Lit Bits: March 17, 2006

From the recent medical literature...

1. Community-Acquired MRSA a Leading Cause of Skin and Soft-Tissue Infections

NEW YORK (Reuters Health) Mar 06 - Prospective surveillance of Staphylococcus aureus infections of skin and soft tissue in urban Atlanta has demonstrated that two-thirds were caused by community-acquired methicillin-resistant S. aureus (MRSA), investigators report in the Annals of Internal Medicine for March 7.

Also, according to a second paper in the Annals, nearly 32% of the noninstitutionalized US population were colonized with methicillin-sensitive S. aureus and 1% with MRSA in 2001-2002. Dr. Henry M. Blumberg, from Emory University School of Medicine in Atlanta, and colleagues identified 389 episodes of skin and soft-tissue infection among 384 persons treated between August and November of 2003. Of these episodes, 72% were caused by MRSA, and of these 63% were community-acquired MRSA.

Most of the community-acquired MRSA isolates (87%) were resistant only to beta-lactams and erythromycin; between 1% and 10% were also resistant to levofloxacin, clindamycin, rifampin, or gentamicin. In contrast, most of the non-community-associated MRSA (88%) were resistant to beta-lactams, erythromycin and at least one other antibiotic. In multivariate analysis, black race (prevalence ratio 1.53), female sex (prevalence ratio 1.16) and hospitalization within the previous year (prevalence ratio 0.80) were independently associated with community-acquired MRSA.

Dr. Blumberg's group notes that clinicians apparently did not recognize that most of these infections were being caused by MRSA since they often prescribed antibiotics lacking activity against MRSA. They recommend that physicians obtain specimens for culture, and that MRSA skin and soft tissue infections be treated with vancomycin or other non-beta-lactam agents. They also advise that in areas with a high prevalence of community-acquired MRSA infections, laboratories should test for inducible clindamycin resistance.

In a related editorial, Dr. Robert C. Moellering Jr., from Beth Israel Deaconess Medical Center in Boston, cites these data as evidence of a rising epidemic of community-acquired MRSA capable of causing severe disease.

In the second paper, Dr. Philip L. Graham, III and colleagues from Columbia University in New York analyzed data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES), for which a national sample of individuals were interviewed. Nasal swabs for culture were obtained from 9622 subjects.

Methicillin-sensitive S. aureus was isolated from 31.6% of subjects and MRSA from 0.84%. Approximately half of the MRSA isolates appeared to be the community-acquired type. Age 65 and older, male gender, having less than a high school education, and asthma were associated with S. aureus colonization, while blacks and individuals born in Mexico were at lower risk than whites and those born in the US.

Factors associated with MRSA colonization included age 65 and older, female gender, diabetes, and residing in a long-term care facility in the previous year. Hispanics were less likely than whites to have MRSA. "Analysis of future NHANES data will be important to track national trends in S. aureus colonization," Dr. Graham and his associates conclude.

In his editorial, Dr. Moellering suggests that the study lags behind the advancing epidemic in terms of the prevalence of community-acquired MRSA. Moreover, community-acquired MRSA may be more likely to colonize sites other than the nares, so that the study by Dr. Graham's group may underestimate the prevalence of MRSA carriage.

Ann Intern Med 2006;144:309-325,368-370.

2a. Epinephrine Underused in Emergency Anaphylaxis Treatment

Paula Moyer, MA. March 7, 2006 (Miami Beach) — Patients who are seen in the emergency department (ED) for anaphylaxis seldom leave with a prescription for epinephrine, the agreed-upon first-line therapy for anaphylactic reactions, according to a team of investigators who presented their findings here at the 62nd annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI).

The presentation of these findings converge with a broadened definition of anaphylaxis, which does not necessarily involve shock, and the urgency that all patients who have such reactions be recognized as having increased risk of life-threatening reactions in the future.

"If the allergic reaction involves more than one organ system, that's anaphylaxis," said presenting investigator Carlos A. Camargo, Jr, MD, DrPH, during a press briefing. "It's important to recognize all such events as anaphylaxis and treat them quickly, and make sure that patients are able to treat themselves quickly if they have a recurrence. If you don't use epinephrine soon enough, it could be too late." Dr. Camargo is an associate professor of medicine and epidemiology at Harvard Medical School in Boston, where he is an attending emergency physician at Massachusetts General Hospital.

Dr. Camargo and coinvestigators wanted to know national trends for treating acute allergic reactions in EDs. Therefore, they used the National Hospital Ambulatory Medical Care Survey to identify a nationally representative sample of ED visits between 1993 and 2003. They identified cases with a diagnosis of acute allergic reaction, including anaphylaxis, by International Classification of Disease version 9 (ICD-9) codes. Within this time period, 11.4 million allergy-related ED visits occurred; these represented 1.0% of all ED visits, so that 1.04 million ED visits annually were allergy-related. Such visits averaged 3.8 per 1000 population in the United States annually.

Patients seen in the ED for allergic reactions were an average of 35 years old. Nearly two thirds (64%) were women, and most (78%) were white. A minority (44%) had private insurance. Although 63% of all visits received a code for an urgent or emergency situation, only 3% required hospitalization. Personnel used the "anaphylaxis" ICD-9 code in 1% of visits. Based on other multicenter ED studies, the percentage of cases of anaphylaxis among the allergic reactions was grossly underestimated, Dr. Camargo said.

