Lit Bits: May 23, 2006

From the recent medical literature...

1. Are Lifestyle Measures Effective in Patients With GERD?

An Evidence-Based Approach by Tonya Kaltenbach, MD; et al. Arch Intern Med. 2006;166:965-971.

Lifestyle modifications are first-line therapy for patients with gastroesophageal reflux disease (GERD). We applied an evidence-based approach to determine the efficacy of lifestyle measures for GERD management. We used PubMed and Ovid to perform a search of the literature published between 1975 and 2004 using the key words heartburn, GERD, smoking, alcohol, obesity, weight loss, caffeine or coffee, citrus, chocolate, spicy food, head of bed elevation, and late-evening meal.

Each study was reviewed by 2 reviewers who assigned one of the following ratings: evidence A, randomized clinical trials; evidence B, cohort or case-control studies; evidence C, case reports or flawed clinical trials; evidence D, investigator experience; or evidence E, insufficient information. We screened 2039 studies and identified 100 that were relevant. Only 16 clinical trials examined the impact on GERD (by change in symptoms, esophageal pH variables, or lower esophageal sphincter pressure) of the lifestyle measure. Although there was physiologic evidence that exposure to tobacco, alcohol, chocolate, and high-fat meals decreases lower esophageal sphincter pressure, there was no published evidence of the efficacy of dietary measures.

Neither tobacco nor alcohol cessation was associated with improvement in esophageal pH profiles or symptoms (evidence B). Head of bed elevation and left lateral decubitus position improved the overall time that the esophageal pH was less than 4.0 (evidence B). Weight loss improved pH profiles and symptoms (evidence B). Weight loss and head of bed elevation are effective lifestyle interventions for GERD. There is no evidence supporting an improvement in GERD measures after cessation of tobacco, alcohol, or other dietary interventions.

2. Is There Cross-Reactivity Between Penicillins and Cephalosporins?

Apter AJ, et al. Am J Med. 2006; 119: 354.e11-354.e19 (April 2006)

Abstract
Background
We sought to determine the risk of an allergic reaction to a cephalosporin exposure in those with prior penicillin reactions.

Methods
We conducted a retrospective cohort study using the United Kingdom General Practice Research Database. We selected all patients receiving a prescription for penicillin followed by a prescription for a cephalosporin and identified allergic-like events within 30 days after each prescription. Allergic events were defined by 2 sets of codes: 1 more restrictive, 1 more inclusive. Comparison was made with a population of patients receiving a prescription for a penicillin followed by a prescription for a sulfonamide antibiotic.

Results
A total of 3 375 162 patients received a penicillin; 506 679 (15%) received a subsequent cephalosporin. Among patients receiving a penicillin followed by a cephalosporin, the unadjusted risk ratio of an allergic-like event for those who had a prior event, compared with those who had no such prior event, narrowly defined, was 10.1 (confidence interval 7.4-13.8). The absolute risk of anaphylaxis after a cephalosporin was less than 0.001%. The unadjusted risk ratio for sulfonamide antibiotic, rather than cephalosporin after penicillin allergic-like events was 7.2 (confidence interval 3.8-13.5).

Conclusion
Patients with allergic-like events after penicillin had a markedly increased risk of events after either subsequent cephalosporins or sulfonamide antibiotics. Cross-reactivity is not an adequate explanation for this increased risk, and the risk of anaphylaxis is very low. Thus, our data indicate that cephalosporins can be considered for patients with penicillin allergy.

3. How Thrombogenic Is Hypoxia of Air Travel? …NOT!

Effect of Hypobaric Hypoxia, Simulating Conditions During Long-Haul Air
Travel, on Coagulation, Fibrinolysis, Platelet Function, and Endothelial
Activation. William D. Toff; et al. JAMA 2006;295 2251-2261

Conclusion: Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.

Abstract: http://jama.ama-assn.org/cgi/content/abstract/295/19/2251?etoc

Review in Science: http://sciencenow.sciencemag.org/cgi/content/full/2006/516/3 (for subscribers only, I think).

4. Can sutures get wet? …YES!

Prospective randomised controlled trial of wound management in general practice. Clare Heal, et al. BMJ 2006;332:1053-1056.

Guidelines for managing surgical wounds that are closed primarily (that is, those with the skin edges re-approximated at the end of the procedure) instruct that patients should keep their wounds dry and covered for 24-48 hours. Before our study, the four participating general practices were implementing these guidelines and advising patients to keep their wounds dry and covered for 48 hours after minor excisions. For patients living in the tropics of North Queensland, with increased heat and humidity, this recommendation is impractical and a nuisance.

Literature on wound management is sparse. As regards wetting sutures, previous studies have compared standard management (keeping wounds dry) with washing with soap and water in the first 48 hours after minor skin excisions or compared standard management with early showering after more major surgery. These relatively few published studies suggest that getting sutures wet does not increase the infection rate. However, numbers of patients studied have been small, and only one previous study was randomised. No previous studies have been done in the general practice setting.

As regards uncovering sutures, some evidence shows that no difference exists in the incidence of infection between wounds left without dressings and those covered with a dry dressing in the early postoperative period. Again, no previous studies had been done in a general practice setting.

As the two factors, wetting and uncovering, are difficult to separate in the immediate postoperative period, we decided to assess these factors together. We proposed to look at the effects of allowing patients to uncover and wet their wounds during the first 48 hours after minor skin excision, hypothesising that infection rates would be non-inferior compared with a control group following the dry wound management recommendations.

Objective To compare standard management of keeping wounds dry and covered with allowing wounds to be uncovered and wet in the first 48 hours after minor skin excision.

Design Prospective, randomised controlled, multicentre trial testing for equivalence of infection rates.

Setting Primary care in regional centre, Queensland, Australia.

Participants 857 patients randomised to either keep their wound dry and covered (n = 442) or remove the dressing and wet the wound (n = 415).

Results The incidence of infection in the intervention group (8.4%) was not inferior to the incidence in the control group (8.9%) (P < 0.05). The one sided 95% confidence interval for the difference of infection rates was to 0.028.
Conclusion These results indicate that wounds can be uncovered and allowed to get wet in the first 48 hours after minor skin excision without increasing the incidence of infection.

5. Race Influences Side Effects of Cardiovascular Drugs

NEW YORK (Reuters Health) May 04 - Compared with patients of other ethnicities, black and East Asian patients are at increased risk for various adverse reactions when taking cardiovascular drugs, according to a report in the May 4th online issue of the British Medical Journal.

Ethnic group "may be one determinant of harms of a given treatment in the individual patient, either because it acts as a surrogate measure of genetic make up or because cultural factors alter the risk," senior author Dr. Robin E. Ferner and colleagues note.

Dr. Ferner, from City Hospital in Birmingham, UK, and colleagues examined ethnic differences in the side effects of cardiovascular agents by conducting a meta-analysis of data from 24 studies identified through a Medline and Embase search.

On pooled analysis, black patients taking ACE inhibitors were three times more likely to develop angioedema than their non-black counterparts. In addition, black ethnicity raised the risk of intracranial hemorrhage from thrombolytic therapy by 50%.

East Asian patients were also at heightened risk for side effects when taking cardiovascular drugs. In particular, they were 2.7-times more likely to experience cough with ACE inhibitor therapy than were white patients. The authors conclude that future studies looking at cardiovascular agents should taking into account the potential for different side effect profiles based on race.
BMJ 2006.

6. Goth subculture is strongly linked with self harm and attempted suicide

Identification with the Goth youth subculture is strongly associated with self harm and attempted suicide. A longitudinal cohort study by Young and colleagues (BMJ 2006;332:1058-1061) of 1258 people aged 19 who had been followed up since they were 11, found that the prevalence of self harm and attempted suicide were 53% and 47% respectively among the participants who identified mostly strongly with the Goth subculture. Prevalences of self harm and attempted suicide in the whole sample were 7% and 6%.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/332/7549/1058

7. High-Dose Corticosteroids Tied to Increased Risk of Atrial Fibrillation

By Megan Rauscher. NEW YORK (Reuters Health) May 09 - Results of a population-based cohort study strongly suggest that treatment with high doses of corticosteroids, regardless of the indication, increases the risk of new-onset atrial fibrillation.

