Monday, July 03, 2006

Lit Bits: July 3, 2006

From the recent medical literature...

1. Increased Cardiovascular Risk Not Seen in Young Diabetics

NEW YORK (Reuters Health) Jun 29 - In general, people with diabetes have about the same risk of cardiovascular disease (CVD) as that of people who are 15 years older without diabetes, Canadian investigators report. However, until about age 40, diabetics do not seem to be at high risk of CVD.

Clinicians often believe that all adults with diabetes have a higher risk of CVD, regardless of age, Dr. Gillian L. Booth and associates note in the July 1st issue of The Lancet. Some guidelines suggest that all adults with diabetes be treated the same -- with lipid-lowering therapy, aspirin, and angiotensin-converting-enzyme inhibitors -- to reduce their CVD risk.

To clarify the relation between age and CVD risk in diabetics, Dr. Booth, an endocrinologist at St. Michael's Hospital in Toronto, and associates conducted a population-based cohort study using Ontario resident databases covering all individuals age 20 years and older in April of 1994.

On that date, 379,003 were identified as diabetics and 9,018,082 were nondiabetic. During follow-up until March 2000, acute MI, stroke, revascularization, or death had occurred in 573,515 individuals, including 104,702 (18%) who had diabetes.

As noted, diabetics had about the same risk of CVD as non-diabetics who were 15 years older. Age-adjusted rates of acute MI and all-cause mortality were about two to four times higher in subjects with diabetes than in those with no diabetes or recent acute MI.

The analysis suggests that the transition from moderate to high risk of CVD takes place at about age 41 for men with diabetes and 48 for women with the disease.

Dr. Booth's group suggests that for middle-aged and older people with diabetes, "aggressive and risk-reduction strategies are warranted." In contrast, they write, "our data support present guidelines recommending that risk-reduction efforts be individualized in patients with diabetes who are less than 40 years of age."

Further study, they add, "to develop appropriate algorithms for CVD risk in young adults with type 1 and type 2 diabetes is critically important to guide therapeutic decision in these individuals."

Lancet 2006;368:29-36.

2. Amino-Terminal Pro-BNP for the Diagnosis of Acute HF in Patients With Previous COPD

Roderick H. Tung, MD, et al. Ann Emerg Med 2006;48: 66-74.

Study objective
We evaluate results from amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with or without those of clinical judgment for the evaluation of dyspneic patients with previous chronic obstructive pulmonary disease or asthma.

As a secondary analysis of previously collected observational data from a convenience sample of 599 breathless patients, 216 patients with previous chronic obstructive pulmonary disease or asthma who presented to the emergency department were analyzed according to results of NT-proBNP, clinical impression, and their final diagnosis. Test performance of NT-proBNP in these patients with chronic obstructive pulmonary disease or asthma was examined for the group as a whole, as well as in patients with and without previous heart failure. NT-proBNP results were compared to clinician-estimated likelihood for heart failure using receiver operating curves and as a function of NT-proBNP plus clinical evaluation. The final diagnosis was determined by 2 independent cardiologists blinded to NT-proBNP using all available data from the 60-day follow-up period.

Overall, 55 patients (25%) had acute heart failure; the median value of NT-proBNP was higher in these patients compared with those without acute heart failure (2,238 vs 178 pg/mL); use of cut points of 450 pg/mL for patients younger than 50 years and 900 pg/mL for patients 50 years or older yielded a sensitivity of 87% (95% confidence interval [CI] 72% to 93%) and a specificity of 84% (95% CI 76% to 88%). In patients without previous heart failure (n=164), median NT-proBNP levels were also higher in patients with heart failure of new onset compared with those with chronic obstructive pulmonary disease or asthma exacerbation (1561 versus 168 pg/mL). High clinical suspicion for acute heart failure (probability >80%) detected only 23% of patients with new-onset heart failure, whereas 82% of these patients had elevated NT-proBNP levels.

