Wednesday, October 17, 2007

Lit Bits: October 17, 2007

From the recent medical literature...

1. Rapid Assessment, Treatment of Minor Stroke Radically Reduces Major Stroke Risk

October 11, 2007 — Rapid assessment and treatment of a first transient ischemic attack (TIA) or minor ischemic stroke dramatically reduces risk for subsequent major stroke. Two separate studies — one in the Lancet and the other in Lancet Neurology — show that such an approach reduces recurrent stroke risk by about 80%.

Initially presented in June 2007 at the 16th European Stroke Conference and reported by Medscape Neurology & Neurosurgery at that time, the Early Use of Existing Preventive Strategies for Stroke (EXPRESS) study from Oxford University, in the United Kingdom, showed a relative risk reduction at 90 days in major recurrent stroke of more than 80% among patients who received early, aggressive treatment for TIA or minor stroke.

"Our data indicate that urgent assessment and early initiation of a combination of existing preventive treatments can reduce risk of early recurrent stroke after TIA or minor stroke by about 80%. . . . Extrapolated across the UK population, this equates to the prevention of nearly 10,000 strokes per year," the EXPRESS investigators write.

"Before-and-After" Study, published online October 9 in the Lancet.

Led by Peter Rothwell, MD, PhD, the EXPRESS study sought to determine whether it was possible to increase the speed at which symptomatic patients were assessed and treated and whether this would ultimately influence stroke recurrence. To do this, investigators used a 5-year, population-based "before-and-after" study design that compared standard management of TIA and minor stroke patients who were not admitted to the hospital with early, aggressive management in specialist clinics.

The EXPRESS study is nested within the Oxford Vascular Study (OXVASC), a population-based study of stroke and TIA that has had complete ascertainment of all incident and recurrent TIA and stroke in the county of Oxfordshire, England. As a result, case investigation and follow-up were complete and identical in both study phases. In the first 30-month study period, patients presenting with TIA or minor stroke were managed in a standard primary care setting. In the second 30-month period, a similar group of patients were assessed and treated in the specialty setting.

Assessment and Treatment Time Reduced

The treatment protocol was the same during both study periods and included a 300-mg loading dose and subsequent 75-mg daily dose of aspirin. This was combined with a 300-mg loading dose followed by a 75-mg daily dose of clopidogrel for 30 days. High-risk individuals were also prescribed 40 mg/day of simvastatin to treat elevated cholesterol, as well as antihypertensive medication when indicated. In addition, anticoagulation therapy and carotid endarterectomy was administered as required.

In phase 1, the median delay to assessment in the clinic was 3 days, with a median time to first prescription of treatment of 20 days. In phase 2 of the study, these values were reduced to 1 day for both assessment and prescription.

A total of 1278 patients presented with TIA or stroke — 634 in phase 1 and 644 in phase 2. Of these individuals, 607 were referred or presented directly to the hospital, and 620 were referred for outpatient assessment. Of those individuals assessed as outpatients, 51 were not referred for secondary care, leaving 591 patients for the final analysis.

Further Follow-Up Required

Investigators found that the 90-day risk for recurrent stroke in phase 1 patients was 10.3% (32 of 310 patients), while in phase 2 it was reduced to 2.1% (6 of 281 patients). They also found that the reduction was independent of age and sex and that early treatment did not increase the risk for intracerebral hemorrhage or other complications.

"Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke," the authors write.

In an accompanying editorial, Naeem Dean, MBBS, MRCP, FRCP, from the Royal Alexandra Hospital, in Edmonton, Alberta, and Ashfaq Shuaib, MD, FRCPC, FAHA, from the University of Alberta, in Edmonton, say the EXPRESS study results are "very important and should promote renewed attention to urgent care of patients with TIAs and minor strokes."

In the second study, Pierre Amarenco, MD, from Bichat-Claude Bernard University Hospital and Denis Diderot University and Medical School, in Paris, France, and colleagues set up a dedicated hospital clinic that provided 24-hour access specifically to assess and treat patients with suspected cerebral or retinal TIAs related to ischemia and whose symptoms lasted less than 24 hours. Patients were referred to the clinic by one of 15,000 family doctors, cardiologists, neurologists, and ophthalmologists who had previously been mailed information about it.

New Standard for Treatment of TIA, published online October 9 in Lancet Neurology.

Known as the SOS-TIA program, neurological, arterial, and cardiac imaging that took place within 4 hours of admission assessed TIA patients. The study's primary outcome was stroke within 90 days. The study included 1085 patients with suspected TIA who entered the SOS-TIA program between January 2003 and December 2005. Of these, 574 were seen within 24 hours of symptom onset; 701 had confirmed TIA or minor stroke and 144 had possible TIA.

The 643 patients with confirmed TIA all began a stroke prevention program, with 43 individuals undergoing urgent carotid revascularization and 44 individuals treated for atrial fibrillation with anticoagulants.

At 90 days, the stroke rate was 1.24%, compared with an expected rate of 5.96%. According to the authors, this suggests immediate treatment through a dedicated clinic reduced the risk for recurrence of TIA by almost 80%.

