Monday, September 22, 2008

Lit Bits. Sept 22, 2008

From the recent medical literature...

1. Kids with Fever: How to Calm It (and Parents!)

1a. Paracetamol [aka Acetaminophen] plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial

Hay AD, et al. BMJ 2008; 337:a1302

Objective: To investigate whether paracetamol (acetaminophen) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home.

Design: Individually randomised, blinded, three arm trial.

Setting: Primary care and households in England.

Participants: Children aged between 6 months and 6 years with axillary temperatures of at least 37.8°C and up to 41.0°C.

Intervention: Advice on physical measures to reduce temperature and the provision of, and advice to give, paracetamol plus ibuprofen, paracetamol alone, or ibuprofen alone.

Main outcome measures: Primary outcomes were the time without fever (<37.2°c) p="0.2)." p="0.008)." p="0.025)" p="0.8)." color="#000099">1b. Editorial: Antipyretic treatment for feverish young children in primary care

Anthony Harnden. BMJ 2008;337:a1409

No persuasive evidence shows benefit of combining paracetemol and ibuprofen

Fever is one of the main concerns that parents have when their child is unwell. Many parents believe fever is potentially harmful and worry about its height and duration. It is standard practice for health professionals to give advice about administering antipyretic drugs to children. The most commonly used drugs are paracetamol (acetaminophen) and ibuprofen. Because these drugs can be given at alternating intervals some doctors tell parents to use a combination of both drugs during the course of a febrile illness.

In the linked study (doi:10.1136/bmj.a1302), Hay and colleagues report a randomised controlled trial of paracetamol, ibuprofen, and a combination of the two drugs in 156 febrile children age 6 months to 6 years in primary care. The trial has two primary outcomes—time without fever in the first four hours and fever associated discomfort after 48 hours.1 Hollinghurst and colleagues compare the costs to parents and the NHS of the three drug regimes.2

The scale of childhood fever and treatment costs is large. In the Avon longitudinal study of parents and children, parents reported fever as a symptom in more than two thirds of children under 5 years, and a third of these children had been taken to a doctor for a consultation.3 The large volume of calls and consultations for childhood fever has a substantial effect on NHS direct, out of hours services, and accident and emergency care services. In 2004 the expenditure in Europe on over the counter paracetamol and ibuprofen for children was £405m (511m; $756m).2

Yet a National Institute for Health and Clinical Excellence review of feverish illness in children found no evidence that reducing temperature shortens the duration of illness or reduces complications, such as febrile convulsions.4 In fact, reducing fever may prolong illness. In a trial of paracetamol in 50 children with Plasmodium falciparum, the clearance time of the malaria parasite was 16 hours longer in children treated with quinine and paracetamol than in those treated solely with quinine.5 Similarly, in a trial of paracetamol in 72 children with chickenpox, the time to total scabbing was significantly longer in the paracetamol group.6

Paracetemol and ibuprofen are effective at reducing temperature and ibuprofen acts for longer than paracetamol.7 The largest trial comparing paracetamol, ibuprofen, and an alternating combination was conducted in paediatric community centres in Israel.8 In total, 464 febrile children age 6-36 months were randomly allocated into three groups. The group that received an alternating combination had a significantly lower mean fever over three days, a decline in a validated checklist of children’s pain, and fewer drug doses. However, the study is difficult to interpret because the investigators used a complicated design, which loaded each of the three groups of children with either paracetamol or ibuprofen at study entry.

When advising parents to use antipyretics, professionals are trying to reduce the child’s discomfort associated with fever and manage the parents’ anxiety. Time without fever is arguably a proxy of parental concern, so the most important primary outcome examined in the trial by Hay and colleagues is discomfort associated with fever at 48 hours. Recruiting large numbers of children with acute illness in primary care into research studies is difficult, and Hay and colleagues were unable to recruit enough children to give sufficient power to detect differences for this outcome. But their data suggest no additional improvement in fever associated discomfort or activity levels in the combined drug group at 24 hours, 48 hours, and five days. A trial with greater power would be needed to confirm this.

Hollinghurst and colleagues’ economic analysis confirms that the cost associated with childhood fever is predominantly borne by parents and primary care. The authors constructed a cost consequences matrix of results at 48 hours and five days using costs to the NHS and parents, and they combined discomfort, activity, appetite, sleep, and resolution of fever to determine a variable "returned to normal for that child." Their data show no significant differences between the drug regimens.

Paracetamol and ibuprofen are safe for children when given at the recommended doses. Despite a commonly held view, no evidence exists that ibuprofen exacerbates wheeze in children.9 However, in the United Kingdom ibuprofen is not licensed for children under 3 months or for those who weigh less than 5 kg. The most worrying aspect of the study by Hay and colleagues is that even under clinical trial conditions, 31 children received a drug overdose. This suggests that parents may often inadvertently exceed the maximum recommended dose and that a more complicated alternating regimen of paracetamol and ibuprofen may be less safe than using either drug alone.

No persuasive evidence exists for recommending a combination or an alternating regimen of paracetamol and ibuprofen. Doctors should try to improve their precision of diagnosis in febrile children, and parents should be reassured that fever itself is not harmful. The importance of fluid intake and sensible clothing should be discussed. Before prescribing it may be important to weigh the child to determine the most appropriate dose of antipyretic. The longer action of ibuprofen makes it the most suitable antipyretic to use.


2. Flu Shot Does Not Reduce Risk of All-Cause Mortality in Elders

NEW YORK -- August 29, 2008 -- The widely-held perception that the influenza vaccination reduces overall mortality risk in the elderly does not withstand careful scrutiny, according to a study in the September issue of the American Journal of Respiratory and Critical Care Medicine.

The vaccine does confer protection against specific strains of influenza, but its overall benefit appears to have been exaggerated by a number of observational studies that found a very large reduction in all-cause mortality among elderly patients who had been vaccinated.

