Tuesday, July 25, 2006

Lit Bits: July 25, 2006

From the recent medical literature...

1. Hospital Quality for AMI: Correlation Among Process Measures and Relationship With Short-term Mortality

Elizabeth H. Bradley, PhD; David J. Magid, MD, MPH [Kaiser, Denver]; et al.

JAMA. 2006;296:72-78.

Context The Centers for Medicare & Medicaid Services (CMS) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) measure and report quality process measures for acute myocardial infarction (AMI), but little is known about how these measures are correlated with each other and the degree to which inferences about a hospital's outcomes can be made from its performance on publicly reported processes.

Objective To determine correlations among AMI core process measures and the degree to which they explain the variation in hospital-specific, risk-standardized, 30-day mortality rates.

Design, Setting, and Participants We assessed hospital performance in the CMS/JCAHO AMI core process measures using 2002-2003 data from 962 hospitals participating in the National Registry of Myocardial Infarction (NRMI) and correlated these measures with each other and with hospital-level, risk-standardized, 30-day mortality rates derived from Medicare claims data.

Main Outcome Measures Hospital performance on AMI core measures; hospital-specific, risk-standardized, 30-day mortality rates for AMI patients aged 66 years or older.

Results We found moderately strong correlations (correlation coefficients 0.40; P values <.001) for all pairwise comparisons between -blocker use at admission and discharge, aspirin use at admission and discharge, and angiotensin-converting enzyme inhibitor use, and weaker, but statistically significant, correlations between these medication measures and smoking cessation counseling and time to reperfusion therapy measures (correlation coefficients <0.40; P values <.001). Some process measures were significantly correlated with risk-standardized, 30-day mortality rates (P values <.001) but together explained only 6.0% of hospital-level variation in risk-standardized, 30-day mortality rates for patients with AMI.

Conclusions The publicly reported AMI process measures capture a small proportion of the variation in hospitals' risk-standardized short-term mortality rates. Multiple measures that reflect a variety of processes and also outcomes, such as risk-standardized mortality rates, are needed to more fully characterize hospital performance.

2. Outpatient DVT Management: Safely Keeping Patients Out of the ED

Vinson DR, Berman DA, Patel PB, Hickey DO. Outpatient management of deep venous thrombosis: Two models of integrated care. Amer J Manag Care. 2006;12:405-410.

Objective: To describe and evaluate the impact, effectiveness, and safety of 2 models of outpatient deep venous thrombosis (DVT) management.
Study Design: Observational health-records survey conducted in 2 community hospitals using a comparative design.

Methods: The model centered around the emergency department (ED) was studied from April 15, 1997, through December 31, 1999; the decentralized model was studied from July 15, 2002, through March 15, 2004. The effect of the decentralized model on processes of care was determined by comparing the percentages of patients who were managed by office-based primary care providers under the 2 models. Two-week clinical outcomes also were compared, including symptomatic pulmonary embolism, symptomatic progression of index DVT, new DVT, major bleeding, minor bleeding, and death.

Results: During the study periods, 187 and 254 outpatients were enrolled in the ED-centered model and the decentralized model, respectively. Under the ED-centered model, 17 (22.1%) of 77 patients who presented to the primary care providers’ offices on weekdays before 1:30 PM (on-hours) were managed exclusively within the clinic setting. Under the decentralized model, 78 (91.8%) of 85 patients who presented on-hours were managed within the clinics­a difference of 69.7 absolute percentage points (95% confidence intervals, 58.7%, 80.7%; P < .001). The models had comparable 2-week clinical outcomes.

Conclusions: The decentralized model for outpatient DVT management allowed more primary care clinic patients to receive their initial care exclusively in the clinic setting. There was no significant difference between the models in short-term effectiveness of therapy and patient safety.

Full-text (free): http://www.ajmc.com/files/articlefiles/AJMC_06julVinson405to410.pdf

3. Aminotransferase Elevations in Healthy Adults Receiving 4 Grams of Acetaminophen Daily: A Randomized Controlled Trial

Paul B. Watkins, MD; et al. JAMA. 2006;296:87-93.

Context During a clinical trial of a novel hydrocodone/acetaminophen combination, a high incidence of serum alanine aminotransferase (ALT) elevations was observed.