"We show prompt evaluation and treatment of patients with TIA in a dedicated outpatient unit is associated with a lower-than-expected risk of subsequent stroke. Because almost three-quarters of patients were discharged home on the same day as the diagnosis, the TIA clinic is also likely to involve lower costs and greater patient satisfaction about their management than is treatment without such a clinic," they write.

In an accompanying comment in Lancet Neurology, Walter Kernan, MD, and Joseph Schindler, MD, from Yale University School of Medicine, in New Haven, Connecticut, say Dr. Amarenco and colleagues have forged an important new paradigm for the early treatment of TIA and minor ischemic stroke. "Rapid assessment and intervention is emerging as the new standard for TIA care. . . . We believe that the time is right to accept this new standard and to begin use of rapid access as a platform for rigorous testing of innovative strategies for TIA care," they write.

The authors of the SOS-TIA study declare they have no conflicts of interest. Dr. Rothwell has received honoraria for talks, payment for occasional consultancy, and research funding from several pharmaceutical companies that manufacture drugs used in the secondary prevention of stroke. All other authors declare that they have no conflict of interest.

2. ED Crowding Linked to Higher ACS Complication Rate

from Heartwire — a professional news service of WebMD. October 16, 2007 (Seattle, WA) - A high level of crowding in the emergency department (ED) was predictive of a higher rate of later cardiovascular complications in patients with potential ACS, a new study has shown [1].

The study was presented by Dr Jesse Pines (University of Pennsylvania, Philadelphia) at the American College of Emergency Physicians (ACEP) 2007 Scientific Assembly, held here on October 8-11, 2007. Pines concluded: "Public policy initiatives to improve emergency-department crowding may improve the care of patients with ACS and potential ACS (and maybe everyone else)."

Pines explained that ED crowding has been associated with poorer quality of care and outcomes among several patient groups (such as antibiotic delays for patients with pneumonia and delays to lysis for patients with MI). One Australian study even suggested that an increased death rate was linked to overcrowded emergency departments, but few studies have examined ACS patients in this regard.

He thus conducted a prospective cohort study of patients aged 30 years or older who presented at the ED of the University of Pennsylvania Hospital with chest pain and potential ACS between September 1999 and March 2006. The primary outcome was adverse cardiovascular events between six hours and 30 days after presenting at the ED. Adverse cardiovascular events were defined as death, cardiac arrest, or the development of heart failure, late MI, ventricular tachycardia or fibrillation, supraventricular dysrhythmias, symptomatic bradycardia, stroke, or hypotension. The study included 6869 patients. Of these, 33% received an ECG within 10 minutes of arrival at the ED, 57% were given aspirin in the ED, and 8% were given beta blockers in the ED. A total of 33% of patients were treated in the ED and discharged; the remaining 67% were admitted to the hospital.

Of the 6646 patients available for follow-up, 831 actually had an ACS--273 had an MI and 558 had unstable angina. Of these, 301 (4%) patients developed a cardiovascular complication that met primary outcome criteria. Patients were more likely to have a cardiovascular complication if the ED was crowded (defined as more than 12 patients in the waiting room, patient care hours more than 142, or occupancy over 72.5%).

Pines commented to heartwire: "We found that at times when the emergency department was crowded, patients with potential ACS were more likely to experience cardiovascular complications within the next 30 days." He noted that the results were not due to longer waiting times to ECG or time to treatment with aspirin or beta blockers; these variables were the same regardless of how busy the ED was because chest-pain patients always get priority.

Instead, Pines believes that ED crowding is a measure of hospital-wide dysfunction--that is, patients are not getting appropriate inpatient testing, and other interventions and treatments are being delayed. "A crowded emergency department is like a canary in a coal mine for the whole hospital. When the emergency department is crowded, the waiting times for tests and procedures in the whole hospital are longer. The overall culture of the whole hospital changes. Inpatient floors feel the pressure to admit more patients, so they discharge patients before they would have done so otherwise. If the hospital is full, ACS patients may be cared for by the inpatient team while still in the ED. If a patient is in the ED for a long time, they get worse care. This may be just because they are not geographically in the best place," he said.

What do we do about it?

Pines noted that the solution to this problem is to try to improve ED crowding. "Across the US, emergency-department crowding is a major issue. Care of ACS patients will continue to suffer as emergency departments continue to be overcrowded. There are 114 million emergency-department visits each year in the US--that is one for every three people. As long as hospitals have to operate at high occupancy to remain competitive, patients admitted through the emergency department will often not get an inpatient bed. They will therefore have to stay in the emergency department, so they are in the wrong place to get the best treatment. We need more funding and better policies to reduce this problem," he added.

3. Computed Tomography Improves Detection of Cervical Spine Injuries

News Author: Jim Kling. October 11, 2007 (Seattle) — In a study of emergency department patients with blunt trauma, cervical computed tomography (CCT) significantly outperformed cervical spine radiographs (CSRs) at detecting spinal injury. The study was presented here at the American College of Emergency Physicians 38th Annual Scientific Assembly.

About 10,000 Americans have cervical spine injuries each year, and delayed diagnosis has important clinical and economical costs. CSRs have a reported sensitivity ranging from 35% to 89%; the study authors conducted a study to determine whether CCT has greater sensitivity in the detection of these injuries than CSR.