In most of the visits (87%), the ED staff prescribed medications. During the study period, histamine-1 blockers were the most commonly prescribed medication, with patients receiving such medications in 62% of cases overall compared with 59% in 1993 and 64% in 2003 (a nonsignificant difference). Corticosteroids were used in 37% of cases overall, with an increase from 22% in 1993 to 45% in 2003 (P = .02). Histamine-2 blockers were used in 11% of visits overall, with an increase from 7% in 1993 to 15% in 2003 (P = .01). Epinephrine was used in 11% of all cases, and inhaled beta2-agonists in 3.3% of cases. Use of these medications was stable throughout the study period.

Two experts discussed the urgency of addressing anaphylaxis more effectively in the emergency setting. "If you wait until the patient develops shock to administer epinephrine, you have missed an opportunity," said F. Estelle R. Simons, MD, during the press briefing. "You don't have to have shock to have anaphylaxis. Patients who have allergic reactions that involve more than one organ system should get epinephrine, because we can't predict who will progress to shock." Dr. Simons is professor and head of the allergy and clinical immunology in pediatrics and child health at the University of Manitoba in Winnipeg, Canada. She was also the 2005-2006 president of AAAAI.

"Emergency-room personnel are operating in a time-sensitive environment, but need to be aware of the current standards regarding the treatment of anaphylaxis," said Clifford W. Bassett, MD, in a phone interview after the presentation. "For example, they should know that patients who have had anaphylaxis are at risk of recurrence and need to be discharged with a prescription for an epinephrine autoinjector and a referral to an allergist for appropriate ongoing evaluation and treatment." Dr. Bassett is medical director of Allergy and Asthma Care of New York in New York City, where he is an allergist affiliated with The Long Island College Hospital, in Brooklyn.

AAAAI 62nd Annual Meeting: Abstract 1185. Presented March 7, 2006.

2b. Sublingual epinephrine tablet promising for anaphylaxis

March 10, 2006. By Megan Rauscher. NEW YORK (Reuters Health) - It may be possible to administer epinephrine sublingually for the emergency treatment of anaphylaxis, according to research presented this week during the annual meeting of the American Academy of Allergy, Asthma and Immunology in Miami Beach.

In a validated rabbit model, a novel, rapidly disintegrating tablet containing 40 mg epinephrine administered under the tongue resulted in plasma epinephrine concentrations similar to those achieved with 0.3 mg epinephrine administered IM in the thigh -- the currently recommended emergency treatment for anaphylaxis -- reported Dr. Keith J. Simons from the University of Manitoba in Winnipeg.

In the dose-equivalence cross-over animal study, sublingual tablets containing 0, 10, 20, and 40 mg epinephrine were retained under the tongue for 5 minutes. EpiPen (0.3 mg) was injected in the thigh. Blood was collected before dosing and at various times afterwards up to 180 minutes post-treatment.

The area under the plasma concentration versus time curves (AUC) of tablets containing 0, 10, and 20 mg epinephrine did not differ significantly from each other, but were significantly lower (p < 0.05) than the AUC after 40 mg epinephrine and after EpiPen (0.3 mg), the team notes in meeting materials. Of note, the AUC, maximum plasma concentration, and time to maximum plasma concentration were similar after 40 mg sublingual epinephrine and EpiPen (0.3 mg) IM injection.

"If this approach is successful," Dr. Simons told Reuters Health, "patients experiencing anaphylaxis in the community could slip a tablet under the tongue instead of self-injecting a dose of epinephrine into the thigh muscle." "This tablet formulation now needs to be tested in humans," he added, noting that "it may provide a non-invasive method for the emergency treatment of anaphylaxis."

3. MRI Accurately Rules out Appendicitis in Pregnant Patients

NEW YORK (Reuters Health) Mar 01 - Magnetic resonance imaging is effective in excluding the diagnosis of appendicitis in pregnant women with acute abdominal pain and in whom a normal appendix is not visualized by ultrasonography (US), a team of physicians reports. Pregnant women are prone to a number of conditions that can mimic appendicitis, including ligamentous laxity, a hemorrhagic corpus luteum cyst, and renal colic, note Dr. Ivan Pedrosa and colleagues at Beth Israel Deaconess Medical Center in Boston. While US is the preferred imaging modality in pregnancy, it often fails to visualize the appendix.

Dr. Pedrosa's team retrospectively assessed the diagnostic performance of MRI in 51 pregnant patients with suspected acute appendicitis between 1999 and 2004. According to their report in the March issue of Radiology, 48 patients underwent US, which diagnosed appendicitis in 2 cases but failed to visualize the appendix in 46 cases. The physicians administered oral contrast media to the patients and obtained half-Fourier single-shot fast spin-echo images in the transverse, coronal, and sagittal planes through the pelvis and lower abdomen. A positive diagnosis of appendicitis was based on an appendix > 7 mm in diameter with high intensity fluid filling the lumen on T2 weighted images or periappendiceal fat stranding or the detection of an abscess.