In patients who had both previous acute heart failure and chronic obstructive pulmonary disease or asthma (n=52), median NT-proBNP levels were significantly higher in those with acute heart failure (4,435 pg/mL) than patients with chronic obstructive pulmonary disease or asthma exacerbation (536 pg/mL). In patients with acute-on-chronic heart failure, NT-proBNP levels were elevated in 91%, whereas clinical impression considered only 39% of cases as high likelihood for acute heart failure.

NT-proBNP may be a useful adjunct to standard clinical evaluation of dyspneic patients with previous obstructive airway disease.

3. Anti-inflammatory Drugs Increase Mortality After Previous AMI

News Author: Laurie Barclay, MD. June 20, 2006 ­ Selective cyclooxygenase-2 (COX-2) inhibitors in normal dosages and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in high dosages increase mortality after acute myocardial infarction (MI), according to the results of a study reported in the June 19 Rapid Access issue of Circulation.

"The selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown," write Gunnar H. Gislason, MD, from Gentofte University Hospital in Hellerup, Denmark, and colleagues. "We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI."

Using nationwide Danish administrative registers, the investigators identified all patients with first-time MI between 1995 and 2002, as well as all prescription claims for NSAIDs after discharge. They determined risk for death and rehospitalization for MI associated with the use of selective COX-2 inhibitors and nonselective NSAIDs, using multivariable proportional hazards models and case-crossover analysis.

Of 58,432 patients who were discharged alive and included in the study, 9773 were rehospitalized for MI, and 16,573 died. In total, 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. The hazard ratios (95% confidence intervals) for death were 2.80 (2.41 - 3.25) for any use of rofecoxib, 2.57 (2.15 - 3.08) for celecoxib, 1.50 (1.36 - 1.67) for ibuprofen, 2.40 (2.09 - 2.80) for diclofenac, and 1.29 (1.16 - 1.43) for other NSAIDs. For all of the drugs, there were dose-related increases in risk for death. There were also trends for increased risk for rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs.

"Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients," the authors write. "The dose relationship found in this study is overall in agreement with previous studies."

"Post-MI patients with pain conditions relieved by these drugs should discuss carefully with their doctor the balance between benefits and risk of treatment," the authors conclude. "Because studies in this field have revealed major safety concerns where none were thought present, the cardiovascular safety of not only the selective COX-2 inhibitors but of all NSAIDs needs to be addressed further."

In an accompanying perspective, Judith S. Hochman, MA, MD, and Nirav R. Shah, MD, MPH, from the New York University School of Medicine in New York, note that there was no information provided on use of naproxen, which has generated great controversy because of conflicting evidence regarding excess risk vs protection from cardiovascular events.

"High dose aspirin (up to 1500 mg/day) is associated with protection from cardiovascular events but also with gastrointestinal toxicity," Drs. Hochman and Shah write. "Used with proton pump inhibitors it is probably the safest choice for post-MI patients. When NSAIDs are used for patients at risk for or with established cardiovascular disease, they should be used at the lowest effective dose, for the shortest necessary duration with concomitant low dose aspirin and proton pump inhibitors as indicated."

Drs. Hochman and Shah have disclosed no relevant financial relationships.

Circulation. Posted online June 19, 2006.

4. Evolving Role of Vasopressin in the Treatment of Cardiac Arrest

Todd A. Miano, Pharm.D.; Michael A. Crouch, Pharm.D.

Sudden cardiac arrest is a major public heath problem, affecting more than 450,000 individuals annually. Response time and the initiation of cardiopulmonary resuscitation (CPR) remain the most important factors determining successful revival. During resuscitation, sympathomimetics are given to enhance cerebral and coronary perfusion pressures in an attempt to achieve restoration of spontaneous circulation. Epinephrine has been the preferred vasopressor since the inception of advanced cardiac life support, although the lack of definitive evidence regarding its effectiveness has created much controversy surrounding its use, including the optimum dosage.