"While such a reduction in all-cause mortality would have been impressive, these mortality benefits are likely implausible. Previous studies were likely measuring a benefit not directly attributable to the vaccine itself, but something specific to the individuals who were vaccinated -- a healthy-user benefit or frailty bias," said Dean T. Eurich, PhD, School of Public Health, University of Alberta, Edmonton, Alberta.

"Over the last 2 decades in the United Sates, even while vaccination rates among the elderly have increased from 15% to 65%, there has been no commensurate decrease in hospital admissions or all-cause mortality. Further, only about 10% of winter-time deaths in the US are attributable to influenza, thus to suggest that the vaccine can reduce 50% of deaths from all causes is implausible in our opinion."

Dr. Eurich and colleagues hypothesised that if the healthy-user effect was responsible for the mortality benefit associated with influenza vaccination seen in observational studies, there should also be a significant mortality benefit present during the off-season as well.

They analysed clinical data of 704 patients aged 65 years and older from 6 hospitals in Alberta. The patients were admitted to the hospital for community-acquired pneumonia during non-flu season; half of the patients had been vaccinated, and half had not.
Each vaccinated patient was matched to a non-vaccinated patient with similar demographics, medical conditions, functional status, smoking status, and current prescription medications.

In examining in-hospital mortality, they found that 12% of the patients died overall, with a median length of stay of approximately 8 days.

While analysis with a model similar to that used in past observational studies indeed showed that patients who were vaccinated were about half as likely to die as unvaccinated patients, a finding consistent with other studies, they found a striking difference after adjusting for detailed clinical information, such as the need for an advanced directive, pneumococcal immunisations, socioeconomic status, as well as sex, smoking, functional status, and severity of disease.

Controlling for those variables reduced the relative risk of death to a statistically nonsignificant 19%.

Further analyses that included more than 3,400 patients from the same cohort did not significantly alter the relative risk. The researchers concluded that there was a difficult to capture healthy-user effect among vaccinated patients.

"The healthy-user effect is seen in … patients who are well-informed about their health, who exercise regularly, do not smoke or have quit, drink only in moderation, watch what they eat, come in regularly for health maintenance visits and disease screenings, take their medications exactly as prescribed, and quite religiously get vaccinated each year so as to stay healthy," said principal investigator Sumit Majumdar, MD, University of Alberta.

"Such attributes are almost impossible to capture in large scale studies using administrative databases." Finally, Dr. Majumder said, the findings are a reminder to researchers that "the healthy-user effect is everywhere you don't want it to be."


3. Six Rules Doctors Need to Know

Why are patients mad at doctors? Maybe, suggests medical blogger Dr. Robert Lamberts, it’s because doctors aren’t following the rules.

Tony Cenicola, The New York Times.

Rule 1: They don’t want to be at your office.
Rule 2: They have a reason to be at your office.
Rule 3: They feel what they feel.
Rule 4: They don’t want to look stupid.
Rule 5: They pay for a plan.
Rule 6: The visit is about them.


4. Preservation of active range of motion after acute elbow trauma predicts absence of elbow fracture

Darracq MA, Vinson DR, Panacek EA. Amer J Emerg Med. 2008;26:779-782. (from UC Davis and Kaiser Sacramento, Roseville, and South Sac)

Previous studies indicate that an inability to fully extend the elbow after elbow trauma is indicative of fracture. We hypothesized that maintenance of active range of motion (ROM) of the elbow in flexion, extension, pronation, and supination after elbow trauma is very specific for the absence of fracture or effusion, and limitation of ROM is sensitive for fracture or effusion.

This was a prospective observational study with convenience sampling of a carefully selected patient population. This would allow certain types of patients to be excluded from the study. Patients with elbow injury receiving radiographs and meeting enrollment criteria were enrolled between June 2006 and March 2007 at 4 emergency departments in the local region.

Demographics, active ROM, and presence of point tenderness at the olecranon, epicondyles, and radial head were recorded by enrolling clinicians. All enrolled patients received standard elbow radiographs. Radiographs were reviewed by blinded radiologists for the presence of fracture and effusion. Sensitivity, specificity, and 95% confidence intervals (CIs) of examination findings were calculated.

One hundred thirteen patients were enrolled. Limitation of active ROM was 100% (95% CI, 0.93-1.00) sensitive for fracture or effusion. Preservation of active ROM was 97% (95% CI, 0.89-1.00) specific for the absence of fracture. Point tenderness was also highly sensitive but not specific.

Individuals with preservation of active ROM after acute elbow trauma have a very low risk of associated fracture and may not require radiographic studies.

Note: We're currently undertaking a multi-center validation study.

5. Deceptive Pharma Tactics under the Guise of Research

Seeding trials are not fictional

Ann Intern Med 2008;149:251-8.

It has long been suggested that drug companies use clinical trials to get doctors into the habit of prescribing newly approved drugs. A systematic review found only six articles that focused on the topic of such trials—four editorials and two observational studies published between 1994 and 2008. However, none of these publications could unequivocally prove that these trials—known as seeding trials—exist and that they are used by drug companies primarily for marketing purposes.

A case study of documents ordered by the court during an investigation of the ADVANTAGE (assessment of differences between Vioxx and naproxen to ascertain gastrointestinal tolerability and effectiveness) trial shows that the trial—which included 600 physician investigators and more than 5500 patients—was designed, executed, and analysed by the marketing division of Merck, the manufacturer of Vioxx. Merck’s internal documents indicate that the increased prescribing rates for Vioxx were of major interest to the company. Moreover, patients, doctors, and review boards members were not informed of the true purpose of the trial.

Institutional review boards should routinely ask—"Is this a seeding trial?"—suggests the linked editorial (p 279). The editorialists believe that companies would think twice before lying to these boards. Also, review boards, doctors, and patients alike should look for clues that a trial might be a seeding trial. Indications include posing research questions that have already been settled, open label design, lack of control group, large number of patients enrolled relative to the importance of the question, a short term study of a chronic disease, and a study of an already approved drug.

6. IV Ketamine Is Effective for Procedural Sedation in Adults

But its safety is not yet clear.

