Lit Bits: March 16, 2010

From the recent medical literature...

1. The Efficacy of Factor VIIa in Emergency Department Patients with Warfarin Use and Traumatic Intracranial Hemorrhage

Nishijima DK, et al. Acad Emerg Med. 2010;17:244-251.

Objectives: The objective was to compare outcomes in emergency department (ED) patients with preinjury warfarin use and traumatic intracranial hemorrhage (tICH) who did and did not receive recombinant activated factor VIIa (rFVIIa) for international normalized ratio (INR) reversal.

Methods: This was a retrospective before-and-after study conducted at a Level 1 trauma center, with data from 1999 to 2009. Eligible patients had preinjury warfarin use and tICH on cranial computed tomography (CT) scan. Patients before (standard cohort) and after (rFVIIa cohort) implementation of a protocol for administering 1.2 mg of rFVIIa in the ED were reviewed. Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS), Injury Severity Score (ISS), INR, and Marshall score were collected. Outcome measures included mortality, thromboembolic complications, and INR normalization.

Results: Forty patients (median age = 80.5 years, interquartile range [IQR] = 63.5–85) were included (20 in each cohort). Age, GCS score, ISS, RTS, initial INR, and Marshall score were similar (p over 0.05) between the two cohorts. Survival was identical between cohorts (13 of 20, or 65.0%, 95% confidence interval [CI] = 40.8% to 84.6%). There were no differences in rate of thromboembolic complications in the standard cohort (1 of 20, 5.0%, 95% CI = 0.1% to 24.9%) than the rFVIIa cohort (4 of 20, 20.0%, 95% CI = 5.7% to 43.7%; p = 0.34). Time to normal INR was earlier in the rFVIIa cohort (mean = 4.8 hours, 95% CI = 3.0 to 6.7 hours) than in the standard cohort (mean = 17.5 hours, 95% CI = 12.5 to 22.6; p less than 0.001).

Conclusions: In patients with preinjury warfarin and tICH, use of rFVIIa was associated with a decreased time to normal INR. However, no difference in mortality was identified. Use of rFVIIa in patients on warfarin and tICH requires further study to demonstrate important patient-oriented outcomes.

2. Lactate Clearance Noninferior to Central Venous Oxygen Saturation as a Goal of Early Sepsis Resuscitation

Laurie Barclay, MD. March 1, 2010 — Lactate clearance is noninferior to central venous oxygen saturation (ScvO2) as a target of early sepsis resuscitation, according to the results of a multicenter, randomized, noninferiority trial reported in the February 24 issue of the Journal of the American Medical Association.

"Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department," write Alan E. Jones, MD, from the Carolinas Medical Center in Charlotte, North Carolina, and colleagues for the Emergency Medicine Shock Research Network Investigators.

"The Surviving Sepsis Campaign guidelines recommend the use of...ScvO2 or mixed venous oxygen saturation to assess the balance of tissue oxygen delivery and consumption; however, since its publication in 2001 a substantial amount of controversy about this single-center study has been generated in the scientific community....In contrast, lactate clearance, derived from calculating the change in lactate concentration from 2 blood specimens drawn at different times, potentially represents a more accessible method to assess tissue oxygen delivery."

At 3 participating US urban hospitals, 300 patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 were randomly assigned to 1 of 2 resuscitation protocols. In the ScvO2 group (n = 150), the goal of resuscitation was to normalize central venous pressure and mean arterial pressure and to achieve ScvO2 of 70% or more. In the lactate clearance group (n = 150), the goal of resuscitation was to normalize central venous pressure and mean arterial pressure and to achieve lactate clearance of 10% or more.

Patients in the 2 treatment groups were well matched by demographic factors, comorbid conditions, and physiologic features. The assigned study protocol was continued until all targets were reached or for up to 6 hours. Clinicians who then took over care of the participants were masked to group assignment. The main study endpoint was absolute in-hospital mortality, with the noninferiority threshold set at delta equal to −10%.

No Differences in Treatments

During the initial 72 hours of hospitalization, there were no differences in treatments administered in the 2 groups. In-hospital mortality rate was 23% in the ScvO2 group (n = 34; 95% confidence interval [CI], 17% - 30%) vs 17% (n = 25; 95% CI, 11% - 24%) in the lactate clearance group. Based on intent-to-treat analysis, this 6% difference between mortality rates did not reach the predefined −10% threshold (95% CI for the difference, −3% to 15%). Both groups had similar treatment-related adverse events.

"Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality," the study authors write. "These data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a computerized spectrophotometric catheter in the resuscitation of sepsis."

Limitations of this study include lack of blinding of the groups, inability to determine whether an indicated therapeutic action was performed in response to a parameter below the intended goal, lack of generalizability to centers that do not routinely perform early quantitative resuscitation, and possible Hawthorne-like effect.

In an accompanying editorial, Roger J. Lewis, MD, PhD, from the Harbor-UCLA Medical Center in Los Angeles, notes that interpretation of the study findings is somewhat complicated because only 10% of enrolled patients received dobutamine or transfusions, which were the only treatments affected by the resuscitation targets being compared.

"Although using the lactate clearance does not obviate the need for a central venous catheter, it does allow the use of a nonspecialized catheter and does eliminate the need for the associated electronic instrumentation," Dr. Lewis writes. "[This study] is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock. Substantial further progress most likely will depend on appropriately designed, rigorously conducted clinical trials (requiring novel strategies, such as adaptive design) that can efficiently and practically address the complicated questions inherent in identifying the optimal and least burdensome combination of resuscitation targets."

The National Institutes of Health supported this study and some of its authors. Some of the study authors have disclosed various financial relationships with Critical Biologics Corp, Hutchinson Technology, Brahms and Siemens, Ikaria, Novo Nordisk, Spectral Diagnostics, Edwards Lifesciences, Biosite, and/or Eli Lilly. One of the study authors (Dr. Kline) has disclosed that he is the inventor on a US patent for a breath-based device that monitors patient response to resuscitation.

Dr. Lewis has disclosed that he serves as the chair of the Data and Safety Monitoring Board for the Protocolized Care for Early Septic Shock trial funded by the National Institute of General Medical Sciences, National Institutes of Health, and that he serves as a medical consultant to Berry Consultants, LLC, a statistical consulting group specializing in the use of Bayesian methods in the design and analysis of adaptive clinical trials.