Objective To characterize the incidence and magnitude of ALT elevations in healthy participants receiving 4 g of acetaminophen daily, either alone or in combination with selected opioids, as compared with participants treated with placebo.

Design, Setting, and Participants A randomized, single-blind, placebo-controlled, 5-treatment, parallel-group, inpatient, diet-controlled (meals provided), longitudinal study of 145 healthy adults in 2 US inpatient clinical pharmacology units.

Intervention Each participant received either placebo (n = 39), 1 of 3 acetaminophen/opioid combinations (n = 80), or acetaminophen alone (n = 26). Each active treatment included 4 g of acetaminophen daily, the maximum recommended daily dosage. The intended treatment duration was 14 days.

Main Outcomes Serum liver chemistries and trough acetaminophen concentrations measured daily through 8 days, and at 1- or 2-day intervals thereafter.

Results None of the 39 participants assigned to placebo had a maximum ALT of more than 3 times the upper limit of normal. In contrast, the incidence of maximum ALT of more than 3 times the upper limits of normal was 31% to 44% in the 4 treatment groups receiving acetaminophen, including those participants treated with acetaminophen alone. Compared with placebo, treatment with acetaminophen was associated with a markedly higher median maximum ALT (ratio of medians, 2.78; 95% confidence interval, 1.47-4.09; P<.001). Trough acetaminophen concentrations did not exceed therapeutic limits in any participant and, after active treatment was discontinued, often decreased to undetectable levels before ALT elevations resolved.

Conclusions Initiation of recurrent daily intake of 4 g of acetaminophen in healthy adults is associated with ALT elevations and concomitant treatment with opioids does not seem to increase this effect. History of acetaminophen ingestion should be considered in the differential diagnosis of serum aminotransferase elevations, even in the absence of measurable serum acetaminophen concentrations.

4. EM in the US

The CDC released their annual report on emergency department (ED) care in the US. This report is based on 2004 visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the following ED statistics were notable.

Visit frequency
- Over 110 million visits were made in 2004, an increase of 18% over 10 years
- There were 38.2 visits per 100 persons, including one-fifth of all US adults in the past 12 months
- The total number of EDs in the US decreased by 12.4% over 10 years

Acuity measures
- Abdominal pain, chest pain and fever, all high-risk, were the most frequent chief complaints
- Medications were prescribed in three-quarters and procedures were performed in half of patients
- 15% arrived by ambulance
- 13% were admitted
- Of those classified, 15% of visits were emergent, 44% were urgent, 26% were semi-urgent and 15% were non-urgent

Overcrowding indices
- The mean time to see a physician was 47 minutes
- The mean time from arrival to admission or discharge was 3.3 hours
- About 2% left before being seen by a healthcare provider

To see a full copy of the report, go to http://www.cdc.gov/nchs/data/ad/ad372.pdf For more information about the ED utilization from the National Center for Health Statistics (NCHS) Ambulatory Health Care, go to http://www.cdc.gov/nchs/nhamcs.htm

5. Diagnostic Accuracy of TEE, Helical CT, and MRI for Suspected Thoracic Aortic Dissection: Systematic Review and Meta-analysis

Toshiya Shiga, MD, PhD; et al. Arch Intern Med. 2006;166:1350-1356.

Background Patients with suspected thoracic aortic dissection require early and accurate diagnosis. Aortography has been replaced by less invasive imaging techniques including transesophageal echocardiography (TEE), helical computed tomography (CT), and magnetic resonance imaging (MRI); however, accuracies have varied from trial to trial, and which imaging technique should be applied to which risk population remains unclear. We systematically reviewed the diagnostic accuracy of these imaging techniques in patients with suspected thoracic aortic dissection.

Methods Published English-language reports on the diagnosis of thoracic aortic dissection by TEE, helical CT, or MRI were identified from electronic databases. Sensitivity, specificity, and positive and negative likelihood ratios were pooled in a random-effects model.