"We suspected this from case reports," Dr. Bruno H. Ch. Stricker from Erasmus University Medical Center, Rotterdam, told Reuters Health. "The effect was, however, higher than anticipated."

In the May 8th Archives of Internal Medicine, Dr. Stricker and colleagues report that among 7,983 adults in the Rotterdam Study who were 55 or older in 1990, 385 developed new-onset atrial fibrillation during an 8-year follow-up period. According to the team, the risk of new-onset atrial fibrillation was significantly higher in individuals who received a corticosteroid prescription within 1 month of the index date (odds ratio, 3.75).

However, only high-dose corticosteroid use -- defined as oral or parenteral steroid at a daily dose of 7.5 mg/day or more of prednisone equivalents -- was associated with increased risk (odds ratio, 6.07). Low- or intermediate-dose corticosteroid use was not associated with increased risk of atrial fibrillation (odds ratio, 1.42). As mentioned, the association of atrial fibrillation with high-dose corticosteroid use was largely independent of the indication for corticosteroid treatment, the authors note.

Clinicians, said Dr. Stricker, need to "be aware that high-dose corticosteroids may increase the risk of atrial fibrillation." High doses of corticosteroids may affect the balance of potassium in cardiac muscle cells, which may induce arrhythmia, the team notes, or may cause sodium and fluid retention, leading to hypertension, left atrial enlargement and congestive heart failure -- all known risk factors for atrial fibrillation.

For individuals on high-dose corticosteroids, careful monitoring "by clinical examination and by performing an electrocardiogram before and after high-dose (pulse) therapy could increase the chances to diagnose and treat this serious arrhythmia as soon as possible," the investigators advise.

Arch Intern Med 2006;165:1016-1020.

8. Elderly Not Adherent to Concomitant Antihypertensive and Lipid-Lowering Therapy

By Martha Kerr. NEW YORK (Reuters Health) May 10 - A retrospective study of elderly patients shows that only 32.9% took concomitant antihypertensive and lipid-lowering medication as prescribed.

"This study emphasizes the importance of considering adherence when caring for high-risk older patients," Dr. Richard H. Chapman commented to Reuters Health. "Despite the relatively high cardiovascular risk of these patients with both hypertension and dyslipidemia, surprisingly few patients were adherent to prescribed medications."

Dr. Chapman of ValuMedics Research in Falls Church, Virginia, and colleagues conducted an analysis of data on 4,052 patients aged 65 and older enrolled in the Protocare Sciences Managed Care Database. Antihypertensive therapy and lipid-lowering agents were initially prescribed within a 90-day period.

The researchers defined adherence as filling prescriptions to cover at least 80% of days for anti-hypertensives and for lipid-lowering therapies. Adherence was evaluated at three-month intervals, and mean follow-up was 19.5 months. The team reported the results at the American Heart Association's 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Diseases and Stroke, being held in Washington, D.C.

Dr. Chapman reported that adherence to both classes of drugs fell rapidly to 40.5% at the 3-month mark, then to 32.7% at 6 months, and stabilized at 32.9% at 1 year. Patients took more of one class of drug or the other, with an additional 27.8% to 35.0% adherent to one medication at each time point over the estimates of adherence for both. Adherence to antihypertensive therapy was higher than with statin therapy.

"From the data in this study we cannot say why adherence was lower with lipid-lowering agents," Dr. Chapman said. "Such differences could be due to differences in side effects or other factors ... For example, patients may believe that their high blood pressure is more of a problem than their high cholesterol." However, "we have no way to tell this for sure from this study."

The researchers found that if both drugs were prescribed at the same time, adherence to both was higher, with an adjusted odds ratio of 1.13. Patients with existing heart disease were more motivated to take medications as prescribed, with an adjusted odds ratio of 1.27 for adherence to both. The factor associated with the lowest adherence to both drugs, with an odds ratio 0.43, was having multiple prescriptions for additional medications.

Based on these findings, Dr. Chapman said that adherence could be improved by initiating antihypertensive and lipid-lowering therapies at the same time if possible. In addition, "attention to polypharmacy is a particularly important issue in the care of older patients," he commented.

9. Codeine Seen to Have No Antitussive Effect in COPD Patients

May 12, 2006 — In patients with stable chronic obstructive pulmonary disease (COPD), codeine treatment had no more effect on cough than did placebo, UK researchers report.

In the April issue of the Journal of Allergy and Clinical Immunology, Dr. Jacyln Smith of South Manchester University Hospital Trusts and colleagues note that codeine is the standard antitussive agent to which others are compared. Laboratory studies suggest it is effective in cough of mixed etiology, but little is known about its impact on cough in COPD patients.

To investigate further, the researchers conducted a double-blind, randomized placebo-controlled study of 21 such patients with stable disease who complained of cough.

They underwent citric acid cough challenge. On two separate occasions after the cough challenge, the subjects were given 60 mg of codeine phosphate or placebo 1 hour before at-home 10-hour daytime ambulatory and 10-hour overnight digital audio recording was started. A lapel microphone was used to capture the sounds of "explosive" coughing.

At baseline, subjects experienced a median of 8.27 seconds of coughing per hour. After placebo this fell to 7.22 seconds per hour. After codeine, it dropped to 6.41 seconds per hour. Although the time spent coughing was significantly less after codeine than at baseline (p = 0.02), there was no significant duration difference between codeine and placebo (p = 0.52) — despite the fact that the dose of codeine used "far exceeds that in over-the-counter cough remedies and is in excess of that used in many previous studies," the researchers note.

They conclude that the findings are "consistent with the view that any antitussive effect of codeine is attributable to a placebo effect." Dr. Smith and colleagues say that studies of cough in other clinical situations are "urgently needed" if codeine is to continue to be used as a cough remedy.

J Allergy Clin Immunol. 2006;117:831-835

10. ST Elevation in Precordial Leads (I)

From Medscape Cardiology. Posted 05/02/2006

For Tracing and Discussion: http://www.medscape.com/viewarticle/530410

11. Signatures Submitted for Tobacco Tax Measure

Source: California Healthline (http://www.californiahealthline.org)
Date: May 5, 2006

Supporters of an initiative to increase the cigarette tax by $2.60 per pack to fund health programs submitted an estimated 1.1 million signatures to county registrars earlier this month to qualify the measure for the November ballot, the Riverside Press-Enterprise reports. The tax, which would raise the combined per-pack tax to $3.47, is expected to generate about $2.1 billion annually. However, that estimate likely will decline as more people stop using tobacco, according to the Legislative Analyst's Office. The initiative calls for:

52.75% of the revenue to be used to fund hospital emergency services, nurse education, community health clinics and tobacco cessation programs;

42.25% to be used for children's health insurance, including an expansion of the Healthy Kids program; smoking prevention campaigns; and cancer, heart, asthma and other disease research; and

5% to be used for cancer- and tobacco disease-related research.

The measure is supported by the Coalition for a Healthy California, which includes the American Lung Association, the California Hospital Association, Children Now and the American Heart Association. Tobacco companies are expected to oppose the measure.

More info? See:
http://www.californiahealthline.org/index.cfm?action=dspItem&itemID=121159&changedID=121113

12. Fever in 2- to 6-Month-Old Infants

Although the pneumococcal and Haemophilus influenzae type B conjugate vaccines have reduced risk for serious bacterial infection in infants, they have changed the landscape of fever management, especially in infants older than 2 months. Investigators at one institution in Connecticut prospectively evaluated 429 consecutive febrile infants (age, 57–180 days) who presented to the emergency department. Evaluation included routine blood and urine laboratory tests and diagnostic tests for viral infection.

Forty-four infants (10.3%) had test results consistent with serious bacterial infections (40 had urinary tract infections, 3 had bacteremia, 1 had both). None of the 58 infants who underwent lumbar puncture had bacterial meningitis. The 163 infants with viral infections were significantly less likely to have serious bacterial infections than the 251 infants without viral infections (4.9% vs. 13.5%). The incidence of urinary tract infections was identical in males and females (9.7%). Among males with known circumcision status, 36% (of 50) uncircumcised infants had UTIs compared with 1.6% (of 128) circumcised infants.

