Saturday, August 27, 2011

Lit Bits: August 27, 2011

From the recent medical literature...

1. Malpractice Risk According to Physician Specialty

Jena AB, et al. N Engl J Med 2011;365:629-636.

Background: Data are lacking on the proportion of physicians who face malpractice claims in a year, the size of those claims, and the cumulative career malpractice risk according to specialty.

Methods: We analyzed malpractice data from 1991 through 2005 for all physicians who were covered by a large professional liability insurer with a nationwide client base (40,916 physicians and 233,738 physician-years of coverage). For 25 specialties, we reported the proportion of physicians who had malpractice claims in a year, the proportion of claims leading to an indemnity payment (compensation paid to a plaintiff), and the size of indemnity payments. We estimated the cumulative risk of ever being sued among physicians in high- and low-risk specialties.

Results: Each year during the study period, 7.4% of all physicians had a malpractice claim, with 1.6% having a claim leading to a payment (i.e., 78% of all claims did not result in payments to claimants). The proportion of physicians facing a claim each year ranged from 19.1% in neurosurgery, 18.9% in thoracic–cardiovascular surgery, and 15.3% in general surgery to 5.2% in family medicine, 3.1% in pediatrics, and 2.6% in psychiatry. The mean indemnity payment was $274,887, and the median was $111,749. Mean payments ranged from $117,832 for dermatology to $520,923 for pediatrics. It was estimated that by the age of 65 years, 75% of physicians in low-risk specialties had faced a malpractice claim, as compared with 99% of physicians in high-risk specialties.

Conclusions: There is substantial variation in the likelihood of malpractice suits and the size of indemnity payments across specialties. The cumulative risk of facing a malpractice claim is high in all specialties, although most claims do not lead to payments to plaintiffs. (Funded by the RAND Institute for Civil Justice and the National Institute on Aging.)

Full-text (free):

2. The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism.

Hugli O, et al. J Thromb Haemost. 2011;9:300-4.

BACKGROUND: The Pulmonary Embolism Rule-out Criteria (PERC) rule is a clinical diagnostic rule designed to exclude pulmonary embolism (PE) without further testing. We sought to externally validate the diagnostic performance of the PERC rule alone and combined with clinical probability assessment based on the revised Geneva score.

METHODS: The PERC rule was applied retrospectively to consecutive patients who presented with a clinical suspicion of PE to six emergency departments, and who were enrolled in a randomized trial of PE diagnosis. Patients who met all eight PERC criteria [PERC((-))] were considered to be at a very low risk for PE. We calculated the prevalence of PE among PERC((-)) patients according to their clinical pretest probability of PE. We estimated the negative likelihood ratio of the PERC rule to predict PE.

RESULTS: Among 1675 patients, the prevalence of PE was 21.3%. Overall, 13.2% of patients were PERC((-)). The prevalence of PE was 5.4% [95% confidence interval (CI): 3.1-9.3%] among PERC((-)) patients overall and 6.4% (95% CI: 3.7-10.8%) among those PERC((-)) patients with a low clinical pretest probability of PE. The PERC rule had a negative likelihood ratio of 0.70 (95% CI: 0.67-0.73) for predicting PE overall, and 0.63 (95% CI: 0.38-1.06) in low-risk patients.

CONCLUSIONS: Our results suggest that the PERC rule alone or even when combined with the revised Geneva score cannot safely identify very low risk patients in whom PE can be ruled out without additional testing, at least in populations with a relatively high prevalence of PE.

3. New Options in Anticoagulation for Atrial Fibrillation

del Zoppo GJ, et al. N Engl J Med 2011; Aug 10. [Epub ahead of print]

The presence of atrial fibrillation significantly increases the risk and burden of thromboembolic stroke.1 Warfarin is the reference standard treatment for the primary prevention of embolic stroke during atrial fibrillation.2 However, the long-term use of warfarin has its limitations. Although guidelines suggest a target international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0) for this indication,2 only about 60% of patients have an INR within the recommended range at a given time in usual clinical practice. This is the reason that is most often given for the search for other oral antithrombotic agents that could be simpler to manage and that might replace warfarin in such patients.

Two recent studies have compared new antithrombotic agents with warfarin for the primary prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. In this issue of the Journal, Patel et al.3 report the results of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in which the investigators compared rivaroxaban, a direct factor Xa inhibitor, with warfarin. This study follows on the heels of the report of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial ( number, NCT00262600),4 showing that dabigatran, a direct thrombin inhibitor, was not inferior to warfarin. Both studies provide some points to ponder for a condition in which placebo-controlled trials are no longer possible.

One interesting point is how the interpretation of ROCKET AF depends on the results from the three different protocol-specified analyses of the primary outcome of stroke or systemic embolism. The primary analysis included only patients who were treated according to protocol and were followed for outcome events only for the period during which they were actually receiving the assigned treatment (or within 2 days after the last dose). This analysis, designated the “per-protocol, as-treated” analysis, resulted in a conservative test for noninferiority5 and showed that rivaroxaban was significantly noninferior to warfarin. The authors also tested for superiority using an intention-to-treat analysis, which did not show superiority for rivaroxaban over warfarin.