Vasopressin is an alternative vasopressor that, when given at high doses, causes vasoconstriction by directly stimulating smooth muscle V1 receptors. The 2000 American Heart Association (AHA) guidelines commented that vasopressin is a reasonable first-line vasopressor in patients with ventricular fibrillation or pulseless ventricular tachycardia. Since release of those guidelines, additional human studies support an expanded role for vasopressin, whereas other studies cast doubt regarding its efficacy compared with epinephrine. The AHA recently released revised guidelines for CPR and emergency cardiovascular care. The consensus was that vasopressors should remain a part of pulseless sudden cardiac arrest management, with epinephrine 1 mg every 3-5 minutes being the recommended adrenergic of choice. In these revised guidelines, the role of vasopressin expanded beyond previous recommendations, despite the recommendation being downgraded to class indeterminate. The guidelines comment that one dose of vasopressin 40 U may replace the first or second dose of epinephrine in all pulseless sudden cardiac arrest scenarios, including asystole and pulseless electrical activity.

A consistent theme with all vasopressors in sudden cardiac arrest is that additional studies are necessary to clearly document greater efficacy compared with no treatment. Further evaluation is warranted to better assess the role of vasopressin in asystolic sudden cardiac arrest, as well as its use with epinephrine, and to determine its optimal timing of administration and potential synergistic effects.

For more, see

5. Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?
Franz H. Messerli, et al. Ann Intern Med 2006;144: 884-893.

Because blood flow in the coronary arteries takes place largely during diastole, an increase in risk for coronary artery disease with excessive lowering of diastolic blood pressure is plausible, although unproven. In this secondary analysis of data from a large randomized trial of 2 antihypertensive drugs in patients with coronary artery disease, the risk for the primary outcome, all-cause death, and myocardial infarction increased with low diastolic blood pressure. This relationship did not occur for stroke.

Editors' Notes

Context: Experts debate the consequences of "excessive" lowering of diastolic pressure in patients with hypertension and coronary artery disease.

Contribution: This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease. The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infarction, with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg, that is, the lower the diastolic pressure, the higher the risk.

Cautions: The study examined associations between blood pressure and outcomes; it could not prove that the antihypertensive therapy that lowered diastolic pressure "too much" caused the adverse outcomes.

6. What Is the Preferred First-Line Therapy for Status Epilepticus?

Lang ES et al. Ann Emerg Med 2006;48:98-100.

…Main results
Eleven studies with analyzable data containing 2,017 participants were included in the review. Five of the 11 trials studied patients with premonitory status, 1 each with established and refractory status, 2 with mixed status, and 2 with the stage poorly defined. Seven of these studies included only adult patients, 4 only children. Fourteen different therapeutic comparisons were made in these trials, but only 3 of these were replicated in multiple studies to permit meta-analysis.

All comparisons of the intravenously administered benzodiazepines diazepam and lorazepam against placebo significantly favored the intervention arms. The comparisons of lorazepam intravenously versus phenytoin intravenously, lorazepam intravenously versus diazepam intravenously, and an examination of diazepam intrarectal gel efficacy are of particular interest and will be presented in detail.

Lorazepam intravenously was superior to phenytoin intravenously in a single study with 198 participants, with lower risk for noncessation of seizures (relative risk [RR] 0.62; 95% confidence interval [CI] 0.45 to 0.86). According to 3 trials with 289 participants, lorazepam intravenously was more effective than diazepam intravenously for decreasing the risk of noncessation of seizures (RR 0.64; 95% CI 0.45 to 0.90) and continuation of status epilepticus requiring a different drug or general anesthesia (RR 0.63; 95% CI 0.45 to 0.88); however, lorazepam did not significantly reduce the requirement for ventilatory support (RR 0.73; 95% CI 0.36 to 1.49) or the number of adverse effects (risk difference [RD] 0.03; 95% CI 0.10 to 0.03).

Furthermore, there was no statistically significant difference in deaths between the groups according to data available from 2 of the studies with 203 patients (RD 0.02; 95% CI 0.04 to 0.08). Diazepam intrarectal gel was superior to placebo gel according to 2 studies with a total of 165 participants, demonstrating lower risk for noncessation of seizures (RR 0.43; 95% CI 0.30 to 0.62).