Comment: The 10% incidence of serious bacterial infection in infants older than 2 months is surprisingly high, but considering that their parents had either sought care in or were referred to the ED, the infants in this study likely were sicker than those seen in practice. Clinicians should be aware of the risk for serious bacterial infections, particularly UTIs, in infants who are 2 to 6 months old.

— Howard Bauchner, MD. Published in Journal Watch May 16, 2006. Source: Hsiao AL et al. Incidence and predictors of serious bacterial infections among 57- to 180-day-old infants. Pediatrics 2006 May; 117:1695-701.

13. Industry-Supported Clinical Trials More Likely to Favor Newer Treatments

NEW YORK (Reuters Health) May 16 - Compared with trials funded by nonprofit organizations, industry-supported studies tend to result in favorable outcomes for new treatments, researchers report in the Journal of the American Medical Association for May 17.

Trials that use surrogate end points, such as serum biomarkers or functional measures, instead of clinical endpoints are also more likely to yield positive findings, add Dr. Paul M. Ridker and Jose Torres of Harvard Medical School in Boston.

Surveys of randomized trials published between 1990 and 2000 showed that research funding affected reported outcomes, the researchers note. Proposals to ensure more reliable reporting included improved academic oversight and required registration and publication of all clinical trials.

To see if these recommendations have altered trial reporting, Dr. Ridker and Torres reviewed 324 human clinical trials of cardiovascular medications and devices published between 2000 and 2005 in JAMA, The Lancet or The New England Journal of Medicine, thus limiting their analysis to "trials considered to be of high quality on the basis of prior rigorous peer and editorial review."

They found that 49% of not-for-profit trials, 56.5% of jointly funded trials, and 67.2% of industry-funded trials significantly favored newer treatments (p for trend = 0.005). Similar patterns were observed for trials of drugs, devices and hard clinical end points. As noted, trials with clinical end points, regardless of funding source, were more likely to report positive findings than those using surrogate end points (67% versus 54.1%).

When similar findings were reported prior to 2000, the discrepancies were blamed on bias, data suppression, and differential data quality, Dr. Ridker and Mr. Torres note. Their current report, on the other hand, shows that trials "funded by for-profit organizations tend to have greater sample size, were more likely to be multicentered, and less likely to use surrogate end points, all characteristics typically associated with high quality."

The findings also show that the direction of effect is not always predictable, with some major industry-funded trials showing superiority of a competing manufacturer's product.

Another explanation for the differences between funding sources is that initial negative results for novel therapy are less likely to receive further funding at all, whereas continued research into positive results will probably be supported by industry.

Other factors affecting outcomes include industry's interest in evaluating proven therapies in previously understudied patient populations, while older therapies in common use often fail to be effective when tested rigorously by not-for-profit organizations.

In conclusion, the authors write, "our observations... strongly reinforce the need for physician decision-making and Food and Drug Administration approval to remain on the basis of clinical rather than surrogate end points."

JAMA 2006;295:2270-2274.

14. Acetaminophen/Paracetamol Analgesia Blocked by (Newer) Anti-Emetic Drugs

NEW YORK (Reuters Health) May 22 - Results of a French study provide the first evidence in humans that co-administration of the anti-emetics tropisetron or granisetron with acetaminophen (also known as paracetamol) blocks the analgesic action of acetaminophen.

This is a potentially important observation, investigators say, given that the anti-emetics are frequently used concomitantly with acetaminophen in patients with cancer.

The interaction between these agents "needs to be evaluated in the clinic to determine whether it is of clinical importance," write Dr. Gisele Pickering from Centre Hospitalier Universitaire in Clermont-Ferrand, France and colleagues in the April issue of Clinical Pharmacology and Therapeutics. Using an experimental electrical stimulus pain model in 26 volunteers, the team showed that the pain-relieving effect of acetaminophen was totally inhibited by co-administration of tropisetron or granisetron, two serotonin antagonists primarily used in the prevention of chemotherapy-induced nausea and vomiting.

These observations in humans support preclinical studies, which have suggested that acetaminophen "involves endogenous serotonin to exert its antinociceptive effects," the authors note.

Dr. Pickering's team also points out that the antagonism of acetaminophen analgesia by the anti-emetics was not a result of a pharmacokinetic interaction, because plasma levels were unchanged when tropisetron or granisetron was given concomitantly with acetaminophen. Rather, the results favor a pharmacodynamic interaction between acetaminophen and tropisetron and granisetron - one that needs to be studied further, the authors conclude.

Clin Pharmacol Ther 2006;79:371-378.

15. Flu Vaccine Recommended for More Americans in 2006-7 Season
By Maggie Fox. WASHINGTON (Reuters) May 19 - The U.S. Centers for Disease Control and Prevention is preparing its broadest and most ambitious vaccination effort yet for the coming influenza season, experts said during a briefing on Thursday.

The new recommendations will cover 218 million Americans, or 73% of the population, for the 2006-2007 influenza season. The hope is to both reduce flu deaths -- 36,000 every year on average -- and to coax vaccine makers back into the uncertain U.S. market.

There will not be enough vaccine for this many people, but historically most Americans who should be vaccinated do not. Furthermore, the CDC expects a record number of doses to be available -- up to 120 million, said Dr. Nicole Smith of the CDC's influenza division. The most ever available before has been 95 million doses.

Smith said the CDC was expected to extend its recommendations to include children aged up to 5 years and all their contacts -- including siblings, parents and caregivers. Last year only children aged 6 months to 2 years were on the priority list. There is also talk of adding all children to the list. Vaccinating schoolchildren could provide indirect protection to other groups via the herd effect, Smith added, including the elderly.

One question was whether to go ahead and recommend that everyone be vaccinated, or concentrate on getting more members of higher-risk groups vaccinated, Smith told the briefing, sponsored by The National Foundation for Infectious Diseases.

Dr. Ardis Hoven, a member of the American Medical Association's Board of Trustees, noted that only 40% of health-care professionals, including doctors, nurses and technicians, get vaccinated against flu every year. At Hoven's hospital at the University of Kentucky College of Medicine, 1,000 doses of flu vaccine went unused last year and had to be sent back to the manufacturer.

Part of the problem is that makers cannot deliver all their influenza vaccine doses right at the start of flu season in October. If people ask for a vaccine and cannot get it immediately, they often fail to come back looking for one later.

Interest in vaccination tends to wane after the Thanksgiving holiday at the end of November, Hoven said, even though the flu season has not even properly geared up. "We know that it peaks in February, but we are seeing cases in March, we are seeing cases in April," she said.

The CDC and NFID say people benefit from getting vaccinated as late as February.

Hoven and the other experts hope that having more vaccine available, and getting more Americans vaccinated, will encourage drug companies to make flu vaccines. Currently just four companies supply the U.S. market, and there have been severe shortages in the past five years. "We have got to increase the number of manufacturers and we have got to stabilize the vaccine supply," Hoven said.

16. Highlights From MMWR: Pre-Transport Stroke Death Rate Remains High

Yael Waknine. May 19, 2006 — The US Centers for Disease Control and Prevention (CDC) reported in the May 19 issue of the Morbidity and Mortality Weekly Report on the continued high prevalence of pre-transport stroke deaths; a link between physical dating violence in teens and risk behaviors such as sexual activity and fighting; and primary diagnoses most commonly associated with hospital admission of patients arriving by emergency transport.

Continued High Rate of Pre-Transport Stroke Deaths Underscores Need for Early Recognition and Timely Response

Approximately half of all stroke deaths occur prior to hospital transport, according to an analysis of 1999-2002 death-certificate data from all 50 states and the District of Columbia. The study found that 49.2% of stroke victims in 2002 died before emergency transportation, while 0.4% were dead on arrival (DOA), and 50.3% died after emergency transportation.

A significant proportion of pre-transport stroke deaths occurred in nursing homes (35.4%) rather than in the home or other place (13.8%), and mortality rates increased with age (particularly among nursing home residents), female sex, and non-Hispanic origin. The most common causes included sequelae of cerebrovascular diseases (72.1%) and other cerebrovascular conditions (69.5%), followed by unspecified stroke (54.5%), cerebral infarction (53.2%), and hemorrhagic stroke (14.2%).

Post-transport deaths were more likely to occur after admission to the hospital than in the emergency department (47.0% vs 3.3%) and were most commonly associated with hemorrhagic stroke (79.6%).