Ketamine is commonly used for procedural sedation in children, but its use in adults has not been well studied. Researchers in England conducted a prospective, observational study of adult patients who received intravenous ketamine for procedural sedation at a single emergency department during a 2-year period. Patients with contraindications to ketamine, such as ischemic heart disease, congestive heart failure, and previous psychotic illness, were excluded. Patients received an initial ketamine dose of 0.5 mg/kg, and the dose was repeated if sedation was inadequate after 5 minutes.

Adequate sedation was achieved in 91 of 92 patients and was achieved after one dose in 46 patients. The procedure was successfully completed in 98% of patients. Overall, 22% of patients had adverse events, including vomiting (4%), clonic movements (4%), and agitation (13%). Midazolam successfully treated agitation in all 7 of the 12 agitated patients who required treatment. During sedation, heart rate increased by a mean of 30.2 beats per minute, and systolic blood pressure increased by a mean of 25.4 mm Hg.

Comment: Ketamine is an attractive agent for procedural sedation because it maintains airway protective reflexes while providing both analgesic and sedative effects. However, emergence reactions and increases in BP and heart rate raise concerns about its use in adults. Emergence reactions necessitated the use of midazolam in 7% of study patients. In addition, patients in whom BP and heart rate increases could cause potential harm were excluded, so no conclusions can be drawn about ketamine’s safety in such patients.

— Diane M. Birnbaumer, MD, FACEP. Published in Journal Watch Emergency Medicine September 5, 2008. Citation: Newton A and Fitton L. Emerg Med J 2008 Aug; 25:498.

7. COPD as a Systemic Disease: Impact on Physical Functional Limitations

Eisner MD, et al. Amer J Med. 2008;121:789-796.

Although chronic obstructive pulmonary disease (COPD) has a major impact on physical health, the specific impact of COPD on physical functional limitations has not been characterized clearly. We aimed to elucidate the physical functional limitations that are directly attributable to COPD compared to a matched referent group without the condition.

We used the Function, Living, Outcomes, and Work (FLOW) cohort study of adults with COPD (n=1202) and referent subjects matched by age, sex, and race (n=302) to study the impact of COPD on the risk of a broad array of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery [SPPB]), submaximal exercise performance (Six Minute Walk Test [SMWT]), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multivariate analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking.

COPD was associated with poorer lower extremity function (mean SPPB score decrement for COPD vs referent −1.0 points; 95% CI, −1.25 to −0.73 pts) and less distance walked during the SMWT (−334 feet; 95% CI, −384 to −282 ft). COPD also was associated with weaker muscle strength in every muscle group tested, including both the upper and lower extremities (P less than .0001 in all cases) and with a greater risk of self-reported functional limitation (OR 6.4; 95% CI, 3.7 to 10.9).

A broad array of physical functional limitations were specifically attributable to COPD. COPD affects a multitude of body systems remote from the lung.

8. Walk-In Urgent Care Clinics Becoming Popular Options for Health Care

The California Healthline. August 06, 2008. Patients seeking prompt care for injuries or illnesses increasingly are turning to walk-in urgent care clinics, the Wall Street Journal reports.

According to the Journal, such clinics require no appointment and offer extended weekend and evening hours, helping to "fill the gap" between the need for care and an increasingly limited supply of primary care physicians and crowded emergency departments.

In addition, care at urgent care clinics often costs less than what EDs charge, even for people with insurance, and many clinics offer additional discounts or payment plans for uninsured patients, according to the Journal.

Urgent care clinics are staffed by physicians and other medical personnel and in many cases have equipment, such as X-ray machines, that physicians in a traditional practice would have to refer patients to other offices or hospitals to receive.

Urgent care clinics are expanding faster than EDs, with a total of more than 8,000 clinics nationwide, allowing for more and faster patient care.

Meanwhile, the number of EDs decreased from 4,176 to 3,795 between 1995 and 2005 while the number of ED visits increased by 20% to 115.3 million during that same time period, according to CDC.

Urgent care clinics have existed for 20 years but experienced a surge in use recently as more patients encountered long waits to schedule appointments with their PCP or to receive care in an ED, the Journal reports.

Concerns About Quality, Safety

As the number of urgent care clinics increases, concerns have risen regarding their safety and quality, the Journal reports.

In addition, there also are concerns that patients may substitute treatment at urgent care clinics for an "ongoing relationship with a primary care doctor who coordinates care and follows them over time," according to the Journal.

Physicians working in urgent care clinics must be licensed but clinics often are not licensed or regulated, leading to large variances and differences between each facility. Some clinics have opted to undergo voluntary accreditation programs that evaluate their quality and safety, but there are no national standards for the facilities.

The Urgent Care Association of America recently reached an agreement with the Joint Commission to take over accreditation of these clinics and publish national quality standards by 2010.

According to UCAOA Executive Director Lou Ellen Horwitz, the goal of having the commission oversee the clinics is to avoid future regulation and to establish guidelines that can help patients and insurers evaluate the clinics. She added that patients should have a PCP and seek care in urgent care clinics when they are unable to see their regular physicians (Landro, Wall Street Journal, 8/6).

For more information, please visit:

9. Management of Acute Peptic Ulcer Bleeding Reviewed

Laurie Barclay, MD. August 27, 2008 — Recommendations for initial triage, medical therapy, and surgical considerations for the management of acute gastrointestinal tract bleeding from a peptic ulcer are reviewed in the August 27 issue of the New England Journal of Medicine.

"Acute upper gastrointestinal hemorrhage, which is defined as bleeding proximal to the ligament of Treitz, is a prevalent and clinically significant condition with important implications for health care costs worldwide," write Ian M. Gralnek, MD, MSHS, from the Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion Israel Institute of Technology in Haifa, Israel, and colleagues. "Negative outcomes include rebleeding and death, and many of the deaths are associated with decompensation of coexisting medical conditions precipitated by the acute bleeding event....In most settings, the vast majority of acute episodes of upper gastrointestinal bleeding (80 to 90%) have nonvariceal causes, with gastroduodenal peptic ulcer accounting for the majority of lesions."