The authors conclude that lorazepam is superior to either diazepam or phenytoin for cessation of seizures, and compared to diazepam carries a lower risk of continuation of status epilepticus requiring the use of a different drug or general anesthesia. Lorazepam and diazepam are both better than placebo for the same outcomes, and diazepam intrarectal gel is useful in premonitory status.

7. A Pilot Study of 1 Versus 3 Days of Dexamethasone as Add-On Therapy in Children With Streptococcal Pharyngitis

Mary-Lynn Niland, MD; Bema K. Bonsu, MBChB; Kathryn E. Nuss, MD; Deborah G. Goodman, RN

Background: Studies in adults, but not in children, have shown a beneficial effect of one dose of steroid on the severity and duration of throat pain in acute pharyngitis. The effectiveness of longer steroid treatment has not been evaluated in children.

Methods: We performed a randomized, double-blind, 3-arm, placebo-controlled trial to estimate the effectiveness of one dose versus 3 daily doses of oral dexamethasone in the treatment of 4- to 21-year-old patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. Participants used the Wong-Baker FACES scale to rate their symptoms at enrollment and twice daily for 5 days. Patient-completed diaries and telephone interviews provided follow-up data. Primary end points-severity of throat pain, improvement in general condition and improvement in activity level-were evaluated by survival analysis.

Results: Ninety patients were enrolled. For each end point, we rejected the null hypothesis of a common survival experience for the 3 study arms. With the exception of 2 days for throat pain in participants receiving one dose of dexamethasone, the median time to improvement for all end points was 1 day for both arms of dexamethasone and 2 days for placebo. There was no difference between study arms in return to a clinical setting for symptoms related to GABHS pharyngitis or absenteeism from work/school. No patient experienced complications related to GABHS pharyngitis in the 30 days after enrollment.

Conclusions: In this pilot study, children with GABHS pharyngitis who receive dexamethasone as add-on therapy have a more rapid improvement in general condition and level of activity and, for those receiving 3 daily doses of dexamethasone, in resolution of throat pain.

8. Most Valuable Clinical Preventive Services Identified

News Author: Laurie Barclay, MD. May 23, 2006 ­ A study posted in the Advance Publications issue of the American Journal of Preventive Medicine identifies the most valuable clinical preventive services that can be offered in medical practice. Services that decision makers should emphasize include discussing aspirin use with high-risk adults, immunizing children, and tobacco-use screening and brief intervention.

"Decision makers at multiple levels need information about which clinical preventive services matter the most so that they can prioritize their actions," write Michael V. Maciosek, PhD, from the HealthPartners Research Foundation in Minneapolis, Minn, and colleagues from The National Commission on Prevention Priorities (NCPP). "This study was designed to produce comparable estimates of relative health impact and cost effectiveness for services considered effective by the U.S. Preventive Services Task Force and Advisory Committee on Immunization Practices [ACIP]."

Using new preventive service recommendations up to December 2004, improved methods, and more complete and recent data and evidence, the NCPP updated the 2001 ranking of clinical preventive services. Each service received a total score ranging from 2 to 10, consisting of 1 to 5 points for clinically preventable burden and cost-effectiveness. By comparing the ranking of these services with what is known of current delivery rates nationally, the NCPP established priorities for improving delivery rates.

The 3 highest-ranking services are discussing aspirin use with high-risk adults, immunizing children, and tobacco-use screening and brief intervention, each receiving a total score of 10. High-ranking services (scores of 6 and above) with current low utilization rates (around 50% or lower) are tobacco-use screening and brief intervention, screening adults aged 50 years and older for colorectal cancer, immunizing adults aged 65 years and older against pneumococcal disease, and screening young women for Chlamydia.

"This study identifies the most valuable clinical preventive services that can be offered in medical practice and should help decision-makers select which services to emphasize," the authors write. "Readers should understand that all services in the ranking are recommended and ideally should be provided to all people in the target population."

Limitations include other evidence-based services that were not included in the ranking; a number of potentially important services lacking sufficient evidence for the US Preventive Services Task Force (USPSTF) to make a recommendation; inability to incorporate all factors important to decision making into the ranking; inability to determine if priorities for racial and ethnic subpopulations would be different; and use of a societal perspective to estimate cost effectiveness, which may not be ideal for all decision makers.