They carried out a prospective study of patients who presented with blunt trauma during the course of 23 months at an urban public hospital's trauma center. Patients received both a 3-view CSR and CCT, each read independently by attending radiologists who were blinded to other tests.

Of 1580 study patients, 60 (4%) had injuries that were detected by CSR or CCT. CSR detected the injury in 21 of these patients (35% sensitivity), whereas CCT detected injuries in 58 patients (97% sensitivity). Of the 60 patients, 45 had injuries that were considered clinically significant (defined as requiring an operating room procedure, halo application, or hard collar). CCT identified all of these cases (100% sensitivity), whereas CSR detected just 15 injuries (33% sensitivity). In 2 cases, injury was identified by CSR and not CCT, but neither injury was clinically significant.

The study had some limitations, including the fact that it was conducted at a single institution and that 78 patients were dropped because of protocol violations. There was also no structured follow-up.

There are also some safety considerations regarding CCT. "We don't know the effects of radiating children or young adults," said Matt Beecroft, MD, from Cook County Hospital, Chicago, Illinois. "The thyroid is right there [where images are being taken]. Radiation levels are 14 times higher in CT than x-ray. I think that question will be answered as time goes on." He called for further research to define a subset of patients who would not require CCT, as well as cost analyses and studies on the effects of CT radiation.

"We thought we had a good decision-making rule" for screening for cervical injuries, said Charles Bennett Cairns, MD, director of research in the Division of Emergency Medicine at Duke University School of Medicine,Durham, North Carolina, who attended the presentation. "It shows that we need to better understand the limitations of the decision-making rules and how they apply to different institutions and different populations."

Pearls for Practice

In patients who had injuries that were detected by CSR or CCT, CCT was more sensitive than CSR in detection of these injuries. For patients with clinically significant injuries, defined as requiring an operating room procedure, halo application, or hard collar, sensitivity was higher with CCT. In 2 cases, injury was identified by CSR and not by CCT, but neither injury was clinically significant.

The safety of CCT in children or young adults is unknown. There is concern regarding inclusion of the thyroid in the field of radiation exposure. The investigators recommend further research regarding the effects of CT radiation.

4. Meds for Pediatric Coughs and Colds may do more Harm than Good

FDA Warns on Hydrocodone in Pediatric Cough Suppressants, May Enforce Ban

The FDA says it will act against the improper use of hydrocodone in pharmaceutical products, especially in over-the-counter cough suppressants marketed for pediatric use.

The narcotic is widely used to treat both pain and coughs. Several products containing hydrocodone are marketed for children, and some contain dosing information for children as young as 2 years old, despite the fact that the drug has not been shown to be safe and effective in children under 6. The agency is particularly concerned over similarities in the names of approved and unapproved products.

Companies have until the end of October to cease manufacturing and marketing the unapproved pediatric products containing hydrocodone and until the end of the year to cease manufacturing and marketing other unapproved products containing the drug.

In addition, the New York Times reports that the FDA is considering an outright ban on OTC cold and cough medications for children younger than 6 years.

FDA Alert:

Infant Cough and Cold Medicines Pulled From the Market

Given concerns that accidental misuse can lead to overdose, many manufacturers of over-the-counter infant cough and cold medicines are voluntarily pulling their products off the market, reports the New York Times.

The withdrawal comes 2 weeks after the industry’s trade group, the Consumer Healthcare Products Association, advised that the oral products not be used in children younger than 2 years. The group says that between 1969 and 2006, at least 45 children died after using decongestants, and 69 after antihistamines.

An FDA advisory panel will meet next week to discuss the medicines' safety.

Not only may the medications be unsafe, but there is scant evidence that they're effective in young children, according to the Times story.

Withdrawn medicines include Dimetapp Decongestant Infant Drops, Pediacare Infant Drops Decongestant, and Tylenol Concentrated Infant Drops Plus Cold and Cough.

5. New Guideline for Low Back Pain Management

Chou R, et al. Ann Intern Med 2007; 147:478-491.

The American College of Physicians and the American Pain Society have published an updated practice guideline for the management of low back pain in primary care.

The guideline, which appears in the Oct 2 issue of Annals of Internal Medicine, includes recommendations on both evaluation and treatment. Among the recommendations:

o Imaging should not be part of the routine work-up of patients with nonspecific pain.

o Clinicians should provide patients with information on the expected course of their condition.

o When considering medication use, clinicians should usually start with acetaminophen or NSAIDs.

o For patients who do not improve, nondrug therapies such as spinal manipulation, acupuncture, and yoga may be considered.

The ACP and APS also provide an algorithm for the initial evaluation and subsequent management of patients.

Ann Intern Med guideline paper (Free):

Ann Intern Med review of evidence on nonpharmacologic therapies for back pain (Free):

Ann Intern Med review of evidence on medications for back pain (Free):

6. Lumbar Puncture Success Rate Is Not Influenced by Family-Member Presence

Nigrovic LE, et al. Pediatrics. 2007;120: e777-e782.

OVERVIEW. The presence of a family member during invasive pediatric procedures such as lumbar puncture has been shown to reduce patient anxiety. However, family presence might also affect clinicians’ stress and anxiety, with uncertain consequences for procedural success.

