Because the former types were thought to be less common in children than in adults, it was hypothesized that survival would be worse in children.

"Our findings indicate that cardiac arrest due to VF or VT is more common in children than previously thought," lead author Dr. Vinay M. Nadkarni, from the University of Pennsylvania School of Medicine in Philadelphia, told Reuters Health. Still, these types of arrests were less common in children than in adults, he added.

Interestingly, even though these better-prognosis arrests were less common in children, they still had improved survival compared with adults, Dr. Nadkarni said. The reason is because in both age groups, asystole- and pulseless electrical activity-type "arrests are the most common and children fare better after these types than do adults. Why this is the case will require further study."

Dr. Nadkarni's group evaluated nearly 37,000 cardiac arrests that occurred at 253 US and Canadian hospitals between January 1, 2000 and March 30, 2004. About 900 of the arrests logged in this data set, the National Registry of Cardiopulmonary Resuscitation, involved children, the rest involved adults.

Overall, 27% of children survived to hospital discharge compared with 18% of adults, yielding an adjusted odds ratio of 2.29. Of the survivors, the percentage of children and adults with a good neurologic outcome was 65% and 73%, respectively.

VF or pulseless VT constituted 14% of the first documented pulseless rhythms in children and 23% in adults. Asystole was seen in 40% of pediatric arrests and 35% of adult arrests, whereas pulseless electrical activity was the cause of 24% of pediatric arrests and 32% of adult arrests.

As for future studies, Dr. Nadkarni said his group is interested in looking at the impact that the timing of chest compressions has on survival. "If you look at the data, you'll see that children receive chest compressions before they're completely pulseless more frequently than do adults. So, we'd like to look at whether this phenomenon of anticipating the arrest and providing blood flow will have an impact on outcomes. We believe it will."

In a related editorial, Dr. Linda Quan, from the University of Washington School of Medicine in Seattle, comments that these findings question the conventional wisdom that the resuscitation approach for children and adults with cardiac arrest should differ.

"What a great relief it would be to say to those individuals involved in resuscitation care, regardless of the arrest patient's age and setting, there is a universal approach," she adds. "What is good for the goose is also good for the gosling."

6. Statins Signicantly Reduce Recurrence Rate of Paroxysmal Atrial Fibrillation in Pts with Elevated C-reactive Protein Levels

Statins, primarily used for lipid lowering, also reduce systemic inflammation, as measured by a reduction in C-reactive protein. This study suggests that statins can be used to reduce PAF (recurrence at 6 months in controls 65% vs. recurrence in statin group 10%--impressive!).

John Dernellis, MD; Maria Panaretou, MD. Am Heart J. 2005;150(5):1064.e7-1064.e12.

Introduction
C-reactive protein (CRP) may be a risk factor for the development of atrial fibrillation (AF). In addition, trials of aggressive CRP lowering have shown a reduction in the incidence of recurrence of persistent AF. This reduction in AF events is proportional to the degree of CRP lowering, which suggests that regression of inflammation may be the principal mechanism by which CRP lowering alters AF risk. It has been suggested that CRP lowering results in improvement of electrical remodeling affecting recurrent AF. The rise in circulating CRP is associated with activation of the classic pathway of complement and, hence, tissue damage.

Previous studies have investigated the effects of lowering CRP by statins or glucocorticoid on the prevention of recurrent hospitalized AF in patients who have been cardioverted into sinus rhythm. These studies analyzed somewhat a secondary prevention of AF. Hence, we sought to determine the effect of CRP lowering on paroxysmal AF (PAF) as measured by ambulatory electrocardiographic (ECG) monitoring in patients with PAF. We aimed to determine the effects of atorvastatin on asymptomatic episodes of PAF in everyday life, representing a kind of primary prevention of AF.

Abstract
Background: C-reactive protein (CRP) lowering is associated with a reduction in recurrent and permanent atrial fibrillation. This study sought to determine whether CRP lowering also results in a reduction of paroxysmal atrial fibrillation (PAF) during daily life.

Methods and Results: We enrolled 80 patients with proven PAF, CRP between 0.8 and 13 mg/L [the normal value of the C-reactive protein is often considered less than 0.8 mg/dl], and at least 1 episode of PAF on ambulatory electrocardiographic monitoring. Forty patients were randomized to placebo (placebo group) and 40 to atorvastatin (treatment group). Plasma CRP levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The 2 groups were comparable with respect to baseline characteristics, number of episodes of PAF, and baseline plasma CRP levels. The treatment group had lower median CRP levels at study end and experienced a significant reduction in the number of episodes of PAF compared with the placebo group. Paroxysmal atrial fibrillation was completely resolved in 26 (65%) of 40 patients in the treatment group versus 4 (10%) of 40 in the placebo group. The treatment group exhibited a highly significant reduction in PAF (P < .001). By logistic regression, treatment with atorvastatin was an independent predictor of PAF resolution.

Conclusions: C-reactive protein lowering with atorvastatin appears to be effective in eliminating PAF during daily life in a significant proportion of patients.

Full-text (free): http://www.ahjonline.com/article/PIIS0002870305006472/fulltext?browse_volume=150&issue_key=TOC%40%40JOURNALS%40YMHJ%400150%400005&issue_preview=no&select1=no&select1=no&start=&startpage=&vol=

7. Sedation and Analgesia for Pediatric Fracture Reduction in the Emergency Department: A Systematic Review

Russell T. Migita, MD; Eileen J. Klein, MD, MPH; Michelle M. Garrison, MPH. Arch Pediatr Adolesc Med. 2006;160:46-51.

Objective To assess the safety and efficacy of various forms of analgesia and sedation for fracture reduction in pediatric patients in the emergency department, as observed in randomized controlled trials in pediatric populations.

Data Sources Cochrane Controlled Trials Register, CINAHL (Cumulative Index to Nursing & Allied Health Literature), and MEDLINE. The search terms "fractures," "manipulation, orthopedic," "an(a)esthetics," "analgesics," and "hypnotics and sedatives" were used.

Study Selection Studies were included if they were randomized controlled trials studying sedative and/or analgesic regimens for fracture reductions in pediatric patients in the emergency department. The search yielded 915 references. From these, 8 studies inclu ding 1086 patients were selected.

Data Extraction Interventions studied included intravenous regional blocks (Bier blocks), nitrous oxide, and parenteral combinations. Data on measures of effectiveness and safety were extracted.

Data Synthesis Ketamine hydrochloride–midazolam hydrochloride was associated with less distress during reduction than fentanyl citrate–midazolam or propofol-fentanyl. Patients receiving ketamine-midazolam required significantly fewer airway interventions than those in whom either fentanyl-midazolam or propofol-fentanyl were used. Data comparing Bier blocks with systemic forms of sedation or analgesia were limited.

Conclusions Ketamine-midazolam seems to be more effective and have fewer adverse events than fentanyl-midazolam or propofol-fentanyl. Data on other forms of analgesia or sedation are too limited to make comparisons. More research is needed to define the regimen that maximizes safety, efficacy, and efficiency for fracture reduction in pediatric patients.