JAMA. 2010;303:739-746, 777-779.

3. Rescue Breathing Improves CPR Outcomes in Kids

Reed Miller. March 10, 2010 (Kyoto, Japan) — A large population-based study of pediatric cardiac-arrest patients shows that conventional cardiopulmonary resuscitation (CPR)--with rescue breathing ventilations--is the best approach to resuscitating children outside the hospital.

In a study supported by the All-Japan Utstein Registry of the Fire and Disaster Management Agency, Dr Tetsuhisa Kitamura (Kyoto University Health Service, Japan) and colleagues collected data from 5170 children 17 and under with an out-of-hospital cardiac arrest. According to the authors, it is the first study powered to measure the benefits of CPR in pediatric patients.

The results, published online March 3, 2010 in the Lancet, show that bystander CPR without rescue breathing had a much higher rate of favorable neurological outcomes than children who received no CPR. Favorable neurological outcome was defined as a Glasgow-Pittsburgh cerebral performance category of 1 or 2 one month after the arrest.

The study also found that, in children older than one year suffering cardiac arrest from a noncardiac cause such as drug overdose, hanging, drowning, or trauma (71% of the children in the study), CPR with rescue-breathing yielded better results than compression-only CPR. In children in cardiac arrest due to cardiac causes, both types of CPR yielded similar success rates.

Outcomes were uniformly poor in infants younger than one year regardless of resuscitation. Neurologically intact survival rates were around 2% with cardiac arrest of noncardiac origin and about 1% for cardiac arrest of cardiac origins in this population.

Based on the results, Kitamura et al "strongly recommend that conventional CPR, including rescue breathing, continue to be the standard treatment for children who have out-of-hospital cardiac arrests with presumed noncardiac causes."

However, previous research shows that bystanders are more willing to do CPR with chest compressions only, without the ventilations, and the American Heart Association's Hands-Only CPR public-education program tells people to just call 911 and begin chest compressions on a person who has collapsed.

Therefore, since the study showed that compression-only CPR was better than no CPR at all, Kitamura et al recommend that the hands-only approach be taught to the general public to increase the overall rate of bystander CPR. People who are likely to witness children in cardiac arrest--teachers, parents, lifeguards--should receive additional training to perform conventional CPR with rescue breathing, they recommend.

"Citizens would be increasingly taught compression-only CPR--a simpler technique that is easier to learn, remember, and undertake than is conventional CPR. If a bystander has learned chest-compression–only CPR, or if a member of the emergency-telephone dispatcher system prefers to teach chest-compression-only CPR rather than conventional CPR because conventional CPR is difficult, the bystander should be encouraged to provide compression-only CPR rather than no bystander CPR."

But Dr Jesus López-Herce and Dr Angel Carrillo Alvarez (Hospital General Universitario Gregorio Marañón, Madrid, Spain) argue, in an accompanying editorial, that the "double-training" strategy advocated by Kitamura and colleagues "could mean that most children would be resuscitated with compression-only CPR, reducing their possibility of survival".

They suggest teaching everyone conventional CPR with ventilations, with the caveat that compression-only CPR is the best approach in adults suspected of cardiac arrest of cardiac origin, but concede that further research is needed to assess the merits of that approach. And, until further research on the best approach to teaching CPR to the whole population can be completed, chest compression plus ventilation should continue to be taught to the whole population, and no changes should be made to the recommendations for pediatric bystander-initiated CPR, López-Herce and Alvarez maintain.

4. Patients Presenting to the Emergency Department with Non-specific Complaints: The Basel Non-specific Complaints (BANC) Study

Nemec M, et al. Acad Emerg Med. 2010;17:284–292.

Objectives: Patient management in emergency departments (EDs) is often based on management protocols developed for specific complaints like dyspnea, chest pain, or syncope. To the best of our knowledge, to date no protocols exist for patients with nonspecific complaints (NSCs) such as "weakness,""dizziness," or "feeling unwell." The objectives of this study were to provide a framework for research and a description of patients with NSCs presenting to EDs.

Methods: Nonspecific complaints were defined as the entity of complaints not part of the set of specific complaints for which evidence-based management protocols for emergency physicians (EPs) exist. "Serious conditions" were defined as potentially life-threatening or those requiring early intervention to prevent health status deterioration. During a 6-month period, all adult nontrauma patients with an Emergency Severity Index (ESI) of 2 or 3 were prospectively enrolled, and serious conditions were identified within a 30-day period.

Results: The authors screened 18,261 patients for inclusion. A total of 218 of 1,611 (13.5%) nontrauma ESI 2 and 3 patients presented with NSCs. Median age was 82 years (interquartile range [IQR] = 72 to 87), and 24 of 218 (11%) were nursing home inhabitants. A median of 4 (IQR = 3 to 5) comorbidities were recorded, most often chronic hypertension, coronary artery disease, and dementia. During the 30-day follow-up period a serious condition was diagnosed in 128 of 218 patients (59%). The 30-day mortality rate was 6%.

Conclusions: Patients with NSC presenting to the ED are at high risk of suffering from serious conditions. Sensitive risk stratification tools are needed to identify patients with potentially adverse health outcomes.

5. What about the PERC Score as an Adjunct to Low-Risk Wells or Low-Risk Gestalt?

Pulmonary Embolism Rule-out Criteria (PERC) Rule*
• Age _ 50 years
• Pulse _ 100 beats/min
• Pulse ox _ 94%
• No unilateral leg swelling
• No hemoptysis
• No recent surgery
• No prior DVT or PE
• No oral hormone use

* Adapted from: Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected
pulmonary embolism. J Thromb Haemost 2004;2:1247–55.

http://www.mdcalc.com/perc-rule-for-pulmonary-embolism

A. Using the PERC Score to Stratify the Subset of Patients who are Low Risk for PE by the Wells Criteria

Carpenter CR, et al. J Emerg Med. 2009;36:317-22.

BACKGROUND: Pulmonary embolism (PE) remains one of the most challenging diagnoses in emergency medicine. The Pulmonary Embolism Rule-out Criteria (PERC) score, a decision aid to reliably distinguish low-risk from very low-risk PE patients, has been derived and validated.

CLINICAL QUESTION: Can a subset of patients with sufficiently low risk for PE be identified who require no diagnostic testing?