Four patients had appendicitis and 47 did not, including three false-positives. Two other patients required surgery, one for an ectopic pregnancy and one for ovarian torsion. Among the 47 patients without appendicitis, MRI visualized the appendix in 39.

Based on the prevalence of acute appendicitis during pregnancy at their hospital, the authors estimate a sensitivity of 100%, specificity of 93.6%, prevalence-adjusted negative predictive value of 100% and prevalence-adjusted positive predictive value of 1.4%.

"The 100% negative predictive value is of great merit, providing an effective means for ruling out a surgical diagnosis in this patient population with a low prevalence of the disorder," Dr. Pedrosa's group maintains.

Radiology 2006;238:891-899.

4. Wine buyers buy healthier food than beer buyers

People who buy—and presumably drink—wine make more purchases of healthy food items than people who buy beer. In a cross sectional study, Johansen and colleagues (BMJ 2006;332:519-522) analysed data from 3.5 million transactions in 98 supermarkets in Denmark and found that customers who bought wine were more likely to buy "Mediterranean" food items (fruit or vegetables, poultry, cooking oil, and low fat products) than people who bought beer, and beer buyers tended to buy more "traditional" food items (ready cooked dishes, sausages, and soft drinks) than those who bought wine.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/332/7540/519

5. Coagulation May Be Activated by Prolonged Air Travel

Web MD. March 14, 2006 — Coagulation factors are activated more during prolonged air travel than in other immobilizing situations, according to the results of a crossover study reported in the March 11 issue of The Lancet. The editorialist recommends appropriate prophylaxis for deep vein thrombosis.

"Activation of coagulation occurs in some individuals after an 8-hour flight, indicating an additional mechanism to immobilization underlying air travel related thrombosis," senior author Frits Rosendaal, MD, from Leiden University Medical Centre in the Netherlands, said in a news release.

To separate the effect of air travel on the coagulation system from those of immobilization and circadian rhythm, the investigators measured markers of activation of coagulation and fibrinolysis in 71 healthy volunteers (15 men, 56 women) before, during, and after an 8-hour flight, and in 2 control exposure situations (8-hour movie marathon and daily life). Of the 71 participants, 30 had no specific risk factors, 11 had the factor V Leiden mutation, 15 took oral contraceptives but did not have the Leiden mutation, and 15 took oral contraceptives and had the Leiden mutation.

Median concentrations of thrombin-antithrombin (TAT) complex increased by 30.1% after the flight (95% confidence interval [CI], 11.2 – 63.2), but decreased by 2.1% (95% CI, -11.2 to 14) after the movie and by 7.9% (95% CI, -16.2 to -1.2) after the daily life situation. Increase in TAT levels was especially marked in 11 (17%) of 66 participants after air travel, in 2 (3%) of 68 during the movie marathon, and in 1 (1%) of 70 in daily life. These increases were most apparent in participants with the factor V Leiden mutation who used oral contraceptives. After the flight, 4 (6.3%) of 63 volunteers had a high response in all variables (prothrombin fragment 1 and 2, TAT, and D-dimer), but none of the participants had this response after either of the control situations.

"Our findings indicate that flight-associated factors — e.g., hypobaric hypoxia — lead to increased thrombin generation after air travel, especially in individuals with the factor V Leiden mutation who also took oral contraceptives," the authors write.

Study limitations include lack of randomization of the order of the 3 exposure situations, lack of blinding of the volunteers, blood drawing more difficult than during a routine blood draw in the clinic, and possible artifacts due to preanalytic activation of coagulation.

The UK Government and the European Commission sponsored this study. The authors have disclosed no relevant financial relationships.

In an accompanying editorial, Hans Stricker, MD, from Ospedale La Carità in Locarno, Switzerland, discusses measures to help prevent potentially fatal thromboembolism during flights. These include intermittent calf contraction and avoiding excessive sedation due to alcohol or sedative drugs.

"We do not favor an indiscriminate use of prophylactic heparin because the incidence of mostly asymptomatic and distal deep vein thrombosis is estimated to be less than 4% after long-haul flights and fatal pulmonary embolism is rare, with an estimated death rate of 1 per 2 million passengers of international flights terminating in Australia," Dr. Stricker writes. "Thus medical prevention should be limited to persons at risk, such as those with a history of VTE [venous thromboembolism], active cancer, or recent major surgery or minor surgery of the lower extremities.

The study by Schreijer and colleagues shows us that women on oral contraception and individuals with a mutation of factor V should be offered the possibility of extended prophylactic measures, such as low-molecular-weight heparin or compressive stockings."

Dr. Stricker has disclosed no relevant financial relationships.

Lancet. 2006;367:792-794, 832-838.

6. “Just Not Right” is what the Parents Tell You

An ED pediatric neuro case from the Journal of Pediatric Health Care

History of Present Illness: S.T. is an 11-year-old girl with a history of cerebral palsy and congenital glaucoma who presents with acute neurologic changes. S.T. was in her usual state of health until 3 days prior to admission, after the family went to the state fair for several hours. Upon returning home from the fair, S.T.'s grandmother noted that S.T. had a low-grade fever of 39.1° Celsius (taken orally) and that she was more sleepy than usual. The next morning, S.T. was noted to have 3 small emesis and decreased oral intake.