Results Sixteen studies involving a total of 1139 patients were selected. Pooled sensitivity (98%-100%) and specificity (95%-98%) were comparable between imaging techniques. The pooled positive likelihood ratio appeared to be higher for MRI (positive likelihood ratio, 25.3; 95% confidence interval, 11.1-57.1) than for TEE (14.1; 6.0-33.2) or helical CT (13.9; 4.2-46.0). If a patient had shown a 50% pretest probability of thoracic aortic dissection (high risk), he or she had a 93% to 96% posttest probability of thoracic aortic dissection following a positive result of each imaging test. If a patient had a 5% pretest probability of thoracic aortic dissection (low risk), he or she had a 0.1% to 0.3% posttest probability of thoracic aortic dissection following a negative result of each imaging test.

Conclusion All 3 imaging techniques, ie, TEE, helical CT, and MRI, yield clinically equally reliable diagnostic values for confirming or ruling out thoracic aortic dissection.

6. Emergent Hyperpyrexia in Children Should Be Treated With Antibiotics

News Author: Laurie Barclay, MD. July 17, 2006 ­ Children presenting to an emergency department (ED) with hyperpyrexia are equally at risk for viral and bacterial infection and should be treated with antibiotics, according to the results of a prospective study reported in the July issue of Pediatrics.

"Previous studies of children with temperatures [of] 106°F (hyperpyrexia) disagree as to whether hyperpyrexia confers a high risk of serious bacterial infection (SBI)," write Barbara W. Trautner, MD, from Baylor College of Medicine in Houston, Tex, and colleagues. "The purpose of our study was to evaluate the incidence of SBI in children presenting to the ED with hyperpyrexia and to determine whether any aspects of their presentation were predictive of the risk of SBI."

During a 2-year period, the investigators prospectively collected data on all children younger than 18 years who presented to a pediatric ED and who had rectal temperatures of 106°F. All patients were evaluated with history, physical examination, complete blood cell counts, blood cultures, and nasopharyngeal viral cultures.

Of 130,828 visits, 103 children had hyperpyrexia, or 1 per 1270 patient visits. Of these 103 subjects, 20 had serious bacterial infection, and 22 had laboratory-proven viral illness. One subject had bacterial/viral coinfection. Chronic underlying illness or diarrhea was associated with increased risk for SBI, and rhinorrhea or any other viral symptom (excluding diarrhea) was associated with decreased risk for SBI. Age, maximum temperature, and total white blood cell count were not helpful in distinguishing bacterial from viral illness.

"Children with hyperpyrexia are at equally high risk for serious bacterial infection and for viral illness," the authors write. "No aspect of the clinical presentation reliably distinguishes between bacterial and viral illness. We recommend consideration of antibiotic treatment for all children presenting to the emergency department with hyperpyrexia without confirmed viral illness."

Study limitations include limited sample size, time of the study before the widespread use of the conjugate pneumococcal vaccine in children, and lack of identified etiology for fever in the majority of febrile children in this study.

"We conclude that hyperpyrexia is a medical emergency that carries a high risk of SBI," the authors conclude. "These findings should hold true despite the subsequent introduction of the conjugate pneumococcal vaccine. We advise treatment with antibiotics for all children with hyperpyrexia who do not have a confirmed viral illness and for all children with hyperpyrexia and a confirmed viral illness who are ill enough to require hospitalization."

The US Public Health Service supported this study. The authors have disclosed no relevant financial relationships.

Pediatrics. 2006;118:34-40

7. A Woman Presenting With Rapidly Progressive Flaccid Paralysis

Hmmm, Sherlock. What’s the diagnosis? http://www.medscape.com/viewarticle/537345_2

8. Degree of Obesity Correlates With Mortality Risk

By Martha Kerr. NEW YORK (Reuters Health) Jul 06 - In women, the risk of all-cause and coronary heart disease mortality continues to increase as body mass index (BMI) rises above 30, according to the latest findings from the Women's Health Initiative (WHI) Observational Study.

"It's not good enough to consider obesity alone," principal investigator Dr. Kathleen McTigue of the University of Pittsburgh, Pennsylvania, told Reuters Health. "You need to look at degree of obesity."

In a study published in the July 5th Journal of the American Medical Association, Dr. McTigue and colleagues studied patterns of morbidity and mortality risk according to BMI in 90,185 women in the WHI study who were not in the diet or hormone treatment arms of the study. Average follow-up was 7 years.