In the United States, there are approximately 160 hospital admissions for acute upper gastrointestinal tract hemorrhage per 100,000 population, or more than 400,000 per year, with an increasing proportion of episodes associated with use of aspirin and nonsteroidal anti-inflammatory drugs. More than two thirds of patients are older than 60 years, and more than one quarter are older than 80 years. Mortality rate is 5% to 10%.

The most frequent presenting signs of acute upper gastrointestinal tract hemorrhage are hematemesis and melena. Initial evaluation should include hemodynamic assessment with orthostatic vital signs, and the first priority in treatment is to correct fluid loss with crystalloid intravenous fluids and restore hemodynamic stability. The use of supplemental oxygen and transfusion of plasma expanders with the use of packed red blood cells should be considered, especially in frail or elderly patients, with tachycardia, hypotension, or a hemoglobin level less than 10 g/dL. Coagulopathy should be corrected.

Nasogastric tube insertion may be helpful during triage, but it is unclear how much additional information it provides. Intravenous erythromycin promotes gastric motility and significantly improves gastric mucosa visualization on initial endoscopy, but it has not been proven to improve diagnostic yield or outcome.

Clinical scores that may be useful to facilitate patient triage include the Blatchford score (see URL below) and the Rockall score; these may reduce the need for urgent endoscopy in low-risk patients. The Forrest classification uses the endoscopic appearance of a bleeding ulcer to predict the likelihood of recurrent bleeding. High-risk lesions are those with active blood spurting (grade IA) or oozing (grade IB), a nonbleeding visible vessel appearing as a pigmented protuberance (grade IIA), and an adherent clot that cannot be dislodged by suction or forceful irrigation (grade IIB). Low-risk lesions are flat, pigmented spots (grade IIC) and clean-base ulcers (grade III).

The approach to an acutely bleeding gastrointestinal tract ulcer should be multidisciplinary, with early involvement of a trained endoscopist and endoscopy assistant. Endoscopy performed within 24 hours after presentation may improve outcomes such as the number of units of blood transfused and the length of the hospital stay for selected high-risk patients. The risk of rebleeding is greatest in the first 72 hours.

High-risk patients should be hospitalized, receive endoscopic therapy, and then triaged to a monitored setting or intensive care unit for the first 24 hours, with total hospital stay usually at least 3 days. Endoscopic hemostasis has been shown to decrease rebleeding rates, the need for urgent surgery, and mortality rates. Other endoscopic treatments may include injection therapy with saline, vasoconstrictors, sclerosing agents, and/or tissue adhesives; thermal therapy with contact or noncontact methods; and mechanical therapy, usually with endoscopic clips.

Each method of endoscopic hemostasis has been proven superior to no endoscopic intervention, but adding a second hemostatic approach further decreases rebleeding rates, the need for surgery, and mortality rates. Epinephrine injection alone should be avoided.

Although a consensus statement recommends combination therapy with epinephrine injection, volume tamponade, and obtaining a clear view of the bleeding vessel, followed by targeted contact thermal therapy, this may be no better than contact thermal therapy alone. Endoscopic therapy in high-risk patients with an adherent clot remains controversial. Endoscopic clips alone may give similar outcomes to those seen with thermal therapy alone, a combination of injection and contact thermal therapy, and clips followed by injection.

Planned, second-look endoscopy within 24 hours after initial endoscopic therapy is not recommended, but a second endoscopy may be considered on a case-by-case basis for clinical signs of recurrent bleeding or uncertainty regarding the effectiveness of initial hemostasis.

After endoscopy, low-risk patients can be discharged home and treated conservatively.

For the treatment of patients with nonvariceal upper gastrointestinal tract hemorrhage, pharmacotherapy has centered on profound acid suppression with proton pump inhibitors. Increasing and maintaining the intragastric pH to 6 or more may promote clot stability, but this goal is theoretical, difficult to achieve, and may not reflect clinical efficacy. Use of histamine H2-receptor antagonists has not significantly improved outcomes.

Meta-analyses have shown that proton pump inhibitors significantly reduce the risk for ulcer rebleeding, the need for urgent surgery, and the risk for death. However, in high-risk patients, mortality rate is lower only in patients who have first undergone endoscopic therapy, suggesting that medical therapy should be an adjunct to, but not a replacement for, endoscopic hemostasis in this group.

The use of an intravenous bolus of proton pump inhibitors followed by a continuous infusion for 72 hours after endoscopic hemostasis may be recommended, but optimal dosing is still controversial. Use of high-dose intravenous proton pump inhibitors while the patient is awaiting endoscopy does not appear to affect the outcome but may be associated with downstaging of endoscopic lesions.

Somatostatin and octreotide inhibit acid and pepsin secretion while decreasing gastroduodenal mucosal blood flow, but they are not routinely recommended in patients with peptic ulcer bleeding.

Surgical rates for management of a bleeding peptic ulcer are currently approximately 5% to 7%. Various surgical approaches include vagotomy or drainage with vagotomy and resection, and alternative options include repeated endoscopic hemostasis or angiography with transcatheter embolization.

"Because of a new understanding of peptic ulcer disease, the role of surgery has changed markedly within the past two decades and now obviates the need for routine early surgical consultation in all patients presenting with acute upper gastrointestinal hemorrhage," the reviewers write. "The aim of emergency surgery is no longer to cure the disease but rather to stop the hemorrhage when endoscopic therapy is unavailable or has failed. The role of early elective surgery is less clear, as is the optimal surgical approach in patients with acute disease."

N Engl J Med. 2008;359:928-937.

Blatchford Score (Lancet 2000):

10. Application of San Francisco Syncope Rule in elderly ED patients

Schladenhaufen R, et al. Amer J Emerg Med. 2008;26:773-778.

The San Francisco Syncope Rule (SFSR) is a decision rule with the potential to identify patients at risk for serious outcomes within 7 days of the emergency department (ED) visit for syncope. The initial studies of the SFSR reported a high sensitivity and specificity for identifying patients, of all ages, with serious outcomes. Our objective was to determine if the SFSR can be safely and accurately applied to ED patients aged 65 and older with syncope or near-syncope.