EVIDENCE REVIEW: The PERC score derivation and validation trials were located using PubMed and Web of Science. A critical appraisal of this research is presented.

RESULTS: One single-center and another multi-center validation trial both confirmed that the eight-item PERC score identified a very low-risk subset of patients in whom PE was clinically contemplated with a negative likelihood ratio 0.17 (95% confidence interval 0.11-0.25) in the larger trial. If applied, the rule would have identified 20% of potential PE patients as very low risk.

CONCLUSION: The PERC score provides clinicians with an easily remembered, validated clinical decision rule that allows physicians to forego diagnostic testing for pulmonary embolus in a very low-risk population.

Comment: “The PERC score should be applied only to low-risk PE patients, which requires application of another PE clinical decision rule, such as Well’s criteria, to the general ED population with suspected PE.”

B. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria (in combo with Physician Gestalt).

Kline JA, et al. J Thromb Haemost. 2008;6:772-80.

BACKGROUND: Over-investigation of low-risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule-out criteria [PERC(-): age less than 50 years, pulse less than 100 beats min(-1), SaO(2) 95% or greater, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(-) would predict a post-test probability of VTE(+) or death below 2.0%.

METHODS: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72-field, web-based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of less than 15%. The main outcome was the composite of image-proven VTE(+) or death from any cause within 45 days.

RESULTS: We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(-), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5-7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(-) patients, 15 were VTE(+) and one other patient died, yielding a false-negative rate of 16/1666 (1.0%, 0.6-1.6%). As a diagnostic test, low suspicion and PERC(-) had a sensitivity of 97.4% (95.8-98.5%) and a specificity of 21.9% (21.0-22.9%).

CONCLUSIONS: The combination of gestalt estimate of low suspicion for PE and PERC(-) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE.

6. Fast versus slow bandaid removal: a randomised trial.

Furyk JS, et al. Med J Aust. 2009 Dec;191:682-3.

OBJECTIVE: To determine whether slow or fast bandaid removal is less painful.

DESIGN, SETTING AND PARTICIPANTS: A prospective, randomised, crossover trial was carried out at James Cook University, Townsville. Participants were healthy volunteers from Years 2 and 3 of the James Cook University medical school program.

INTERVENTIONS: Medium-sized bandaids were applied bilaterally in three standard body locations and removed using slow and fast techniques.

MAIN OUTCOME MEASURES: Pain scores were assessed using an 11-point verbal numeric pain scale.

RESULTS: 65 participants were included in the study. The overall mean pain score for fast bandaid removal was 0.92 and for slow bandaid removal was 1.58. This represents a highly significant difference of 0.66 (P less than 0.001).

CONCLUSION: In young healthy volunteers, fast bandaid removal caused less pain than slow bandaid removal.

7. Mortality Rate in Older Adults Persistently Increased 5- to 8-Fold After Hip Fracture

Laurie Barclay, MD. March 15, 2010 — All-cause mortality rate in older adults is increased 5- to 8-fold 3 months after hip fracture and persists with time, according to the results of a meta-analysis reported in the March 15 issue of the Annals of Internal Medicine.

"Although an increased risk for death after hip fracture is well established, whether this excess mortality persists over time is unclear," write Patrick Haentjens, MD, PhD, from the Universitair Ziekenhuis Brussel in Jette, and colleagues. "We summarize longitudinal evidence about the magnitude and duration of excess mortality after hip fracture in older men and women."

The goal of this study was to assess excess mortality rate after hip fracture in older adults. An electronic search of MEDLINE and EMBASE for English-language and non–English-language articles from 1957 to May 2009 and a manual search of bibliographies from identified articles allowed 2 independent reviewers to select prospective cohort studies.

Inclusion criteria were determination of mortality rate in women (22 cohorts) or in men (17 cohorts) 50 years or older with hip fracture. In addition, the included studies had to display a life-table analysis and survival curves of the hip fracture group and age- and sex-matched control groups. Two reviewers independently extracted survival curve data and information regarding study validity and generalizability.

In the first 3 months after hip fracture, relative hazard for all-cause mortality was 5.75 (95% confidence interval [CI], 4.94 - 6.67) in women and 7.95 (95% CI, 6.13 - 10.30) in men, based on time-to-event meta-analyses. Although relative hazards declined markedly with time, they did not return to rates seen in the age- and sex-matched control groups.

Using life-table methods, the investigators estimated excess annual mortality rate attributable to hip fracture. At 1, 2, 5, and 10 years after injury, white women having a hip fracture at age 80 years had excess annual mortality rates of 8%, 11%, 18%, and 22%, respectively, compared with white women of the same age without a fracture. For men aged 80 years, excess annual mortality rates attributable to hip fracture was estimated to be 18%, 22%, 26%, and 20% at 1, 2, 5, and 10 years after injury, respectively.

"Older adults have a 5- to 8-fold increased risk for all-cause mortality during the first 3 months after hip fracture," the study authors write. "Excess annual mortality persists over time for both women and men, but at any given age, excess annual mortality after hip fracture is higher in men than in women."

Limitations of this meta-analysis included possible publication bias, as well as variation among cohort studies in sample size, duration of observation, selection of control groups, ascertainment of death, and adjustment for comorbid conditions. Results were modeled for a white US population, and the analysis could not determine the cause(s) for persistent excess risk.

"The absolute risk for death and the excess all-cause mortality in patients with hip fracture are largely dependent on age," the study authors conclude. "These findings may be helpful when performing cost-effectiveness analyses of hip fracture prevention strategies or designing treatment strategies in patients with hip fracture."

The Fund for Scientific Research, Leuven University; National Institutes of Health; the Paul B. Beeson Award; and the Willy Gepts Foundation, Universitair Ziekenhuis Brussel, supported this study.

Ann Intern Med. 2010;52:380-390.

8. Anaphylaxis Management in the Pediatric Emergency Department: Opportunities for Improvement

Russell S, et al. Pediatr Emerg Care. 2010;26:71-76.

Purpose: To determine the rate, immediate treatment, and outpatient management for anaphylaxis in patients receiving care in a pediatric emergency department (ED).

Methods: This is a retrospective cross-sectional descriptive study of patients (21 years or younger) who received care for anaphylaxis for a 5-year period in the ED of the Children's Hospital of Alabama in Birmingham, AL, which has an annual census of 55,000. The diagnostic criteria for anaphylaxis were symptoms and/or signs involving 2 or more organ systems (dermatologic, respiratory, gastrointestinal, and cardiovascular), hypotension for age, 1 organ system involvement with admission to the hospital, and/or dermatologic system involvement treated with intramuscular epinephrine.