8. Cough medicines’ effect is mainly placebo

Abergavenny Roger Dobson (BMJ 2006;332:8)

Cough medicines work mostly through their sweet tastes and placebo effect, says a new report. The sweet syrups used in most over the counter medicines may contribute to the cough suppressant and expectorant activity, says a review published online in Respiratory Physiology and Neurobiology on 2 December

Ronald Eccles. Mechanisms of the placebo effect of sweet cough syrups. Respiratory Physiology & Neurobiology, In Press, Corrected Proof, Available online 2 December 2005.

“The review proposes that the major benefit of cough medicines for treatment of cough associated with common cold is related to the placebo effect rather than the pharmacological effect of an active ingredient,” says the author, Ron Eccles, head of the Common Cold Centre at the University of Cardiff.

All but two of the 60 over the counter cough medicines available in the United Kingdom contain a sweetener, such as sucrose, glucose, honey, treacle, or, in children’s medicines, a sugar-free sweetener. The sweet or bitter taste of a medicine may trigger salivation and the secretion of mucus, the report says: “Cough syrups that contain sapid substances, such as sugar, honey; spicy substances, such as capsicum; and bitter tasting substances, such as lemon and citric acid, will readily cause reflex salivation and may also promote secretion of airway mucus,” it says.

A sweet taste may also have a beneficial effect on a cough by influencing the production of endogenous opioids. And the true placebo effect of a cough medicine may be linked to this generation of opioids, the report says.

Professor Eccles points out other examples of similar beneficial effects: “It is interesting to note that application of crystalline sugar to the tongue has also been reported to inhibit another respiratory reflex—the hiccup. This indicates that the pharmacological activity of most cough medicines is questionable,” he adds, “but it does not mean that cough medicines are ineffective in treating cough. The major benefits of over the counter cough medicines may be related to the different components of the placebo effect.”

9. Implications of Incidentally Discovered Bundle-Branch Block

Bundle-branch block (BBB) is found occasionally on the electrocardiogram of an apparently healthy person. The prognostic significance of this finding has varied in previous studies. In this retrospective observational study, Mayo Clinic researchers used a medical database from Olmsted County, MN, to identify 723 patients (mean age, 63) with isolated BBB (58% with left BBB [LBBB] and 42% with right BBB [RBBB]). None of the patients had known cardiovascular disease when the BBB was discovered, and all had normal left ventricular function as determined by imaging studies.

During long-term follow-up, patients with BBB had significantly lower estimated 20-year survival than expected from general population data (about 50% vs. 60%). In another analysis, 540 patients with BBB were compared with 540 age- and sex-matched controls who did not have cardiovascular disease or ventricular dysfunction. Because BBB patients were more likely than controls to have cardiac risk factors, a multivariate analysis was performed: After adjustment for diabetes, hypertension, and hyperlipidemia, LBBB (but not RBBB) remained independently associated with increased risk for death compared with no BBB (hazard ratio, 1.5). Time to onset of any first cardiovascular event was also significantly shorter for LBBB patients than for controls.

Comment: These data suggest that isolated asymptomatic left bundle-branch block is a cardiovascular risk factor. Although the therapeutic implications are unclear because BBB is not modifiable, an incidentally discovered LBBB should at least prompt close attention to whatever modifiable risk factors are present.

— Allan S. Brett, MD. Published in Journal Watch January 6, 2006. Source: Miller WL et al. Risk factor implications of incidentally discovered uncomplicated bundle branch block. Mayo Clin Proc 2005 Dec; 80:1585-90.

10. Radiculopathy Quiz

Question: What is the most common anatomic cause of cervical radicuopathy and how does it differ from the most common cause of lumbar radiculopathy?

The Answer is: Foramen encroachment due to decreased disc height and DJD causes 70-75% of cervical radiculopathies. In contrast to lumbar radiculopathy, a herniated nucleus pulposus is the cause of only 20-25% of cervical cases (S. Carette and M. G. Fehlings. Cervical Radiculopathy
NEJM. 2005;353:392-399).

11. Attenuated Vaccine Against Severe Rotavirus Gastroenteritis May Be Safe, Effective

[Here’s another stab at making a rotavirus vaccine, hopefully without increasing the rate of intussusception, which aborted the utility of the last attempt. --DRV]

News Author: Laurie Barclay, MD; Medscape Medical News

Jan. 5, 2006 — Attenuated G1P[8] human rotavirus vaccine (HRV) is highly efficacious in protecting infants, with no increase in incidence of intussusception, according to the results of a randomized, double-blind, phase 3 trial reported in the January 5 issue of The New England Journal of Medicine.

"Every year, rotavirus is associated with 25 million clinic visits, 2 million hospitalizations, and more than 600,000 deaths worldwide among children younger than five years of age," write Guillermo M. Ruiz-Palacios, MD, from the Instituto Nacional de Ciencas Medicas y Nutricion, México Distrito Federal in Mexico, and colleagues from the Human Rotavirus Vaccine Study Group. "Development of a safe and effective rotavirus vaccine is therefore a high priority, particularly but not exclusively in developing countries, where the burden of disease is highest. Since the withdrawal from the market of the tetravalent rhesus–human reassortant vaccine (RotaShield, Wyeth Laboratories) because of an association with intussusception, ruling out such a risk has become critical for the licensure and universal use of any new rotavirus vaccine."

The investigators studied 63,225 healthy infants from 11 Latin American countries and Finland who received 2 oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately 2 months and 4 months of age. Active surveillance identified severe gastroenteritis episodes, and the 20-point Vesikari scale was used to grade disease severity.

In a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients), the efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85% (P < .001 vs placebo), and it was 100% effective against more severe rotavirus gastroenteritis.

The vaccine was associated with a 42% reduction in hospitalization for diarrhea of any cause (95% confidence interval [CI], 29% - 53%; P < .001). Definite intussusception occurred in 6 vaccine recipients and in 7 placebo recipients during the 31-day window after each dose (difference in risk, -0.32 per 10,000 infants; 95% CI, -2.91 to 2.18; P = .78).

"Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception," the authors write. "Efforts should now be focused on bringing this vaccine to infants as part of routine immunization programs, especially in areas where rotavirus is associated with an important proportion of the burden of illness and childhood death. Wide use of this vaccine will require parallel implementation of post-marketing surveillance, including follow-up investigations of deaths among HRV vaccine recipients, to answer a number of remaining questions."

GlaxoSmithKline Biologicals, the maker of the HRV vaccine, funded and coordinated the study. Some of the authors have disclosed various relevant financial relationships with GlaxoSmithKline Biologicals and/or Merck Sharp & Dohme.

In an accompanying editorial, Roger I. Glass, MD, PhD, and Umesh D. Parashar, MB, BS, MPH, from the Centers for Disease Control and Prevention in Atlanta, Ga, discuss safety and efficacy of the monovalent G1P[8] and a pentavalent vaccine, based on this study and on a second study reported in the same issue.

"These trials leave open the question of whether either vaccine might cause intussusception if administered to older infants or to a larger number of infants," Drs. Glass and Parashar write. "Given the troubling legacy of RotaShield and concern among the public and physicians over intussusception, an effective system of surveillance should be put in place after licensure to monitor this rare outcome. Hundreds of thousands of children will need to be immunized before a clean bill of health can be given to these vaccines."

Drs. Glass and Parashar have disclosed no relevant financial relationships.

N Engl J Med. 2006;354:11-22, 75-77.