A retrospective review of ED patients aged 65 years and older with syncope or near-syncope between January 2000 and August 2001 was performed. Charts were reviewed for evidence of SFSR risks for the ED visit and serious outcomes within 7 days of the ED visit.

Of 773 subjects identified as having syncope or near-syncope, 517 subjects were included. There were 98 patients with serious outcomes. Twenty-three patients who were negative on SFSR had serious outcomes. The sensitivity and specificity of the SFSR were 76.5% (95% confidence interval [CI], 66.7%-84.3%) and 36.8% (95% CI, 32.2%-41.6%), respectively. The negative and positive predictive values were 87.0% (95% CI, 80.9%-91.4%) and 22.1% (95% CI, 17.8%-26.9%), respectively.

In our cohort of elderly ED patients, the SFSR had a lower sensitivity and specificity. The SFSR may not be applicable to the elderly ED population. Future prospective validation is necessary before application to the ED elderly population.

To review the history of the SF syncope rule and its 5 elements, go here:

11. Nuts, corn, and popcorn don’t seem to be bad for diverticular disease

Strate LS, et al. JAMA 2008;300:907-14.

Nuts may protect people from cardiovascular disease, diabetes, cancer of the colon and prostate, and cholelithiasis. But people who have diverticular disease are usually advised to avoid nuts, along with seeds, popcorn, corn, and other high residue foods because they might mechanically damage the intestinal mucosa and precipitate inflammation and bleeding. A large prospective cohort study failed to find the evidence to support this theory.

The study included more than 47 000 men, aged 40-75 years, who at baseline did not have diverticulosis, cancer, or inflammatory bowel disease. During the 18 year follow-up, these men provided information, collected by questionnaires, on their health (every two years) and on nutrition (every four years). The occurrence of diverticulosis and its complications had little to do with consuming nuts, corn, or popcorn. The researchers found that, in fact, nuts and popcorn might protect against developing diverticulitis. Compared with men who reported eating popcorn less than once a month, men who ate it at least twice a week had a lower risk of diverticulitis (hazard ratio 0.72, 95% CI 0.56 to 0.92; the corresponding numbers for nuts were 0.80, 0.63 to 1.01).

The researchers admit that, despite extensive adjustment for confounders, because of the observational nature of the study they couldn’t exclude residual confounding by a lifestyle factor or other unmeasured factor as a potential explanation for the study’s findings. Still, the results do suggest that the current advice should be reconsidered.

12. Severe Community-Associated Staphylococcus aureus Infections in California: The First Six Months of Reporting

Severe Staphylococcus aureus infection in a “previously healthy person” has been a reportable condition in California since February 13, 2008. For this surveillance, a severe infection is defined as one resulting in death or admission to an intensive care unit, and a previously healthy person is defined as one who has not been hospitalized or had surgery, dialysis, or residency in a long-term care facility in the past year, and did not have an indwelling catheter or percutaneous medical device at the onset of illness. A S. aureus infection in a person without these healthcare-associated risk factors would be considered community-associated.

Between February 13 and August 15, 2008, 92 cases of severe community-associated S. aureus were reported from 23 counties to CDPH. Included in the 92 cases were 36 deaths. The median age is toward an older adult but 13 (14%) cases and 3 (8%) deaths were less than 18 years old. There were more male than female cases and deaths. Of the types of infection, cases with pneumonia were more commonly reported than other types. Methicillin-resistant S. aureus (MRSA) represented 73% of cases, similar to the 50-75% nationwide prevalence of MRSA.
Underlying conditions (not shown) were reported in 69 (75%) cases. Of these, diabetes was most common and reported in 20 (22%) cases; 7 of these patients with diabetes had skin and soft tissue infections.

We appreciate the effort by staff of local health departments and hospitals in providing these reports. After a full year of reporting, we will provide a more detailed summary of this surveillance. Please continue to identify and report patients with severe community-associated Staphylococcus aureus infections who fit the surveillance case definition. For any questions about potential cases or this surveillance, please contact Dr. Jon Rosenberg of the Infectious Diseases Branch of CDPH at or (510) 620-3434.

13. Helical CT Is More Accurate Than Clinical Judgment for Diagnosing Appendicitis

Even in cases of clinically apparent appendicitis

The role of multidetector computed tomography (MDCT) scanning in the diagnosis of appendicitis is evolving as technology and resolution improve. Researchers in Korea compared the diagnostic accuracy of 16-detector MDCT scanning and clinical impression in 157 consecutive patients who presented to two emergency departments with signs or symptoms that raised concern for possible appendicitis.

All patients were evaluated by emergency physicians and senior residents who determined whether the clinical diagnosis was appendicitis. All patients then underwent MDCT with intravenous contrast only. MDCT scans were read by two radiologists who specialized in CT interpretation. The final diagnosis of appendicitis was based on surgical pathology or clinical follow-up. The positive predictive value of the examining physician’s clinical impression was 73%, and the negative predictive value was 56%. Corresponding values for MDCT were 97% and 97%.

Comment: These findings suggest that MDCT scanning is more accurate than clinical judgment for diagnosing appendicitis, even in cases that are considered to be "clinically apparent." However, not all radiologists who interpret CT scans are CT specialists, and CT scans are not read by two radiologists in most EDs. Patients with suspected appendicitis, especially women, should undergo abdominal CT scanning to confirm or exclude the diagnosis, with the exception of patients whose diagnosis is considered "certain" by the attending surgeon and who are taken directly to the operating room without imaging.

— Diane M. Birnbaumer, MD, FACEP. Published in Journal Watch Emergency Medicine September 5, 2008. Citation: Kim K et al. Emerg Med J 2008 Aug; 25:477.

14. Groups Tout Program Aimed at Cutting ED Use in California

August 18, 2008. Supporters of a five-year pilot program that directed frequent users of hospital emergency departments to other sources of health care are lobbying the Legislature to approve a similar effort, the Fresno Bee reports.