Results: There were 124 patient visits by 103 patients (4.5 events/10,000 ED patient visits) who met the diagnostic criteria for anaphylaxis. This included 114 (92%) patients who had involvement of two or more organ systems. There were 66 (64%) males and 33 (27%) patient visits that resulted in hospitalization. The most common organ system involvement was dermatologic in 121 (98%), followed by respiratory in 101 (81%), gastrointestinal in 33 (27%), and cardiovascular in 11 (9%). Medical interventions include 69 patients treated with intramuscular epinephrine (56%; either in pre-hospital setting and/or during ED visit), 97 patients treated with corticosteroids (79%), 114 patients treated with H1 and/or H2 antihistamine (93%), 15 patients treated with intravenous fluid bolus (12%), and 37 patients treated with albuterol nebulization (30%). Food was the most common inciting allergen (in 45 or 36% of patients). Among the foods that were listed as causing reactions were peanuts, shellfish, milk, ice cream, fruit, nuts, and fried chicken. Compared with ED care-only patients, the hospitalized patients had a significantly greater rate of cardiovascular system involvement and of receiving more ED interventions. Of 91 ED care-only patients, autoinjection epinephrine was prescribed to 63% and referral to an allergist was recommended to 33%. Patients treated with intramuscular epinephrine had a significantly greater rate of hospitalization and of receiving more ED interventions compared with patients who were not treated with epinephrine. There were no patient deaths.

Conclusions: This study is the first to describe the management of anaphylaxis in a pediatric ED. The results revealed opportunities for improvement. Although our ED treatment and outpatient management of patients with anaphylaxis did not meet the recommended standards of care with regard to administration of intramuscular epinephrine, prescribing autoinjection epinephrine, or referral to an allergist for all patients who had a diagnosis of anaphylaxis, we do report a higher concordance with published recommendations than those reported in previous studies performed in adults.

9. Ondansetron Use in the Pediatric Emergency Department and Effects on Hospitalization and Return Rates: Are We Masking Alternative Diagnoses?

Sturm JJ, et al. Ann Emerg Med. 2010; in press.

Study objective
We evaluate the effect of ondansetron use in cases of suspected gastroenteritis on the proportion of hospital admissions and return visits and assess whether children who receive ondansetron on their initial visit to the pediatric emergency department (ED) for suspected gastroenteritis return with an alternative diagnosis more frequently than those who did not receive ondansetron.

Methods
This is a retrospective review of visits to 2 tertiary care pediatric EDs with an International Classification of Diseases, Ninth Revision diagnosis of vomiting or gastroenteritis. A logistic regression model was developed to determine the effect of ondansetron use during the initial pediatric ED visit on hospital admission, return to the pediatric ED within 72 hours, and admission on this return visit. For patients who returned within 72 hours and were admitted, hospital discharge records were reviewed. The proportions of alternative diagnoses, defined as a hospital discharge diagnosis that was not a continuation of gastroenteritis or vomiting, were compared between the groups.

Results
During the 3-year study period (2005 to 2007), 34,117 patients met study criteria. Ondansetron was used for 19,857 (58.2%) of these patients on their initial pediatric ED visit. After controlling for differences between the groups, patients who received ondansetron were admitted on their initial visit less often: odds ratio (OR) 0.47 (95% confidence interval [CI] 0.42 to 0.53). However, those who received ondansetron were more likely to return to the pediatric ED within 72 hours (OR 1.45; 95% CI 1.27 to 1.65) and be admitted on the return visit (OR 1.74; 95% CI 1.39 to 2.19). The proportions of alternative diagnoses at hospital discharge were not significantly different in the group that received ondansetron on the initial pediatric ED visit (14.9%) compared with the group that did not (22.4%) (absolute difference 7.5% [95% CI –0.5% to 16.4%).

Conclusion
Ondansetron use in the pediatric ED reduces hospital admissions for suspected gastroenteritis and vomiting. However, children who receive ondansetron in the pediatric ED appear more likely to return to the pediatric ED and be admitted on this return visit than their counterparts. Furthermore, the use of ondansetron does not appear to be associated with increased risks of masking serious diagnoses in children.

10. Dopamine vs. Norepinephrine in Treatment of Shock

A large randomized trial shows no difference in death rates with the two agents overall but significantly higher mortality with dopamine among patients with cardiogenic shock.

When fluid therapy is not successful in reversing a shock state, adrenergic agents are used, most commonly dopamine or norepinephrine. These agents differ in their modes of action, as they affect -adrenergic and β-adrenergic receptors differently. Observational studies have shown higher death rates with dopamine than with norepinephrine in patients with shock; the few randomized trials to date have been too small to provide meaningful data.

In the current multicenter European study, 1679 adult patients with shock (signs of tissue hypoperfusion and systolic blood pressure less than 100 mm Hg or mean arterial pressure below 70 mm Hg) that persisted after treatment with "adequate" fluids (at least 1000 mL of crystalloids or 500 mL of colloids) were randomized to receive dopamine or norepinephrine. Patients who had already received vasopressors for more than 4 hours were excluded. Treating physicians were blinded to drug assignment. Patients with hypovolemic shock, cardiogenic shock, and septic shock were included. The primary endpoint was the rate of death at 28 days. Secondary endpoints included time to hemodynamic stability and incidence of adverse events, such as serious arrhythmias and myocardial necrosis.

Rates of death at 28 days and times to hemodynamic stability did not differ significantly between the dopamine and norepinephrine groups. However, significantly more patients in the dopamine group than in the norepinephrine group experienced arrhythmias (24% vs. 12%). A predefined subgroup analysis according to type of shock showed that among 280 patients with cardiogenic shock, the death rate at 28 days was significantly higher in dopamine recipients than in norepinephrine recipients. An editorialist notes the relatively low amount of fluids considered by the investigators to be adequate to gauge response before starting vasopressors.

Comment: The authors "strongly challenge" the current American College of Cardiology–American Heart Association guidelines that recommend dopamine as a first-line agent for cardiogenic shock. In such cases, norepinephrine seems to be the prudent choice. No evidence supports one agent over the other for different forms of shock.