One day prior to admission, she continued to sleep a lot, and at times she was difficult to arouse. The morning of admission, she appeared to be confused when she got up in the morning and was very weak. Within a few hours, she had to be carried to the bathroom because of weakness and complained that her neck was sore when she was being carried. Her grandmother put her in the car and drove her to the emergency department. Upon arrival at the hospital, her grandmother noted that S.T. did not move her right side as much as her left side.

What’s the rest of the assessment and treatment? Go to: http://www.medscape.com/viewarticle/521914_1

7. Ketosis-Prone Type 2 Diabetes Mellitus

Guillermo E. Umpierrez, Dawn Smiley, and Abbas E. Kitabchi. Ann Intern Med. 7 March 2006 Volume 144 Issue 5 Pages 350-357

Several investigators have reported that more than half of African-American persons with new diagnoses of diabetic ketoacidosis have clinical, metabolic, and immunologic features of type 2 diabetes during follow-up. These patients are usually obese, have a strong family history of diabetes, have a low prevalence of autoimmune markers, and lack a genetic association with HLA.

Their initial presentation is acute, with a few days to weeks of polyuria, polydipsia, and weight loss and lack of a precipitating cause of metabolic decompensation. At presentation, they have markedly impaired insulin secretion and insulin action, but intensified diabetic management results in significant improvement in ß-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within a few months of follow-up. On discontinuation of insulin therapy, the period of near-normoglycemic remission may last for a few months to several years.

The absence of autoimmune markers and the presence of measurable insulin secretion have proven useful in predicting near-normoglycemic remission and long-term insulin dependence in adult patients with a history of diabetic ketoacidosis. This clinical presentation is commonly reported in African and African-American persons but is also observed in Hispanic persons and those from other minority ethnic groups. The underlying mechanisms for ß-cell dysfunction in ketosis-prone type 2 diabetes are not known; however, preliminary evidence suggests an increased susceptibility to glucose desensitization.

8. Coffee Intake, Slow Caffeine Metabolism May Increase Risk for Nonfatal MI

News Author: Laurie Barclay, MD. March 7, 2006 — Individuals with a CYP1A2*1F allele (*1F allele) linked to slow caffeine metabolism are at increased risk of developing nonfatal myocardial infarction (MI) from caffeinated coffee, according to the results of a case-control study reported in the March 8 issue of JAMA.

"The association between coffee intake and risk of MI remains controversial," write Marilyn C. Cornelis, BSc, from the University of Toronto in Ontario, and colleagues. "Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A allele [*1A/*1A genotype] are 'rapid' caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are 'slow' caffeine metabolizers."

The investigators compared 2014 case subjects with a first acute nonfatal MI, and 2014 population-based control subjects living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence. Subjects were genotyped by restriction fragment–length polymorphism polymerase chain reaction, and they completed a food frequency questionnaire to evaluate caffeinated coffee intake. The primary endpoint was relative risk for nonfatal MI associated with coffee intake, calculated using unconditional logistic regression.

The slow *1F allele was present in 55% of cases (n = 1114) and in 54% of controls (n = 1082). For carriers of this allele, the multivariate adjusted odds ratios (ORs) of nonfatal MI associated with consuming less than 1, 1, 2 to 3, and 4 or more cups of coffee per day were 1.00 (reference), 0.99 (95% confidence interval [CI], 0.69 - 1.44), 1.36 (95% CI, 1.01 - 1.83), and 1.64 (95% CI, 1.14 - 2.34), respectively. For individuals with the rapid *1A/*1A genotype, corresponding ORs were 1.00, 0.75 (95% CI, 0.51 - 1.12), 0.78 (95% CI, 0.56 - 1.09), and 0.99 (95% CI, 0.66 - 1.48; P = .04 for gene x coffee interaction).

For carriers of the *1F allele younger than the median age of 59 years, the corresponding ORs were 1.00, 1.24 (95% CI, 0.71 - 2.18), 1.67 (95% CI, 1.08 - 2.60), and 2.33 (95% CI, 1.39 - 3.89), respectively, compared with 1.00, 0.48 (95% CI, 0.26 - 0.87), 0.57 (95% CI, 0.35 - 0.95), and 0.83 (95% CI, 0.46 - 1.51) for those with the *1A/*1A genotype.

"Intake of coffee was associated with an increased risk of nonfatal MI only among individuals with slow caffeine metabolism, suggesting that caffeine plays a role in this association," the authors write.

Study limitations include possible recall bias, and inability to rule out the possibility that the observed interaction may affect survival after an acute MI. The Canadian Institutes of Health Research and the National Institutes of Health supported this study. The authors have disclosed no relevant financial relationships.

JAMA. 2006;295:1135-1141.

9. High-Intensity Statin Therapy May Help Regress Atherosclerosis Burden

Web MD. Laurie Barclay, MD. March 14, 2006 — Rosuvastatin, 40 mg, can regress the atherosclerosis burden, according to the results of a prospective, open-label study published in the March 13 JAMA Express issue of JAMA. However, the editorialists temper the enthusiasm for these findings.

"Although statins rank among the most extensively studied therapies in contemporary medicine, the optimal target levels for low-density lipoprotein cholesterol (LDL-C) remain controversial," write Steven E. Nissen, MD, from Cleveland Clinic Foundation in Ohio, and colleagues from the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) Investigators. "Prior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression."