12. Physicians' Beliefs May Lead to Racial Disparities in Cardiac Treatment

NEW YORK (Reuters Health) Jan 05 - Physicians' perceptions of patients' characteristics can lead to racial disparities in the treatment of coronary artery disease, according to a report to be published in the February issue of American Journal of Public Health.

"Under certain conditions, it seems that we are capable of becoming aware of how unconscious beliefs influence our expectations of others," Dr. Michele van Ryn from University of Minnesota Medical School, Minneapolis, told Reuters Health. "These conditions include having the motivation and cognitive resources to self-monitor (put effort into becoming aware of unconscious processes), to actually self-monitor and identify automatic beliefs, and to examine whether these automatic beliefs are accurate in the individual case."

Dr. van Ryn and colleagues evaluated the factors associated with provider recommendations for coronary artery bypass graft surgery (CABG) in a subset of 532 patients who were appropriate candidates for this procedure but not for other aggressive treatments. Thirty-four percent were white, 30% were black and 36% were Hispanic.

Only 21% of black men received a recommendation for CABG, the authors report, compared with 40% of white and Hispanic men. There were no differences in treatment based on race or ethnicity among women.

Black patients were significantly younger than whites, the results indicate, and they had only about half the rate of left main coronary artery disease.

White patients were significantly less likely than black patients to have Medicaid or no insurance coverage, at 3% and 21%, respectively.

Overall, physicians were significantly less likely to rate blacks as likely to comply with medical advice, have significant career demands, have social support and have a physically active lifestyle, and to rate them as significantly more likely to abuse drugs.

Physicians' perception that the patient desired a physically active lifestyle and was educated was significantly associated with a recommendation for CABG, the researchers note.

When these variables were added to the model, the effect of patient race and ethnicity on physician recommendations for CABG disappeared.

"I think it might be worthwhile for providers to try to self-monitor and then treat these unconscious beliefs as hypotheses to be tested in the clinical encounter," Dr. van Ryn said. "For example, if a cardiologist monitored herself and became aware that she had concerns about whether a patient would engage in high-risk behaviors or wouldn't participate in cardiac rehab...that could be...a cue to explore these matters with the patient."

"Although we know that patient race can influence physician decision-making, we know little about the individual characteristics that make the physician more or less susceptible to unconscious bias," Dr. van Ryn added. "To develop effective interventions, we need to know a lot more about the factors that mediate and moderate this effect."

Am J Public Health, 2006;96.

13. Use of a pacifier is associated with reduced risk of SIDS

[And for your parents of newborns…Here’s a study performed in CA, and published in the BMJ. --DRV]

The reduction in the incidence of sudden infant death syndrome (SIDS) after the Back to Sleep campaign in the United States and other countries showed that sleep environment strongly influences the risk of SIDS, although the underlying mechanisms remain poorly understood. Despite the considerable reduction in the incidence of SIDS after this public health intervention, it remains one of the leading causes of infant mortality. Identification of new preventative measures to further reduce the incidence continues to be a priority. Some studies have reported that use of a dummy (pacifier) is associated with a reduced risk of SIDS, though few have examined the association in detail and in the context of other risk factors.

Dummies usually have a bulky external handle, which could alter the infant's sleep environment by changing the configuration of the airway passage surrounding the nose and mouth. For example, pacifiers may prevent accidental hypoxia as a result of the face being buried into soft bedding or overlaying by objects (such as blankets, cosleepers, etc) by providing an air passage created by the bulky handle. Sucking on a dummy may enhance the development of neural pathways that control the potency of the upper airway.

We examined data collected in a population based case-control study of risk factors for SIDS in California to determine whether use of a dummy during sleep is associated with a reduced risk of SIDS, what factors may modify the association between use and SIDS, and whether use influences other risk factors related to sleep environment.

Infants who died of sudden infant death syndrome (SIDS) were less likely to sleep with dummies (pacifiers) in their mouths than controls. Li and colleagues carried out a population based case-control study with mothers or caretakers of 185 babies whose deaths were attributed to the syndrome and 312 randomly selected controls matched for race, ethnicity, and age. After known confounders were adjusted for, the odds ratio for SIDS in infants who used a dummy during their last sleep was 0.08 (95% CI 0.03 to 0.21) compared with infants not given dummies. Use of a dummy may reduce the influence of known risk factors in the sleep environment, say the authors.

BMJ 2006;332:18-22. Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/332/7532/18

14. Childhood and Adolescent Immunization Schedule updated for 2006

January 6, 2006. NEW YORK (Reuters Health) - The 2006 Childhood and Adolescent Immunization Schedule includes new recommendations for immunizing against meningococcal disease, pertussis, influenza, hepatitis A and hepatitis B, the US Centers for Disease Control and Prevention reported today.

Some key changes are as follows:

-- Meningococcal conjugate vaccine (MCV4) should be administered to all children between 11 and 12 years old as well as to unvaccinated adolescents at high school entry (age 15 years), and college freshmen living in dormitories should also be vaccinated with MCV4 or meningococcal polysaccharide vaccine (MPSV4). Vaccination with MPSV4 for children 2 to 10 years old and with MCV4 for older children in certain high-risk groups is also recommended.

-- To protect adolescents against whooping cough, a new tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap adolescent preparation) is recommended for adolescents 11 to 12 years, and for those aged 13 to 18 years who missed their earlier Tdap booster dose. Subsequent Td boosters are recommended every 10 years.

-- Annual influenza vaccine is now recommended for children younger than 6 months who have certain risk factors, including conditions that can cause breathing or swallowing difficulties, such as spinal cord injuries, seizure disorders, or other neuromuscular disorders.

-- Hepatitis A vaccine is now universally recommended for all children at age 1 year. Children not vaccinated at 1 to 2 years of age should be vaccinated during the preschool years.

-- The importance of the hepatitis B vaccine (HepB) birth dose is emphasized in the new schedule, which recommends screening of all pregnant women for hepatitis B surface antigen (HbsAg). The birth dose should be delayed only under rare circumstances and then only if a physician's order to withhold the vaccine and a copy of the mother's original HBsAg-negative laboratory report are documented in the infant's medical record.

The full 2006 immunization schedule is in the CDC's Morbidity and Mortality Weekly Report that is located at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5451-Immunizationa1.htm

MMWR 2006;54:Q1-Q4.

15. CDC Health Advisory

Distributed via Health Alert Network. January 14, 2006, 15:25 EST (03:25 PM EST); CDCHAN-00240-06-01-14-ADV-N

CDC Recommends against the Use of Amantadine and Rimandatine for the
Treatment or Prophylaxis of Influenza in the United States during the
2005-06 Influenza Season

Recent evidence indicates that a high proportion of currently circulating Influenza A viruses in this country are resistant to these medications

While the primary strategy for preventing complications of influenza infections is annual vaccination, antiviral medications with activity against influenza viruses can be effective for the prophylaxis and treatment of influenza. Two classes of antivirals are currently available-the M2 ion channel inhibitors (i.e., the two adamantanes amantadine and rimantadine) and the neuraminidase inhibitors (i.e., oseltamivir and zanamivir). The neuraminidase inhibitors are effective for the treatment and prophylaxis of influenza A and B, while the adamantanes are only active against influenza A viruses. This alert provides new information about the resistance of influenza viruses currently circulating in the United States to the adamantanes, and it makes an interim recommendation that these drugs not be used during the 2005-06 influenza season. Amantadine is also used to treat the symptoms of Parkinson's disease, and should continue to be used for this indication.