OBJECTIVE. Our goal was to evaluate the association between family-member presence and lumbar puncture success rates.

DESIGN/METHODS. We performed a prospective cohort study of all children who underwent a lumbar puncture in a single pediatric emergency department between July 2003 and January 2005. The presence of a family member was documented by the physician who performed the lumbar puncture. Success rates were assessed by using 2 main outcomes: (1) the rate of traumatic (cerebrospinal fluid red blood cells 10000 cells per µL) or unsuccessful lumbar puncture (no cerebrospinal fluid sent for cell counts) and (2) the number of lumbar puncture attempts. Multivariate analyses were adjusted for patient age, race, time of day, physician experience, use of local anesthetic, catheter stylet removal, and patient movement during the procedure.

RESULTS. Of the 1474 eligible lumbar punctures, 1459 (99%) were included in the analysis. A family member was present for 1178 (81%) of the procedures studied. A total of 1267 (87%) lumbar punctures were nontraumatic, and 192 (13%) were traumatic or unsuccessful. Neither the rate of traumatic or unobtainable lumbar punctures nor the number of lumbar puncture attempts differed based on whether a family member was present for the procedure.

CONCLUSIONS. The presence of a family member was not associated with an increased risk of traumatic or unobtainable lumbar puncture, nor was it associated with more attempts at the procedure. The benefits of having a family member present during the procedure were not counterbalanced by adverse effects on procedural success.

7. Best Method for Placing Pediatric Tubes to the Correct Depth

Positioning of the tip too close to the carina results in endobronchial intubation when the neck is flexed.

Endotracheal tubes ideally are placed with the tip near the midtrachea, thereby minimizing the likelihood that either endobronchial intubation or accidental extubation will occur when the patient’s neck is flexed or extended. In pediatric patients, tube positioning is challenging because of variations in the length of both the tube and the trachea. Investigators in Korea randomized 107 children (aged 2–8 years) who were undergoing general anesthesia to one of three methods for initially positioning the tube at the correct depth.

In group I, the tube was inserted deliberately into a mainstem bronchus and then withdrawn 2 cm (in children aged 2–5 years) or 3 cm (in children older than 5) farther than the point at which bilateral breath sounds were heard. In group II, the tube was placed with the recommended centimeter marking aligned with the vocal cords (i.e., the 4-cm mark for tubes with an internal diameter of 4 or 4.5 cm and the 5-cm mark for tubes with a diameter 5 cm). In group III, the tube was manipulated until its tip could be palpated in the suprasternal notch (anatomically near the midtrachea). The position of the tip relative to the carina and vocal cords was then measured using a fiber-optic bronchoscope, with the neck in neutral position, full flexion, and full extension.

In groups II and III, the tip of the tube initially was placed near the midtrachea (at positions 46.5% and 43.4%, respectively, of the distance from the carina to the vocal cords), whereas in group I, the tube was placed significantly closer to the carina (21.4% of the distance). Flexion brought the tube very close to the carina (9.5% of the distance) in group I, but not in groups II and III (38.3 and 32.4% of the distance, respectively). Extension brought the tube tip near the midtrachea in group I (44.3% of the distance) and into the upper third for groups II and III (71.7% and 67.9% of the distance, respectively). Flexion produced endobronchial intubation in 5 of 35 patients in group I (most aged 2 to 5 years), but not in any patients in the other groups. No patient was extubated by extension.

Comment: This study strongly affirms the importance of placing endotracheal tubes in children in the midtrachea, where neither endobronchial intubation nor accidental extubation will occur through the entire range of motion of the neck. The often- recommended method that was used for group I is clearly inferior for correct placement and should not be used.

— Ron M. Walls, MD. Published in Journal Watch EM October 5, 2007. Citation: Yoo S-Y et al. A comparative study of endotracheal tube positioning methods in children: Safety from neck movement. Anesth Analg 2007 Sep; 105:620.

8. Knee Buckling: Prevalence, Risk Factors, and Associated Limitations in Function

Felson DT, et al. Ann Intern Med 2007;147:534-540

Knee buckling is the sudden loss of postural support at the knee during weight bearing. In their cross-sectional, population-based study, Felson and coworkers examined the prevalence of knee buckling in the community, its associated risk factors, and its relationship to functional limitation. Among 2351 middle-age and older community-dwelling adults, 278 (12%) reported at least 1 episode of knee buckling in the past 3 months, and 13% of them fell during the episode. Knee pain, quadriceps weakness, and worse physical function were associated with buckling.


9. Doctors Rank AMI as most "prestigious" disease and Fibromyalgia as least

BMJ 2007;335:632

Fibromyalgia and anxiety neurosis are the illnesses with the lowest prestige among doctors, according to a survey of Norwegian doctors.

The survey found that heart attacks top the prestige league, closely followed by leukaemia, and that neurosurgery is regarded as the most prestigious specialty (Social Science & Medicine doi: 10.1016/j.socscimed.2007.07.003).

"Results show that there exists a prestige rank order of diseases as well as of specialties in the medical community," write the authors. "Our interpretation of the data is that diseases and specialties associated with technologically sophisticated, immediate and invasive procedures in vital organs located in the upper parts of the body are given high prestige scores, especially where the typical patient is young or middle-aged."