Between these two analyses, the authors conducted another analysis in the “as-treated safety population.” Here, they included all patients who received at least one dose of a study drug and were followed for events while receiving the drug (or within 2 days after the last dose), regardless of adherence to protocol. It is not surprising that the annual event rates in the two study groups in this analysis were much closer to those of the per-protocol analysis than to those in the intention-to-treat analysis. As a consequence, in the safety analysis, the between-group P value was significant, even though the results do not show superiority for rivaroxaban over warfarin, since the intention-to-treat analysis was negative. Thus, the multiple analyses have muddied the waters regarding rivaroxaban's efficacy and effectiveness over warfarin.

Trials comparing new oral antithrombotic agents with warfarin are dependent on the quality of the management of the warfarin cohort. Overall compliance varies. Trials like ROCKET AF and RE-LY use algorithms for imputing the dummy INR of the warfarin placebo in patients who are not receiving warfarin in order to maintain blinding. They also use the concept of “time in therapeutic range” to assess the quality of warfarin management. Such trials typically use a method described by Rosendaal et al.,6 in which the measured INR values and the interval between INR tests are both taken into account. On the basis of this approach, INR values were within the therapeutic range a mean of 55% of the time in ROCKET AF and 64% in the RE-LY trial. So the interpretation of noninferiority in a given trial may also depend both on the homogeneity and treatment accuracy of the warfarin cohort and on the dummy INR algorithm that is used.

Overall, the frequency of major hemorrhagic events in ROCKET AF did not differ significantly between the rivaroxaban group and the warfarin group. A similar finding was seen in the RE-LY study. However, interestingly, both studies showed a reduction in the rate of intracranial hemorrhage with the new oral antithrombotic agent, as compared with warfarin. The reasons for the potential reduction in intracranial hemorrhage that was associated with these agents are not clear, but one possibility is the effect on a single target in the hemostatic system by the new antithrombotic agents versus the multiple targets by warfarin.7 More intriguing is the possibility that cerebral vascular beds have protective features that are more apparent at the doses of either of the new agents tested. The presence of large amounts of tissue factor in the cerebral vascular neighborhood could modulate vascular hemostatic activity within brain vessels. It is possible that neither rivaroxaban nor dabigatran affects the complex made up of tissue factor and factor VIIa, whereas warfarin decreases factor VII activity. Does this difference influence the risk of hemorrhage? Fundamental studies of cerebral vascular responses to these agents and of the differential risk of intracranial hemorrhage in the two trials would be instructive.

For the management of atrial fibrillation, oral alternatives to warfarin have arrived. Their simplicity of use is attractive, and they appear to have an efficacy similar to that of warfarin, with the proviso that comparisons seem to depend on how easily the patient can be treated with warfarin. An important concern that these clinical trials do not address is the absence of antidotes to rapidly reverse the anticoagulant effects of either rivaroxaban or dabigatran in the case of life-threatening hemorrhage or surgery. All these issues need to be taken into account in clinical decision making. Further studies will be necessary to refine the treatment of a growing population of patients with atrial fibrillation in order to reduce the risk of stroke.


4. ECG Findings in ED Patients with Syncope

Quinn J, et al. Acad Emerg Med. 2011; 18:714–718

Objectives: To determine the sensitivity and specificity of the San Francisco Syncope Rule (SFSR) electrocardiogram (ECG) criteria for determining cardiac outcomes and to define the specific ECG findings that are the most important in patients with syncope.

Methods: A consecutive cohort of emergency department (ED) patients with syncope or near syncope was considered. The treating emergency physicians assessed 50 predictor variables, including an ECG and rhythm assessment. For the ECG assessment, the physicians were asked to categorize the ECG as normal or abnormal based on any changes that were old or new. They also did a separate rhythm assessment and could use any of the ECGs or available monitoring strips, including prehospital strips, when making this assessment. All patients were followed up to determine a broad composite study outcome. The final ECG criterion for the SFSR was any nonsinus rhythm or new ECG changes. In this specific study, the initial assessments in the database were used to determine only cardiac-related outcomes (arrhythmia, myocardial infarction, structural, sudden death) based on set criteria, and the authors determined the sensitivity and specificity of the ECG criteria for cardiac outcomes only. All ECGs classified as “abnormal” by the study criteria were compared to the official cardiology reading to determine specific findings on the ECG. Univariate and multivariate analysis were used to determine important specific ECG and rhythm findings.

Results: A total of 684 consecutive patients were considered, with 218 having positive ECG criteria and 42 (6%) having important cardiac outcomes. ECG criteria predicted 36 of 42 patients with cardiac outcomes, with a sensitivity of 86% (95% confidence interval [CI] = 71% to 94%), a specificity of 70% (95% CI = 66% to 74%), and a negative predictive value of 99% (95% CI = 97% to 99%). Regarding specific ECG findings, any nonsinus rhythm from any source and any left bundle conduction problem (i.e., any left bundle branch block, left anterior fascicular block, left posterior fascicular block, or QRS widening) were 2.5 and 3.5 times more likely associated with significant cardiac outcomes.

Conclusions: The ECG criteria from the SFSR are relatively simple, and if used correctly can help predict which patients are at risk of cardiac outcomes. Furthermore, any left bundle branch block conduction problems or any nonsinus rhythms found during the ED stay should be especially concerning for physicians caring for patients presenting with syncope.