Six counties -- Alameda, Los Angeles, Sacramento, Santa Clara, Santa Cruz and Tulare -- participated in the pilot, which is set to end next month. It was funded by $10 million in grants from the California Endowment and the California HealthCare Foundation.


According to the Bee, ED visits declined by about 35% for participants in the program.

In addition, preliminary findings from the Lewin Group, a Virginia-based consulting firm, show that:

- Hospital and ED charges decreased by $9,715 for each frequent user of EDs identified in the program;
- Hospital admissions decreased by 30%; and
- Between 24% and 69% of people identified in the program were successfully enrolled in other services, including Medi-Cal.

Lobbying Efforts

Supporters of the program estimate that it would cost the state about $10 million to launch the initiative statewide but that the cost of the program would be offset by savings from preventing hospital ED visits.

Groups lobbying the Legislature for the program include the:

- California Association of Public Hospitals;
- California Medical Association;
- California State Association of Counties; and
- Western Center on Law and Poverty (Correa, Fresno Bee, 8/16).

15. Placebo effect may be greater in children than in adults

Rheims S, et al. PLoS Med 2008;5:e166

Children are too often prescribed drugs without evidence from paediatric trials. A systematic review compared the 50% responder rate—50% or greater reduction in seizure frequency during the treatment period compared with baseline—between active antiepileptic treatment and placebo in five trials in children and 27 trials in adults with drug resistant partial epilepsy.
The treatment effect was significantly lower in children than in adults (relative risk ratio 0.67, 95% CI 0.51 to 0.89) because children because children had a greater response to placebo (19% v 9.9%; P less than 0.001). The response to the active treatment was comparable in children and adults (37.2% v 30.4%, respectively; P=0.364).

The linked perspective (e172) stresses that children are not just small adults, and that trials are lacking in many paediatric specialties. The authors outline the methodological features that researchers should embrace in future trials. In particular, trials in children may need to be bigger than trials of the same drugs in adults to avoid false negative findings as a result of children responding better to placebo.

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16. A Little Hand Hygiene Goes a Long Way

Meta-analysis results of community-based intervention studies indicate that use of nonantibacterial soap and hand-hygiene education significantly reduce respiratory and GI illnesses.

Does hand washing really reduce the incidence of gastrointestinal (GI) and respiratory illnesses in the community, and, if so, by how much? Which is better: alcohol-based hand sanitizers, nonantibacterial (plain) soap, or antibacterial soap? To answer these questions, investigators from the University of Michigan and Columbia University identified more than 5000 relevant studies published from 1960 to 2007 and pooled results from 30 community-based intervention studies (conducted in developed and developing countries) that met criteria for review (19 of the 30 studies focused on children aged 5 years and younger).

Compared with no education, hand-hygiene education alone (7 studies) significantly reduced the risk for GI illness by 31% and for respiratory illness (4 studies) by 14%. Education plus use of nonantibacterial soap (6 studies) significantly reduced the risk for GI illness by 39% and for respiratory illness (1 study) by 51%, compared with control conditions, but had no significant effect in the two studies that combined the two outcomes. In two studies, use of antibacterial soaps did not offer an advantage over plain soap for either illness. Although alcohol-based hand sanitizer plus education did not reduce the risk for either illness alone, this strategy showed a protective effect in the three studies that combined the two outcomes (21% reduction). In two studies, benzalkonium chloride–based hand sanitizer significantly reduced the risk for GI and respiratory illnesses alone and the two outcomes combined by about 40%.

Comment: This meta-analysis provides us with solid community-based (vs. hospital-based) research to use when educating patients about the virtues of hand washing. Education is essential: The authors cite results from a U.S. study of 7800 participants indicating that only 67% (75% of women and 58% of men) washed their hands after using a public restroom. The finding that plain soap works as well as antibacterial soaps is reassuring, given concerns that use of antibacterial soaps might actually promote emergence of antibiotic-resistant bacteria. When I extolled the virtues of hand washing in my annual flu-prevention message to students, one responded that my advice seemed mundane. If parents and children discount this simple but effective prevention technique because it is not high-tech, that would be unfortunate. I’m going to keep washing my hands and telling students to do the same.

— Alain Joffe, MD, MPH, FAAP. Published in Journal Watch Pediatrics and Adolescent Medicine September 10, 2008. Citation: Aiello AE et al. Am J Public Health 2008 Aug; 98:1372.

17. Aspirin/Dipyridamole vs. Clopidogrel to Prevent Recurrent Stroke: A Toss-Up?

Sacco RL, et al. N Engl J Med. 2008; Published on-line August 27, 2008.

Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extended-release dipyridamole (ASA–ERDP) versus clopidogrel.

Methods: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.

Results: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).

Conclusions: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.

18. Thrombolysis Appears to Be Safe Up to 4.5 Hours After Stroke Onset

Susan Jeffrey. September 17, 2008 — Observational data from a large European registry suggest that thrombolysis may be safe up to 4.5 hours after stroke onset, an hour and a half longer than current recommendations of a 3-hour limit.

Results from the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS-ISTR), an observational audit of patients treated with intravenous alteplase, a tissue plasminogen activator (tPA), for acute ischemic stroke showed no significant difference in outcomes between patients treated between 3 and 4.5 hours after symptom onset and those treated before the recommended threshold of 3 hours.

If these findings are confirmed in the soon-to-report European Cooperative Acute Stroke Study 3 (ECASS 3) randomized trial comparing tPA treatment vs placebo in patients presenting between 3 and 4.5 hours after symptom onset, more patients with ischemic stroke may be eligible for therapy.

"Today, only a minority of stroke patients can be treated, mainly because of the restriction of the time window, and an increase of that window by 50% would make it possible to treat more patients," first author Nils Wahlgren, MD, at Karolinska University Hospital in Stockholm, Sweden, said in an interview. "We don't want to encourage a delay in treatment, but for patients who are not available before that time limit, it would be an advantage to be treated after 3 hours."

The SITS-ISTR results are published in the September 15 Online First issue of The Lancet. The ECASS 3 results are scheduled to be presented on September 25, 2008, during the World Stroke Congress in Vienna, Austria, and will be reported at that time by Medscape Neurology & Neurosurgery.