— J. Stephen Bohan, MD, MS, FACP, FACEP. Published in Journal Watch Emergency Medicine March 3, 2010. Citation(s): De Backer D et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010 Mar 4; 362:779. Levy JH. Treating shock — Old drugs, new ideas. N Engl J Med 2010 Mar 4; 362:841.

11. Diagnosis of Pulmonary Embolism, Aortic Dissection Sharpened by Hindsight: An Expert Interview With David Manthey, MD

Daniel M. Keller, PhD. February 23, 2010 — Editor's note: Hindsight makes events seem more predictable than they were, and it can be a great teaching tool to enable behavior change and improvement. In this Expert Interview with Medscape Emergency Medicine, David Manthey, MD, associate professor of emergency medicine and vice chair of emergency medicine education at Wake Forest University School of Medicine in Winston-Salem, North Carolina, discusses what hindsight teaches us about the diagnosis of pulmonary embolism (PE) and aortic dissection, messages he delivered at the American Academy of Emergency Medicine 16th Annual Scientific Assembly, held February 15 to 17, 2010 in Las Vegas, Nevada. Dr. Manthey gives a lesson on how physicians can simulate hindsight while trying to reach a diagnosis.

Medscape: How does hindsight work to improve diagnostic capabilities?

Dr. Manthey: Anytime we miss a disease process, we look back at the evaluation to see if we could have prevented the miss. The problem is we're looking back through a set of eyes that already knows the diagnosis. So now all those "maybe" clues take on more importance and weight.

For the rest of the interview: http://www.medscape.com/viewarticle/717454

12. ED Lactate Is Associated with Mortality in Older Adults Admitted With and Without Infections

del Portal DA, et al. Acad Emerg Med. 2010;17:260–268.

Objectives: Serum lactate values in the emergency department (ED) have been associated with mortality in diverse populations of critically ill patients. This study investigates whether serum lactate values measured in the ED are associated with mortality in older patients admitted to the hospital, both with and without infections.

Methods: This is a retrospective cohort study performed at two urban teaching hospitals. The study population includes 1,655 older ED patients (age 65 years or more) over a 3-year period (2004–2006) who had serum lactate measured prior to admission. The presence or absence of infection was determined by review of International Classification of Diseases Ninth Revision (ICD-9) admission diagnosis codes. Mortality during hospitalization was determined by review of inpatient records. Mortality at 30 and at 60 days was determined using a state death registry.

Results: In patients with infections, increasing serum lactate values of 2.0 mmol/L or greater were linearly associated with relative risk (RR) of mortality during hospitalization (RR = 1.9 to 3.6 with increasing lactate), at 30 days (RR = 1.7 to 2.6), and at 60 days (RR = 1.4 to 2.3) when compared to patients with serum lactate levels of less than 2.0 mmol/L. In patients without infections, a similar association was observed (RR = 1.1 to 3.9 during hospitalization, RR = 1.2 to 2.6 at 30 days, RR = 1.1 to 2.4 at 60 days). In both groups of patients, serum lactate had a greater magnitude of association with mortality than either of two other commonly ordered laboratory tests, leukocyte count and serum creatinine.

Conclusions: Higher ED lactate values are associated with greater mortality in a broad cohort of admitted patients over age 65 years, regardless of the presence or absence of infection.

13. Warfarin-Treated Patients at Higher Risk for ICH Following tPA for Stroke

Allison Gandey. March 10, 2010 — Patients taking warfarin are more likely to have an intracerebral hemorrhage after treatment of an acute ischemic stroke with tissue plasminogen activator (tPA), a new study suggests.

The surprising finding is calling current practice into question.

"Given there is a lack of prior evidence on the safety of tPA in patients taking warfarin, this study should give some pause and encourage further study," lead investigator Shyam Prabhakaran, MD, from Rush University Medical Center in Chicago, Illinois, told Medscape Neurology.

Dr. Prabhakaran points out there are no published data assessing the safety of tPA among warfarin-treated patients. These patients were excluded from the National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study trials of tPA for stroke, and yet warfarin users represent an increasing group of patients.

This study should give some pause and encourage further study.

Still, American Heart Association and American Stroke Association guidelines permit intravenous tPA use in patients taking oral anticoagulants with a baseline international normalized ratio (INR) less than 1.7.

In this new study, published online March 8 in Archives of Neurology, the investigators report that warfarin-treated patients are at higher risk for stroke despite INRs in a safe range.

With the estimated prevalence of atrial fibrillation in the United States approaching 3 million and expected to double by 2050, the researchers point out that the prevalence of anticoagulant use among stroke patients is not trivial.

Investigators studied 107 ischemic stroke patients treated with tPA. Of these, 12.1% were taking warfarin at baseline.

The overall rate of symptomatic intracerebral hemorrhage was 6.5%. Dr. Prabhakaran says that his team was surprised to see that this rate was nearly 10-fold higher among patients taking warfarin.

The researchers report that the stroke risk remained high even after adjusting for relevant covariates, including age, atrial fibrillation, National Institutes of Health Stroke Scale score, and INR.

The investigators propose that the fibrinolytic effects of tPA may be enhanced by the anticoagulant effects of warfarin. Higher recanalization rates with this combination may lead to a greater rate of reperfusion hemorrhage into infarcted tissue.

They suggest that warfarin use may also be a marker for patients with cardioembolic stroke in whom hemorrhagic transformation is more common and infarct volume is greater.

Dr. Prabhakaran acknowledges that although there is reason to be concerned, this work should be considered hypothesis generating, and further study is necessary.

This study was funded by the National Institute of Neurological Disorders and Stroke. The researchers have disclosed no relevant financial relationships.

Arch Neurol. Published online March 8, 2010.

14. Amiodarone or Procainamide for the Termination of Sustained Stable Ventricular Tachycardia: An Historical Multicenter Comparison

Marill KA, et al. Acad Emerg Med. 2010;17:297–306.

Objectives: The objective was to compare the effectiveness of intravenous (IV) procainamide and amiodarone for the termination of spontaneous stable sustained ventricular tachycardia (VT).