Body mass index (BMI) was classified using NIH definitions of normal, overweight and obesity. Normal weight BMI ranged from 18.5 to 24.9 and overweight was defined as a BMI of 25-29.9. The investigators defined three categories of obesity: obesity 1 (BMI of 30-34.9), obesity 2 (BMI 35-39.9) and extreme obesity (BMI 40 and higher).

"The risks of extreme obesity have not been well-defined," Dr. McTigue noted. "This was a large enough sample to assess risk."

The prevalence of extreme obesity varied by ethnicity, occurring in 10% of black women and 1% of Asian and Pacific Islanders. However, all-cause mortality, coronary heart disease mortality and coronary heart disease incidence did not vary by ethnicity.

"There is an increasing risk of all-cause mortality with increasing weight, but it doesn't reach statistical significance until obesity exists," Dr. McTigue told Reuters Health. Compared with normal-weight women, she continued, "the risk of dying was increased 12% in all women in obesity category 1, while risk was increased 86% over seven years in women in obesity category 3."

Summing up, she said, "The coronary heart disease and all-cause mortality risk increases along a continuum."

In a University of Pittsburgh release, the researcher pointed out that "earlier studies, which tended to reflect lower degrees of obesity, may underestimate the risks of extremely obese individuals and overestimate the risk for mildly obese individuals in diverse groups."

She concluded, "More accurately assessing weight-related health risk may both improve policy decisions about obesity and assist women in making informed decisions about their health."

JAMA 2006;296:79-86.

9. Migraine With Aura Linked to Increased Risk for MI and Stroke

News Author: Laurie Barclay, MD. July 18, 2006 ­ Migraine with aura is associated with increased risk for myocardial infarction and stroke, whereas migraine without aura is not, according to the results of a large, prospective study in women reported in the July 19 issue of JAMA.

"Migraine with aura has been associated with an adverse cardiovascular risk profile and prothrombotic factors that, along with migraine-specific physiology, may increase the risk of vascular events," write Tobias Kurth, MD, ScD, from Brigham and Women's Hospital and Harvard Medical School in Boston, Mass, and colleagues. "Although migraine with aura has been associated with increased risk of ischemic stroke, an association with cardiovascular disease (CVD) and, specifically, coronary events remains unclear."

This prospective cohort study evaluated 27,840 US women aged 45 years or older who were enrolled in the Women's Health Study, were free of CVD and angina at study entry (1992-1995), and who had data on self-reported migraine and aura status, and lipid measurements. Follow-up data for this analysis were available through March 31, 2004.

The main endpoint was the combined end point of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD). Secondary outcomes were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD.
At study entry, 5125 women (18.4%) reported any history of migraine. Of the 3610 women with active migraine, defined as migraine in the prior year, 1434 (39.7%) reported aura symptoms. During a mean of 10 years of follow-up, there were 580 major CVD events.

Compared with women with no migraine history, those who reported active migraine with aura had multivariable-adjusted hazard ratios of 2.15 (95% confidence interval [CI], 1.58 - 2.92; P < .001) for major CVD, 1.91 (95% CI, 1.17 - 3.10; P = .01) for ischemic stroke, 2.08 (95% CI, 1.30 - 3.31; P = .002) for myocardial infarction, 1.74 (95% CI, 1.23 - 2.46; P = .002) for coronary revascularization, 1.71 (95% CI, 1.16 - 2.53; P = .007) for angina, and 2.33 (95% CI, 1.21 - 4.51; P = .01) for ischemic CVD death.
Adjustment for age resulted in 18 additional major CVD events attributable to migraine with aura per 10,000 women per year. Women who reported active migraine without aura were not at increased risk for any vascular events or angina.

"In this large, prospective cohort of women, active migraine with aura was associated with increased risk of major CVD, myocardial infarction, ischemic stroke, and death due to ischemic CVD, as well as with coronary revascularization and angina," the authors write. "Active migraine without aura was not associated with increased risk of any CVD event."

Study limitations include self-reported migraine and aura status not classified according to strict International Headache Society criteria; and use of a broad definition of aura, difficulty in distinguishing some aura features from symptoms of transient ischemic attack, lack of detailed information regarding the use of migraine-specific drugs, possible residual confounding because of observational study design, and lack of data regarding the duration of migraine prior to study entry or migraine frequency during follow-up.