Viral resistance to adamantanes can emerge rapidly during treatment because a single point mutation at amino acid positions 26, 27, 30, 31, or 34 of the M2 protein can confer cross-resistance to both amantadine and rimantadine. The transmissibility of adamantane-resistant viruses is not impaired by any of these amino acid changes. A recent report on the global prevalence of adamantane-resistant influenza viruses showed a significant increase (from 1.9% to 12.3%) in drug resistance over the past 3 years. In the United States, the frequency of drug resistance increased from 1.9% in 2004 to 14.5% during the first 6 months of the
2004-05 influenza season.

For the 2005-06 season, 120 influenza A (H3N2) viruses isolated from patients in 23 states have been tested at CDC through January 12, 2006; 109 of the isolates (91%) contain an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine and rimantadine. Three influenza A(H1N1) viruses have been tested and demonstrated susceptibility to these drugs. All influenza viruses from the United States that have been screened for antiviral resistance at CDC have demonstrated susceptibility to the neuraminidase inhibitors.

On the basis of available antiviral testing results, CDC is providing an interim recommendation that neither amantadine nor rimandatine be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005-06 influenza season. During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza. Testing of influenza isolates for resistance to antivirals will continue throughout the 2005-06 influenza season, and recommendations will be updated as needed. Annual influenza vaccination remains the primary means of preventing morbidity and mortality associated with influenza.

Additional information about the prevention and control of influenza is available at http://www.cdc.gov/flu/ Specific information regarding the use of the neuraminidase inhibitors is available at http://www.cdc.gov/flu/protect/antiviral/index.htm
These websites will be updated as new information becomes available.

Categories of Health Alert messages: Health Alert conveys the highest level of importance; warrants immediate action or attention. Health Advisory provides important information for a specific incident or situation; may not require immediate action. Health Update provides updated information regarding an incident or situation; unlikely to require immediate action.

##This Message was distributed to State and Local Health Officers, Public Information Officers, Epidemiologists, State Laboratory Directors, Weapons of Mass Destruction Coordinators and HAN Coordinators, as well as Public Health Associations and Clinician organizations##

Lit Bits: January 2, 2006

From the recent medical literature...

1. ED Management of Recent-onset Atrial Fibrillation (AF)

AF is the most common arrhythmia seen in the ED. Traditionally, most patients with acute AF are admitted to exclude a serious cardiac condition, and to monitor for complications.

Several studies demonstrate that acute AF can be managed successfully in the ED with high short term conversion and discharge rates, for example, cf. the Kaiser Sacramento study by Burton JH, et al. Electrical cardioversion of emergency department patients with atrial fibrillation. Ann Emerg Med. 2004;44:20-30. Reports have shown that biphasic defibrillators are more effective and deliver less energy than monophasic defibrillators. These studies were performed in a cardiology outpatient setting, and there are very few data describing biphasic cardioversion of acute AF in the ED.

Fatovich and Haig report the effectiveness and outcome of biphasic cardioversion of acute AF in a tertiary referral ED.

Biphasic cardioversion of acute atrial fibrillation in the emergency department. Emerg Med J 2006;23:51-53.

ABSTRACT
Introduction: There is a trend towards accelerated management of acute atrial fibrillation (AF) in the emergency department (ED). We report our experience with biphasic cardioversion of acute AF.

Methods: This was a prospective, descriptive study at a tertiary hospital ED over a 6 month period. Acute AF was defined as symptoms that had been present for <48 hours. Patients who received biphasic cardioversion for acute AF in the ED were enrolled. Data collected included: patient demographics, past medical history, details of biphasic cardioversion, outcome, complications, disposition, and length of stay.

Results: There were 34 attempts at cardioversion in 33 patients. The mean (SD) age was 56 (16) years and 21 patients (64%) were men. Biphasic cardioversion was successful in 31 attempts (91%). In 24 attempts (71%), 100 J was selected as the initial energy level. This was successful in 21 attempts (88%). There were three minor complications related to sedation. The mean (SD) length of stay was 5.6 (2.8) hours in the ED and 15 (25) hours in the hospital. The three patients who failed to revert were older (mean age 64 years), had underlying cardiovascular disease, and spent longer in hospital (50 v 12 hours, p = 0.01). Telephone follow up was conducted with 32 patients (97%) at 3 months. Recurrence of AF occurred in 7 patients (22%). Most patients (31, 97%) were satisfied with the biphasic cardioversion.

Conclusions: Biphasic cardioversion of acute AF is effective. The majority of patients can be managed as outpatients, and there is very high patient satisfaction with this approach. An initial shock energy level of 100 J is usually effective

EXCERPTS
There are no current recommendations on the initial energy level used in biphasic cardioversion. We usually found 100 J to be effective and recommend that as the starting level.

Recently, there have been several clinical trials demonstrating that rate control is not inferior to rhythm control in AF. These studies examined patients with significant cardiovascular comorbidities and the patients were older (70 years), had persistent or permanent AF, and were minimally symptomatic. In our study, the patients were younger (56 years), healthier, had acute AF, and were highly symptomatic.

2. ED Pt Acutely Agitated? Which drug is best?

Droperidol (Inapsine)? Midazolam (Versed)? Or some new antipsychotic (ziprasidone)?

“Agitated patients commonly present to the ED and present a unique problem for the health care provider. The etiology is typically unclear and complicates the evaluation and expeditious management of the patient. In general, the goal of the emergency physician is to manage the patients' agitation, assess for the presence of any acute medical or traumatic conditions, and subsequently arrange appropriate disposition.

“Acute undifferentiated agitation (AUA) may be the result of trauma, acute psychiatric or medical disorders, or intoxication from alcohol or illicit substances. The etiology of acute agitation and altered mental status is infrequently studied in the ED setting. As a result of excessive agitation, both the patient and the health care providers are placed at risk of injury.

“The decision to use physical and chemical restraints is often difficult, because complications can occur with the use of either modality. Several sudden deaths have been reported in the physically restrained, agitated patient. High-potency antipsychotics and benzodiazepines have been the traditional "chemical restraint" for agitation management. Both classes of medications have been shown to be effective in the ED setting but have the potential for undesirable side effects. Benzodiazepines, such as lorazepam and midazolam, have potential central nervous system and cardiovascular depressant effects. These include significant sedation, respiratory depression requiring airway management, and hypotension. The potential adverse affects of antipsychotics such as droperidol include hypotension, seizures, dystonia, akathisia, and dysrhythmia (QT prolongation and torsades de pointes). Little has been published on the use of the newer parenteral atypical antipsychotics, such as ziprasidone, in the ED management of AUA” (from Martel et al below).

Below are two recent studies on this topic. The first was a randomized comparison of midazolam and droperidol; the second threw in a third comparator.

A. Randomized Clinical Trial Comparing Intravenous Midazolam and Droperidol for Sedation of the Acutely Agitated Patient in the Emergency Department. Knott JC, Taylor DM, Castle DJ. Ann Emerg Med. 2006; 47:61-67
Study objective
We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department (ED).