Methods: A historical cohort study of consecutive adult patients with stable sustained VT treated with IV amiodarone or procainamide was performed at four urban hospitals. Patients were identified for enrollment by admissions for VT and treatment with the study agents in the emergency department (ED) from 1993 to 2008. The primary measured outcome was VT termination within 20 minutes of onset of study medicine infusion. A secondary effectiveness outcome was the ultimate need for electrical therapy to terminate the VT episode. Major adverse effects were tabulated, and blood pressure responses to medication infusions were compared.

Results: There were 97 infusions of amiodarone or procainamide in 90 patients with VT, but the primary outcome was unknown after 14 infusions due to administration of another antidysrhythmic during the 20-minute observation period. The rates of VT termination were 25% (13/53) and 30% (9/30) for amiodarone and procainamide, respectively. The adjusted odds of termination with procainamide compared to amiodarone was 1.2 (95% confidence interval [CI] = 0.4 to 3.9). Ultimately, 35/66 amiodarone patients (53%, 95% CI = 40 to 65%) and 13/31 procainamide patients (42%, 95% CI = 25 to 61%) required electrical therapy for VT termination. Hypotension led to cessation of medicine infusion or immediate direct current cardioversion (DCCV) in 4/66 (6%, 95% CI = 2 to 15%) and 6/31 (19%, 95% CI = 7 to 37%) patients who received amiodarone and procainamide, respectively.

Conclusions: Procainamide was not more effective than amiodarone for the termination of sustained VT, but the ability to detect a significant difference was limited by the study design and potential confounding. As used in practice, both agents were relatively ineffective and associated with clinically important proportions of patients with decreased blood pressure.

15. New Federal Report Details Health of US Population; Diagnostic Imaging Has Tripled

Emma Hitt, PhD. February 18, 2010 — New data are now available from "Health, United States, 2009," the federal government's 33rd annual report to the president and Congress on the health of America.

The report was released yesterday by the Centers for Disease Control and Prevention's National Center for Health Statistics and contains 150 tables detailing various aspects of the health of the American population.

"The United States spends more on health per capita than any other country, and health spending continues to increase," according to the report's executive summary. "In 2007, national health expenditures in the United States totaled $2.2 trillion — a 6% increase from 2006," representing 16% of the total US gross domestic product.

In 2007, 20% of adults aged 18 years and older visited the emergency department at least once in the past year, and 7% went at least twice.

In a special section on medical technology, it was reported that the use of computed tomography, positron emission tomography, and magnetic resonance imaging increased 3-fold in the United States from 1996 to 2006.

Overall life expectancy is now estimated at 77.9 years, with a decrease in the gap between white and black life expectancy.

Other key findings from the report included the fact that the rate of knee replacement procedures in patients older than 45 years increased by 70% from 1996 to 2006. In addition, the use of antidiabetic drugs and cholesterol drugs in that age group increased by about 50% and by 10-fold, respectively. Organ transplantations also increased by 31% and 42% for kidney and liver transplants, respectively.

In addition, the report indicates that the percentage of the population taking at least 1 prescription drug during the previous month increased from 38% in 1988-1994 to 47% in 2003-2006, and the percentage of the population taking at least 3 prescription drugs increased from 11% to 21% between the same time periods.

Twenty-one percent of men smoke cigarettes compared with 17% of American women. Overall, the rate of cigarette smoking decreased by about 1% during a 3-year period ending in 2007.

Rates of mortality from heart disease, stroke, and cancer have continued to decline in recent years, although mortality from chronic lower respiratory diseases and unintentional injuries has not.

The full report is available (free) online: http://www.cdc.gov/nchs/hus.htm

16. ED Bedside Ultrasonographic Measurement of the Caval Index for Noninvasive Determination of Low CVP

Nagdev AD, et al. Ann Emerg Med. 2010;55:290-295.

Study objective
Among adult emergency department (ED) patients undergoing central venous catheterization, we determine whether a greater than or equal to 50% decrease in inferior vena cava diameter is associated with a central venous pressure of less than 8 mm Hg.

Methods
Adult patients undergoing central venous catheterization were enrolled in a prospective, observational study. Inferior vena cava inspiratory and expiratory diameters were measured by 2-dimensional bedside ultrasonography. The caval index was calculated as the relative decrease in inferior vena cava diameter during 1 respiratory cycle. The correlation of central venous pressure and caval index was calculated. The sensitivity, specificity, and positive and negative predictive values of a caval index greater than or equal to 50% that was associated with a central venous pressure less than 8 mm Hg were estimated.

Results
Of 73 patients, the median age was 63 years and 60% were women. Mean time and fluid administered from ultrasonographic measurement to central venous pressure determination were 6.5 minutes and 45 mL, respectively. Of the 73 participants, 32% had a central venous pressure less than 8 mm Hg. The correlation between caval index and central venous pressure was –0.74 (95% confidence interval [CI] –0.82 to –0.63). The sensitivity of caval index greater than or equal to 50% to predict a central venous pressure less than 8 mm Hg was 91% (95% CI 71% to 99%), the specificity was 94% (95% CI 84% to 99%), the positive predictive value was 87% (95% CI 66% to 97%), and the negative predictive value was 96% (95% CI 86% to 99%).

Conclusion
Bedside ultrasonographic measurement of caval index greater than or equal to 50% is strongly associated with a low central venous pressure. Bedside measurements of caval index could be a useful noninvasive tool to determine central venous pressure during the initial evaluation of the ED patient.

17. Bedside Ultrasonography in the ED Detects Acute Cholecystitis

By Will Boggs, MD. NEW YORK (Reuters Health) Mar 05 - Bedside ultrasonography allows acute cholecystitis to be confirmed or ruled out as effectively in the emergency department as in the radiology suite, new research shows.

"Regardless of a surgeon's need for radiology studies, if I can rule out gallbladder disease at the time of presentation I don't have to wait 2 hours for radiology to do that for me," Dr. William Scruggs, an emergency physician and an author of the report, told Reuters Health by email. "I can move on to whatever study really needs to be done (if any). That decreases costs and time for patients in the emergency department."

Dr. Scruggs and his colleagues at the University of California, Irvine, compared the accuracy of bedside ultrasonography -- performed by emergency physicians -- and radiology ultrasonography for diagnosing cholecystitis in a convenience sample of 189 patients, including 125 who received additional radiology ultrasound exams.

Overall, 26 patients had urgent cholecystectomy, with acute cholecystitis confirmed by pathology in 23. The remaining 163 patients were discharged. Among 140 patients who could be reached by phone afterward, only 1 reported cholecystectomy after discharge from the emergency department.