The SF Syncope Rule:

Related syncope abstract on the ROSE Decision Instrument in Ann Emerg Med Sept 2011:

5. Cycling is good for you—even in the big city

The health risks and benefits of cycling in urban environments compared with car use: health impact assessment study

Rojas-Rueda D, et al. BMJ 2011;343:d4521

Objective: To estimate the risks and benefits to health of travel by bicycle, using a bicycle sharing scheme, compared with travel by car in an urban environment.

Design: Health impact assessment study.

Setting: Public bicycle sharing initiative, Bicing, in Barcelona, Spain.

Participants: 181 982 Bicing subscribers.

Main outcomes measures: The primary outcome measure was all cause mortality for the three domains of physical activity, air pollution (exposure to particulate matter smaller than 2.5 µm), and road traffic incidents. The secondary outcome was change in levels of carbon dioxide emissions.

Results: Compared with car users the estimated annual change in mortality of the Barcelona residents using Bicing (n=181 982) was 0.03 deaths from road traffic incidents and 0.13 deaths from air pollution. As a result of physical activity, 12.46 deaths were avoided (benefit:risk ratio 77). The annual number of deaths avoided was 12.28. As a result of journeys by Bicing, annual carbon dioxide emissions were reduced by an estimated 9 062 344 kg.

Conclusions: Public bicycle sharing initiatives such as Bicing in Barcelona have greater benefits than risks to health and reduce carbon dioxide emissions.

6. Low Prevalence of Bacteremia in Children with Community Acquired Pneumonia

Shah SS et al. Pediatr Infect Dis J 2011;30:475

Blood culture results rarely changed management, and did so mainly in children with complicated CAP.

Background: Blood cultures are frequently obtained in the emergency department (ED) evaluation of children with community-acquired pneumonia (CAP).

Objectives: To determine the prevalence of bacteremia in children presenting to the ED with CAP, identify subgroups at increased risk for bacteremia, and quantify the effect of positive blood cultures on management.

Methods: This case–control study was nested within a cohort of children followed up at 35 pediatric practices. Patients from this cohort who were ≤18 years of age, evaluated in the ED in 2006–2007, and diagnosed with CAP were eligible. Cases were those with bacteremia. Controls included those with negative blood cultures and those without blood cultures performed.

Results: A total of 877 (9.6%) of 9099 children with CAP were evaluated in the ED. The mean age was 3.6 years; 53% were male. Blood cultures were obtained from 291 children (33.2%). Overall, the prevalence of bacteremia was 2.1% (95% confidence interval [CI]: 0.8%–4.4%). Bacteremia occurred in 2.6% (95% CI: 1.0%–5.6%) with an infiltrate on chest radiograph and in 13.0% (95% CI: 2.8%–33.6%) with complicated pneumonia. Streptococcus pneumoniae accounted for 4 of the 6 cases of bacteremia. Blood culture results altered management in 5 of the 6 bacteremic patients; 1 had an appropriate broadening and 4 had an appropriate narrowing of coverage. The contamination rate was 1.0% (95% CI: 0.2%–3.0%).

Conclusion: Children presenting to the ED for evaluation of CAP are at low-risk for bacteremia. Although positive blood cultures frequently altered clinical management, the overall impact was small because of the low prevalence of bacteremia..

7. Diagnosis of Spinal Cord Compression in Nontrauma Patients in the ED

Dugas AF, et al. Acad Emerg Med. 2011;18:719–725

Objectives:  The objectives were to evaluate the presenting signs and symptoms of spinal cord and cauda equina compression (SCC) and to determine the incidence of emergency department (ED) misdiagnosis.

Methods:  This was a retrospective chart review at an urban, tertiary care hospital of patients discharged from an inpatient stay (April 2008 through July 2009) with an International Classification of Diseases, Ninth Revision (ICD-9) code indicating spinal disease, who had visited the ED for a related complaint within the previous 30 days, and who had a final diagnosis of new SCC. Trauma and transferred patients were excluded. The authors defined a misdiagnosis as no ED-documented diagnosis of SCC and failure to perform an appropriate diagnostic study either prior to arrival, in the ED, or immediately upon admission.

Results:  Of 1,231 charts reviewed, 63 met inclusion criteria. The most common presenting symptoms in patients with SCC were pain (44, 70%), difficulty ambulating (38, 60%), and weakness (35, 56%). On physical examination, motor deficits (45, 71%) were more common than sensory deficits (27, 43%); however, 15 (24%) patients had no motor or sensory deficit, and 13 (23%) patients only had unilateral findings. Impaired gait was present in 14 patients of only 20 tested, three of whom had no associated motor or sensory deficit. SCC was misdiagnosed in 18 (29%, 95% confidence interval [CI] = 19% to 41%) cases, which resulted in a significant delay to diagnosis (median = 54 hours, interquartile range [IQR] = 38 to 77 vs. 5.3 hours, IQR = 3.0 to 15) in these patients.

Conclusions:  SCC can have a subtle presentation with absent or unilateral motor and sensory deficits, but gait ataxia may be an additional finding. ED misdiagnosis of SCC in nontrauma patients is common.

8. Intraosseous Versus Intravenous Vascular Access during Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial

Reades R, et al. Ann Emerg Med. 2011; in press

Study objective: Intraosseous needle insertion during out-of-hospital cardiac arrest is rapidly replacing peripheral intravenous routes in the out-of-hospital setting. However, there are few data directly comparing the effectiveness of intraosseous needle insertions with peripheral intravenous insertions during out-of-hospital cardiac arrest. The objective of this study is to determine whether there is a difference in the frequency of first-attempt success between humeral intraosseous, tibial intraosseous, and peripheral intravenous insertions during out-of-hospital cardiac arrest.