"The goal of this study was to summarize the best available data on clinical preventive services to assist all types of decision makers in choosing where to focus their prevention efforts," the authors conclude. "Those who are currently less engaged in prevention also may be motivated by these findings to take the first steps necessary to improve the delivery of those clinical preventive services that will lead to the largest improvements in population health and most efficient allocation of resources."

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality supported this study. One of the authors has disclosed receiving research funds from Sanofi-Pasteur, GSK pharmaceuticals, and TAP pharmaceuticals to conduct safety research.

Am J Prevent Med. Posted online May 2006.

9. New Agents Linked to Medication Overuse Headache

NEW YORK (Reuters Health) Jun 21 - Medication overuse headache (MOH) "remains an important problem," but the drugs mostly likely associated with the overuse have changed dramatically in the past 15 years, according to a report in the May issue of the journal Headache.

Triptans are now an important cause of probable MOH, although these drugs cause headaches less frequently than do other medications, report Dr. Chelsea A. Meskunas from Princeton University in New Jersey and colleagues. "NSAIDs are more important now than they were in the past; ergotamine overuse is very rare."

The findings are based on a review of the charts of 1200 acute headache patients seen at one headache center during the years of 2005, 2000, 1995, and 1990. To gauge trends in MOH, the investigators selected 300 patients per year of interest.

The number of patients with a diagnosis of probable MOH remained "remarkably stable" over the study period, varying from 64% of all cases seen in the headache center in 1990 to 59.3% in 2005, Dr. Meskunas and colleagues found.

The relative frequency of probable ergotamine overuse headache fell significantly, from 18.6% to 0% (p < 0.0001), whereas the frequency of probable overuse headache involving triptans, a newer class of drugs, rose significantly, from 0% to 21.6% (p < 0.0001). The frequency of overuse headache due to simple analgesics increased from 8% to 31.8% (p < 0.05), and for combinations of acute medications from 9.8% to 22.7% (p = 0.01). The rate of opioid overuse headache declined, but the change was not significant.

"Acquiring up-to-date knowledge on the substances associated with probable MOH is a necessary step for planning strategies to address and relieve the burden of a sizeable number of headache patients," the authors write. "Since many patients are overusing prescribed medications, public health initiatives should focus on educating doctors and patients about the importance of setting limits on the prescription and taking of acute medication, emphasizing that overuse of specific acute migraine medications may also be associated with probable MOH," they conclude. Headache 2006;46:766-772.

10. Urinary Catheter Use Often “Inappropriate” in Hospitalized Elderly Patients

Hampton, Tracy PhD. JAMA Medical News & Perspectives, June 21, 2006.

ABOUT 1 OF 4 URINARY catheters implanted in hospitalized patients aged 70 years or older and 1 of 3 in hospitalized patients aged 85 years or older are unnecessary, according to a new study (Holroyd-Leduc JM et al. J Patient Saf. 2005;1:201–207).

Patient interviews and medical record reviews conducted at two teaching hospitals in Ohio­the University Hospitals of Cleveland and the Akron City Hospital­reveal that 378 of 1586 patients admitted without a specific medical indication for urinary catheterization received the devices. Risk factors for unnecessary catheterization included female gender; chronic illness; cognitive impairment; incontinence; inability to carry out common activities of daily living; a physician's order for bed rest; and geriatric conditions including confusion, falls, and failure to thrive at home. Patients with 5 or more risk factors had a 50% risk of being catheterized unnecessarily.

The high use of urinary catheters among hospitalized patients may be due to pressures to reduce nursing time spent caring for patients, the authors wrote. But unnecessary catheterization may cause more harm in the long run, as previous research has shown that catheterization carries well-defined risks, including urinary tract infections (Nicolle LE. Drugs Aging. 2005;22:627–639).