The CDC notes that although the national age-adjusted stroke death rate per 100,000 population decreased from 1999 to 2002 (61.6 vs 56.2 people), overall trends and characteristics associated with place of death among decedents remained consistent during this period, and with 1998 data (pre-transport deaths, 46.1%; DOA, 0.6%; hospital deaths, 49.5%).

According to CDC, the findings highlight the need for early patient and bystander recognition of stroke symptoms and improved emergency response times to reduce the continued high rate of pre-transport deaths and serious sequelae that can lead to severe disabilities.

MMWR. 2006;55:529-550

17. Accuracy of B-Type Natriuretic Peptide Tests to Exclude Congestive Heart Failure: Systematic Review of Test Accuracy Studies

Markus Battaglia; et al. Arch Intern Med. 2006;166:1073-1080.

Background Congestive heart failure (CHF) is a major public health problem. The use of B-type natriuretic peptide (BNP) tests shows promising diagnostic accuracy. Herein, we summarize the evidence on the accuracy of BNP tests in the diagnosis of CHF and compare the performance of rapid enzyme-linked immunosorbent assay (ELISA) and standard radioimmunosorbent assay (RIA) tests.

Methods We searched electronic databases and the reference lists of included studies, and we contacted experts. Data were extracted on the study population, the type of test used, and methods. Receiver operating characteristic (ROC) plots and summary ROC curves were produced and negative likelihood ratios pooled. Random-effect meta-analysis and metaregression were used to combine data and explore sources of between-study heterogeneity.

Results Nineteen studies describing 22 patient populations (9 ELISA and 13 RIA) and 9093 patients were included. The diagnosis of CHF was verified by echocardiography, radionuclide scan, or echocardiography combined with clinical criteria. The pooled negative likelihood ratio overall from random-effect meta-analysis was 0.18 (95% confidence interval [CI], 0.13-0.23). It was lower for the ELISA test (0.12; 95% CI, 0.09-0.16) than for the RIA test (0.23; 95% CI, 0.16-0.32). For a pretest probability of 20%, which is typical for patients with suspected CHF in primary care, a negative result of the ELISA test would produce a posttest probability of 2.9%; a negative RIA test, a posttest probability of 5.4%.

Conclusions The use of BNP tests to rule out CHF in primary care settings could reduce demand for echocardiography. The advantages of rapid ELISA tests need to be balanced against their higher cost.

18. Aspirin Plus Dipyridamole Better Than Aspirin Alone for Secondary Stroke Prevention

News Author: Laurie Barclay, MD. May 22, 2006 -- Aspirin plus dipyridamole is better than aspirin alone for secondary prevention of stroke in patients who have had transient ischemic attacks or small strokes, according to the results of a randomized trial reported in the May 20 issue of The Lancet. The editorialist agrees and also comments on the importance of other interventions including lifestyle changes.

"Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent," write A. Algra, MD, from University Medical Center Utrecht in the Netherlands, and colleagues from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) Study Group. "Because of these conflicting results, the routine use of the combination of dipyridamole and aspirin in the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin is controversial."

Within 6 months of a transient ischemic attack or minor stroke of presumed arterial origin, patients were randomized to aspirin (30 - 325 mg daily) with (n = 1363) or without (n = 1376) dipyridamole (200 mg twice daily). The main outcome was the composite of death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication or whichever occurred first. Treatment was open, but auditing of outcome events was blinded, and primary analysis was by intent-to-treat. Mean follow-up was 3.5 ± 2.0 years.

Median aspirin dose was 75 mg in both treatment groups (range, 30 - 325), and 1131 patients (83%) on the combination regimen used extended-release dipyridamole. Primary outcome events occurred in 173 patients (13%) receiving aspirin and dipyridamole and in 216 patients (16%) taking aspirin alone (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66 - 0.98; absolute risk reduction, 1.0% per year; 95% CI, 0.1 - 1.8).

Adding the ESPRIT data to the meta-analysis of previous trials yielded an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI, 0.74 - 0.91). Patients taking aspirin and dipyridamole discontinued trial medication more often than those taking aspirin alone (470 vs 184) primarily because of headache.

"The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin," the authors write.

Study limitations include lack of blinding, long duration but relatively large proportion of patients with incomplete follow-up, no firm restrictions as to the dose of aspirin prescribed, lower than anticipated rate of primary outcome events in the aspirin group, exclusion of 24 patients from one hospital because of incomplete data, and classification of large and small vessel disease based on clinical features.

The Council of Singapore, European Commission, Janivo Foundation, French Ministry of Health, Netherlands Heart Foundation, Thrombosis Foundation, and University Medical Center Utrecht sponsored this study. The authors have disclosed no relevant financial relationships.

In an accompanying editorial, Bo Norrving, MD, from University Hospital in Lund, Sweden, notes that therapy with dipyridamole and aspirin is difficult to maintain in the long term and that one third of the patients discontinued therapy mainly because of headaches.

"With today's report dual dipyridamole and aspirin therapy joins the podium of well-established interventions to be applied in routine clinical practice in secondary stroke prevention," Dr Norrving writes. "In clinical practice, secondary stroke prevention is still far from being ideal. Antiplatelet therapy, even if dual, is far from being the sole panacea for stroke prevention: risk factor and lifestyle modification should not be forgotten." Dr Norrving has disclosed no relevant financial relationships.

Lancet. 2006;367:1638-1639, 1665-1673.

Lit Bits: May 3, 2006

From the recent medical literature...

1. Cardiocerebral Resuscitation: A Newsmaker Interview With Gordon A. Ewy, MD

Laurie Barclay, MD

April 17, 2006 ­ Editor's Note: Cardiocerebral resuscitation (CCR) ­ employing chest compressions but no ventilations ­ improves survival of out-of-hospital cardiac arrest, according to the results of an observational study published by Michael J. Kellum, MD, and colleagues in the April issue of the American Journal of Medicine. Unlike traditional cardiopulmonary resuscitation (CPR), which was designed both for cardiac and respiratory arrest, CCR is designed only for unexpected, witnessed, cardiac arrest, which is by far more common than respiratory arrest as a cause of sudden collapse in adults.

Animal experiments showed that the most important factor determining survival after CPR is cardiac perfusion pressure, achieved by continuous chest compressions. Ventilations may actually be harmful because they interrupt chest compressions, decrease venous return to the heart, and increase intrathoracic pressure. When paramedics in Wisconsin employed the new CCR protocol, with chest compressions before and after defibrillation but no intubation or ventilations, they achieved a 300% increase in survival compared with use of traditional CPR.

To learn more about the clinical implications of this new protocol, Medscape's Laurie Barclay interviewed study coauthor Gordon A. Ewy, MD, director and pioneer of the CPR Research Group at the University of Arizona Sarver Heart Center in Tucson.

See http://www.medscape.com/viewarticle/530114?sssdmh=dm1.189554&src=nldne

2. Viewpoint: Appendicitis -- How Much Time Do We Have Until Rupture?

Posted 04/11/2006. Albert B. Lowenfels, MD

Bickell NA, Aufses AH, Rojas M, Bodian C. J Am Coll Surg. 2006;202:401-406

Summary
The aim of this report was to study the timing between the onset of symptoms of appendicitis and the risk for rupture. The investigators studied the records of 219 patients from a total of 731 with documented appendicitis over a 2-year period in 2 metropolitan hospitals. At the time of surgery, 16% (n = 36) of the patients had sustained appendiceal rupture. The frequency of rupture was low in the first 36 hours after the onset of symptoms (< 2%), but increased to 5% in each of the ensuing 12-hour periods. In a multivariate analysis, total time since the beginning of the attack was the strongest risk factor (relative risk, 6.6). Other significant factors were age 65 (relative risk, 4.2), fever, and tachycardia.
Viewpoint
This report quantifies the relationship between the duration of symptoms and risk for appendiceal rupture with well-known complications. Important factors that were associated with delay in diagnosis included the absence of right lower quadrant tenderness (19% of patients) and performance of a computed tomographic (CT) scan (18% of patients). The study results emphasize the benefit to the patient of making a diagnosis within a "golden" period of 36 hours.