Methods: This was a randomized trial of adult patients experiencing a nontraumatic out-of-hospital cardiac arrest in which resuscitation efforts were initiated. Patients were randomized to one of 3 routes of vascular access: tibial intraosseous, humeral intraosseous, or peripheral intravenous. Paramedics received intensive training and exposure to all 3 methods before study initiation. The primary outcome was first-attempt success, defined as secure needle position in the marrow cavity or a peripheral vein, with normal fluid flow. Needle dislodgement during resuscitation was coded as a failure to maintain vascular access.

Results: There were 182 patients enrolled, with 64 (35%) assigned to tibial intraosseous, 51 (28%) humeral intraosseous, and 67 (37%) peripheral intravenous access. Demographic characteristics were similar among patients in the 3 study arms. There were 130 (71%) patients who experienced initial vascular access success, with 17 (9%) needles becoming dislodged, for an overall frequency of first-attempt success of 113 (62%). Individuals randomized to tibial intraosseous access were more likely to experience a successful first attempt at vascular access (91%; 95% confidence interval [CI] 83% to 98%) compared with either humeral intraosseous access (51%; 95% CI 37% to 65%) or peripheral intravenous access (43%; 95% CI 31% to 55%) groups. Time to initial success was significantly shorter for individuals assigned to the tibial intraosseous access group (4.6 minutes; interquartile range 3.6 to 6.2 minutes) compared with those assigned to the humeral intraosseous access group (7.0 minutes; interquartile range 3.9 to 10.0 minutes), and neither time was significantly different from that of the peripheral intravenous access group (5.8 minutes; interquartile range 4.1 to 8.0 minutes).

Conclusion: Tibial intraosseous access was found to have the highest first-attempt success for vascular access and the most rapid time to vascular access during out-of-hospital cardiac arrest compared with peripheral intravenous and humeral intraosseous access

9. Placebo by Proxy: Effects on the Patient’s Friends and Family

Grelotti DJ, et al. BMJ 2011;343:d4345

Clinicians’ and family members’ feelings and perceptions about a treatment may influence their judgments about its effectiveness

The effect of placebo on the patient and the patient’s environment is often debated, but people other than the patient may also feel better when a patient receives placebo treatment. The anthropologist Claude Lévi-Strauss alluded to this when he described how medical treatments, including those where ritual alone provides the cure, occur in a social context and convey a “sense of security” to the social group.1

Clinicians and family members may have an emotional response to a patient’s treatment and think that the treatment is helping the patient even in the absence of any direct physiological benefit to the patient or indication from the patient that the treatment is working. These feelings and perceptions may arise when placebos, including “impure” placebos, such as active drugs or operations that have no effect on the disease process, are used in clinical practice and research settings. Because these feelings and perceptions are not accounted for in descriptions of the placebo effect and can exist independently of any placebo effect on the patient, they can be described as placebo effects by proxy, or placebo by proxy for short. Although placebo by proxy has important implications, the phenomenon is underappreciated and rarely discussed.

Placebo by proxy could be as ubiquitous as the placebo effect, and in some situations placebo by proxy can dominate clinical decision making. For example, the parents of a child with a viral upper respiratory illness may believe that the child needs antibiotics, and parental expectations or the doctor’s perception of parental expectations (or both) may influence prescribing patterns.2 3 Antibiotics are overprescribed in these situations and function as impure placebos4; the psychological benefit to the parent, such as a relief from worry, represents placebo by proxy.

In the absence of evidence to support long term use of antipsychotics in patients with dementia and a history of agitation, aggression, or psychosis,5 6placebo by proxy may help to explain why clinicians often maintain their patients on these drugs. In a controlled double blind study of discontinuation of psychotropics in a sample of patients with dementia who were taking these drugs because of a history of agitation (67.3% were taking antipsychotics), the authors found a lack of an effect of psychotropics when they compared mean scores on behaviour rating scales during the treatment and placebo phases of the trial.6 However, clinical workers were resistant to stopping treatment because they had “a great deal of faith in the utility of these drugs to control agitation in this population.”6 Psychotropics functioned as impure placebos for many of these patients, and the concern of clinicians that patients would decompensate without these drugs provides another example of placebo by proxy.

In addition to influencing clinical decision making, placebo by proxy could influence estimations of treatment outcome in trials, especially when the perceptions of clinicians or family members are favoured over objective markers of patient response.7 In placebo controlled clinical trials of secretin to reduce symptoms of autism, the patient’s response to secretin was primarily based on the opinions of parents, teachers, or clinicians (or a combination thereof).8 Ten randomised controlled trials and a meta-analysis showed robust and consistent reductions in core symptoms of autism as measured by standardised rating scales in both the treatment and placebo groups, but no significant differences were seen between the groups on these measures.8 9 The robust response to placebo may have been influenced by anecdotal reports, which generated positive press about secretin and gave rise to the need for clinical trials.8 9 Perception or misperception by parents may also partially explain a larger placebo response in children than in adults participating in clinical trials of treatment resistant epilepsy.10

Placebo by proxy may also explain findings from meta-analyses where improvement measured by observers is much higher than improvement reported by patients. For example, for depression, the mean effect size of observer rated improvement is 1.85 (95% confidence interval 1.69 to 2.01), compared with 0.67 (0.49 to 0.85) for patient reported improvement.11 For irritable bowel syndrome, the pooled placebo response rate for physician rated improvement is 53.0%, compared with 37.4% for patient rated improvement (P=0.005).12

The different mechanisms that underlie the placebo effect are likely to shape placebo by proxy also.12 These processes may include seeing other patients respond to the same drug, associative learning such as conditioning, a supportive physician-patient relationship, and reduced anxiety.