To determine whether very intensive statin therapy could regress coronary atherosclerosis measured by IVUS imaging, the ASTEROID study was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to evaluate, in a blinded fashion, coronary atheroma burden at baseline and after 24 months of treatment. Of 507 patients who had a baseline IVUS examination and received at least 1 dose of study drug between November 2002 and October 2003, 349 patients had evaluable serial IVUS examinations after 24 months. All patients received intensive statin therapy with rosuvastatin, 40 mg/day. Two prespecified, primary outcome measures for efficacy were change in PAV and change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary prespecified efficacy outcome was change in normalized total atheroma volume for the entire artery.
Mean baseline LDL-C level decreased from 130.4 ± 34.3 mg/dL at baseline to 60.8 ± 20.0 mg/dL (mean reduction, 53.2%; P <.001). Mean high-density lipoprotein cholesterol (HDL-C) level increased from 43.1 ± 11.1 to 49.0 ± 12.6 mg/dL (mean increase, 14.7%; P < .001).

For the entire vessel, the mean change in PAV was -0.98% ± 3.15% (median, -0.79%; 97.5% confidence interval [CI], -1.21% to -0.53%; P < .001 vs baseline). Mean change in atheroma volume in the most diseased 10-mm subsegment was -6.1 ± 10.1 mm3 (median, -5.6 mm3; 97.5% CI, -6.8 to -4.0 mm3; P < .001 vs baseline). Median reduction in total atheroma volume was 6.8% (mean reduction, -14.7 ± 25.7 mm3; median, -12.5 mm3; 95% CI, -15.1 to -10.5 mm3; P < .001 vs baseline). Adverse events were infrequent and similar to those reported in other statin trials.

"Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden," the authors write. "Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome."

Study limitations include lack of a control group receiving either placebo or a less active statin; withdrawal of 22 patients for ischemic events creating a potential source of bias; and inability to determine the degree to which regression documented by IVUS will translate into a reduction in morbidity and mortality.

AstraZeneca, the maker of rosuvastatin, funded this study. Several authors have disclosed relevant financial relationships with AstraZeneca, Eli Lilly, Pfizer, Takeda, Sankyo, Sanofi-Aventis, diaDexus, GeneLogic, GlaxoSmithKline, Integrated Therapeutics, Kos, Merck, Novartis, Roche, Sanofi-Synthelabo, Schering-Plough, Bayer, and/or Reliant.

In an accompanying editorial, Roger S. Blumenthal, MD, and Navin K. Kapur, MD, from The Johns Hopkins Ciccarone Preventive Cardiology Center in Baltimore, Md, note various study limitations.

"Unfortunately, the ASTEROID study does not provide definitive information regarding the relationship of LDL-C lowering and extent of coronary atherosclerosis regression to determine if high-intensity treatment is required to achieve regression," Drs. Blumenthal and Kapur write. "While IVUS-documented atherosclerotic regression is an intriguing finding, clinicians must remember that this may not be the best measure of the treatment's effect on hard cardiovascular end points.... The results of several ongoing trials will help determine what agent or combination of pharmacologic agents is most efficacious in the long-term management of at-risk patients."

Dr. Blumenthal has disclosed receiving clinical research support and honoraria from speakers' bureau activities from Pfizer, Merck, Schering Plough, AstraZeneca, KOS, and Sanofi during the past 12 months. Dr. Kapur has disclosed no relevant financial relationships.

JAMA. 2006 Posted online March 13, 2006.

10. AMA develops measures of doctors’ performance

BMJ News: New York Janice Tanne. The American Medical Association (AMA) has agreed to government requests to develop evidence based measures of doctors’ performance in collaboration with groups representing medical specialties and the federal Centers for Medicare and Medicaid Services.
The association has convened the Physician Consortium for Performance Improvement to develop by consensus 140 evidence based measures of doctors’ performance in 34 clinical areas. The consortium includes representatives from more than 70 national medical specialty and state medical societies, the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services, which administer the Medicare health insurance programme for elderly people and the Medicaid programme for children and people with low incomes.

Medicare payments to doctors do not currently take into account the quality of care that doctors provide. The level of these payments is frozen at the moment, and Congress has delayed proposals to make cuts in each of the next eight years, expressing interest in rewarding improved performance. Arguing that consumers can shop for most things apart from state funded health care, based on price and quality, the Bush administration is promoting “pay for performance” standards for healthcare providers to publicise how well they are doing and to link their performance to Medicare payments.

The AMA says that the aim of the agreement is to develop a common set of performance measures so that doctors do not have to comply with different standards set by health insurance companies, health plans, and government agencies. So far, the consortium has developed 90 measures covering 15 conditions, including adult diabetes, asthma, chronic obstructive pulmonary disease, chronic stable coronary artery disease, community acquired bacterial pneumonia, heart failure, hypertension, major depressive disorder, osteoarthritis, prenatal testing, and preventive care and screening.

The association says that doctors’ groups will work during this year with the Medicare and Medicaid centres to develop the best method for doctors to report quality data to the centres. They will also work with the centres and with congressional committees to implement additional reforms to tackle payment and quality objectives.