Methods
This was a double-blind, randomized, clinical trial set in the ED of a university teaching hospital. Subjects were adults, acutely agitated because of mental illness, intoxication, or both, who received midazolam or droperidol, 5 mg intravenously, every 5 minutes until sedated. We analyzed time to sedation using survival analysis, median times to sedation, and proportions sedated at 5 and 10 minutes.

Results
Seventy-four patients received midazolam; 79 patients, droperidol. Survival analysis showed no difference in time to sedation (hazard ratio 0.86; 95% confidence interval [CI] 0.61 to 1.23), P=.42. Median time to sedation was 6.5 minutes for midazolam (median dose 5 mg) and 8 minutes for droperidol (median dose 10 mg), P=.075 (effect size 1.5 minutes; 95% CI 0 to 4 minutes). At 5 minutes, 33 of 74 (44.6%) patients from the midazolam group were adequately sedated compared with 13 of 79 (16.5%) patients from the droperidol group, a difference of 28.1% (95% CI 12.9% to 43.4%; P<.001). By 10 minutes, 41 of 74 (55.4%) from the midazolam group were sedated compared to 42 of 79 (53.2%) from droperidol, a difference of 2.2% (95% CI −14.9% to 19.3%; P=.91). Eleven adverse events occurred in the midazolam group and 10 in the droperidol group. Three patients required active airway management (3 patients with assisted ventilation and 1 patient intubated); all received midazolam.

Conclusion
There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol. Patients sedated with midazolam may have an increased need for active airway management.

B. Management of Acute Undifferentiated Agitation in the Emergency Department: A Randomized Double-Blind Trial of Droperidol, Ziprasidone, and Midazolam. Martel M, et al. Acad Emerg Med. 2005 12: 1167-1172

Our objective was to compare the efficacy of sedation of droperidol, ziprasidone, and midazolam for the treatment of AUA in ED patients. Additionally, we evaluated the need for rescue sedation, rates of respiratory depression, and other clinically significant complications.

Methods: A prospective, randomized, double-blind trial of agitated ED patients requiring emergent sedation was performed. Patients were randomized to receive droperidol 5 mg, ziprasidone 20 mg, or midazolam 5 mg intramuscularly. Interval measurements were made at 0, 15, 30, 45, 60, and 120 minutes and included Altered Mental Status Scale (AMS) scores, oxygen saturations, and end-tidal carbon dioxide levels.

Results: A total of 144 patients were enrolled; 50 patients received droperidol, 46 received ziprasidone, and 48 received midazolam. Adequate sedation (mean AMS score <0) was achieved at 15 minutes in patients receiving midazolam (mean AMS score, –0.81) and 30 minutes for patients receiving droperidol (mean AMS score, –1.3) and ziprasidone (mean AMS score, –0.74). Rescue medication for sedation was necessary in 38 of 144 patients (droperidol, 5 of 50; ziprasidone, 9 of 46; midazolam, 24 of 48; p < 0.05). No cardiac dysrhythmias were identified in any treatment group. Respiratory depression that clinically required treatment with supplemental oxygen occurred in 21 of 144 patients (droperidol, 4 of 50; ziprasidone, 7 of 46; midazolam, 10 of 48; p = 0.20). No patients required endotracheal intubation.

Conclusions: Acutely agitated ED patients sedated with droperidol or ziprasidone required rescue medications to achieve adequate sedation less frequently than those sedated with midazolam. The onset of adequate sedation is delayed with ziprasidone, relative to the other agents.
Discussion (excerpt): Droperidol, ziprasidone, and midazolam are commonly used medications in the ED for agitation of any etiology. The medication dosages used were determined based on our clinical experience in addition to previous studies. The recommended dosing of ziprasidone ranges from 10 to 20 mg. Ziprasidone 20 mg was used based on research by Daniel et al. and discussion with Pfizer representatives. To our knowledge, there are no available data on the equivalence of dosing for droperidol, midazolam, and ziprasidone.

Droperidol has been used extensively in our ED for more than a decade. It continues to be a mainstay of treatment in a variety of acute medical conditions. The safe and efficacious use of droperidol has been established in ED patients. Similarly, we have found increased complications and resource utilization associated with the use of midazolam in out-of-hospital patients with AUA as compared with droperidol. Ziprasidone is a novel, atypical antipsychotic approved for the treatment of schizophrenia. To the best of our knowledge, the use of ziprasidone in the ED and for undifferentiated agitation has not been previously studied. This study was subsequently performed in an effort to prospectively evaluate our out-of-hospital findings and compare a novel method of agitation management.

Overall, each studied medication was successful at managing acute agitation, although with ziprasidone there were more agitated patients at 15 minutes than with either droperidol or midazolam. Deeper sedation was seen in these patients treated with ziprasidone when assessed between 60 and 120 minutes. The duration of agitation control with midazolam appeared shorter than with either droperidol or ziprasidone. There were an increased number of agitated patients in the midazolam group at 45 minutes. A significant number of these patients required subsequent rescue sedation. The shorter duration of effective sedation and the need for repeated injections may limit the utility of midazolam in the ED setting. However, the rapid onset of action of midazolam may be more appropriate for the out-of-hospital setting, despite its shorter duration of sedation. In contrast to the previous retrospective study of out-of-hospital midazolam use, midazolam does not appear to be associated with increased resource utilization or intensive care unit admission in this prospective study.

3. Chest Pain in the ED. Who can go home?

Are there some clinical prediction rules to help determine which chest pain patients are safe to send home, along the lines of the NEXUS or Ottawa? Yes, indeed, conclude these Canadian researchers. Their introduction and abstract follow.

A Clinical Prediction Rule for Early Discharge of Patients With Chest Pain. Christenson J, Innes G, McKnight D, et al. Ann Emerg Med. 2006;47:1-10

Approximately 15% to 25% of patients who present to EDs with undifferentiated chest pain prove to have acute coronary syndrome within 30 days. US data suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are initially misdiagnosed, whereas a recent Canadian study identified 11 of 241 (4.6%) missed cases of acute myocardial infarction and 10 of 157 (6.4%) cases of missed unstable angina. Chest pain units reduce the rate of missed myocardial infarction but do so in part by including very-low-risk patients in extensive rule-out myocardial infarction protocols.

Many investigators have developed chest pain risk stratification tools. Goldman et al developed a clinical/ECG algorithm that identified patients with less than 7% risk of acute myocardial infarction. Limkakeng et al subsequently found that 4.9% of patients who had low-risk Goldman criteria and a negative initial troponin I assay result experienced death, acute myocardial infarction, or revascularization within 30 days. Pozen et al developed a 7-item predictive equation that reduced coronary care unit admissions but not inappropriate discharges. Selker et al modified this to create the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), which defined low risk as less than 10% chance of acute coronary syndrome. The Erlanger protocol is an intense 2-hour assessment that includes serial ECGs and creatine kinase-MB (CK-MB) and troponin measurements, but it does not define a subset of patients who can forgo nuclear stress testing.