Placebo by proxy and the placebo effect may interact to create positive change. For example, if clinicians and family members feel empowered and optimistic about a disease, the patient’s environment can become less stressful and more supportive. Clinicians and family members may react to placebo by smiling more, paying more attention to the patient, promoting treatment adherence, encouraging the patient to engage in new activities, or creating other targets for behavioural change.8 9 In this way, placebo by proxy may elicit changes in the patient’s psychosocial context that mediate the placebo effect.

Although placebo by proxy may enhance clinical outcomes, it might also cause harm. If treatment related decisions are unduly weighted towards providing a psychological benefit to people other than the patient, the patient may not benefit from the treatment yet may still bear the risks. The treatments mentioned above cost money and are not benign: antibiotics cause diarrhoea and are associated with antibiotic resistance, antipsychotics are associated with an increased risk of death in elderly patients with dementia related psychosis, and secretin infusion may result in a life threatening allergic reaction. Placebo by proxy may create a false sense that a patient is getting better and thereby prevent more appropriate treatment,7 8 or it may produce changes in attitude and behaviour towards the patient that lead to neglect. Placebo by proxy is probably more likely to cause harm when decisions are made in the absence of clinical evidence and when patients cannot make decisions for themselves.

Treatment benefits could be maximised and harms mitigated if placebo by proxy were taken into account when making clinical decisions. For many of the above clinical situations, an appreciation of placebo by proxy may prompt clinicians to question attachments to treatment practices that are not supported by evidence. Placebo by proxy could be used as a potential clinical tool. For example, it may be possible to boost the psychological benefit of a patient’s treatment by generating appropriate enthusiasm for treatment among those involved in the patient’s care. Because almost every treatment related decision is shared and patients sometimes agree to treatment to make their clinicians and family members happy, clinicians should be aware of placebo by proxy when guiding clinical decisions and evaluating treatment response.

10. Evidence-based Diagnostics: Adult Septic Arthritis

Carpenter CR, et al. Acad Emerg Med. 2011;18:782-796.

Background:  Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality.

Objectives:  The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy.

Methods:  Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits.

Results:  The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 109–25 × 109/L was 0.33; for 25 × 109–50 × 109/L, 1.06; for 50 × 109–100 × 109/L, 3.59; and exceeding 100 × 109/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (–LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts above 50 × 109/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%.

Conclusions:  Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (above 50 × 109/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate.

11. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study

Douma RA, et al. Ann Intern Med. 2011;154(11):709-18.

BACKGROUND: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared.

OBJECTIVE: To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE.

DESIGN: Prospective cohort study.

SETTING: 7 hospitals in the Netherlands.

PATIENTS: 807 consecutive patients with suspected acute PE.

INTERVENTION: The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care.

MEASUREMENTS: Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up.

RESULTS: Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result.

LIMITATION: Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing.

CONCLUSION: All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice.

12. Three Evidence Based Summaries

A. Does Therapeutic Hypothermia Benefit Survivors of Cardiac Arrest?

Seupaul RA, et al. Ann Emerg Med 2011;58:282-283

Take Home Message: Therapeutic hypothermia with conventional cooling methods improves survival and neurologic outcomes at hospital discharge for patients who have experienced a cardiac arrest.

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B. Do Triptans Effectively Treat Acute Cluster Headache in the Emergency Department?

Seupaul RA, et al. Ann Emerg Med 2011;58:284-285

Take Home Message: Triptans, particularly if administered subcutaneously, provide rapid relief for acute cluster headache.

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C. Is the Canalith Repositioning Maneuver Effective in the Acute Management of Benign Positional Vertigo?

Brown MD. Ann Emerg Med 2011;58:286-287

Take Home Message: The Epley maneuver is a very effective treatment for benign paroxysmal positional vertigo.

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13. Diagnostic Accuracy of High-Sensitivity Troponin Assays at 2 Hours

The high negative predictive value provides one more stone in the road to a 2-hour rule-out protocol for AMI.

New high-sensitivity troponin (hs-Tn) assays can detect minute amounts of troponin, potentially allowing earlier definitive diagnosis of acute myocardial infarction (AMI) than is currently possible (JW Emerg Med Apr 16 2010). In a prospective observational international study, researchers compared the diagnostic accuracy of absolute and relative changes in troponin I and T levels measured with hs-Tn assays in 1197 consecutive patients who presented to emergency departments with symptoms suggesting AMI and without ST-segment elevation on the initial electrocardiogram. Usual care was provided. The final diagnosis of AMI was determined by independent cardiologists who were blinded to the hs-Tn assay results.