They say that any such ranking among doctors could have effects on practice.

In the study, the authors, from the University of Oslo and the University of Science and Technology, Oslo, sent questionnaires to 305 senior doctors, 500 general practitioners, and 490 final year medical students.

Respondents were asked to rank 38 diseases as well as 23 specialties on a scale of one to nine. The item concerning the prestige of diseases said, "Please give each disease a number based on the prestige you imagine it has among health personnel."

The authors say that the prestige scores for diseases and for specialties were remarkably consistent across the three samples.

Myocardial infarction, leukaemia, spleen rupture, brain tumour, and testicular cancer were given the highest scores by all three groups. Prestige scores for fibromyalgia, anxiety neurosis, hepatic cirrhosis, depressive neurosis, schizophrenia, and anorexia were at the other end of the range.

"The existence of a prestige rank order of medical specialties has been known for a long time," write the authors.

"Our results show that two different samples of physicians scored diseases according to prestige with only minor differences, and a sample of medical students in their final year scored them in much the same way. This is remarkable, as the prestige order of diseases is not openly debated, but must arise as a result of the numerous talks and actions going on in connection with the daily practice of medicine."

They add that disease is a "nexus around which many medical activities are organised, such as categorising patients, planning and allocating work, setting priorities at all levels, pricing services, and teaching and developing medical knowledge.

"A widespread, and at the same time tacit, prestige ordering of diseases may influence many understandings and decisions in the medical community and beyond, possibly without the awareness of the decision makers."

10. Hospitalist Care Reduces Length of Stay, Especially for Some Illnesses

Hospitalist care is associated with shorter lengths of stay, particularly in some patient groups, a study in Archives of Internal Medicine reports.

Researchers analyzed hospital discharge data from a single academic medical center for a 2-year period. In the study population, comprising some 9000 patients, two-thirds had received care from non-hospitalist teams. Those under hospitalist care cut their length of stay by nearly 1 day (the reductions were most pronounced among those with stroke, sepsis, asthma, chronic obstructive pulmonary disease, and urinary tract infection).

There were no differences between groups with regard to readmission rates, or with in-hospital or 30-day mortality rates.

Abstract (full text requires subscription):

11. Does Early Treatment of Infant Urinary Tract Infection Prevent Renal Damage?

Doganis D, et al. Pediatrics. 2007;120: e922-e928.

OBJECTIVE. Therapeutic delay has been suggested as the most important factor that is likely to have an effect on the development of scarring after acute pyelonephritis. However, this opinion has not been supported by prospective studies, so we tested it.

METHODS. In a prospective clinical study, we evaluated whether the time interval between the onset of the renal infection and the start of therapy correlates with the development of acute inflammatory changes and the subsequent development of renal scars, documented by dimercaptosuccinic acid scintigraphy. A total of 278 infants (153 male and 125 female) aged 0.5 to 12.0 months with their first urinary tract infection were enrolled in the study.

RESULTS. The median time between the onset of infection and the institution of therapy was 2 days (range: 1–8 days). Renal inflammatory changes were documented in 57% of the infants. Renal defects were recorded in 41% of the patients treated within the first 24 hours since the onset of fever versus 75% of those treated on day 4 and onward. Renal scarring was developed in 51% of the infants with an abnormal scan in the acute phase of infection. The frequency of scarring in infants treated early and in those whose treatment was delayed did not differ, suggesting that once acute pyelonephritis has occurred, ultimate renal scarring is independent of the timing of therapy. Acute inflammatory changes and subsequent scarring were more frequent in the presence of vesicoureteral reflux, especially that which is high grade. However, the difference was not significant, which suggests that renal damage may be independent of the presence of reflux.

CONCLUSIONS. Early and appropriate treatment of urinary tract infection, especially during the first 24 hours after the onset of symptoms, diminishes the likelihood of renal involvement during the acute phase of the infection but does not prevent scar formation.

12. Flu Vaccination Helps the Elderly Avoid Hospitalization, Death

A long-term study in New England Journal of Medicine adds to previous short-term evidence indicating that influenza vaccination reduces the risk of hospitalization for pneumonia or influenza, as well as all-cause mortality, among community-dwelling elderly adults.

Researchers evaluated data, covering 10 flu seasons, from HMOs across the U.S. After multivariate adjustment, vaccinated adults ages 65 and older were 27% less likely to be hospitalized for pneumonia or influenza during the flu season — and 48% less likely to die from any cause — compared with unvaccinated adults. The risk reductions remained significant in a sensitivity analysis designed to control for residual confounding.

The authors call for strategies to improve the "stagnant" vaccination rates in this population. In addition, an editorialist stresses the importance of immunizing those in frequent contact with the elderly, noting the "appalling" vaccination rates among healthcare workers, who "can easily serve as vehicles of doom for their unsuspecting patients."

NEJM article (Free):

13. Saline, Not Albumin, for Patients with Head Injury

Albumin use is associated with a significantly higher death rate.