The American Heart Association/Agency for Health Care Policy and Research guidelines suggest early discharge only for patients with “evidence” of an alternate diagnosis. Unfortunately, few patients clearly fall into this category. Our own study of patients with chest pain at Vancouver hospitals identified that 5.4% of patients with acute coronary syndrome were discharged from the ED without a diagnosis or planned investigations and only 30% of those without acute coronary syndrome were discharged less than three hours after ED admission.

Importance
Clinical prediction rules are decision-making tools for clinicians that contain elements of the medical history, physical examination, and simple diagnostic tests. An objective clinical prediction rule to identify very-low-risk patients with chest pain who can be safely discharged without prolonged ED observation, expensive rule-out protocols, or provocative testing is needed. Such a rule would help reduce emergency crowding, minimize patient inconvenience, and improve cost-effectiveness of acute coronary syndrome diagnostic testing.

Goals of This Investigation
Our specific objective was to develop a clinical prediction rule that would improve on current practice by identifying patients with chest pain who are safe for discharge after 2 hours of ED evaluation. The rule will miss fewer than 2% of acute coronary syndrome patients and allow discharge within 2 to 3 hours of at least 30% of patients without acute coronary syndrome.

Study objective
Current risk stratification tools do not identify very-low-risk patients who can be safely discharged without prolonged emergency department (ED) observation, expensive rule-out protocols, or provocative testing. We seek to develop a clinical prediction rule applicable within 2 hours of ED arrival that would miss fewer than 2% of acute coronary syndrome patients and allow discharge within 2 to 3 hours for at least 30% of patients without acute coronary syndrome.

Methods
This prospective, cohort study enrolled consenting eligible subjects at least 25 years old at a single site. At 30 days, investigators assigned a diagnosis of acute coronary syndrome or no acute coronary syndrome according to predefined explicit definitions. A recursive partitioning model included risk factors, pain characteristics, physical and ECG findings, and cardiac marker results.

Results
Of 769 patients studied, 77 (10.0%) had acute myocardial infarction and 88 (11.4%) definite unstable angina. We derived a clinical prediction rule that was 98.8% sensitive and 32.5% specific. Patients have very low risk of acute coronary syndrome if they have a normal initial ECG, no previous ischemic chest pain, and age younger than 40 years. In addition, patients at least 40 years old and with a normal ECG result, no previous ischemic chest pain, and low-risk pain characteristics have very low risk if they have an initial creatine kinase-MB (CK-MB) less than 3.0 μg/L or an initial CK-MB greater than or equal to 3.0 μg/L but no ECG or serum-marker increase at 2 hours.

Conclusion
The Vancouver Chest Pain Rule for early discharge defines a group of patients who can be safely discharged after a brief evaluation in the ED. Prospective validation is needed.

4. Parents’ Views of Shared Decision Making in Otitis Media Management

It has been shown of late that acute otitis media in well children over the age of 2 may not require antibiotic intervention. This allows then for variations of acceptable management. These investigators sought to determine the impact on parent satisfaction of allowing them an active role in the choice of management. What do you think? Does shared decision making increase parent satisfaction?

Many clinicians advocate shared decision making (SDM) between physicians and patients. To examine parents’ preferences for SDM, investigators randomly assigned 466 parents at two family practices in Baltimore to receive a survey that presented one of three clinical vignettes.

All vignettes described a 2.5-year-old child with acute otitis media (AOM) and a physician who informed parents that AOM is not contagious, that some children get better without antibiotics, and that three treatment options are available: immediate 10-day prescription for antibiotics; acetaminophen first, followed by a call back to the doctor if the child does not improve in 2 to 3 days; or a prescription for an antibiotic, to be used only if the child is not better in 2 to 3 days. The vignette ended in one of three ways: the physician suggested that the child receive antibiotics (paternalistic vignette); the physician indicated that treatment is the parents’ choice (SDM vignette); or the physician recommended treatment with acetaminophen first and provided an antibiotic prescription to use if needed (acetaminophen-SDM vignette).

Parents who were presented with either of the two SDM vignettes reported more satisfaction with the child’s care than parents who were presented with the paternalistic vignette (93% and 84% for SDM and acetaminophen–SDM groups, respectively, vs. 76%), and they were significantly less likely to want antibiotics immediately (7% and 7% vs. 26%, respectively).

Comment: AOM is an excellent diagnosis in which to incorporate shared decision making because the need for treatment is uncertain, the diagnosis can be difficult to make, and complications are rare. The benefits are substantial: greater parental satisfaction and probably less antibiotic use.

— Howard Bauchner, MD. Published in Journal Watch December 16, 2005. Source: Merenstein D et al. An assessment of the shared-decision model in parents of children with acute otitis media. Pediatrics. 2005 Dec; 116:1267-75.

5. Prevalence of peptic ulcers high during low-dose aspirin use

[Low-dose aspirin. So many of our patients are on it. How big a contributor is it to the development of peptic ulcers? --DRV]

December 13, 2005. NEW YORK (Reuters Health) - The prevalence of gastroduodenal ulcers is about 10% among patients taking low-dose aspirin for vascular protection, and these ulcers often cause no symptoms, investigators report.

Although aspirin is associated with ulcers, it is unclear whether patients taking aspirin get ulcers more often, or if they are just more likely to bleed from ulcers caused by other factors due to aspirin's antiplatelet effects, Dr. Neville D. Yeomans and colleagues note in their paper, published in the November issue of Alimentary Pharmacology and Therapeutics.

To answer this question, Dr. Yeomans, a gastroenterologist at the University of Western Sydney in Australia, and his team performed endoscopic assessments on 187 patients who had been taking aspirin at doses of 75 to 325 mg daily for at least a month. The investigators found the point prevalence of ulcers measuring at least 3mm in diameter was 10.7%. "Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer," the team reports.

When they repeated endoscopy after 3 months among the 113 patients with no ulcers at baseline, they observed that 7.1% had developed an ulcer during the interim, which translates to an annual ulcer incidence of 28%. Age 70 and older or the presence of H. pylori infection raised the risk of an ulcer by about 3-fold, the authors report. However, smoking, higher aspirin doses, previous ulcer history and gender did not significantly affect risk.

"Aspirin can be of great benefit to those at high risk of heart attack or stroke," Dr. Yeomans says in a University press release, "but the risks as well as the benefits need to be carefully weighed before embarking on its long-term use in people who are at only low cardiovascular risk."

Aliment Pharmacol Ther. 2005;22:795-801.

6. Possible Renal Colic? Do we really need a CT?

[Maybe. But for the diagnostic work-up these docs suggest that in many cases just a bedside US and a UA may be sufficient. --DRV]

Gaspari RJ, et al. Emergency Ultrasound and Urinalysis in the Evaluation of Flank Pain. Acad Emerg Med. 2005; 12: 1180-1184.

Objectives: To determine the sensitivity and specificity of limited emergency ultrasonography of the kidney in diagnosing renal colic.

Methods: This was a prospective observational trial from December 2001 to December 2003 at a suburban emergency department. Patients who presented with flank pain suspicious for renal colic were enrolled. Exclusion criteria included fever, trauma, known current kidney stone, unstable vital signs, and inability to provide consent. All patients underwent sequential emergency ultrasonography and computed tomography of the kidneys and bladder. Data were analyzed using chi-square analysis. The primary outcome was the sensitivity and specificity of ultrasonography. Results were also stratified for presence of hematuria.