"Since migraine without aura is far more common than migraine with aura, our data demonstrate no increased risk of CVD for the majority of migraine patients," the authors conclude. "Future research should focus on a better understanding of the relationship between migraine, aura status, and cardiovascular events."

The Donald W. Reynolds Foundation, Las Vegas, Nev, and the National Institutes of Health supported this study. The authors have disclosed no relevant financial relationships.

In an accompanying editorial, Richard B. Lipton, MD, and Marcelo E. Bigal, MD, PhD, from the Albert Einstein College of Medicine and the Montefiore Headache Center in Bronx, NY, discuss potential explanations for the association between migraine with aura and CVD. "For patients with migraine with aura, clinicians should have heightened vigilance for modifiable cardiovascular risk factors, such as hypertension, hyperlipidemia, and smoking," Drs. Lipton and Bigal write. "Ultimately, it will be important to determine whether migraine with aura is itself a modifiable risk factor for CVD. Future studies should investigate the possibility that preventive medications for migraine or antiplatelet therapy might reduce the risk of CVD in patients with migraine with aura."

Drs. Lipton and Bigal have disclosed no relevant financial relationships.

JAMA. 2006;296:283-291, 332-333

10. Heart Failure With Preserved Ejection Fraction Becoming More Common

NEW YORK (Reuters Health) Jul 19 - Findings from a new study indicate that the prevalence of heart failure with preserved ejection fraction (EF) has increased in recent years, according to a report in the July 20th issue of The New England Journal of Medicine.

The results of a related study suggest that a preserved EF does not significantly affect the survival of heart failure patients.

In the first study, Dr. Margaret M. Redfield and colleagues, from the Mayo Clinic in Rochester, Minnesota, assessed trends in heart failure prevalence and outcome by analyzing data from all consecutive patients who were hospitalized at their center for decompensated heart failure between 1987 and 2001.

A total of 6076 patients were identified during the study period and EF data was available for 4596 of them. Overall, 47% of patients had a preserved EF (50% or greater) and 53% had a reduced EF.

The proportion of heart failure patients with a preserved EF climbed from 38% at the beginning of the study period to 54% at the end. The authors also found that rates were higher among community patients than among referrals: 55% vs. 45%.

Prevalence rates of diabetes, hypertension, and atrial fibrillation among heart failure patients increased during the study period, the report indicates. Heart failure patients with a reduced EF experienced an improvement in survival over time, whereas those with preserved EF did not.

In the second study, Dr. Peter P. Liu, from Toronto General Hospital, and colleagues focused on the outcomes of 2802 patients who were admitted to 103 hospitals in Ontario, Canada between April 1999 and March 2001.

Dr. Liu's team found no significant survival benefit for an EF of 50% or greater. The 1-year mortality rates with preserved and reduced EFs were 22% and 26%, respectively (p = 0.07). The authors also found that having a preserved EF did not reduce heart failure readmission rates or in-hospital complications.

In a related editorial, Dr. Gerard P. Aurigemma, from the University of Massachusetts Medical School in Worcester, comments that "the two current studies remind us that ejection fraction is not a good predictor of clinical disability and suggest that congestive symptoms are more closely related to the filling properties of the ventricles than to the ejection properties."

He adds that the findings are provocative in that they challenge "the widely held perception that the survival rate among patients with most forms of heart disease is inversely related to the ejection fraction."

N Engl J Med 2006;355:251-269.

11. FDA Warns Against Use of Triptans With Certain Antidepressants

Yael Waknine. July 20, 2006 ­ The US Food and Drug Administration (FDA) has warned healthcare professionals regarding the risk for life-threatening serotonin syndrome associated with use of 5-hydroxytryptamine receptor antagonists (triptans) in conjunction with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs).

Coadministration of these drugs has an additive effect on serotonin levels that can lead to serotonin syndrome, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program. Symptoms may include restlessness, hallucinations, loss of coordination, tachycardia, rapid blood pressure changes, increased body temperature, overactive reflexes, nausea, vomiting, and diarrhea.