3. Oral Ondansetron Appears Beneficial for Emergent Pediatric Gastroenteritis

News Author: Laurie Barclay, MD. April 19, 2006 ­ Orally disintegrating ondansetron may be beneficial for the treatment of pediatric patients with gastroenteritis in the emergency department, according to the results of a randomized study published in the April 20 issue of The New England Journal of Medicine.

"Vomiting limits the success of oral rehydration in children with gastroenteritis," Stephen B. Freedman, MDCM, from the Hospital for Sick Children, University of Toronto. "Thus, a safe and effective method of controlling vomiting is likely to increase the use and success rate of oral rehydration... We conducted a double-blind trial to determine whether a single oral dose of ondansetron, an antiemetic, would improve outcomes in children with gastroenteritis."

At a pediatric emergency department, 215 children ranging in age from 6 months through 10 years who were being treated for gastroenteritis and dehydration were randomized to treatment with orally disintegrating ondansetron tablets or placebo. The primary outcome was the proportion that vomited while receiving oral rehydration, according to a standardized protocol, and secondary outcomes were the number of episodes of vomiting and the proportions of children who were treated with intravenous rehydration or hospitalized.

Compared with the placebo group, children in the ondansetron group were less likely to vomit (14% vs 35%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.26 - 0.61). They also had a lower mean number of vomiting episodes per child (0.18 vs 0.65; P < .001), greater oral intake (239 vs 196 mL; P = .001), and lower rate of treatment by intravenous rehydration (14% vs 31%; RR, 0.46; 95% CI, 0.26 - 0.79).

The mean length of stay in the emergency department was 12% lower in the ondansetron group than in the placebo group (P = .02). However, the rates of hospitalization (4% vs 5%; P = 1.00) and of return visits to the emergency department (19% vs 22%; P = .73) did not differ significantly between groups.

To prevent vomiting in 1 child, 5 children had to receive ondansetron (95% CI, 3.2 - 10.6). To prevent 1 child from having to be treated by intravenous rehydration, 6 had to receive ondansetron (95% CI, 3.6 - 17.0).

"In children with gastroenteritis and dehydration, a single dose of oral ondansetron reduces vomiting and facilitates oral rehydration and may thus be well suited for use in the emergency department," the authors write. "Our data suggest that it is safe to administer oral ondansetron to children with gastroenteritis, with diarrhea being the most notable side effect."

Study limitations include inability to rule out the possibility that viruses or bacteria may explain the differences in the frequency of diarrhea between groups; use of an invalidated scale for dehydration; and duration of oral rehydration limited to 1 hour.

"We found that treatment with orally disintegrating ondansetron tablets was beneficial in children with vomiting and dehydration due to gastroenteritis," the authors conclude. "The ondansetron tablet is easy to administer, has few side effects, and is safe and effective. Therefore, it may be a useful therapy in the emergency department for children with vomiting and mild-to-moderate dehydration as a result of gastroenteritis."

The National Center for Research, the National Institutes of Health, and GlaxoSmithKline, the maker of ondansetron, supported this project. The authors have disclosed no relevant financial relationships.

N Engl J Med. 2006;354:1698-1704

4. Ximelagatran May Cause Less Bleeding Than Warfarin in Patients With Nonvalvular AFib

News Author: Laurie Barclay, MD. April 28, 2006 ­ Ximelagatran is associated with less bleeding then warfarin for patients with nonvalvular atrial fibrillation, according to the results of a pooled analysis of the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III and V participants reported in the April 24 issue of the Archives of Internal Medicine.

"Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring," write James D. Douketis, MD, from McMaster University in Hamilton, Ontario, and colleagues. "Managing warfarin therapy is problematic because of the need for anticoagulant monitoring, with INR [International Normalized Ratio] testing required every 1 to 4 weeks for dose adjustments. Warfarin also interacts with other drugs, food, genetic polymorphisms, and acute illness, with the potential to cause excessive anticoagulation and bleeding."

This pooled analysis included 7329 patients with nonvalvular atrial fibrillation enrolled in the SPORTIF III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target INR, 2.0 - 3.0). Outcome measures included annual risk of any and major bleeding, case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment.

The annual incidence of any bleeding was 31.75% for ximelagatran and 38.82% for warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0 - 23.1; P < .001); and incidence of major bleeding was 2.01% vs 2.68% (relative risk reduction, 25.1%; 95% CI, 3.2 - 42.1; P = .03). The case-fatality rate of bleeding was similar with ximelagatran and warfarin (8.16% vs 8.09%; P = .98). After 24 months of treatment, the cumulative incidence of major bleeding was higher with warfarin than with ximelagatran (4.7% vs 3.7%; P = .04). Both treatments were similar in terms of anatomic sites of bleeding.

Risk factors for bleeding with ximelagatran treatment were diabetes mellitus (hazard ratio [HR], 1.81; 95% CI, 1.19 - 2.77; P = .006), previous stroke or transient ischemic attack (HR, 1.78; 95% CI, 1.16 - 2.73; P = .008), age 75 years or older (HR, 1.70; 95% CI, 1.33 - 2.18; P < .001), and aspirin use (HR, 1.68; 95% CI, 1.08 - 2.59; P = .02). In warfarin-treated patients, risk factors for bleeding were previous liver disease (HR, 4.88; 95% CI, 1.55 - 15.39; P = .007); aspirin use (HR, 2.41; 95% CI, 1.69 - 3.43; P < .001); and age 75 years or older (HR, 1.26; 95% CI, 1.03 - 1.52; P = .02).

Study limitations include pooling of the study sample from 2 studies of different design; the inclusion of intracerebral bleeding episodes as major episodes, which might have exaggerated the number of major bleeding episodes if some intracerebral episodes initially were ischemic strokes with subsequent hemorrhagic transformation; and lack of evidence of causality.

"Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation," the authors write. "Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.... These potential benefits of ximelagatran therapy should be weighed against potential risks of treatment, which include elevated serum liver enzyme levels in approximately 6% of patients with atrial fibrillation and, rarely, severe and possibly fatal hepatitis."

AstraZeneca, the maker of ximelagatran, employs one of the authors. The other authors have disclosed no relevant financial relationships.

Arch Intern Med. 2006;166:853-859

5. Distraction Can Help Make Laceration Repair More Tolerable for Children

NEW YORK (Reuters Health) Apr 14 - Using age-appropriate distractors, such as listening to a CD player, may help reduce the anxiety and pain of laceration repair in children presenting to the ER, new research suggests.

Previous reports have suggested beneficial effects using distraction techniques, but until now no controlled studies have evaluated their ability to facilitate completion of painful procedure in the pediatric ER setting.

As reported in the April issue of Pediatrics, Dr. Madhumita Sinha, from Maricopa Medical Center in Phoenix, Arizona, and colleagues assessed the outcomes of 240 children, between 6 and 18 years of age, who were randomized to receive a distractor or no distractor during laceration repair. All of the children received a topical anesthetic and a supplemental local anesthetic was given if deemed necessary.

Children in the intervention group were given a choice of a music, video game, or cartoon video distractors. If the child showed no interest in any of these, a certified child life worker offered to read a book or blow bubbles with them. In children younger than 10 years of age, the average change in Facial Pain Scales scores did not differ significantly between the groups. However, parental perception of pain distress was lower in the distractor group than in the control group.

In older subjects, the distractors seemed to have no effect on pain, but were tied to a reduction in situational anxiety. Distraction techniques "may have a role in improving the quality of management of procedural pain in a pediatric ER setting," the authors note. Because such interventions "require minimal training and effort, integrating these techniques into existing pain management protocols might complement standard pharmacologic therapy in the pediatric ER and even in other outpatient settings."

Pediatrics 2006;117:1163-1167.

6. CT Angiography for the Evaluation of Aneurysmal SAH

Shaun D. Carstairs, MD, et al. Acad Emerg Med Volume 13, Number 5 486-492.

Objectives: Computed tomography (CT) followed by lumbar puncture (LP) is currently the criterion standard for diagnosing subarachnoid hemorrhage (SAH) in the emergency department (ED); however, this is based on studies involving a limited number of patients. The authors sought to assess the ability of CT angiography (CTA), a new diagnostic modality, in conjunction with CT/LP to detect SAH.