The Saline versus Albumin Fluid Evaluation (SAFE) study was a randomized, double-blind comparison of saline and albumin in a heterogeneous population of intensive care unit patients. The study showed no difference in outcomes between treatment groups but suggested an increased death rate in patients with traumatic brain injury who received albumin. However, the trial was not directed specifically toward patients with head injury.

Researchers reevaluated data from the SAFE study for patients with traumatic brain injury (SAFE-TBI study), using specific measures of injury severity, including Glasgow Coma Scale (GCS) score and intracranial pressure. In addition, whereas the original study measured outcomes up to 28 weeks after admission, this study measured outcomes (death and disability) at 24 months.

Of 460 patients with traumatic brain injury, 69% had severe injury (GCS score of 3–8). At 24 months, 33.2% of the albumin group had died, as compared to 20.4% of the saline group. This difference was due to a marked disparity in survival in the subgroup of patients with severe head injury; mortality rates were 41.8% in those treated with albumin and 22.2% in those treated with saline (relative risk, 1.88). Among survivors, neurologic outcomes were similar in the two treatment groups.

Comment: The albumin versus saline debate has been going on for a long time, and albumin has never been shown to be better, despite its much higher cost. In this study, albumin was associated with significantly worse outcomes. For patients with head injury, albumin should be allowed to gather dust in the pharmacy. The money would be better spent elsewhere.

— J. Stephen Bohan, MD. Published in Journal Watch EM September 28, 2007. Citation: The SAFE Study Investigators. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007 Aug 30; 357:874.

14. Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil

Levine M, et al. Critical Care Medicine. 2007; 35:2071-2075

Background: Overdoses of calcium channel blocker agents result in hyperglycemia, primarily due to the blockade of pancreatic L-type calcium channels and insulin resistance on the cellular level. The clinical significance of the hyperglycemia in this setting has not previously been described.

Methods: This study is a retrospective review of all adult (age, 15 yrs or older) patients with a discharge diagnosis of acute verapamil or diltiazem overdose at five university-affiliated teaching hospitals. The severity of overdose was assessed by determining whether a patient met the composite end points of in-hospital mortality, the necessity for a temporary pacemaker, or the need for vasopressors. We compared the initial and peak serum glucose concentrations with hemodynamic variables between patients who did and did not meet the composite end points.

Results: A total of 40 patients met inclusion criteria, with verapamil and diltiazem accounting for 27 of 40 (67.5%) and 13 of 40 (32.5%) of the ingestions, respectively. For those patients who did and did not meet the composite end points, the median initial serum glucose concentrations were 188 (interquartile range, 143.5-270.5) mg/dL and 129 (98.5-156.5) mg/dL, respectively (p = .0058). The median peak serum glucose concentrations for these two groups were 364 (267.5-408.5) mg/dL and 145 (107.5-160.5) mg/dL, respectively (p = .0001). The median increase in blood glucose was 71.2% for those who met composite end points vs. 0% for those who did not meet composite end points (p = .0067). Neither the change in the median heart rate nor the change in systolic blood pressure was significantly different in any group.

Conclusion: Serum glucose concentrations correlate directly with the severity of the calcium channel blocker intoxication. The percentage increase of the peak glucose concentration is a better predictor of severity of illness than hemodynamic derangements. If validated prospectively, serum glucose concentration alone might be an indicator to begin hyperinsulinemia-euglycemia therapy.

15. Induced Hypothermia is Underused after Resuscitation from Cardiac Arrest: a Current Practice Survey

Abella BS, et al. Resuscitation. 2005;64:181-6.

BACKGROUND: Important recent work has demonstrated that the use of induced hypothermia can improve survival and neurologic recovery after cardiac arrest. We wished to ascertain the extent to which physicians were using this treatment, and what opinions are held by clinicians regarding its use.

METHODS: An internet-based survey of physicians was conducted, with physicians chosen at random from published directories of the Society for Academic Emergency Medicine, the American Thoracic Society, and the American Heart Association. Physicians were questioned regarding use of therapeutic hypothermia, methods employed, and/or reasons why they had not incorporated hypothermia into their care of cardiac arrest patients.

RESULTS: Completed surveys were collected from 265 physicians, including those practicing emergency medicine (41%), critical care (13%), and cardiology (24%). Respondents were geographically well distributed and the majority (94%) were at post-training level. Most respondents (78%) practiced at either larger referral hospitals or academic medical centers. When asked if they had ever used hypothermia following cardiac arrest, 87% said they had not. Among reasons cited for non-use, 49% felt that there were not enough data, 32% mentioned lack of incorporation of hypothermia into advanced cardiovascular life support (ACLS) protocols, and 28% felt that cooling methods were technically too difficult or too slow.

CONCLUSION: Despite compelling data supporting its use, hypothermia has yet to be broadly incorporated into physician practice. This highlights the need for improved awareness and education regarding this treatment option, as well as the need to consider hypothermia protocols for inclusion in future iterations of ACLS.

16. Stored Blood Lacks Nitric Oxide, Vital to its Function

By RANDOLPH E. SCHMID – Oct 8, 2007. WASHINGTON (AP) — Much of the stored blood given to millions of people every year may lack a component vital for it to deliver oxygen to the tissues. Nitric oxide, which helps keep blood vessels open, begins breaking down as soon as blood goes into storage, two research teams report in separate studies in this week's online edition of Proceedings of the National Academy of Sciences.