Provisional Approval

Subsequent to results of the major clinical trials of tPA during the 1990s, alteplase was approved for use in the United States in 1996 and in Canada in 1999 for patients with ischemic stroke treated within 3 hours of symptom onset. However, the European Medicines Evaluation Agency was more conservative, giving only provisional approval in 2002. One of 2 conditions for licensing was that an observational study be implemented to assess the safety of tPA in routine practice.

The results from that study, called the Safe Implementation of Thrombolysis in Stroke Monitoring Study, were reported last year and confirmed that the rates of symptomatic intracerebral hemorrhage, mortality, and independence reflecting good functional outcome were similar in clinical practice to those seen in the randomized trials, although the analysis was limited to those patients who met approved criteria for treatment (Wahlgren N et al. Lancet. 2007;369:275-282).

The second condition was the randomized trial ECASS 3. Results of a meta-analysis of pooled data from randomized trials had suggested that the proportion of patients who benefit from tPA declines with time, the authors note, but that there is still significant benefit for up to 4.5 hours after symptom onset (Hacke W. et al. Lancet 2004;363:768-774).

In this study, Dr. Wahlgren and colleagues used data from the SITS, a prospective, Internet-based audit of the ISTR. SITS represents the collaboration of more than 700 clinical centers in 35 countries documenting the use of tPA, where all treated patients are registered whether they meet approved criteria for treatment.

In this analysis, they compared outcomes in 664 patients who were given tPA between 3 and 4.5 hours after symptom onset vs those of 11,865 patients treated within the recommended 3-hour window. Except for the time window in which they were treated, all patients still met the criteria for treatment, including a computed tomography scan clear of any evidence of bleeding.

Dr. Wahlgren noted that the decision to treat with tPA after 3 hours was made in the institutions and would have been made on an individual basis. For example, if a patient has given informed consent and has been prepared for treatment, he pointed out, "it would be very difficult to say to the patient we cannot treat you any longer because you have past the time line of 3 hours."

In the 3- to 4.5-hour cohort, treatment was started at a median of 55 minutes later after symptom onset, at approximately 195 minutes vs 140 minutes in the 3-hour cohort (P less than .001). These patients were also significantly younger and had less severe strokes than those treated within 3 hours.

In the end, the investigators found no significant differences between patients treated within 3 hours and those treated between 3 and 4.5 hours in the rate of symptomatic intracerebral hemorrhage, mortality rate, or the rate of those who were independent (modified Rankin scale 0 - 2) at 3 months.

After the results of ECASS 3 are reported, discussions during the Karolinska Stroke Update Consensus Conference in November will provide some direction for any adjustments to current guidelines on the time window for treatment by the European Stroke Organization, Dr. Wahlgren said.

A Safe Option

In a commentary accompanying the publication, Georgios Tsivgoulis, MD, from the Democretus University of Thrace, University Hospital Alexandroupolis, Greece, and Andrei V. Alexandrov, MD, from the University of Alabama at Birmingham, call the results, "promising nonrandomized data which show that extension of the time frame of thrombolysis might be a safe and feasible option."

They note that after adjustment for potential confounders, there was a nonsignificant increase in the risk for symptomatic intracerebral hemorrhage and mortality in this study, amounting to absolute differences of 0.6% and 0.5% respectively, although imbalances in baseline characteristics may have accounted for this.

In addition, half of the patients in the 3- to 4.5-hour cohort were treated just 15 minutes after the 3-hour limit, they point out, with 60% treated within 180 to 200 minutes after symptom onset. Although understandable, "this skew could weaken the overall impression that reliable data are available for 3 - 4.5 hours," they note. Drs. Tsivgoulis and Alexandrov also add that symptomatic intracerebral hemorrhage was self-reported by the investigators, which means potential selection bias cannot be ruled out, and because patients older than 80 years and those with more severe strokes (NIHSS score above 25) were excluded, these results cannot be generalized to these patients.

"Whether ECASS 3 is positive or not, the SITS-ISTR findings support continuing efforts to extend the time frame for thrombolysis," Drs. Tsivgoulis and Alexandrov write. Another trial in this extended period, the International Stroke Trial 3 is also ongoing, and other trials selecting patients for treatment on the basis of imaging studies are also underway.

"We are looking forward to moving away from rigid timeframes to treatment on the basis of imaging that can assess brain pathophysiology and tissue viability," they conclude.

The SITS-ISTR is funded by an unrestricted grant from Boehringer Ingelheim and the European Union Public Health Executive Authority. Dr. Wahlgren has received expenses from Boehringer Ingelheim for this role as member of the Steering Committee in relationship to the ECASS 3 trial with alteplase and has served as a consultant to Thrombogenics as chairman of the data safety and monitoring board. He has also received lecture fees from Boehringer Ingelheim and from Ferrer. A complete list of disclosures is available in the original article.

Drs. Tsivgoulis and Alexandrov have disclosed no relevant financial relationships.

Lancet. Published online September 15, 2008.

19. Telemedicine for Stroke Patients

Telemedicine consultation with a stroke-certified neurologist might increase appropriate use of thrombolytic agents in stroke patients.

Many patients with ischemic stroke who are eligible for alteplase therapy do not receive it because the agent must be administered within 3 hours from onset of symptoms and because emergency physicians might want to involve stroke neurologists in primary decision making regarding the use of thrombolytics. Researchers evaluated whether remote consultation with a stroke neurologist could increase appropriate use of thrombolytic agents for stroke patients.

Patients with acute stroke symptoms who presented to one of four remote hospitals from 2004 to 2007 were randomized to telemedicine or telephone-only consultation by neurologists who were National Institute of Health Stroke Scale (NIHSS) certified. During the telemedicine consultation, the consultant took a medical history, performed a physical assessment, calculated the NIHSS score, and reviewed head computed tomography (CT) scans, in concert with the local EP. Telephone consultations differed in that the consultant could not speak directly with or view the patient and relied on the local radiologist’s interpretation of the CT scan. In both scenarios, the consultant made a decision about whether to administer thrombolytic agents. The correctness of the decision — the primary outcome measure — was determined by an independent committee of stroke specialists.