Methods: Consecutive patients presenting to the ED with symptoms concerning for SAH were approached. All patients had an intravenous catheter placed and underwent a noncontrast head CT followed by CTA. Patients whose CT did not reveal evidence of SAH or other pathology underwent LP in the ED. CTAs were read within 24 hours by a neuroradiologist blinded to the patient's history.

Results: A total of 131 patients were approached, 116 were enrolled, and 106 completed the study. In six of 116 patients (5.1%), aneurysm was found on CTA with normal CT and positive findings on LP; three had a positive CTA with normal CT and LP findings (one of which had a negative cerebral angiogram), and there was one false-positive CTA. Follow-up of all 131 patients showed no previously undiagnosed intracranial pathology. In this patient population, 4.3% (5/116) were ultimately found to have an SAH and/or aneurysm.

Conclusions: In this pilot study, CTA was found to be useful in the detection of cerebral aneurysms and may be useful in the diagnosis of aneurysmal SAH. A larger multicenter study would be useful to confirm these results.

7. Necessity breeds invention: a study of outpatient management of low velocity gunshot wounds

A Byrne, et al. Emergency Medicine Journal 2006;23:376-378

Background: Since the late 1980s, the emergency department (ED) at the Mater Hospital, Belfast, has implemented a policy of treating conservatively patients who sustain low velocity gunshot wounds to the lower limbs. Wounds are cleaned and minimally debrided under local anaesthetic in the ED. Patients are given oral antibiotics, and reviewed 48 hours later at the ED review clinic.

Objective: To investigate the outcome of outpatient ED management of low velocity gunshot wounds to the lower limbs.

Method: This was a retrospective, observational study from January 2000 to September 2004 inclusive. Notes were retrieved of those patients who had gunshot wound mentioned in the triage text. Patients were included if they presented with a low velocity gunshot wound to the lower limbs. Demographics and treatment regimen were recorded.

Results: In total, 90 patients sustained low energy injuries to the lower limb, with 70.5% of wounds involving the skin and soft tissue only. Most patients (n = 67) were treated as outpatients, which included 80% of unilateral injuries and 46.6% of bilateral injuries presented. There were 56 patients reviewed at clinic. Three patients developed minor complications

Conclusion: Irrigation and minimal debridement in the outpatient setting is an acceptable method of treatment for low energy gunshot wounds to the lower limbs, without orthopaedic or vascular involvement.

8. Effect of population ageing on emergency department speed and efficiency: a historical perspective from a district general hospital in the UK

G George, et al. Emergency Medicine Journal 2006;23:379-383

Objective: To examine changes in the rate of seeing patients between 1990 and 2004 and to see whether performance might be related to patient age, using data held on the patient administration system.

Method: Data collected in 1990 were compared with those collected in 2004. Age related data were examined for the following parameters: the number of patients arriving by ambulance; the time taken to process the attendance; the number of investigations; the number of emergency admissions; and the length of inpatient stay.

Results: Emergency department (ED) performance has fallen markedly since 1990. Between 1990 and 2004, there was a 54% increase in total patients with a disproportionate 198% increase in patients aged more than 70 years, including a 671% increase in those aged more than 90 years. The time taken to manage patients increased with age. In 2004, there was a marked rise in investigation rates, and the probability of having investigations increased with age. In 2004, older patients (aged more than 70 years) were 4.9 times more likely to require admission to hospital than younger patients (aged 30 years or less). Their average length of stay was 6.9 times longer. Younger patients were 3.3 times more numerous than older patients but older patients occupied 9.8 times more emergency bed days.

Conclusions: Pressure on emergency care is associated with a disproportionate increase in the number of elderly patients and with an increased tendency to investigate them. Population ageing is of central importance in planning health services.

9. Alzheimer's Disease Among the 2004 Top Causes of Death in US

WASHINGTON (Reuters) Apr 20 - Americans are living longer, healthier lives -- and among the top 10 causes of death -- only Alzheimer's disease is increasing, the U.S. federal government reported on Wednesday.

Alzheimer's disease moved to seventh place from eighth place among the leading causes of death in 2004, passing influenza and pneumonia, the National Center for Health Statistics reported. "The life expectancy of Americans in 2004 -- 77.9 years -- is the highest it has ever been," the NCHS said in a statement.

"The life expectancy for women in the United States is 80.4 years; the life expectancy for U.S. men is 75.2 years. The life expectancy gender gap is narrowing -- the 5.2 year difference in 2004 was the smallest difference since 1946," according to the report.
This change is related to the 7.3% drop in mortality from influenza and pneumonia, compared with the 1.4% increase in mortality from Alzheimer's disease.

The NCHS, part of the U.S. Centers for Disease Control and Prevention, reported that 2.39 million Americans died in 2004.

The U.S. death rate fell to a record low of 801 deaths per 100,000 people, down from nearly 833 deaths per 100,000 in 2003. Overall, 50,000 fewer people died between 2003 and 2004, the biggest 1-year drop in decades.

The 10 leading causes of death in 2004 were:

1. Heart disease -- 654,000 deaths
2. Cancer -- 550,000 deaths
3. Stroke -- 150,000 deaths
4. Chronic lower respiratory diseases -- 123,000
5. Accidents -- 108,000
6. Diabetes -- 72,800
7. Alzheimer's disease -- 65,829
8. Influenza and pneumonia -- 61,472
9. Kidney disease -- 42,762
10. Septicemia -- 33,464.

10. Coffee May Not Increase Risk for Heart Disease

News Author: Laurie Barclay, MD. April 25, 2006 ­ Coffee does not increase the risk for coronary heart disease (CHD) in men or women, according to the results of a large, prospective cohort study reported in the April 24 Rapid Access issue of Circulation.

"We found that coffee consumption was not associated with an increased risk of CHD," lead author Esther Lopez-Garcia, DrPH, from the Universidad Autonoma de Madrid in Spain, said in a news release. "This lack of effect is good news, because coffee is one of the most widely consumed beverages in the world.... The length of follow up is important because it allowed us to examine the long-term effects of coffee consumption."

The study cohort consisted of 44 005 men and 84 488 women without history of cardiovascular disease or cancer. The investigators first evaluated coffee consumption in 1986 for men and in 1980 for women and then repeatedly every 2 to 4 years. During follow-up through 2000, there were 2173 incident cases of CHD in men, including 1449 nonfatal myocardial infarctions and 724 fatal cases of CHD; and 2254 cases in women, including 1561 nonfatal myocardial infarctions and 693 fatal cases of CHD.

After adjustment for age, smoking, and other CHD risk factors, the relative risks (RRs) of CHD for men across categories of cumulative coffee consumption were 1.0 for less than 1 cup/month; 1.04 (95% confidence interval [CI], 0.91 - 1.17) for 1 cup/month to 4 cups/week; 1.02 (95% CI, 0.91 - 1.155 for 7 cups/week; 1.07 (95% CI, 0.88 - 1.31) for 2 to 3 cups/day; 0.97 (95% CI, 0.86 - 1.11) for 4 to 5 cups/day, and 0.72 (95% CI, 0.49 - 1.07) for more than 6 cups/day (P for trend = .41). For women, the corresponding RRs were 1.0, 0.97 (95% CI, 0.83 - 1.14), 1.02 (95% CI, 0.90 - 1.17), 0.84 (95% CI, 0.74 - 0.97), 0.99 (95% CI, 0.83 - 1.17), and 0.87 (95% CI, 0.68 - 1.11; P for trend = .08).

Stratification by smoking status, alcohol consumption, history of type 2 diabetes mellitus, and body mass index did not alter the findings nor did examining the most recent coffee consumption. RRs for quintiles of caffeine intake ranged from 0.97 (95% CI, 0.84 - 1.10) in the second quintile to 0.97 (85% CI, 0.84 - 1.11) in the highest quintile (P for trend = 0.82) in men and from 1.02 (0.90 - 1.16) to 0.97 (0.85 - 1.11; P for trend = 0.37) in women.

"We believe this study clearly shows there is no association between filtered coffee consumption and CHD," Dr. Lopez-Garcia says. "However, because of the modest consumption of non-filtered coffee among participants, this study does not exclude a relationship between high non-filtered consumption and increased CHD risk."