“The people who are most likely to suffer the adverse effects of a urinary tract infection are exactly the people who seem to be getting unnecessary catheterizations,” said principal investigator Seth Landefeld, MD, of the University of California, San Francisco, and the San Francisco VA Medical Center, referring to the hospitalized elderly. The study did not examine why unnecessary catheters are being placed or what happens to patients who have been unnecessarily catheterized. But according to the investigators, the study suggests that catheters may be inserted to manage patients with limited functional independence rather than for accepted medical indications, such as treating urinary retention or monitoring of urine output.

“Although computer reminders have been shown to help limit inappropriate catheterization, other interventions to reduce urinary catheter use need to be explored,” the investigators concluded.

11. Adherence to treatment or placebo is linked to lower mortality

Adherence to drug therapy may be a surrogate marker for overall healthy behaviour. Simpson and colleagues carried out a meta-analysis of 21 observational studies that reported the mortality and good or poor adherence to drug therapy of > 45 000 participants. For participants with good adherence to placebo or beneficial drug therapy, the risk of mortality was about half of that of participants with poor adherence. This supports the existence of a "healthy adherer" effect, say the authors.


12. Patients' views are not enough to judge quality of care

Elderly patients' own assessments of technical quality of care in general practice are not closely related to independently ascertained practice records based measures of technical quality of care. A cross sectional study by Rao and colleagues carried out the general practice assessment survey with > 3000 patients aged 65 years in 18 English general practices. Correlations between survey scores from the patients' own assessments and the objective records based measures of good clinical practice were 0.22 for hypertension monitored, 0.30 for hypertension controlled, and - 0.05 for influenza vaccination.


13. Clinical Assessment of Acute Cholecystitis in Adults

Roe J. Ann Emerg Med 2006;48:100-103.

…No single clinical or laboratory finding demonstrated a likelihood ratio sufficiently low to rule out or sufficiently high to rule in the diagnosis of acute cholecystitis. The authors point out that 2 confounding variables with this disease process are the elderly, in whom right upper quadrant signs are often absent, and the nonspecific presentation of acalculous cholecystitis, a disease more often observed in critically ill inpatients.

Interestingly, elevation of any one of the 3 classically elevated liver function markers only improved sensitivity to 0.70 and did not improve the likelihood ratio. Similarly, the combination of leukocytosis and fever increased specificity to 0.85 but did not appreciably affect the likelihood ratios. No other combinations of findings were evaluated.

The evaluation of clinical and laboratory findings to diagnose acute cholecystitis is hampered by a lack of sufficient investigation and methodologic flaws in existing literature. Future study of combinations of various findings may allow identification of patients who do not require additional testing. However, for the moment, for patients with abdominal pain suggestive of acute cholecystitis, we must rely on the clinical impression supplemented by diagnostic imaging.

See also RL Trowbridge, NK Rutkowski, KG Shojania. The rational clinical examination: does this patient have acute cholecystitis? JAMA. 2003;289:80-86.

14. Severe Sepsis and Septic Shock: Review of the Literature and ED Management Guidelines

H. Bryant Nguyen, MD, Gregory J. Moran, MDc, David A. Talan, MDc, et al.
Ann Emerg Med 2006;48: 54.e1 (July 2006)

Severe sepsis and septic shock are as common and lethal as other acute life-threatening conditions that emergency physicians routinely confront such as acute myocardial infarction, stroke, and trauma. Recent studies have led to a better understanding of the pathogenic mechanisms and the development of new or newly applied therapies. These therapies place early and aggressive management of severe sepsis and septic shock as integral to improving outcome.

This independent review of the literature examines the recent pathogenic, diagnostic, and therapeutic advances in severe sepsis and septic shock for adults, with particular relevance to emergency practice. Recommendations are provided for therapies that have been shown to improve outcomes, including early goal-directed therapy, early and appropriate antimicrobials, source control, recombinant human activated protein C, corticosteroids, and low tidal volume mechanical ventilation.

15. Blood Cultures Do Not Change Management in Hospitalized Patients with Community-acquired Pneumonia

Prasanthi Ramanujam, MD and Niels K. Rathlev, MD. Acad Emerg Med 2006;13:740-745.