Blood samples drawn at presentation and at 1, 2, 3, and 6 hours were available for 590 patients. AMI was the final diagnosis in 108 patients (13%). Absolute changes in troponin levels performed significantly better than relative changes on all performance measures. The absolute change in troponin T within 2 hours had a sensitivity of 89%, specificity of 93%, positive predictive value of 64%, and negative predictive value of 98% for AMI; results were similar for troponin I. Absolute changes at 6 hours (available for 305 patients) did not improve on the accuracy of those at 2 hours.

Comment: This was a study of chemical measurements, not of clinical care, which proceeded in the usual fashion; thus, the findings should not change practice. The study does, however, offer the prospect of changes to guidelines, which could speed throughput and allow more rapid determination of the need for interventional cardiology measures.

— J. Stephen Bohan, MD, MS, FACP, FACEP. Published in Journal Watch Emergency Medicine August 12, 2011. Citation: Reichlin T et al. Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation 2011 Jul 12; 124:136.

14. Neuron overload and the juggling physician

Danielle Ofri. The Lancet. 2010; 376:1820 – 1821.

Patients often complain that their doctors don't listen. Although there are probably a few doctors who truly are tone deaf, most are reasonably empathic human beings, and I wonder why even these doctors seem prey to this criticism. I often wonder whether it is sheer neuron overload on the doctor side that leads to this problem. Sometimes it feels as though my brain is juggling so many competing details, that one stray request from a patient—even one that is quite relevant—might send the delicately balanced three-ring circus tumbling down.

…Studies have debunked the myth of multitasking in human beings. The concept of multitasking was developed in the computer field to explain the idea of a microprocessor doing two jobs at one time. It turns out that microprocessors are in fact linear, and actually perform only one task at a time. Our computers give the illusion of simultaneous action based on the microprocessor “scheduling” competing activities in a complicated integrated algorithm. Like microprocessors, we humans can't actually concentrate on two thoughts at the same exact time. We merely zip back and forth between them, generally losing accuracy in the process. At best, we can juggle only a handful of thoughts in this manner.

The more thoughts we juggle, the less we are able to attune fully to any given thought. To me, this is a recipe for disaster. Today I only forgot an insurance company form. But what if I'd forgotten to order her mammogram, or what if I'd refilled only five of her six medicines? What if I'd forgotten to fully explain the side-effects of one of her medications? The list goes on, as does the anxiety.

The remainder of the essay (full-text free):

15. Vasopressin During Resuscitation May Help Asystolic Patients

NEW YORK (Reuters Health) Aug 09 - Vasopressin has no overall benefit in cardiac arrest, but it may be useful in asystole - especially when administered promptly, according to a meta-analysis reported July 25 in Resuscitation.

"The novel finding... was that in the large asystole subgroup (n=3,210), vasopressin use was associated with an increased probability of long-term survival," the authors report.

They said the absolute increase was about 1.0%, corresponding to 10 additional survivors for every 1,000 treated patients.

Furthermore, the vasopressin-related survival benefit was quadrupled in the 642 asystole patients whose average time-to-drug was under 20 minutes. That subgroup had an absolute increase of 4.0%, corresponding to 40 additional survivors for every 1,000 treated patients.

Dr. Spyros D. Mentzelopoulos, with Evaggelismos General Hospital in Athens, Greece, and colleagues say they undertook the study because there had been new trial data reported since the last review in 2004, and also because there was a possibility of increased vasoconstricting efficacy of current vasopressin regimens during CPR.

The team identified six high-quality randomized controlled trials comparing vasopressin-containing regimens with adrenaline/epinephrine alone in 4,475 adults with cardiac arrest.

Overall, vasopressin didn't increase the chance of sustained return of spontaneous circulation (odds ratio 1.25; p=0.18), long-term survival (OR 1.13; p=0.61) or favorable neurologic outcome (OR 0.87; p=0.62), the report indicates.

However, when the initial cardiac rhythm was identified as asystole (as opposed to pulseless electrical activity or ventricular fibrillation or tachycardia), vasopressin use was associated with a higher likelihood of long-term survival (OR 1.80; p=0.04). Moreover, in asystolic patients treated within 20 minutes of collapse, the odds ratio increased to 2.84 (p=0.02), Dr. Mentzelopoulos and colleagues found.

They conclude, "New randomized controlled trials specifically assessing vasopressin effects on subgroup neurological outcome are warranted."

Resuscitation 2011. In press. Abstract:

16. Images in Medicine

Fixed Drug Eruption

An Unusual Cause of Trigger Finger

“Thumb Sign” of Epiglottitis

Hemorrhagic Herpes Zoster

Bed Bugs

*More on Bed Bugs*
Case presentation: (with link to full-text)

Criado PR, et al. Bedbugs (Cimicidae infestation): the worldwide renaissance of an old partner of human kind. Braz J Infect Dis. 2011 Feb;15(1):74-80. (with link to full-text)

National Geographic Video (2 minutes):

17. Flu Update: Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza

CDC. Ann Emerg Med. 2011;58:299-303.