Frequent or heavy coffee consumption was strongly associated with smoking cigarettes, drinking alcohol, and using aspirin and with lower frequency of tea drinking, exercise, and use of multivitamin and vitamin E supplements. Risk for CHD was not significantly different in women who frequently drank decaffeinated coffee and in those who did not. Total cholesterol, low-density and high-density lipoprotein cholesterol levels in men and women coffee drinkers did not differ in those who drank caffeinated or decaffeinated coffee. CHD risk associated with drinking coffee did not differ in people with or without type 2 diabetes.

"We can't exclude the association between coffee consumption and the risk of CHD in small groups of people," says coauthor Rob van Dam, PhD, from Harvard University School of Public Health in Boston, Mass. "For example, a recent study suggested coffee could be detrimental in people with certain genotypes, although that finding requires confirmation."

The National Institutes of Health funded this study. Two authors have disclosed that they are supported by Ministerio de Educacion y Cultura de España, Fondo Social Europeo, and/or the American Heart Association. The authors have disclosed no financial relationships.

Circulation. Posted online April 24, 2006.

11. ACS Patients Do Better at Hospitals That Follow Treatment Guidelines

NEW YORK (Reuters Health) Apr 25 - There is a strong link between hospital adherence to treatment guidelines for acute coronary syndromes (ACS) and outcome, according to a new study, which shows that greater adherence to the guidelines is associated with decreased in-hospital mortality in ACS patients.

"Our work supports the central hypothesis of hospital quality improvement; namely, better adherence with evidence-based care practices will result in better outcomes for patients who are treated," write Dr. Eric Peterson and colleagues from Duke University Medical Center in Durham, North Carolina in the April 26th issue of the Journal of the American Medical Association.

The study is based on an analysis of 64,775 ACS patients at 350 academic and nonacademic US medical centers. Overall, the nine treatments recommended by the American College of Cardiology and American Heart Association for non-ST-segment elevation ACS were followed 74% of the time.

"This shows that the care being delivered is not ideal, as in up to one in four cases, patients are not receiving medicines that are proven to save lives," Dr. Peterson noted in a statement from Duke. The data also show that there is wide variance among hospitals -- "some are near perfect in the use of certain drugs while others are in the 50% to 60% range of adherence," he noted.

Specifically, the research team found that hospitals with the highest levels of adherence to the nine different ACS treatment guidelines had an in-hospital death rate of 4.15%, compared with a rate of 6.31% for hospitals with the lowest levels of adherence.

Additionally, after risk adjustment, every 10% improvement in ACS treatment guideline adherence led to a 10% decline in in-hospital mortality. Adherence to proven guidelines "may serve as a marker for the overall culture of the hospital and its commitment to providing the best possible care," Dr. Peterson said.

The team also found that hospitals with high adherence to ACS treatment guidelines were also more likely to use "newer" recommended therapies such as glycoprotein IIb/IIIb inhibitors, clopidogrel and lipid-lowering drugs. "Again, keeping up with the latest is another indicator of a hospital's overall culture of providing the best possible care," Dr. Peterson said.

JAMA 2006;295:1912-1920.

12. PALS GUIDELINES

2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and Neonatal Patients: Pediatric Advanced Life Support

PEDIATRICS Vol. 117 No. 5 May 2006, pp. e1005-e1028 (doi:10.1542/peds.2006-0219)

Full text, see: http://pediatrics.aappublications.org/cgi/content/full/117/5/e1005

13. Stress Testing: It Is Safe to Wait

David Magid, MD, MPHa, S. Adam Hill, MDb. Ann Emerg Med. 2006;47:436-437.

Patients who present to the emergency department (ED) with chest pain suggestive of a possible acute coronary syndrome pose a diagnostic and disposition challenge. The patient medical history, physical examination, and laboratory and ECG results have limited diagnostic sensitivity for acute coronary syndrome. As a result, a small but significant number of acute coronary syndrome patients are discharged from the ED, some of whom die or experience other adverse outcomes.

In an effort to reduce the rate of inadvertent discharge of acute coronary syndrome patients, many emergency physicians have a low threshold for admitting patients who present to the ED with chest pain. In some studies, fewer than 30% of patients admitted to the hospital with possible acute coronary syndrome receive a final hospital discharge diagnosis of acute myocardial infarction or unstable angina. Such liberal admission policies consume significant resources, contribute to hospital crowding, and drive up the cost of health care. Some estimates place the cost of this practice at upwards of $3 billion annually.

Several approaches have been proposed as alternatives to this traditional approach of ED evaluation and hospital admission for patients with chest pain. These include accelerated inpatient, observation unit, or ED rule-out acute myocardial infarction protocols that include serial ECGs and cardiac biomarkers. A common theme of these approaches is to use risk stratification to identify low-risk patients who can be further evaluated in a more cost-effective manner than a typical hospital admission. Patients whose initial hospital-based evaluation is negative for acute coronary syndrome typically undergo stress testing before discharge.

However, at some hospitals stress testing is not available on all days of the week or times of the day. As a result, patients may have to stay in the hospital overnight just to receive a stress test the next morning. To address this issue, some have suggested that for appropriately selected low-risk patients, it may be safe and more efficient to discharge them from the ED and obtain a stress test as an outpatient.

14. Aspirin May Reduce the Risk for Aminoglycoside-Related Hearing Loss

Yael Waknine. April 26, 2006 ­ Concurrent administration of aspirin therapy significantly reduces the risk for gentamycin-induced hearing loss, according to the results of a prospective, randomized, double-blind, placebo-controlled Chinese trial reported in a letter to the editor in the April 27 issue of the New England Journal of Medicine.

"The incidence of aminoglycoside-induced hearing loss averages 8% but the numbers may be higher in developing countries where aminoglycosides are frequently the only affordable antibiotics and are sold over the counter," lead author Su-Hua Cha, MD, associate laboratory director of the Kresge Hearing Research Institute's biochemistry laboratory at the University of Michigan (U-M) Medical School in Ann Arbor, says in a news release.

For the study, investigators randomized 195 adult patients at the Xijing Hospital and Airforce Chengdu Hospital scheduled for 5 to 7 days of intravenous gentamycin therapy to receive 2 weeks of supplementation with 1 g of aspirin 3 times daily (n = 89) or to placebo (n = 106). Results at 5 to 7 weeks posttherapy showed that aspirin therapy significantly reduced the risk for ototoxicity, defined as a unilateral or bilateral shift from baseline of 15 dB or more at both 6 and 7 kHz (3% vs 13%; P = .013; relative risk, 0.26 [95% confidence interval, 0.08 - 0.86]). The efficacy of gentamycin was similar in both groups.

Potential drawbacks to use of aspirin in this setting include the off-label nature of the indication and the risk for gastric bleeding. In the study, gastrointestinal symptoms were more commonly reported among aspirin-treated patients and gastric bleeding led to discontinuation of treatment in 3 patients.

Nevertheless, aspirin is commonly available and inexpensive. "We would like to see the word get around to the medical community in the world that you can take some precautions to minimize the risk to your patients," senior author Jochen Shacht, PhD, professor of biological chemistry in otolaryngology at the U-M Medical School and director of the Kresge Hearing Research Institute, says in a news release.

Dr. Schacht notes that although gentamycin is not commonly used in the United States and its use has been declining in other industrialized countries, it is unlikely to be replaced in the near future due to the specificity of its applications and its widespread and inexpensive availability in poorer countries.

While aspirin shows promise for reducing the risk for aminoglycoside-induced ototoxicity, the authors conclude that further studies are needed to develop a prophylactic drug with fewer adverse effects and/or new and safer antibiotics.

N Engl J Med. 2006;354:1856-1857.

15. Promethazine Products Contraindicated in Children Under 2 Years

Yael Waknine. April 26, 2006 ­ The US Food and Drug Administration (FDA) is warning healthcare professionals, parents, and caregivers against the use of promethazine HCl in children younger than 2 years due to the risk for fatal respiratory depression, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.

The FDA has received postmarketing reports of serious adverse events, including 7 deaths and 22 cases of respiratory depression, that were associated with use of promethazine in children younger than 2 years. As a result, all promethazine-containing syrups, tablets, suppositories, and injectables are contraindicated in this population.