In recent years, doctors have become increasingly concerned about levels of heart attack and stroke in patients receiving transfusions and the new findings may help explain that. "It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide," said Dr. Jonathan Stamler of Duke University, leader of one of the research groups.

Blood vessels relax and constrict to regulate blood flow and nitric oxide opens up blood vessels, allowing red blood cells to deliver oxygen, he explained. "If the blood vessels cannot open, the red blood cells back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," he said.

"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine," said Stamler. Several of the researchers, including Stamler, have consulting and/or equity relationships with Nitrox/N30, a company developing nitric oxide based therapies.

The second research team, led by Dr. Timothy McMahon, also at Duke, studied the changes in stored blood over time. Currently blood is allowed to be kept in blood banks for up to 42 days. After that it must be discarded. An estimated 14 million units of red blood cells are administered to about 4.8 million Americans annually.

"We were surprised at how quickly the blood changes — we saw clear indications of nitric oxide depletion within the first three hours," McMahon said in a statement.

Stamler said in a telephone interview that the researchers knew that nitric oxide is responsible for opening up small blood vessels, but had not previously measured the amount of that chemical in stored blood. "Surprisingly, we found blood depleted profoundly by day one and it remained depleted through day 42," he said.

But if they restored the nitric oxide at any point, the red blood cells were again able to open blood vessels and deliver oxygen to tissues, they said. They tested the blood with added nitric oxide both in the laboratory and in dogs. "This is an important observation and it needs to be followed up," said Dr. Louis Katz, a past president of America's Blood Centers, which provides about half the nation's blood.

"If you are going to store red cells, is there a way to make sure appropriate nitric oxide levels are maintained?" said Katz, who was not part of the research teams.

It is possible that these findings may make the public concerned about transfusions, Katz said: "There is no doubt, if you are bleeding to death from a trauma" you need a transfusion.

Stamler agreed that "physicians need to be able to give blood if people are bleeding profusely."

Overall, Katz said: "This is neat research. It needs to be proven that it's clinically relevant."

Stamler agreed on the need for clinical trials. "Banked blood is truly a national treasure that needs to be protected," Stamler said. "Blood can be life saving, only it is not helping the way we had hoped and in many cases it may be making things worse. In principle, we now have a solution to the nitric oxide problem — we can put it back — but it needs to be proven in a clinical trial."

The research was supported by the National Institutes of Health, Duke Anesthesiology Fund, the American Heart Association and N30 Pharma, which has a license agreement with Duke to develop nitric oxide-based therapies.

17. Myocardial Infarction in Healthy Adolescents? Rare but possible.

Lane JR, et al. Pediatrics. 2007;120:e938-e943.

OBJECTIVE. Chest pain in children and adolescents is a frequent cause for office or emergency department visits. However, it is unclear whether myocardial infarction occurs in children with no anatomic abnormality presenting with chest pain.

METHODS. Clinical history, electrocardiography, echocardiography, and cardiac enzyme levels were evaluated in patients presenting to the emergency department over a period of 11 years (June 1995 to May 2006). Patients in whom findings were suggestive of acute myocardial infarction, in addition, underwent drug screening, serum lipid profile, and hypercoagulability workup and, when myocardial infarction was diagnosed, heart catheterization with coronary angiography.

RESULTS. Nine patients (8 boys; age range: 12–20 years; mean: 15.5 years) met established criteria for myocardial infarction. Abnormal electrocardiograms were found in 8 patients (6 with ST elevation and 2 with nonspecific ST-T abnormalities), abnormal cardiac enzyme levels in all, and echocardiographic abnormalities in 3. Cardiac dysrhythmias were found in 4 patients, 3 with nonsustained ventricular tachycardia. Drug abuse, lipid profile, and hypercoagulability studies were negative in all. Left ventricular focal hypokinesia was seen by echocardiogram or angiography in 5 patients and abnormal coronary anatomy in none. Cardiac function normalized in 8 patients. One patient had a persistent focal inferior hypokinesis. Calcium channel blocker therapy was initiated in all of the patients with no recurrence of anginal chest pain on follow-up. One patient complained of chest pain distinct from anginal pain.

CONCLUSIONS. Myocardial infarction can occur in adolescents with normal coronary arterial anatomy. Adolescents who present for emergency care with typical chest pain need electrocardiographic and cardiac enzyme workups. Those with results that are suggestive of acute infarction require additional workup. Coronary vasodilation therapy seems helpful, but given the lack of coronary thrombosis in these patients, thrombolytic therapy seems unwarranted. Long-term follow-up is necessary, and adjustments in therapy may be required with time.

18. Risk of Venous Thromboembolism after a Long Haul Flight is less than one in 5000

Long haul flights roughly triple travellers' baseline risk of a symptomatic venous thrombosis. But for most people the absolute risk remains low—less than one event for every 5000 flights, according to a study of international corporate employees.

The researchers used records of business travel kept by international companies, combined with a web survey of 8755 employees, to calculate the risks associated with flights longer than four hours.