Healthcare professionals prescribing a triptan, SSRI, or SNRI are advised to consider that triptans are often used intermittently, and that drugs from all 3 classes may be prescribed by different clinicians; the potential risk for serotonin syndrome should be weighed against the potential benefit of using a triptan with an SSRI or SNRI.

SSRI- or SNRI-treated patients receiving triptans should be followed closely, particularly during initiation of therapy, dose increases, or the addition of another serotonergic drug.

Patients receiving combination therapy should be made aware of the risk for serotonin syndrome and advised to seek immediate medical attention for associated symptoms.
The FDA has requested that safety labeling for triptans, SSRIs, and SNRIs be changed to reflect the potential for this additive reaction.

Triptans are used to treat migraines, and the class includes drugs such as naratriptan HCl (Amerge, made by GlaxoSmithKline); almotriptan malate (Axert, made by Ortho-McNeil Pharmaceutical, Inc); frovatriptan succinate (Frova, made by Endo Pharmaceuticals); sumatriptan/sumatriptan succinate (Imitrex, made by GlaxoSmithKline); rizatriptan benzoate (Maxalt and Maxalt-MLT, made by Merck and Company, Inc); eletriptan HBr (Relpax, made by Pfizer, Inc); and zolmitriptan (Zomig and Zomig ZMT, made by AstraZeneca Pharmaceuticals LP).

SSRIs and SNRIs are used to treat depression and other mood disorders.

SSRIs include citalopram HBr (Celexa, made by Forest Laboratories, Inc); fluvoxamine (previously marketed as Luvox by Solvay Pharmaceuticals, Inc, and now available in generic formulations); escitalopram oxalate (Lexapro, made by Forest Laboratories, Inc); paroxetine HCl (Paxil, made by GlaxoSmithKline); fluoxetine HCl (Prozac, made by Eli Lilly and Company); olanzapine/fluoxetine (Symbyax, made by Eli Lilly); and sertraline HCl (Zoloft, made by Pfizer, Inc). SNRIs include duloxetine HCl (Cymbalta, made by Eli Lilly) and venlafaxine HCl (Effexor, made by Wyeth Pharmaceuticals Inc).

Healthcare professionals are encouraged to report adverse events related to use of triptans in conjunction with SSRIs or SNRIs 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.

Reviewed by Gary D. Vogin, MD.

12. The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones.

Yilmaz E, et al. J Urol. 2005 Jun;173(6):2010-2.

INTRO: Several factors are thought to influence the spontaneous passage of ureteral stones, such as stone size, configuration and location, smooth muscle spasm, submucosal edema, and anatomy. To ease the spontaneous passage of the distal ureteral stones in recent years, some adjunctive pharmacological medications have been started on trial. To achieve the spontaneous passage, [alpha]-adrenergic blockers, calcium channel blockers, prostaglandin synthesis inhibitors, glyceryl trinitrate and steroid treatment to relieve edema are being used.

Currently [alpha]1-adrenergic receptor antagonists represent the treatment of choice for lower urinary tract symptoms, as shown in many randomized controlled trials as well as in several studies. [alpha]1-adrenergic receptors were demonstrated in human, pig, dog and horse ureters. [alpha]1-adrenergic receptors are found more densely in the ureter smooth muscle than the other adrenergic receptors. They inhibit the basal tonus, peristaltic wave frequency and the ureteral contraction in the intramural parts. While the [alpha]1A receptors are found widespread in the proximal urethra, prostate and bladder outflow, [alpha]1B receptors are found more densely in the vascular smooth muscles, and [alpha]1D receptors are predominantly found in the detrusor. [alpha]1D receptors are effective in the relaxation of the detrusor and the spasm of the 1/3 distal part of the ureter (especially the intramural part). In our study the efficacies of 3 different [alpha]1-adrenergic blockers are evaluated, and their comparison with respect to each other is made.

METHODS SPECIFICS: A total of 114 patients between 18 and 65 years old, and who had radiopaque stones 10 mm or smaller located in the distal tract of the ureter (juxtavesical tract and ureterovesical junction) were included in the study.

The exclusion criteria were the presence of urinary system infection, radiolucency stones, severe hydronephrosis, diabetes, ulcer disease, hypotension and having calcium antagonist medication. Also, patients who had had distal ureter surgery were excluded from the study.