Because these adverse events were not directly related to individualized weight-based dosing, promethazine should be administered with caution and at the lowest effective dose for pediatric patients aged 2 years and older. Concurrent administration of other drugs with the potential for respiratory depression should also be avoided.

Promethazine-containing products are marketed in the United States as brand name (Phenergan, made by Wyeth Pharmaceuticals, Inc) and generic formulations. They are indicated for use in treating hypersensitivity reactions and as an antiemetic and/or sedative in various settings. The FDA notes that antiemetics are not recommended for the treatment of uncomplicated vomiting in pediatric patients; use of these agents should be limited to prolonged vomiting of known etiology.

Because the drug's extrapyramidal effects may be confused with central nervous system signs of undiagnosed primary disease, promethazine should not be used in pediatric patients with signs and symptoms suggestive of Reye's syndrome or other hepatic diseases.

Healthcare professionals are encouraged to report promethazine-related adverse events to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

16. Age Effect on Efficacy and Side Effects of Two Sedation and Analgesia Protocols on Patients Going through Cardioversion: A Randomized Clinical Trial

Mine Parlak, MD, et al. Acad Emerg Med Volume 13, Number 5 493-499.

Background: Cardioversion (CV), a painful procedure, requires sedation and analgesia. Although several sedation agents currently are in use for CV, data on age-specific efficacy and side effects of midazolam and propofol have been limited.

Objectives: To compare the efficacy and side effects of midazolam and propofol in patients of two different age groups, younger than 65 years and 65 years and over, who were going through CV.

Methods: Seventy consented patients with CV indications caused by atrial fibrillation were included in this clinical trial. The participants were placed into four groups by using a stratified randomization method: patients aged younger than 65 years who were receiving midazolam (n = 12) or propofol (n = 11) and patients 65 years and over who were receiving midazolam (n = 25) or propofol (n = 22). Medications were administered by slow intermittent bolus injections. During CV, time to reach Ramsay Sedation Scale level 5 (RSS-5; induction time); time to reach RSS-2 (recovery time); and side effects including desaturation, apnea, and changes in hemodynamic parameters were recorded by a person blinded to the patient treatment allocation.

Results: Mean induction time was similar in all four groups. Mean recovery time (min ± SD) was shorter in both propofol groups when compared with both midazolam groups: 18.8 (± 4.06) and 40.33 (± 20.8) in the group younger than 65 years and 18.2 (± 5.12) and 54.2 (± 20.85) in the group 65 years or older, respectively (p < 0.001). Older participants in each medication group needed less medication than younger patients. There were no hemodynamic differences between the groups. Desaturation was higher in both midazolam groups as compared with individuals in the age-matched propofol groups (both p < 0.05). Patient reactions were less in propofol groups with similar joules during CV procedures than were those in the midazolam groups.

Conclusions: Propofol appears to be a better choice for CV sedation in elders because of its short recovery time, fewer side effects, and its more comfortable sedative effect.

17. Does End-tidal Carbon Dioxide Monitoring Detect Respiratory Events Prior to Current Sedation Monitoring Practices?

John H. Burton, MD, et al. Acad Emerg Med Volume 13, Number 5 500-504.

Objectives: The value of ventilation monitoring with end-tidal carbon dioxide (ETCO2) to anticipate acute respiratory events during emergency department (ED) procedural sedation and analgesia (PSA) is unclear. The authors sought to determine if ETCO2 monitoring would reveal findings indicating an acute respiratory event earlier than indicated by current monitoring practices.

Methods: The study included a prospective convenience sample of ED patients undergoing PSA. Clinicians performed ED PSA procedures with generally accepted patient monitoring, including oxygen saturation (SpO2), and clinical ventilation assessment. A study investigator recorded ETCO2 levels and respiratory events during each PSA procedure, with clinical providers blinded to ETCO2 levels. Acute respiratory events were defined as SpO2 92%, increases in the amount of supplemental oxygen provided, use of bag-valve mask or oral/nasal airway for ventilatory assistance, repositioning or airway alignment maneuvers, and use of physical or verbal means to stimulate patients with depressed ventilation or apnea, and reversal agent administration.

Results: Enrollment was stopped after independent review of 20 acute respiratory events in 60 patient sedation encounters (33%). Abnormal ETCO2 findings were documented in 36 patients (60%). Seventeen patients (85%) with acute respiratory events demonstrated ETCO2 findings indicative of hypoventilation or apnea during PSA. Abnormal ETCO2 findings were documented before changes in SpO2 or clinically observed hypoventilation in 14 patients (70%) with acute respiratory events.

Conclusions: Abnormal ETCO2 findings were observed with many acute respiratory events. A majority of patients with acute respiratory events had ETCO2 abnormalities that occurred before oxygen desaturation or observed hypoventilation.

18. Withholding Resuscitation: A New Approach to Prehospital End-of-Life Decisions

Sylvia Feder, MA, MICP; et al. Ann Intern Med. 2 May 2006 Volume 144 Issue 9 Pages 634-640.

This study tested the use of new guidelines that allowed emergency medical services (EMS) personnel to withhold resuscitation if a patient had a terminal condition and if the patient, family, or caregivers asked them not to resuscitate. The EMS units that implemented the guidelines withheld more resuscitations as a result of verbal requests than EMS units that did not implement the guidelines.

Background: Emergency medical services (EMS) personnel often are not permitted to honor requests to withhold resuscitation at the end of life, particularly if there is no written do-not-resuscitate (DNR) order.

Objective: To determine whether EMS personnel from agencies implementing new guidelines would be more likely to withhold resuscitation from persons having out-of-hospital cardiac arrests than would personnel from agencies that did not implement the guidelines.

Design: Observational study in which 16 of 35 local EMS agencies volunteered to implement new guidelines for withholding resuscitation.

Setting: King County, Washington.

Patients: 2770 patients with EMS-attended cardiac arrest.

Intervention: New guidelines adopted by participating agencies permitted EMS personnel to withhold resuscitation if the patient had a terminal condition and if the patient, family, or caregivers indicated, in writing or verbally, that no resuscitation was desired.

Measurements: Proportion of resuscitations withheld in agencies that implemented new guidelines compared with those that did not.

Results: Emergency medical services personnel from agencies implementing new guidelines withheld resuscitation in 11.8% of patients (99 of 841 patients) having cardiac arrests, compared with an average of 5.3% (range, 4.2% to 5.9%) of patients (103 of 1929 patients) in 3 historical and contemporary control groups. Honoring verbal requests alone accounted for 53% of withheld resuscitations in the intervention group (52 of 99 patients) compared with an average of 8% (range, 7% to 9%) in the control groups (8 of 103 patients).

Limitations: The study was not a randomized, controlled trial; individual agencies chose whether to implement the guidelines.

Conclusions: Implementation of new guidelines was associated with an increase in the number of resuscitations withheld by EMS personnel. This increase was primarily due to honoring verbal requests.

19. Patients' Global Ratings of Care Don't Reflect Technical Quality of Care

NEW YORK (Reuters Health) May 01 - Patients' global ratings of their healthcare are not associated with the technical quality of care they receive, according to a new survey. Therefore, "assessments of quality of care should include both patient evaluations and independent assessments of technical quality," conclude researchers in the May 1st issue of the Annals of Internal Medicine.

Patient ratings of care are often used by health plans, payers, providers, and consumers to assess the quality of care received, note the authors. However, the extent to which these assessments of care are related to the technical quality of care received is unclear.

To investigate, a team led by Dr. John T. Chang, from the David Geffen School of Medicine at the University of California, Los Angeles asked 236 independently living frail elderly adults to rate the care they received in two managed care groups over a 12-month period. Dr. Chang's group also reviewed patient medical records to gauge adherence to standard of care for common conditions.

The team found that overall ratings of care were high and correlated strongly and directly with the physician's interpersonal communication skills. "Better communication was associated with higher global ratings of health care," Dr. Chang and colleagues report.

However, higher patient global ratings of health care were not significantly associated with technical quality of care received.

This hints that "technical quality of care and reports about interpersonal quality of care seem to be separate domains, and patients' global ratings of health relate only to the former," Dr. Chang and colleagues conclude.

Ann Intern Med 2006;144:665-672.