Next year, each doctor would voluntarily report to the centres on between three and five quality measures. Doctors who do so “should receive an additional quality update to offset administrative costs,” the association said.

By the end of 2007, doctors’ groups are expected to have developed performance measures for most clinical services paid for by Medicare.

Some specialty groups have complained that they had not been consulted about the agreement with Congress and that they could not meet the planned schedule. Frederick Blum, the president of the American College of Emergency Physicians, said in a report, “We are concerned that the push to measure quality will become just a smoke screen to cut costs and reduce the resources devoted to health care” (Kaiser Daily Health Policy Report 21 February 2006).
Michael Maves, the executive vice president of the AMA responded that the schedule was not too ambitious, because 90 measures had already been developed and 10 were being developed. He added that Congress would have to pass legislation before a pay for performance system could be put in place and said the agreement was necessary because Congressional leaders would not continue to protect doctors from Medicare pay cuts unless there was movement toward quality improvement. (Kaiser Daily Health Policy Report 23 February 2006).

More information about the Physician Consortium for Performance Improvement is available at www.physicianconsortium.org

11. Helmets protect skiers and snowboarders

More than 3000 skiers and snowboarders were injured in eight Norwegian ski resorts during the 2002 winter season. Five hundred and seventy eight of them (18%) had head injuries severe enough to need attention from the ski patrol. A case-control study comparing this group with 2992 uninjured controls found that wearing a helmet was associated with a 60% reduction in the risk of head injury (adjusted odds ratio 0.4, 95% CI 0.30 to 0.55). Being male, young, a beginner, and a snowboarder were all associated with an increased risk of head injury, but wearing a helmet protected all subgroups to about the same degree. Odds ratios were comparable on and off the piste, and in the snowboard park.

To find out if helmets seemed safer simply because the people who wear them are more cautious and less accident prone, the researchers asked a random sample of 700 uninjured skiers and snowboarders about their attitude to risk. Those describing themselves as risk takers were significantly more likely to wear a helmet (odds ratio 1.48, 1.21 to 1.81), whatever their age or experience.

These researchers found no evidence that the weight of a helmet increases the chance of neck injury. If anything, wearing a helmet seemed to reduce the risk, although this study was too small to be conclusive.

JAMA 2006;295: 919-24.

12. Carotid Sinus Hypersensitivity in Asymptomatic Older Persons: Implications for Diagnosis of Syncope and Falls

Simon R. J. Kerr, MB, MRCP; et al. Arch Intern Med. 2006;166:515-520.

Background Carotid sinus hypersensitivity is the most commonly reported cause of falls and syncope in older persons. Recent guidelines recommend 5 to 10 seconds of carotid sinus massage in supine and upright positions with beat-to-beat monitoring. The aim of this study was to determine the prevalence of carotid sinus hypersensitivity in (1) an unselected community sample of older people and (2) a subsample with no history of syncope, dizziness, or falls using recently standardized diagnostic criteria.

Methods One thousand individuals older than 65 years were randomly sampled from a single general practice register; 272 participants underwent supine and upright carotid sinus massage with continuous heart rate and phasic blood pressure monitoring. Carotid sinus hypersensitivity was defined as asystole of 3 seconds or greater and/or a drop in systolic blood pressure of 50 mm Hg or greater.

Results Carotid sinus hypersensitivity was present in 107 individuals (39%); 24% had asystole of 3 seconds or greater during carotid sinus massage; and 16% had symptoms (including syncope) with carotid sinus hypersensitivity. Age (odds ratio, 1.05; 95% confidence interval, 1.00-1.09) and male sex (odds ratio, 1.71; 95% confidence intervals, 1.04-2.82) were the only predictors of carotid sinus hypersensitivity. In 80 previously asymptomatic individuals, carotid sinus hypersensitivity was present in 28 (35%) and accompanied by symptoms in 10. The 95th percentile for carotid sinus massage response was 7.3 seconds' asystole and a 77–mm Hg drop in systolic blood pressure.

Conclusions Carotid sinus hypersensitivity is common in older persons, even those with no history of syncope, dizziness, or falls. The finding of a hypersensitive response should not necessarily preclude further investigation for other causes of syncope.

13. Fondaparinux reduces mortality without risk of bleeding in STEMI

March 15, 2006. ATLANTA (Reuters Health) - The use of fondaparinux in patients with ST-elevation myocardial infarction (STEMI) reduces the rates of mortality and reinfarction without increasing the risk of major bleeding, according to results of the Organization for the Assessment of Strategies for Ischemic Syndromes (OASIS-6) trial. However, there seems to be little benefit for patients with STEMI who undergo angioplasty.

Fondaparinux is a synthetic pentasaccharide that inhibits factor Xa in the coagulation cascade.

Dr. Salim Yusuf, from McMaster University in Hamilton, Ontario, and his associates compared fondaparinux with usual care among 12,092 patients with STEMI treated at 447 centers in 41 countries. Patients were randomly assigned to fondaparinux 2.5 mg once daily for up to 8 days or usual care, which consisted of placebo in those for whom unfractionated heparin was not indicated or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days.

The findings were reported today at the 55th annual conference of the American College of Cardiology and were also published online in The Journal of the American Medical Association. "There was a decrease in mortality at all time points, and there was actually a tendency toward a decrease in bleeding, with no increase in intracranial hemorrhage," Dr. Yusuf told Reuters Health. "There were no safety problems."