The 29 patients in group 2 received tamsulosin (0.4 mg daily), the 28 patients in group 3 received terazosin [Hytrin] (5 mg daily) and the 29 patients in group 4 received doxazosin (4 mg daily). Tamsulosin was recommended to be taken after breakfast in the morning, whereas terazosin and doxazosin were to be taken before going to bed in the evening. These agents were given for up to 1 month. All patients were allowed to use symptomatic therapy with injections of 75 mg diclofenac (on demand) and were required to consume a minimum of 2 liters of water daily.

ABSTRACT:
PURPOSE: alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones. We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose.

MATERIALS AND METHODS: A total of 114 patients between 18 and 65 years old who had lower ureteral stones were included in the study. Patients were randomly divided into 4 groups. Group 1 consisted of 28 patients and acted as the control group. Group 2 comprised 29 patients who received tamsulosin, group 3 was 28 patients receiving terazosin and group 4 was 29 patients receiving doxazosin. These agents were given for up to a month and hydration was also recommended simultaneously. Every week patients were controlled with x-rays of the kidneys, ureters, bladder and urinary ultrasonography. Meanwhile the number of pain episodes, analgesic dosage and the number of days for spontaneous passage of the calculi through the ureter were also recorded.

RESULTS: There were no differences between the groups with respect to age, weight, height, sex and stone size. The calculi passed through the ureter spontaneously in 15 patients in group 1 (53.57%), in 23 patients in group 2 (79.31%), in 22 patients in group 3 (78.57%), and in 22 patients in group 4 (75.86%). In groups 2 to 4 the number of pain episodes, expulsion time and analgesic dosage were found to be lower compared with those in group 1. CONCLUSIONS: alpha1-Adrenergic blockers increase the frequency of spontaneous passage of the distal ureteral calculi. All 3 agents tested were equally efficacious.

13. Women prefer speculum examinations without stirrups

Women feel less vulnerable and experience less discomfort when speculum examinations (as part of routine gynaecological examination) are carried out without stirrups. Seehusen and colleagues (BMJ 2006;333:171; 22 July) randomised 197 adult women from a US family medicine outpatient clinic who were undergoing routine gynaecological examination and cervical smear to examination with or without stirrups. When the women's perceived levels of physical discomfort were measured on 100 mm visual analogue scales, the level for those examined without stirrups was 17.2 compared with 30.4 in the stirrups group. Sense of vulnerability in the group of women examined without stirrups was reduced from 23.6 to 13.1, whereas sense of loss of control was the same in both groups.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7560/171

14. Consider whooping cough even if a child has been immunised

A substantial proportion of immunised children of school age who present to primary care with a persistent cough may have had a recent infection with Bordetella pertussis. Harnden and colleagues (BMJ 2006;333:174; 22 July) recruited 179 children aged 5 to 16 years (from 18 UK general practices) who had been coughing for two weeks or more. Serological evidence of a recent Bordetella pertussis infection was found in 37% of the children, and 86% of these children had been fully immunised. Making a secure diagnosis of whooping cough may reassure the parents and prevent inappropriate investigations and treatment, conclude the authors.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7560/174

15. A Simple Way to Diagnose the Restlessness of Akathisia

Vinson DR. J Emerg Med. 2006;31:139-145.

What is akathisia? Akathisia is an extrapyramidal syndrome most often caused by medications that modulate central neurotransmitters. This dysphoric movement disorder is characterized by a compulsive urge to move and an inability to maintain a posture for several minutes. Restless behavior observed in akathisic patients includes rocking back and forth, shifting side to side, purposeless leg and foot movements while seated, foot tapping, walking in place, and pacing.

What causes it? Akathisia occurs commonly in EM as a side-effect of parenteral metoclopramide, droperidol, prochlorperazine, and chlorpromazine (dopamine receptor D2 antagonists) used in the treatment of nausea, headache, and agitation. Despite the frequency with which emergency physicians encounter akathisia, this adverse drug reaction is commonly overlooked. Failure to diagnose akathisia may be attributable, in part, to the lack of diagnostic criteria applicable to the emergency setting. To be readily applied at the bedside, diagnostic criteria must be simple, straightforward, logical, and easy to remember. It is here the assessment of akathisia could be improved. Simpler diagnostic criteria would likely achieve wider utilization.