Influenza viruses can cause disease among persons in any age group, but rates of illness are highest among children.1, 2 During most influenza seasons, rates of serious illness and death are highest among persons aged 65 years or older, children younger than 2 years, and persons of any age who have medical conditions that place them at increased risk for complications from influenza.3, 4 In addition, data from epidemiologic studies conducted during the 2009 influenza A (H1N1) pandemic indicated that the risk for influenza complications was also increased among persons who are morbidly obese (body mass index ≥40 kg/m2) and American Indians/Alaska Natives.5, 6, 7, 8 In the postpandemic period, 2009 H1N1 virus strains now are considered to be the predominant seasonal influenza A (H1N1) virus strains. On the basis of epidemiologic studies of seasonal influenza or 2009 H1N1, persons at higher risk for influenza complications include:

• children younger than 5 years (especially those younger than 2 years);

• adults aged 65 years or older;

• persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), or metabolic disorders (including diabetes mellitus) or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)9;

• persons with immunosuppression, including that caused by medications or by HIV infection;

• women who are pregnant or postpartum (within 2 weeks after delivery);

• persons aged 18 years or younger who are receiving long-term aspirin therapy;

• American Indians/Alaska Natives;

• persons who are morbidly obese (ie, body mass index ≥40 kg/m2); and

• residents of nursing homes and other chronic-care facilities.

For children, the risk for severe complications from seasonal influenza is highest among those younger than 2 years, who have much higher rates of hospitalization for influenza-related complications compared with older children.3 Medical care and emergency department (ED) visits attributable to influenza are increased among children younger than 5 years compared with older children.10

Annual influenza vaccination is the most effective method for preventing seasonal influenza virus infection and its complications. All persons aged 6 months or older should receive annual influenza vaccination.11 Antiviral medications are effective for the prevention of influenza and, when used for treatment, can reduce the duration and severity of illness.6, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 Early antiviral treatment can reduce the risk for severe illness or death related to influenza.6, 12, 23, 24, 25, 26, 27 However, the emergence of resistance to one or more of the 4 licensed antiviral agents (oseltamivir, zanamivir, amantadine, and rimantadine) among some circulating influenza virus strains during the past 5 years has complicated antiviral treatment and chemoprophylaxis recommendations. The selection of antiviral medications should be considered in the context of any available information about surveillance data on influenza antiviral resistance patterns among circulating influenza viruses; local, state, and national influenza surveillance information on influenza virus type or influenza A virus subtype; the characteristics of the person who is ill; and results of influenza testing if testing is conducted. Empiric antiviral treatment often is required to avoid treatment delays.28

Primary Changes and Updates in the Recommendations

These recommendations include 6 principal changes or updates from previous recommendations for use of antivirals for the prevention and control of influenza:

• Antiviral treatment is recommended as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness or who require hospitalization.

• Antiviral treatment is recommended as soon as possible for outpatients with confirmed or suspected influenza who are at higher risk for influenza complications because of their age or underlying medical conditions; clinical judgment should be an important component of outpatient treatment decisions.

• Recommended antiviral medications include oseltamivir and zanamivir, according to recent viral surveillance and resistance data indicating that greater than 99% of currently circulating influenza virus strains are sensitive to these medications. Amantadine and rimantadine should not be used because of the high levels of resistance to these drugs among circulating influenza A viruses, but information about these drugs is provided for use if current recommendations change because of the reemergence of adamantane-susceptible strains.

• Oseltamivir may be used for treatment or chemoprophylaxis of influenza among infants younger than 1 year when indicated.

• Antiviral treatment also may be considered according to clinical judgment for any outpatient with confirmed or suspected influenza who does not have known risk factors for severe illness if treatment can be initiated within 48 hours of illness onset.

• Because antiviral resistance patterns can change over time, clinicians should monitor local antiviral resistance surveillance data.

The remainder of the text (free):

Abridged from MMWR Morb Mortal Wkly Rep. 2011;60:1-24. Full-text (free):

18. Captain Morgan, The Rum Pirate, Lends A Knee To Hip Dislocation

Linda Thrasybule, NPR blog, August 12, 2011

If you were to dislocate your hip, you'd need the able hands of a physician to push your thighbone back into the socket where it belongs. But that effort of "reducing" a hip dislocation can be a tricky and even risky task.

That's why some doctors now look to Captain Morgan — yes, the pirate on the bottle of rum — for inspiration. If you've ever looked closely at the label, you might notice Morgan standing confidently, one foot on top of a barrel. That pose turns out to be a good way for doctors to apply force to the hip without having to crawl up on the patient's gurney.

A case series out this week in the Annals of Emergency Medicine found the technique to be a success for 12 out of 13 patients. But study authors caution that they haven't yet proved the technique is any faster, easier, or has fewer complications than other way of fixing hip dislocations.

"We actually started the technique in our hospital a couple of years ago," Gregory Hendey, a professor of clinical emergency medicine at the University of California, San Francisco, Fresno and one of the study authors, tells Shots. "One day, while watching a Captain Morgan's commercial, it just struck me that that's the position we do."

Hip dislocation happens when the head of the thighbone — the femur — slips out of its socket in the hipbone. Car accidents are the most common cause, according to the American Academy of Orthopedic Surgeons. People with hip replacements are also prone to them, as are athletes who play high contact sports like football.

"It's extremely painful," says Hendey. "You can't walk. You're incapacitated. It has to be taken care of immediately."

Other techniques for fixing hip dislocations can be precarious. Consider the Allis Maneuver, which requires the doctor to straddle the patient on a gurney, then bend the affected leg 90 degrees, while keeping the other leg down. The doctor then lifts the leg and applies force to the hip, popping the leg bone back into the hip socket. Doctors can injure their backs or fall off the gurney, the study said.