Of 222 patients, 104 in the telemedicine group and 103 in the telephone group completed the study. Mean NIHSS scores at presentation were significantly higher in the telemedicine group than in the telephone group (11.4 vs. 7.7). Correct decision making was significantly more likely in the telemedicine group than in the telephone group (98% vs. 82%; odds ratio, 10.9). However, no differences were noted between groups in any of the secondary outcome variables, including rate of alteplase administration (28% vs. 23%), 90-day functional outcomes, mortality, or rate of intracranial hemorrhage after alteplase administration (7% vs. 8%). The time from call to decision making was significantly longer in the telemedicine group than in the telephone group (65 vs. 55 minutes).

Comment: This study suggests that remote consultation with a stroke neurologist can obviate the need for an on-site neurologist and enable high and appropriate rates of thrombolytic administration for patients with ischemic stroke. Telemedicine, which is expensive and not routinely available, provided better decision making but no other derivative advantages.

— John A. Marx, MD, FAAEM, FACEP. Published in Journal Watch Emergency Medicine August 22, 2008. Citation: Meyer BC et al. Lancet Neurol 2008 Sep; 7:787

20. Professionalism During Residency Linked to Better Test Scores, Clinical Skills

By Anthony J. Brown, MD. NEW YORK (Reuters Health) Sept 16 - Residents regarded as highly professional by their peers score better on In-Training Examinations (ITE) and exhibit better clinical skills and more conscientious behaviors than their less-professional colleagues, according to a report in the Journal of the American Medical Association for September 17.

"Most prior studies on professionalism focus on unprofessional behaviors while this study has a very positive focus on the knowledge, skills, and behaviors demonstrated by highly professional physicians," lead author Dr. Darcy A. Reed told Reuters Health.

"The assessment of professionalism in this study," she added, "is also unique in that it incorporates observation-based assessments from multiple groups (peers, senior residents, faculty, medical students, and non-physician professionals) rather than a single measure of professionalism."

Dr. Reed and colleagues from the Mayo Clinic in Rochester, Minnesota, investigated the link between professionalism and ITE scores, clinical skills (Mini-Clinical Evaluation Exercise), conscientious behaviors, and residency warning/probation notices in 148 first-year internal medicine residents.

A professionalism score was generated for each subject based on observation ratings from peers, senior residents, medical students, faculty, and non-physician professionals over 1 year. Residents were considered to be highly professional if the total professionalism score was at the 80th percentile or higher.

Highly professional residents had significantly higher ITE scores and were more skilled clinically than less-professional residents, the report indicates. In addition, highly professional residents completed a greater percentage of required evaluations, a measure of conscientious behavior. Multivariate analysis confirmed the independent nature of all three associations.

Conversely, a low professionalism score correlated with receipt of a warning or probation from the residency program. Of the eight residents who received a warning/probation, six had professionalism scores at or below the 20th percentile.

"The results of this comparative study further the understanding of professionalism in medicine," the authors conclude. "Our findings strengthen the notion of professionalism as a multidetermined construct by contributing new information about specific knowledge, skills, and behaviors associated with professionalism during residency."

Dr. Reed added that "the relationship between professionalism and other competencies, both medical knowledge and clinical practice assessed in this study, as well as other competencies such as systems-based practice, practice-based learning and improvement require further investigation."

JAMA 2008;300:1326-1333.

21. Clinical Guidelines Released for Identifying, Treating Cerumen Impaction--STAT

ALEXANDRIA, Va -- August 29, 2008 -- The American Academy of Otolaryngology -- Head and Neck Surgery Foundation (AAO-HNSF) will issue the first comprehensive clinical guidelines to help healthcare practitioners identify patients with cerumen impaction.

The guidelines emphasise evidence-based management of cerumen impaction by clinicians and inform patients of the purpose of ear wax in hearing health.

"Approximately 12 million people a year in the United States seek medical care for impacted or excessive cerumen," said Richard Rosenfeld, MD, AAO-HNSF Guideline Development Task Force, Alexandria, Virginia.

"This leads to nearly 8 million cerumen removal procedures by healthcare professionals. Developing practical clinical guidelines for physicians to understand the harm versus benefit profile of the intervention was essential."

Recognising that patients may seek care from many different types of healthcare providers, the taskforce developed guidelines intended for all clinicians who are likely to diagnose and manage patients with cerumen impaction.

Key features of the new guidelines include:
· Cerumen is a beneficial, self-cleaning agent, with protective, lubricating (emollient), and antibacterial properties.
· Clinicians should examine patients with hearing aids for cerumen impaction because it may cause feedback, reduce sound intensity, or damage the hearing aid.
· Cerumen may cause reversible hearing loss when it blocks 80% or more of the ear canal diameter.
· Appropriate options for cerumen impaction are (1) cerumenolytic agents, which include water, saline, and other agents of comparable efficacy; (2) irrigation or ear syringing, which is most effective when a cerumenolytic is instilled 15 to 30 minutes prior; and (3) manual removal with special instruments or a suction device, which is preferred for patients with narrow ear canals, eardrum perforation or tube, or immune deficiency.
· Inappropriate or harmful interventions are cotton-tipped swabs, oral jet irrigators, and ear candling.
· Clinicians should assess patients at the conclusion of in-office treatment for cerumen impaction and document resolution of the impaction.
· There are no proven ways to prevent cerumen impaction, but not inserting cotton-tipped swabs or other objects in the ear canal is strongly advised; individuals at high risk should consider seeing a clinician every 6 to 12 months for routine cleaning.

"The complications from cerumen impaction can be painful and ongoing, including infections and hearing loss," said Dr. Roland. "It is hoped that these guidelines will give clinicians the tools they need to spot an issue early and avoid serious outcomes."

Otolaryngology–Head and Neck Surgery (2008) 139, S1-S21. Full-text (free):