As expected, the incidence of deep vein thrombosis or pulmonary embolus was three times higher during the eight weeks after a long haul flight than at other times (incidence rate ratio 3.2, 95% CI 1.8 to 5.6). The absolute risk of an event was one for every 4656 flights, but the authors found a clear dose response effect—the longer the flight, the higher the risk. Frequent flying was also associated with a greater likelihood of venous thrombosis. The risks were highest in women—especially those taking oral contraceptives—short people, and tall people. Perhaps airlines should be encouraged to fit adjustable seats, say the authors, so tall people are less cramped, and short people don't have to sit with their legs dangling off the floor. Both problems could conceivably put pressure on the poplitial vein.

References: PLoS Med 2007;4:1508-14

19. HDL and LDL Cholesterol Independently Predict Cardiovascular Risk

Low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol are both important determinants of cardiovascular risk. Doctors treating patients with heart disease tend to concentrate most of their efforts on bringing down serum concentrations of LDL cholesterol with statins. But HDL cholesterol matters too, even in patients with LDL cholesterol concentrations below the recommended targets.

In a reanalysis of data from one statin trial, researchers found a clear inverse relation between the risk of serious cardiovascular events and HDL cholesterol concentration in patients with heart disease who were taking atorvastatin. Patients were divided into five groups according to HDL concentration. Patients in the highest fifth were significantly less likely to have heart attacks or strokes or to die from coronary disease than those in the lowest fifth. The inverse relation persisted across all concentrations of LDL cholesterol and in a subgroup of patients with concentrations of LDL cholesterol below 1.8 mmol/l (hazard ratio 0.61; 95% CI 0.38 to 0.97 when comparing the highest fifth with the lowest fifth).

These findings suggest that the two types of cholesterol can independently predict serious cardiovascular events in patients treated with statins, say the authors. The 9770 patients in this trial took either 10 mg or 80 mg atorvastatin a day.

References: N Engl J Med 2007;357:1301-10

20. Ig Nobel Prizes Stranger Than Fiction

By Mary Beckman. ScienceNOW Daily News. 5 October 2007. Ice cream may never be the same now that Mayu Yamamoto of the International Medical Center of Japan has discovered how to extract vanillin, the essence of vanilla flavor, from cow dung. Don't pooh-pooh Yamamoto's accomplishment. It may not win her a Nobel Prize, but it has netted her an honor equally exclusive. At a ceremony at Harvard University last night, Yamamoto received the 2007 Ig Nobel Prize for chemistry. A local ice cream shop even whipped up a special flavor in her honor--Yum-a-Moto Vanilla Twist--although the ice cream makers avoided scatological coloring.

Yamamoto was one of 10 new laureates crowned in the 17th annual Ig Nobel ceremony, which was sponsored by the science humor magazine Annals of Improbable Research. In all, dozens of scientists, five Nobel laureates, and a paper-airplane-throwing throng gathered to celebrate the gems of funny, odd, or questionable research found amid the serious stuff. The medicine prize went to radiologist Brian Witcombe of Gloucester, U.K., and entertainer Dan Meyer of Antioch, Tennessee, for their work describing the side effects of sword swallowing, which include sore throats and gastrointestinal bleeding. Lakshminarayanan Mahadevan of Harvard University and Enrique Cerda Villablanca of the University of Santiago in uncovering how sheets wrinkle. Biology winner Johanna van Bronswijk of Eindhoven University of Technology in the Netherlands described how bedbugs congregate in those sheets.

Diego Golombek of the Universidad Nacional de Quilmes, Argentina, accepted the aviation prize for his group's discovery that Viagra can help jetlagged hamsters get their circadian rhythms back on schedule. Juan Manuel Toro, Josep Trobalon, and Núria Sebastián-Gallés of the Universitat de Barcelona in Spain bagged the linguistics prize for demonstrating that rats can't tell the difference between two languages--Dutch or Japanese--when they are spoken backward.

Behavior researcher Brian Wansink of Cornell University took home the Ig Nobel in nutrition for his soup bowl that inconspicuously refills as a person slurps from it. He used the deceptive device to examine how people judge how much to eat in a study reported in the journal Obesity Research. Wansink, author of the book Mindless Eating: Why We Eat More Than We Think and a microcelebrity, took pride in winning the award.

21. What Questions about Patient Care do Physicians have during and after Patient Contact in the ED? The Taxonomy of Gaps in Physician Knowledge

Graber MA, et al. Emerg Med J 2007;24:703-706

Objectives: To categorise questions that emergency department physicians have during patient encounters.

Methods: An observational study of 26 physicians at two institutions. All physicians were followed for at least two shifts. All questions that arose during patient care were recorded verbatim. These questions were then categorised using a taxonomy of clinical questions.

Results: Physicians had 271 questions in the course of the study. The most common questions were about drug dosing (35), what drug to use in a particular case (28), "what are the manifestations of disease X" (23), and what laboratory test to do in a situation (21). Notably lacking were questions about medication costs, administrative questions, questions about services in the community, and pathophysiology questions.

Conclusions: Emergency department physicians tend to have questions that cluster around practical issues such as diagnosis and treatment. In routine practice they have fewer epidemiologic, pathophysiologic, administrative, and community services questions.