Objectives: To determine if blood cultures identify organisms that are not appropriately treated with initial empiric antibiotics in hospitalized patients with community-acquired pneumonia, and to calculate the costs of blood cultures and cost savings realized by changing to narrower-spectrum antibiotics based on the results.

Methods: This was a retrospective observational study conducted in an urban academic emergency department (ED). Patients with an ED and final diagnosis of community-acquired pneumonia admitted between January 1, 2001, and August 30, 2003, were eligible when the results of at least one set of blood cultures obtained in the ED were available.

Exclusion criteria included documented human immunodeficiency virus infection, immunosuppressive illness, chronic renal failure, chronic corticosteroid therapy, documented hospitalization within seven days before ED visit, transfer from another hospital, nursing home residency, and suspected aspiration pneumonia. The cost of blood cultures in all patients was calculated. The cost of the antibiotic regimens administered was compared with narrower-spectrum and less expensive alternatives based on the results.

Results: A total of 480 patients were eligible, and 191 were excluded. Thirteen (4.5%) of the 289 enrolled patients had true bacteremia; the organisms isolated were sensitive to the empiric antibiotics initially administered in all 13 cases (100%; 95% confidence interval = 75% to 100%). Streptococcus pneumoniae and Haemophilus influenzae were isolated in 11 and two patients, respectively. The potential savings of changing the antibiotic regimens to narrower-spectrum alternatives was only $170.

Conclusions: Appropriate empiric antibiotics were administered in all bacteremic patients. Antibiotic regimens were rarely changed based on blood culture results, and the potential savings from changes were minimal.

16. Immunization Advisory Panel Recommends HPV Vaccine for All Girls

By Maggie Fox

WASHINGTON (Reuters) Jun 29 - Girls as young as 11 and young women up to age 26 should receive Merck and Co.'s Gardasil vaccine aimed at preventing human papillomavirus infection, responsible for most cases of cervical cancer, a panel of U.S. experts said on Thursday.

In a complicated vote, the Advisory Committee on Immunization Practices (ACIP) agreed to recommend the vaccine for three age groups: all girls between 11 and 12; girls and women 13 to 26 who have not received the vaccine yet; and women who have had abnormal Pap smears, genital warts or some other conditions.

At their discretion, physicians could vaccinate girls as young as 9, the panel decided.

The ACIP advises the U.S. Centers for Disease Control and Prevention.

The U.S. Food and Drug Administration licensed Gardasil for use in women and girls 9 to 26 years of age earlier this month. It protects against four types of HPV.

"I think this is going to be a great cancer prevention tool, but it is not going to be effective for about 10 years," said Dr. Carol Baker of the national Foundation for Infectious Disease, referring to the incubation period for cervical cancer.

Clinical trials have shown that a three-dose course of the vaccine can prevent close to 100% of lesions that cause genital warts and cervical cancer. The HPV 16 and 18 strains of virus are responsible for about 70% of cervical cancer cases. The CDC has no enforcement powers. It will be up to insurers to decide whether to pay for the $125-a-dose vaccine, school districts and universities to decide if they will require or recommend it, and individuals to decide if they will get the vaccine.

Dr. Cynthia Rand of the University of Rochester in New York said she believed most people would get the vaccine. She has started a series of studies on how many people would accept the vaccine if offered. "Most were accepting of the vaccine," Rand said in a telephone interview. "Teens were surprising in that they seemed to know more about HPV than their parents did."

Rand has no hard numbers yet but found no controversy about whether the vaccine might somehow encourage young people to have sex. "The minority of parents we interviewed didn't think their children would be needing it because their children wouldn't be having sex. But they thought it would be needed in the general community," she said.

At least one state legislative group, Women In Government, will be supporting the vaccine.

"Many state legislators around the country are ready to support a public health effort that will make sure that all age-appropriate girls and women can receive the HPV vaccine, regardless of their socioeconomic status," said Sarah Wells of the group, a nonprofit, bipartisan organization representing women state legislators.

GlaxoSmithKline has a slightly different HPV vaccine in development.