Results: Fifty-eight of the 104 patients enrolled in the study were diagnosed with renal colic. The overall sensitivity and specificity of bedside ultrasonography for the detection of hydronephrosis were 86.8 (95% confidence interval [CI] = 78.8 to 92.3) and 82.4 (95% CI = 74.1 to 88.1), respectively. In patients with hematuria, hydronephrosis by emergency ultrasonography demonstrated a sensitivity and specificity of 87.8 (95% CI = 80.3 to 92.5) and 84.8 (95% CI = 73.7 to 91.9), respectively. In 55 of the cases, the initial computed tomograph was read by a resident and later re-read by an attending physician. Using the reading of the attending physician as the criterion standard resulted in a sensitivity and specificity of 83.3 (95% CI = 73.2 to 88.0) and 92.0 (95% CI = 79.9 to 97.6), respectively.

Conclusions: Emergency ultrasonography of the kidneys shows very good sensitivity and specificity for diagnosing renal colic in patients with flank pain and hematuria.

7. Glucosamine and chondroitin. Do they really work?

Too often these OTC dietary supplements remain untested. Fortunately, in this case, the NIH undertook a $14 million RCT to test the effects of glucosamine and chondroitin for treatment of knee osteoarthritis (the GAIT study). This was the largest placebo controlled, double blind, clinical trial ever conducted to test the effectiveness of these agents. All 1,258 patients who completed the study were over the age of 40 with knee pain and randomly assigned placebo; glucosamine 1500 mg; chondroitin 1200mg; glucosamine/chondroitin at above mentioned doses; or celecoxib (Celebrex) 200 mg daily for 6 months. The abstract, presented in November at the American College of Rheumatology’s Scientific Meeting in San Diego, concluded that 79% of patients with moderate-to-severe osteoarthritis pain who received a combination of glucosamine and chondroitin experienced pain relief as compared to 69% who took celecoxib and 54% who were given a placebo.

From Prescriber’s Letter: “People are asking about glucosamine and chondroitin for osteoarthritis now that NIH's big GAIT study is making news. But the study merely adds to the debate. Proponents are using this study to say that glucosamine and chondroitin are effective for osteoarthritis of the knee. Opponents say these supplements are a waste of time and money. The two camps are citing different conclusions from the same study. Opponents point out that most patients in the GAIT study showed NO improvement in knee pain...proponents are saying that a small group with moderate to severe pain did get SOME improvement.

“The study design also leaves other issues unresolved. For example, the NIH used glucosamine HYDROCHLORIDE 500 mg TID. But most studies showing benefit used glucosamine SULFATE 1500 mg DAILY. The different salts or dosing regimens MIGHT make a difference. There's also still no answer on whether combining glucosamine and chondroitin works any better than either one alone. For now, tell people that these supplements are worth a try. Adverse effects are mild...patients may have some GI distress. Suggest starting with glucosamine ALONE...preferably glucosamine SULFATE if available. The combo with chondroitin is okay to try. Tell patients it can take up to 8 weeks to see an improvement... but if it doesn't help by then, to stop it and save their money.

8. Sedative Use in Older People Causes More Harm than Benefit

Physicians often prescribe sedative hypnotics to older people with insomnia, but the risks and benefits are not well defined. In this meta-analysis published in the BMJ, investigators identified 24 randomized, controlled trials of pharmacologic treatment in 2411 people with insomnia. All treatments were given for at least five consecutive nights, and the mean age in each study population was at least 60. A total of 830 participants received a benzodiazepine, 609 zaleplon (Sonata), 468 placebo, 384 zolpidem (Ambien), 106 zopiclone (Lunesta), and 14 diphenhydramine.

Based on four studies, 13 people would need to be treated with sedatives for one to have an improvement in sleep quality. Although sleep-quality scores were significantly better with sedatives than with placebo, the effect size was very small (a 0.1 improvement on a 7-point scale). Compared with placebo, sedatives added an average of 25 minutes to sleep time and reduced the average number of awakenings by 0.63.

Based on 16 studies, the number needed to harm was 6. Common adverse effects of sedatives included drowsiness or fatigue, headache, nightmares, and nausea or gastrointestinal disturbances. Compared with placebo, sedatives were significantly associated with more adverse effects on cognition and with greater impairment in performing tasks the morning after treatment.

Comment: The average benefit of sedatives in this analysis was statistically significant but not clinically meaningful, and adverse effects were twice as likely to occur as beneficial effects. Older patients should be informed of these data when considering the use of sedatives to improve sleep. At the time of publication, the full text of the original article was available free of charge.

— Keith I. Marton, MD. Published in Journal Watch December 27, 2005. Source: Glass J et al. Sedative hypnotics in older people with insomnia: Meta-analysis of risks and benefits. BMJ 2005 Nov 19; 331:1169-73.

9. Cardiac Risk Factors….Don’t Forget to Ask about Siblings.

Sibling Cardiovascular Disease as a Risk Factor for Cardiovascular Disease in Middle-aged Adults. Joanne M. Murabito, MD, et al. JAMA. 2005;294:3117-3123.

Context While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear.
Objective To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors.

Design, Setting, and Participants The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least 1 sibling in the study; all were followed up for 8 years.

Main Outcome Measures Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence.

Results Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% CI, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% CI, 1.32-3.00) exceeded that for parental CVD (1.45; 95% CI, 1.02-2.05).

Conclusion Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults.

10. Antithrombotic Drugs Often Misdosed in Non-ST-Segment Elevation ACS

By Anthony J. Brown, MD. NEW YORK (Reuters Health) Dec 28 - In a study of nearly 400 US hospitals, 42% of patients with a non-ST-segment elevation acute coronary syndrome (ACS) received a dose of an antithrombotic agent that fell outside the recommended range. The report also confirms that the more excessive the dose, the greater the bleeding risk.

Dr. Karen P. Alexander, from Duke University Medical Center in Durham, North Carolina, and colleagues analyzed data from more than 30,000 patients with a non-ST-segment elevation ACS to assess the frequency and correlates of misdosing unfractionated heparin, low-molecular weight heparin, and glycoprotein IIb/IIIa inhibitors. The findings appear in the December 28th issue of the Journal of the American Medical Association.

"There have been studies looking at dosing accuracy of antithrombotic agents in clinical trial populations," Dr. Alexander told Reuters Health. "To my knowledge, our study is the first to look at this in a large, broad 'real world' setting."

As noted, 42% of subjects treated with at least one antithrombotic agent received a dose outside the recommended range. The rates of excess dosing ranged from 13.8% for low-molecular weight heparin to 32.8% for unfractionated heparin. Correlates of misdosing including female gender, older age, renal insufficiency, low body weight, diabetes mellitus, and congestive heart failure, the report indicates.

Receiving an excess dose of an antithrombotic agent increased the risk of major bleeding, mortality, and length of stay. The increased risk of bleeding ranged from 8% to 39% for excessive dosing of unfractionated heparin and low-molecular weight heparin, respectively.

In patients receiving both a heparin agent and a glycoprotein inhibitor, the risk of bleeding was 6.6% if neither agent was given in excess to 22.2% if both were given in excess. Based on their analysis, the researchers estimate that 15% of the bleeding seen in the study population was associated with excess dosing of antithrombotic agents.