"We saw a 20% reduction in death and recurrent MI at 9 days" in the fondaparinux group, he added. "The effect was persistent, with a 13% to 14% reduction still remaining at 180 days." The difference was particularly notable in patients deemed to be at high risk. Fondaparinux was also associated with a trend toward fewer patients developing heart failure, cardiogenic shock and severe hemorrhage.

"The benefits observed with fondaparinux may be partly due to enhanced efficacy compared with unfractionated heparin and partly due to the more prolonged duration of antithrombotic therapy," the authors suggest.

A total of 2,231 patients in the placebo or unfractionated heparin group and 2,228 patients in the fondaparinux group underwent percutaneous coronary intervention. Fondaparinux did not appear to alter outcomes in any of these patients. "The simplicity of this regimen, lack of monitoring, its safety and efficacy in the full spectrum of acute coronary syndrome facilitates the use of fondaparinux in a range of settings," the authors indicate.

"There was a superiority with fondaparinux in every way you look at it," Dr. Yusuf concluded.

In a JAMA editorial, Dr. Robert M. Califf, from Duke Clinical Research Institute in Durham, North Carolina, states that "the results of the OASIS-6 trial are certain to lead to an outburst of competitive pronouncements by companies and by leaders in the clinical community about the question of which regimen is truly best."

He suggests that as electronic health records and professional databases become available, "an unbiased assessment of multiple medical permutations" will become possible.

JAMA 2006;295.

14. Clopidogrel added to aspirin does not reduce cardiac events

March 14, 2006. ATLANTA (Reuters Health) - Adding clopidogrel (Plavix) to a daily dose of aspirin does not lower the risk of death, myocardial infarction or stroke in high-risk patients, researchers reported at the 55th annual meeting of the American College of Cardiology on Sunday.

"The overall findings were negative, but a benefit was seen in patients with established cardiovascular disease," said lead investigator Dr. Deepak Bhatt, of the Cleveland Clinic Cardiovascular Coordinating Center in Ohio.

A study of more than 15,000 patients showed that combining clopidogrel with aspirin may do more harm than good for patients at risk of heart disease, but it may help those who have already had an MI or stroke.

The results confirm aspirin as "the gold standard" for treating patients at risk of heart disease, according to Dr. Charles Hennekens, of the University of Miami School of Medicine. The study findings "redouble the message that aspirin has the best benefit-to-risk and the best benefit-to-cost ratios of any heart drug out there," he added.

The study included patients who had a previous MI, stroke, or impaired circulation (stable heart disease group), along with patients with cardiovascular risk factors, such as diabetes, hypertension or hyperlipidemia.

At 28-month follow-up, the researchers found a 7.3% risk of mortality, MI or stroke in patients assigned to placebo plus aspirin, compared with 6.8% for those patients on clopidogrel plus aspirin -- a nonsignificant difference. The addition of clopidogrel did reduce hospitalization rate from 17.9% to 16.7%.

When the analysis was limited to the 12,153 patients with established heart disease, clopidogrel reduced the combined risk of mortality, MI or stroke from 7.9% to 6.9%.

"There is no reason to use the combination therapy for primary prevention, whereas it might be useful in patients who have already had a heart attack or stroke," Dr. Bhatt said.

The trial showed no significant increase in severe bleeding in patients with cardiovascular disease. But the addition of clopidogrel may have increased the risk of severe bleeding and death in patients with risk factors for heart disease, the researchers said.

"Aspirin is tough to beat, but it too has bleeding risk," Dr. Bhatt added.

15. Experienced emergency medicine physicians cannot safely inflate or estimate endotracheal tube cuff pressure using standard techniques

Robert J. Hoffman, MD, et al. Amer J Emerg Med 2006;24: 139-143.

Objective
Tracheal necrosis, stenosis, and rupture may result from overinflated endotracheal tube cuffs (ETTcs). We sought to determine the ability of faculty emergency medicine (EM) physicians to safely inflate ETTc as well as to estimate pressure of previously inflated ETTc.

Methods
Using a previously tested tracheal simulation model, we assessed EM physician inflation of ETTc pilot balloons. Participants also palpated the pilot balloon of 9 ETTc inflated to pressures ranging from extremely low to extremely high in a random order and reported their estimate of pressure.

Results
We sampled 41 faculty EM physicians from 5 EM residency programs. Using palpation, participants were only 22% sensitive detecting overinflated ETTc. The average ETTc pressure produced by inflation was more than 93 cm H2O (normal, 15-25 cm H2O).

Conclusions
Participants were unable to inflate ETTc to safe pressures or estimate pressure of ETTc by palpation. The risk posed by overinflation of an ETTc coupled with the availability of inexpensive, easy-to-use devices for measurement of ETTc pressure warrants consideration of use of such devices in the ED. Endotracheal intubation with cuffed endotracheal tubes could easily be accompanied by objective measurement of the ETTc pressure. In medical specialties that involve frequent contact with endotracheally intubated patients, such as anesthesiology and respiratory therapy, use of such instruments to measure pressure in ETTcs is often routine, standard practice.