In a February 8th online article in the Annals of Emergency Medicine, the authors report that bedside ultrasonography yielded 20 true positives, 115 true negatives, 26 false positives, and 3 false negatives, resulting in 87% sensitivity and 82% specificity.

Radiology ultrasonography yielded 19 true positives, 77 true negatives, 13 false positives, and 4 false negatives, for a sensitivity of 83% and specificity of 86%.

None of the secondary ultrasound findings (Murphy's sign, gallbladder wall thickening, or pericholecystic fluid) was sensitive enough to exclude cholecystitis either at bedside or in the radiology department, the researchers note.

"Because emergency physicians in our study tended to be highly experienced in bedside ultrasonography, our results may not be applicable to the general community or reproducible at centers without ultrasonographic training programs," the investigators caution. Use of bedside ultrasonography "in community hospitals or at academic centers without ultrasonographic fellowships" still needs to be tested, they add.

"Radiology probably should be involved if there is anything beyond nuts and bolts cholelithiasis or cholecystitis," Dr. Scruggs said.

"Emergency physician ultrasound (can) decrease CT use," he added. "A huge number of smaller emergency departments in this country don't have radiology ultrasound most of the day, but they do have a CT scanner. In those places, what study does the patient with possible cholecystitis get? Because of our training, patient expectations, and the medico-legal environment, the answer isn't none. It's a CT scan that costs the patient more money, and in a small percentage, their health or even their life."

Ann Emerg Med 2010.

18. Patient Identification Errors Are Common in a Simulated Setting

Henneman PL, et al. Ann Emerg Med. 2010; in press.

Study objective
We evaluate the frequency and accuracy of health care workers verifying patient identity before performing common tasks.

Methods
The study included prospective, simulated patient scenarios with an eye-tracking device that showed where the health care workers looked. Simulations involved nurses administering an intravenous medication, technicians labeling a blood specimen, and clerks applying an identity band. Participants were asked to perform their assigned task on 3 simulated patients, and the third patient had a different date of birth and medical record number than the identity information on the artifact label specific to the health care workers' task. Health care workers were unaware that the focus of the study was patient identity.

Results
Sixty-one emergency health care workers participated—28 nurses, 16 technicians, and 17 emergency service associates—in 183 patient scenarios. Sixty-one percent of health care workers (37/61) caught the identity error (61% nurses, 94% technicians, 29% emergency service associates). Thirty-nine percent of health care workers (24/61) performed their assigned task on the wrong patient (39% nurses, 6% technicians, 71% emergency service associates). Eye-tracking data were available for 73% of the patient scenarios (133/183). Seventy-four percent of health care workers (74/100) failed to match the patient to the identity band (87% nurses, 49% technicians). Twenty-seven percent of health care workers (36/133) failed to match the artifact to the patient or the identity band before performing their task (33% nurses, 9% technicians, 33% emergency service associates). Fifteen percent (5/33) of health care workers who completed the steps to verify patient identity on the patient with the identification error still failed to recognize the error.

Conclusion
Wide variation exists among health care workers verifying patient identity before performing everyday tasks. Education, process changes, and technology are needed to improve the frequency and accuracy of patient identification.

19. 25 Years in the Emergency Department -- Lessons Learned: An Expert Interview With Robert McNamara, MD

Daniel Keller, PhD. March 4, 2010 — Editor's note: Based on 25 years as an emergency medicine attending physician and program director, Robert McNamara, MD, imparted some of the lessons he has learned to attendees at the American Academy of Emergency Medicine (AAEM) 16th Annual Scientific Assembly, held February 15 to 17 in Las Vegas, Nevada. Dr. McNamara is professor and chair of the Department of Emergency Medicine at Temple University School of Medicine in Philadelphia, Pennsylvania, and is a founding director and past president of the AAEM. In this interview with Medscape Emergency Medicine, Dr. McNamara discussed some of these lessons, including the best use of the expertise of other healthcare providers, establishing rapport with patients and with colleagues on other medical services, and an early clue in the diagnosis of some newly emerged soft tissue infections.

Medscape: In your 25 years as an emergency medicine attending physician, and in your time as a program director, what are some of the lessons that you would pass on to physicians entering the field of emergency medicine today?

Dr. McNamara: Emergency physicians get input from many different sources — emergency medical services (EMS), nursing, patients, and families. It's been my experience that physicians really need to pay attention to the nursing staff if they tell you they think the patient is sick. That should be a red flag. Nurses have the same gestalt, a lot of them have a lot of experience, and if they come to you and they want you to take a look at a patient because they are worried about them, you can't ignore that.

On the other hand, if they think the patient is faking or malingering, that should raise an alarm in your mind because often the patients that we have that kind of reaction to actually have something wrong with them. If the nurses think the patient is faking, try to block that out and objectively evaluate the patient.

Medscape: How do you deal with patients' attitudes and anger?...

For the full interview: http://www.medscape.com/viewarticle/717927

20. Pediatric Lyme Arthritis Twice as Common as Septic Arthritis in Endemic Areas of Lyme Disease

Fran Lowry. March 15, 2010 (New Orleans, Louisiana) — Almost half of children with fluid in the knee in the Northeastern United States are likely to have Lyme arthritis, according to a new study presented here at the American Association of Orthopaedic Surgeons 2010 Annual Meeting.

"In a pediatric population, Lyme arthritis is probably the first diagnosis to consider if you are in an endemic area," Matthew D. Milewski, MD, from Yale–New Haven Children's Hospital in Connecticut, told meeting attendees.

Connecticut has the highest rate of Lyme disease, but other areas of the United States are considered endemic, including the northeast from Maine to the mid-Atlantic states, Minnesota, Wisconsin and other Midwestern states, and Northern California.

Lyme arthritis is on the rise, increasing almost 100% in the past 15 years, according to data from the Centers of Disease Control and Prevention.

Children are nearly twice as likely to develop arthritis with Lyme disease than adults, and also to have it as the initial manifestation. Distinguishing children who have Lyme arthritis from those who have septic arthritis can be a challenge in the emergency department (ED), but doing so is essential because their treatment is so different, Dr. Milewski said.