While the findings show that misdosing of antithrombotic drugs is a common and concerning problem, Dr. Alexander believes there is a positive message as well. "Patients who do get the correct dosing adjustments have a much lower rate of bleeding than those who don't. This a positive message because it is something we can actually do something about. It confirms that there is a benefit for taking the time to make careful dosage calculations."

JAMA 2005;294:3108-3116.

11. Avian Flu: Is a Pandemic Coming?

Three avian influenza pandemics occurred in the 20th century. The 1957 and 1968 pandemics were caused by avian viruses that recombined with human flu viruses, creating viruses that were both virulent and easily transmissible among humans. In contrast, the 1918 virus was an avian virus that had not swapped genes with a human flu virus. Rather, it had mutated in some other way — still unclear — that allowed it to be transmissible among humans

(Kaiser J. Resurrected influenza virus yields secrets of deadly 1918 pandemic. Science. 2005 Oct 7; 310:28-9.).

Since a 1997 outbreak of bird and human disease caused by a new avian virus (called H5N1) in Hong Kong, people have feared that a new pandemic would emerge. Although the Hong Kong outbreak and several others were stifled by killing hundreds of millions of domestic poultry, the virus did not disappear. Indeed, since 2003, it has adapted to infect migratory birds and has spread to many Asian countries and to Europe. The H5N1 virus is virulent in birds and humans. More than 100 humans who were in close contact with sick birds have become infected with H5N1, and about half of them have died. So the good news is that the current H5N1 virus does not easily infect humans, but the bad news is that it’s lethal when it does (Ungchusak K et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med. 2005 Jan 27; 352:333-40.).

How bad could a pandemic be? The 1918 virus infected approximately 40% of the human race in a matter of months and had a mortality rate of about 2% to 3%, leading to 20–50 million deaths. In 2005, a team at the CDC reconstructed the 1918 virus, based on its RNA sequence, and tested its virulence in mice. All infected mice died, with their alveoli filled with mucin and blood cells — a pathological picture similar to that seen in humans who died in 1918. The virulence genes of the 1918 virus are similar to those of the current H5N1 virus.
What can be done to prevent an H5N1 pandemic? In vitro, most strains are susceptible to oseltamivir (Tamiflu).

However, a recent case report demonstrates that the virus can rapidly develop resistance to this drug (Le QM et al. Isolation of drug-resistant H5N1 virus. Nature 2005 Oct 20; 437:1108). Experimental vaccines have elicited an antibody response against H5N1, but that fact does not assure clinical efficacy. And, production of either antivirals or vaccine on the scale that would be required to protect the world population would take years.

Most authorities believe that an H5N1 human pandemic is likely, although how severe it might be is unknown. If H5N1 recombines with a human flu virus, it could produce less severe disease than if it leaps directly to humans, as the 1918 virus did. Some experts argue that the risk of a pandemic is overblown. They note that the technologies for diagnosis, treatment, and immunization today are vastly superior to the technologies available during the 20th-century pandemics. They take comfort in the facts that H5N1, although now widespread, is not yet spread easily among humans and that all known past pandemics involved H1, H2, and H3 flu viruses, not H5 strains. Time will tell.
— Anthony L. Komaroff, MD; Published in Journal Watch December 30, 2005.

12. Age no bar to thrombolysis for stroke in octogenarians

December 30, 2005; By David Douglas. NEW YORK (Reuters Health) - Although elderly stroke patients have a greater risk of dying following therapy with IV recombinant tissue plasminogen activator (rtPA), age is not an independent predictor of outcome, Swiss researchers report in the December 13th issue of Neurology.

Dr. S. T. Engelter of University Hospital Basel and colleagues came to this conclusion after studying 325 rtPA-treated stroke patients. Of these, 38 were 80 years old or more and the remaining 287, who ranged in age from 14 to 79 years, had a mean age of 63 years.

The rate of intracranial hemorrhage did not differ between the two groups and overall there was a favorable outcome in 29% of the older patients and 37% of the younger patients. At 3 months, 32% of the elderly patients had died compared with 12% of the younger patients. Among patients who survived for 3 months, the rate of favorable outcome was 42% in the older patients and 43% in the younger patients.

"Logistic regression showed that stroke severity, time to thrombolysis, glucose level, and history of coronary heart disease independently predicted outcome, whereas age did not," the researchers report. Commenting on the findings, Dr. J. Claude Hemphill III, co-author of an accompanying editorial told Reuters Health, "IV rtPA should not be withheld from acute stroke patients just because they are very old."

Dr. Hemphill of the University of California, San Francisco, added that "while older patients might have a higher risk of bleeding from rtPA, we know that older patients also are more likely to die and less likely to recover from the stroke itself."

Neurology 2005;65:1795-1798.

13. New pneumonia category associated with health care

Not all community-acquired pneumonia is alike. Patients with pneumonia who were transferred from another health-care facility, had been receiving long-term hemodialysis, or had prior hospitalization within 30 days were classified into the Health-care-associated pneumonia. As this study explains, it might be important to distinguish this subset of pts from run-of-the-mill CAP pts.

December 29, 2005. NEW YORK (Reuters Health) - Health-care-associated pneumonia (HCAP) is associated with more severe disease, higher mortality rates, and higher costs than is community-acquired pneumonia, according to a report in the December issue of Chest.

Recent research suggests that health-care-associated infections have a unique epidemiology and different outcomes from those seen with community-acquired or nosocomial infections, the authors explain.

Dr. Marin H. Kollef From Washington University School of Medicine, St. Louis, and colleagues evaluated their hypothesis that HCAP is a distinct clinical entity by analyzing the records of patients with culture-positive pneumonia registered in a large US database.

Patients with pneumonia who were transferred from another health-care facility, had been receiving long-term hemodialysis, or had prior hospitalization within 30 days were classified into the HCAP group.

The database included 2221 patients with community-acquired pneumonia, 988 patients with HCAP, 835 patients with hospital-acquired pneumonia and 499 patients with ventilator-associated pneumonia. Patients with HCAP were significantly older than patients with community-acquired pneumonia or ventilator-associated pneumonia but comparable in age to those with hospital-acquired pneumonia, the report indicates. Nearly half the patients with HCAP were admitted from skilled nursing facilities.

Infection with Staphylococcus aureus was more common in the HCAP, hospital-acquired pneumonia and ventilator-associated pneumonia groups, the authors report, and the rate of methicillin-resistant S. aureus was significantly higher in HCAP patients than in patients with all other pneumonia types.

Mortality rates were similar with HCAP and hospital-acquired pneumonia, at about 20%, which were significantly higher than that associated with community-acquired pneumonia (10%) and lower than that associated with VAP (29%). Hospital length of stay was the highest for patients with ventilator-associated pneumonia and the lowest for those with community-acquired pneumonia, the researchers note.

Mean total hospital charges for patients with HCAP ($27,647) were higher than those for patients with community-acquired pneumonia ($25,218) but lower than those for patients with hospital-acquired pneumonia ($65,292) or ventilator-associated pneumonia ($150,841).

The findings suggest that "HCAP, traditionally classified into the community-acquired pneumonia category, is clinically more similar to hospital-acquired pneumonia and should be treated as such until culture data become available," the authors conclude.

Chest 2005;128:3854-3862.