We believe that use of devices to prevent overinflation of ETTc, such as the use of pulse oximeters or capnometers, is a practice of anesthesiologists and intensivists that may be appropriate in the EM setting. Emergency medicine physicians should consider measuring the ETTc pressure in their endotracheally intubated patients.

16. Antiemetics in the ED: a randomized controlled trial comparing 3 common agents

Darren Braude, MD, MPHa, et al. Amer J Emerg Med 2006;24: 177-182.

Abstract
We sought to compare the efficacy of 3 intravenous antiemetic medications in ED patients complaining of moderate to severe nausea. This randomized, placebo-controlled, double-blind trial compares 1.25 mg droperidol, 10 mg metoclopramide, 10 mg prochlorperazine, and saline placebo.

Adult ED patients complaining of nausea were eligible. Nausea was measured on a 100-mm visual analog scale at 0 and 30 minutes after treatment. A convenience sample of 100 patients was enrolled; 97 had complete data available for analysis. Of these, 22 patients received droperidol, 25 received metoclopramide, 24 received prochlorperazine, and 26 received placebo.

Droperidol (−54.5 mm) was significantly better than metoclopramide (−40.2 mm) or prochlorperazine (−40.5 mm) at reducing nausea at 30 minutes (P = .04). There were no significant differences in rescue medication or patient satisfaction; however, droperidol had significantly higher akathisia (71.4% vs 23.5%) at 24-hour follow-up.

When administered intravenously to adult patients with moderate to severe nausea, droperidol was more effective than metoclopramide or prochlorperazine but caused more extrapyramidal symptoms. Metoclopramide and prochlorperazine were not more effective than saline placebo. All patients improved over time and possibly with intravenous hydration.

17. Actaminophen causes most liver failure in UK and US

New York. Janice Tanne. BMJ 2006;332:628 (18 March)

Unintentional overdose with the painkiller paracetamol (acetaminophen) is the most common cause of acute liver failure in United Kingdom, a study has found (Gastroenterology 2006;130:687-94). Acetaminophen-protein adducts are specific biomarkers of drug toxicity and were detected in the serum of all patients with acute liver failure due to acetaminophen and in no patients with failure due to other causes, providing a useful diagnostic test.

Paracetamol’s toxicity is also the single biggest cause of acute liver failure in the United States. Cases have been rising for six years, according to a study published in December (Hepatology 2005;42:1364-72). By 2003, the drug accounted for just over half the cases of acute liver failure, and about half of these cases were the result of unintentional overdose.

Package recommendations tell consumers not to exceed 4 grams a day. Overdose is more likely to occur with acute use. Those most likely to have acetaminophen induced liver failure are depressed, in chronic pain, misuse alcohol or narcotics, or take several preparations at the same time. There are 50 000 to 60 000 overdoses each year in the United States, but only a small number of people develop liver failure.

18. High Humidity May Not Be Indicated for Croup

News Author: Laurie Barclay, MD. March 17, 2006 — High humidity (100%) does not improve symptoms of croup any better than 40% humidity or humidity by blow-by technique, according to the results of a randomized study reported in the March 15 issue of JAMA.

"Children with croup are often treated with humidity even though this is not scientifically based, consumes time, and can be harmful," write Dennis Scolnik, MB, ChB, from The Hospital for Sick Children and the University of Toronto in Ontario, and colleagues. "Although humidity using the traditional blow-by technique is similar to room air and no water droplets reach the nasopharynx, particles sized for laryngeal deposition (5-10 μm) could be beneficial."

Between 2001 and 2004 in a tertiary care pediatric emergency department, 140 previously healthy children aged 3 months to 10 years with Westley croup score of 2 or higher (scoring range, 0-17) were randomized into 3 treatment groups. These groups received 30-minute administration of humidity using traditional blow-by technique (commonly used placebo, n = 48), controlled delivery of 40% humidity (optimally delivered placebo, n = 46), or 100% humidity (n = 46) with water particles of mass median diameter of 6.21 μm. Twenty-one families refused participation. The primary end point was a priori defined change in the Westley croup score from baseline to 30 and 60 minutes. The 3 groups were comparable before treatment.

At 30 minutes, the difference in the improvement in the croup score was 0.03 between the blow-by and low-humidity groups (95% confidence interval [CI], −0.72 to 0.66), 0.16 between low- and high-humidity groups, (95% CI, −0.86 to 0.53), and 0.19 between blow-by and high-humidity groups (95% CI, −0.87 to 0.49).

At 60 minutes, the findings were similar. There were no significant differences between groups in pulse and respiratory rates, oxygen saturation changes, proportions of excellent responders, proportions with croup score of 0 at study conclusion, and proportions receiving dexamethasone, epinephrine, or requiring additional medical care or hospitalization.

Study limitations include single-blinded design, lack of generalizability to children with either mild or more severe croup or to children treated at home, and possible inclusion of a few patients with disease of different mechanism or etiology.

"One hundred percent humidity with particles specifically sized to deposit in the larynx failed to result in greater improvement than 40% humidity or humidity by blow-by technique," the authors write. "This study does not support the use of humidity for moderate croup for patients treated in the emergency department." The Physicians' Services Incorporated Foundation of Ontario funded this study. The authors report no financial conflicts of interest.

JAMA. 2006;295:1274-1280