The CDC says genital HPV infection is the most common sexually transmitted infection in the United States. More than 50% of sexually active women and men will be infected with one or more genital HPV types during their lifetimes.
Merck has already been planning ahead for sales of the vaccine.

17. Asthma Symptoms Among Adolescents Who Attend Public Schools That Are Located Near Confined Swine Feeding Operations

Maria C. Mirabelli, Steve Wing, Stephen W. Marshall, and Timothy C. Wilcosky. Pediatrics 2006; 118: e66-e75.

[This explains why teen-aged asthmatics are leaving Modesto by the droves.]

18. Graduated Driver Licensing Programs and Fatal Crashes of 16-Year-Old Drivers: A National Evaluation

Li-Hui Chen, MS, PhDa, Susan P. Baker, MPHa and Guohua Li, MD, DrPHb

PEDIATRICS Vol. 118 No. 1 July 2006, pp. 56-62

CONTEXT. Implementation of graduated driver licensing programs is associated with reductions in crash rates of young drivers, but graduated driver licensing programs vary in their components. The impact of programs with different components is unknown.

OBJECTIVE. The purpose of this work was to determine which graduated driver licensing programs are associated with the greatest reductions in fatal motor vehicle crashes involving 16-year-old drivers.

METHODS. We conducted a retrospective study of all 16-year-old drivers involved in fatal crashes in the United States from 1994 through 2004 using data from the Fatality Analysis Reporting System and the US Census Bureau. We measured incidence rate ratios of fatal motor vehicle crashes involving 16-year-old drivers according to graduated driver licensing programs, adjusted for state and year.

RESULTS. Compared with state quarters with no graduated driver licensing program components, reductions of 16% to 21% in fatal crash involvement rates of 16-year-old drivers occurred with programs that included 3-month mandatory waiting period, nighttime driving restriction, and either 30 hours of supervised driving or passenger restriction. Reductions of 18% to 21% occurred in state quarters with programs that included 5 of the 7 components examined. Drivers aged 20 to 24 or 25 to 29 years did not experience significant reductions.

CONCLUSION. Comprehensive graduated driver licensing programs are associated with reductions of 20% in 16-year-old drivers’ fatal crash involvement rates. The greatest benefit seems to be associated with programs that include age requirements and 3 months of waiting before the intermediate stage, nighttime driving restriction, and either 30 hours of supervised driving or passenger restriction.

19. The Trial of Infant Response to Diphenhydramine: The TIRED Study­: A Randomized, Controlled, Patient-Oriented Trial

Dan Merenstein, MD; et al. Arch Pediatr Adolesc Med. 2006;160:707-712.

Objective To determine if infants aged 6 to 15 months with frequent parent-reported nighttime awakenings require reduced parental aid during a week of diphenhydramine hydrochloride treatment and 2 and 4 weeks after its discontinuation.

Design Double-blind, randomized, controlled clinical trial.

Setting The study was conducted from May 1, 2004, through May 1, 2005; patients were recruited nationally.

Participants Forty-four participants aged 6 to 15 months.

Interventions Placebo or diphenhydramine was administered in infants 30 minutes before anticipated bedtime.

Main Outcome Measures The primary outcome was dichotomous: a parental report of improvement in the number of night awakenings requiring parental assistance during the intervention week, which ended on day 14. Secondary outcomes were improved sleep during the 2 weeks before days 29 and 43, parental overall happiness with sleep, and improved sleep latency.

Results On June 6, 2005, the data safety monitoring board voted unanimously to stop the trial early because of lack of effectiveness of diphenhydramine over placebo. Only 1 of 22 children receiving diphenhydramine showed improvement compared with 3 of 22 receiving placebo. To reach the a priori determined sample size and have a positive outcome (ie, rejecting the null hypothesis), the trial would have needed to enroll 16 more participants in each arm, with 15 of the 16 in the diphenhydramine group and 0 of 16 in the placebo group improving.

Conclusion During 1 week of therapy and at follow-up 2 and 4 weeks later, diphenhydramine was no more effective than placebo in reducing nighttime awakening or improving overall parental happiness with sleep for infants.