Although Hendey admits the study doesn't prove whether the Captain Morgan technique is better than other techniques, he does believe it's safer and easier for doctors to perform. "Once they start using the Captain, they never go back," he says.

Full-text (with an image of the Captain):

Hendley GW, et al. Ann Emerg Med 2011; in press. Full-text (currently free):

19. Value of post-resuscitation ECG in the diagnosis of AMI in out-of-hospital cardiac arrest patients

Sideris G, et al. Resuscitation. 2011;82:1148-1153.

Background: Diagnosis of acute myocardial infarction (AMI) in out-of-hospital cardiac arrest (OHCA) patients is important because immediate coronary angiography with coronary angioplasty could improve outcome in this setting. However, the value of acute post-resuscitation electrocardiographic (ECG) data for the detection of AMI is debatable.

Methods: We assessed the diagnostic characteristics of post-resuscitation ECG changes in a retrospective single centre study evaluating several ECG criteria of selection of patients undergoing AMI, in order to improve sensitivity, even at the expense of specificity. Immediate post resuscitation coronary angiogram was performed in all patients. AMI was defined angiographically using coronary flow and plaque morphology criteria.

Results: We included 165 consecutive patients aged 56 (IQR 48–67) with sustained return of spontaneous circulation after OHCA between 2002 and 2008. 84 patients had shockable, 73 non-shockable and 8 unknown initial rhythm; 36% of the patients had an AMI. ST-segment elevation predicted AMI with 88% sensitivity and 84% specificity. The criterion including ST-segment elevation and/or depression had 95% sensitivity and 62% specificity. The combined criterion including ST-segment elevation and/or depression, and/or non-specific wide QRS complex and/or left bundle branch block provided a sensitivity and negative predictive value of 100%, a specificity of 46% and a positive predictive value of 52%.

Conclusion: In patients with OHCA without obvious non-cardiac causes, selection for coronary angiogram based on the combined criterion would detect all AMI and avoid the performance of the procedure in 30% of the patients, in whom coronary angiogram did not have a therapeutic role.

20. Correction Factor for CSF Protein Levels in Traumatic Lumbar Puncture

Nigrovic LE et al. J Pediatr 2011 Jul; 159:158

Subtract 1.1 mg/dL protein for every 1000-cell increase in CSF red blood cell count.

Abstract: We sought to determine the relationship between cerebrospinal fluid (CSF) protein and CSF red blood cells in children with traumatic lumbar punctures. For every 1000 cell increase in CSF red blood cells per mm(3), CSF protein increases by 1.1 mg/dL (95% CI, 0.9-1.1 mg/dL).

21. More U.S. Children Being Diagnosed with Youthful Tendency Disorder

Redlands, CA--Nicholas and Beverly Serna's daughter Caitlin was just 4 years old, but they already knew there was a problem.

Day after day, upon arriving home from preschool, Caitlin would retreat into a bizarre fantasy world. Sometimes she would pretend to be people and things she was not. Other times, without warning, she would burst into nonsensical song. Some days she would run directionless through the backyard of the Sernas' comfortable Redlands home, laughing and shrieking as she chased imaginary objects. When months of sessions with a local psychologist failed to yield an answer, Nicholas and Beverly took Caitlin to a prominent Los Angeles pediatric neurologist for more exhaustive testing. Finally, on September 20, the Sernas received the heartbreaking news: Caitlin was among a growing legion of U.S. children suffering from Youthful Tendency Disorder.

"As horrible as the diagnosis was, it was a relief to finally know,' Beverly said. At least we knew we weren't bad parents.'

Youthful Tendency Disorder (YTD), a poorly understood neurological condition that afflicts an estimated 20 million U. S. children, is characterized by a variety of senseless, unproductive physical and mental exercises, often lasting hours at a time. In the thrall of YTD, sufferers run, jump, climb, twirl, shout, dance, do cartwheels, and enter unreal, unexplainable states of 'make-believe.'

Slowly, methodically through an elaborate system of rewards and punishments, Caitlin has shown improvement. But the road ahead is long.

"We get a lot of platitudes from the so-called experts,' Mr. Serna said. 'We hear a lot of, 'Oh, she'll grow out of it, just give it time.' That's easy for them to say--their kid's not running around the neighborhood claiming to be Superwoman."

--Near constant running, jumping, skipping
--Sudden episodes of shouting and singing
--Preferring playtime and flights of fancy to schoolwork
--Confusing self with animals and object, including tiger, dinosaurs, and airplanes
--Conversations with "imaginary friends"
--Poor impulse control with regard to sugared snacks

Help for families struggling with YTD may soon be on the way. Last month, Pfizer unveiled Juvenol, a promising YTD drug which, pending FDA approval, could reach the U.S. market as early as next spring.

But until such help arrives, the parents of YTD sufferers can do little more than try to get through each day.

'I love my child with all my heart,' said Caitlin's mother. 'But when she's in the throes of one of her skipping fits, it's hard not to feel a little envious of parents with normal, healthy children.'"

The Onion. 2000;36:34.

22. Selected Readings that Promote Thriving, Personally and Globally

Kristoff and WuDunn, Half the Sky: Turning Oppression into Opportunity for Women Worldwide (New York: Knopf, 2011).

David Brooks, The Social Animal: The Hidden Sources of Love, Character, and Achievement (New York: Random House, 2011).