"In Connecticut, where Lyme disease is endemic, a lot of kids would come into our [ED] with a swollen joint, and we would be forced to try to decide whether this person had septic arthritis or Lyme arthritis," Dr. Milewski told Medscape Orthopaedics. "Septic arthritis is traditionally considered a surgical indication in most cases, and Lyme arthritis is considered something that can be treated with antibiotics. This is a big difference in treatment options and we wanted to help the providers in the [ED] try to decide between these 2 courses of treatment."

In their study, Dr. Milewski and colleagues sought to determine how often children presented with Lyme arthritis at their center, and how they differed from children with septic arthritis.

They undertook a retrospective review of all joint aspirations done from January 1992 to April 2009 in children younger than 18 years. They collected data on cell count, fluid differential, culture, hematologic inflammatory markers (including peripheral white blood cell count, peripheral blood differential, erythrocyte sedimentation rate, and C-reactive protein), and Lyme disease serological testing.

They also reviewed charts for the presence of fever and weight-bearing status at the time the children presented, and for radiographic or ultrasound evidence of effusion.

Of the 391 patients who were analyzed, 123 (31%) tested positive for Lyme disease and 51 (13%) had septic arthritis.

They also found that children with septic arthritis had a higher nucleated cell count than those with Lyme arthritis (123,000 vs 60,200 cells/mm; P = .007).

They were also more likely to have fever. Twenty-seven of 49 septic arthritis patients (55%) had temperatures of at least 101.5 °F, as did 26 of 120 Lyme patients (22%); 33 of 49 septic arthritis patients (67%) had a low-grade fever, defined as a temperature of at least 100.4 °F, as did 46 of 120 Lyme patients (38%).

Both of these temperature cut-offs were found to be significantly different between the 2 cohorts (P less than .001 and 0.001, respectively).

In addition, virtually all of the children with septic arthritis refused to bear weight, compared with only 39% of the children with Lyme arthritis (P less than .001).

Erythrocyte sedimentation rate and C-reactive protein values were similar in the 2 groups and did not help to distinguish between them, Dr. Milewski noted.

This study gives providers more tools to help determine their course of treatment, Dr. Milewski told Medscape Orthopaedics.

"We don't have a rapid Lyme test that helps the care provider at the point of initial presentation to decide if this is Lyme or not, but this information gives us a way to start to lean a practitioner one way or the other if they are on the fence. It speaks to the fact that Lyme disease is so common that it really needs to be considered every time you evaluate a kid for septic arthritis."

Commenting on this study for Medscape Orthopaedics, Theodore J. Ganley, MD, director of sports medicine at the Children's Hospital of Philadelphia and associate professor at the University of Pennsylvania School of Medicine in Philadelphia, agreed. "The emphasis from this study is that if you have a child with a mild injury and you have a significant knee effusion that is atraumatic or with minimal trauma, for these kids you really need to consider Lyme and test for Lyme."

He called the study helpful to clinicians because it raises awareness about the "fairly high" incidence of Lyme arthritis. "This is not a rare, reportable case. The incidence is very real."

Dr. Milewski and Dr. Ganley have reported no relevant financial relationships.

American Association of Orthopaedic Surgeons (AAOS) 2010 Annual Meeting: Abstract 141. Presented March 10, 2010.

21. Early Marijuana Use Heightens Psychosis Risk in Young Adults

Allison Gandey. March 4, 2010 (Updated with comment March 10, 2010) — Experimenting with marijuana at a young age increases the risk for hallucinations or delusions later in life, a new study shows.

"Early cannabis use increases the risk of psychosis in young adults," lead investigator John McGrath, MD, from the Queensland Centre for Mental Health Research in Brisbane, Australia, told Medscape Psychiatry.

"Apart from having an increased risk of having a disorder like schizophrenia, the longer the young adults reported since their first cannabis use, the more likely they were to report isolated symptoms of psychosis."

Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks. Psychotic disorders are common and typically affect 1 or 2 people of every 100. "Despite our best efforts with treatment, not everyone makes a full recovery," Dr. McGrath said. "We need to think about prevention. Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks."

Dr. McGrath says he was surprised that the results were so strong and so consistent.

The study was published online March 1 in Archives of General Psychiatry.

Investigators studied 3800 young adults born at an Australian hospital taking part in the Mater-University Study of Pregnancy.

Prospective studies have already identified an association between marijuana use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables.

Dr. McGrath and his team focused instead on 228 sibling pairs in the prospective birth cohort to reduce the influence of unmeasured residual confounding.

Investigators followed up study participants at ages 5, 14, and 21 years. The researchers assessed first marijuana use and 3 psychosis-related outcomes. These outcomes included nonaffective disease, hallucinations, and the Peters et al delusions inventory score.

Investigators evaluated all associations between duration of marijuana use and psychosis-related outcomes using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up.

The results mirror those of another study published in the November issue of the American Journal of Psychiatry (2009;166:1251–1257). That work suggests a link between daily cannabis or tobacco use and early-onset psychosis.

In that study, investigators looked at 109 patients in a psychiatric unit and found that daily marijuana and tobacco use was common. More than 40% of patients used one or both substances.

Of those who abused cannabis, almost 88% were classified as weekly or daily users before the onset of psychosis.

Escalating Marijuana Use Hastened Psychosis

It is not clear why escalating marijuana use may hasten psychosis, lead investigator Michael Compton, MD, from the Emory University School of Medicine in Atlanta, Georgia, noted in November. However, studies have shown increased cannabinoid receptor density in areas of the brain and elevated levels of endogenous cannabinoids in the blood of some patients with psychosis.

This new study, Dr. McGrath points out, provides additional evidence that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.

Asked by Medscape Psychiatry to comment, Emma Barkus, PhD, from the University of Wollongong in New South Wales, Australia, says the findings are consistent with the substance literature, which suggests that those who are engaging in risk behaviors at the age of 14 years are more likely to persist as they get older.

"Despite the restrictions of the methodologies," she noted, "such as use of retrospective recall and the pseudoquantification of cannabis exposure, the sample size and the persistence of the findings in the face of controlling for confounding variables and analyses on subsets of participants lend strength to an area of literature which is still fraught with controversy."

Dr. Barkus says the findings add further support to the role of cannabis use in psychoses in outcomes.

This study was funded by the National Health and Medical Research Council of Australia. Coauthor Dr. Rosa Alati is supported by a National Health and Medical Research Council Career Development Award in Population Health.

Arch Gen Psychiatry. Published online March 1, 2010.