How does this new diagnostic tool work? Simple. Ask the patient “Do you feel a restless urge to move, especially in your legs?” before and after administration of a dopamine antagonist. If they answer “Yes”, have them grade the restlessness as mild, moderate, or severe. If the grade increases after having received the drug and you observe any corroborating restless motor activity, you have the diagnosis. Proceed to treatment with diphenhydramine (J Emerg Med. 2004; 26:265-70). This simplified instrument is an accurate as the fancier, more cumbersome ones, but is far easier to use. It should facilitate the detection and treatment of akathisia in EM.

16. Management of burns blisters: What’s the evidence?

Jonathan Shaw. Emergency Medicine Journal 2006;23:648-649;
Best evidence topic reports (BETs)

A short cut review was carried out to establish whether leaving intact, deroofing, or aspirating the blisters of partial thickness burns best minimised infection and promoted healing. In total, 153 papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. It is concluded that the evidence remains poor, but that leaving the blister intact seems to reduce infection rates and should therefore be the default option.

Clinical scenario
A 30 year old chef attends the emergency department, having sustained burns to his forearm from hot fat. Clinical examination reveals blistering to the area and some erythema. You are not sure whether to leave, aspirate, or completely deroof the blisters, and wonder if there is any research to point you in the right direction.

Three-part question
In adults with partial thickness burns is de-roofing or aspirating the blisters better than conservative management in minimising infection and promoting healing?

Comments
There seems to be a paucity of good clinical evidence related to this subject, despite several review articles. The sole paper found involved a small sample, but showed infection rates to be higher if blisters are aspirated or deroofed, and that pain scores were higher in the group that underwent deroofing.

CLINICAL BOTTOM LINE
Based on the current available evidence, blisters should, wherever possible, be left intact to reduce the risk of infection, but if anatomical position necessitates intervention for functional purposes, aspiration appears to result in less pain than deroofing.

17. Cope’s early diagnosis of the acute abdomen, 21st ed

Z Cope, revised by W Silen. Oxford Oxford University Press, 2005, £35.99, ISBN 0-19-517546-8

Reviewed by G Hughes in Emergency Medicine Journal 2006;23:662.

This classic textbook was first published in 1921. It comes around as regularly as the Olympic Games and as reliably as the full moon.

Why is it so good? Its emphasis is on clinical and not laboratory or radiological diagnosis and it does not rely on algorithms, protocols, pathways, or a plethora of long lists to memorise. Its style initially seems old fashioned, and to many eyes it may seem turgid; however, if you stick with it, it grows on you. It becomes very readable.

In our specialty, which tends towards a "rule out" approach to diagnosis and assessment, many will think this book has no place. Nothing can be further from the truth. It should be required reading for all trainees. Consultants who have not read it before will also learn from it.

Including the index, it is 298 pages long. Although the line drawings (which are plentiful) are fine, the radiological illustrations are nothing to write home about. It doesn’t matter. It’s all in the history and examination, not the investigations. Read it.

18. Multidetector CT for Coronary Stenosis

Multidetector computed tomography (MDCT) has been proposed as a noninvasive method of detecting coronary artery stenosis. In a multicenter trial of patients referred for nonemergent coronary angiography, Garcia and colleagues assessed the accuracy of 16-row MDCT to detect a more than 50% luminal narrowing in coronary artery segments. The authors found an unacceptably high number of false-positive and nonevaluable segments using MDCT, limiting the utility of 16-row MDCT for primary diagnosis of coronary artery stenosis.

Accuracy of 16-Row Multidetector Computed Tomography for the Assessment of Coronary Artery Stenosis. Mario J. Garcia, MD; Jonathan Lessick, MD, DSc; Martin H. K. Hoffmann, MD; for the CATSCAN Study Investigators

JAMA. 2006;296:403-411.

Abstract: http://jama.ama-assn.org/cgi/content/abstract/296/4/403

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.

Methods
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.

Results
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.

Conclusion
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.

Abstract
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 http://www.medscape.com/viewarticle/534012?src=mp

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).

Conclusions
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

Abstract
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.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7557/15

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.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7557/19

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.

Conclusions
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.