Biopsychosocial sequelae and recovery trajectories from whiplash injury following a motor vehicle collision.

BACKGROUND CONTEXT: Five out of 10 injured in a motor vehicle collision (MVC) will develop persistent pain and disability. It is unclear if prolonged symptoms are related to peritraumatic pain/disability, psychological distress, muscle fat, lower extremity weakness. PURPOSE: To test if widespread muscle fat infiltration (MFI) was (1) unique to those with poor recovery, (2) present in the peritraumatic stage, (3) related to known risk factors. STUDY DESIGN/SETTING: A cohort study, single-center academic hospital. PATIENT SAMPLES: A total of 97 men and women (age 18-65) presenting to an urban academic emergency medicine department following MVC, but not requiring inpatient hospitalization. PRIMARY OUTCOME MEASURE: Neck disability at 12-months. METHODS: Participants underwent magnetic resonance imaging (MRI) to quantify neck and lower extremity MFI, completed questionnaires on pain/disability and psychological distress (< 1-week, 2-weeks, 3-, and 12-months) and underwent maximum volitional torque testing of their lower extremities (2-weeks, 3-, and 12-months). Percentage score on the Neck Disability Index at 12-months was used for a model of (1) Recovered (0%-8%), (2) Mild (10%-28%), and (3) Moderate/Severe (≥ 30%). This model was adjusted for BMI and age. RESULTS: Significant differences for neck MFI were revealed, with the Recovered group having significantly lower neck MFI than the Mild and Moderate/Severe groups at all time points. The Mild group had significantly more leg MFI at 12-months (p=.02) than the Recovered group. There were no other significant differences at any other time point. Lower extremity torques revealed no group differences. The Traumatic Injury Distress Scale (TIDS) and MFI of the neck at 1-week postinjury significantly predicted NDI score at 12-months. CONCLUSIONS: Higher neck MFI and distress may represent a risk factor though it is unclear whether this is a pre-existing phenotype or result of the trauma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02157038.

Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.

Overuse of the d-dimer to screen for possible pulmonary embolism (PE) can have negative consequences. This study derives and tests clinical criteria to justify not ordering a d-dimer. The test threshold was estimated at 1.8% using the method of Pauker and Kassirer. The PE rule-out criteria were derived from logistic regression analysis with stepwise backward elimination of 21 variables collected on 3148 emergency department patients evaluated for PE at 10 US hospitals. Eight variables were included in a block rule: Age < 50 years, pulse < 100 bpm, SaO(2) > 94%, no unilateral leg swelling, no hemoptysis, no recent trauma or surgery, no prior PE or DVT, no hormone use. The rule was then prospectively tested in a low-risk group (1427 patients from two hospitals initially tested for PE with a d-dimer) and a very low-risk group (convenience sample of 382 patients with chief complaint of dyspnea, PE not suspected). The prevalence of PE was 8% (95% confidence interval: 7-9%) in the low-risk group and 2% (1-4%) in the very low-risk group on longitudinal follow-up. Application of the rule in the low-risk and very low-risk populations yielded sensitivities of 96% and 100% and specificities of 27% and 15%, respectively. The prevalence of PE in those who met the rule criteria was 1.4% (0.5-3.0%) and 0% (0-6.2%), respectively. The derived eight-factor block rule reduced the pretest probability below the test threshold for d-dimer in two validation populations, but the rule's utility was limited by low specificity.

Assessment of cardiac stress from massive pulmonary embolism with 12-lead ECG.

BACKGROUND: Massive pulmonary embolism (PE) that causes severe pulmonary hypertension can produce specific ECG abnormalities. We hypothesized that an ECG scoring system would vary in proportion to the severity of pulmonary hypertension and would help to distinguish patients with massive PE from patients with smaller PE and those without PE. METHODS: A 21-point ECG scoring system was derived (relative weights in parentheses): sinus tachycardia (2), incomplete right bundle branch block (2), complete right bundle branch block (3), T-wave inversion in leads V(1) through V(4) (0 to 12), S wave in lead I (0), Q wave in lead III (1), inverted T in lead III (1), and entire S(1)Q(3)T(3) complex (2). ECGs obtained within 48 h prior to pulmonary arteriography were located for 60 patients (26 positive for PE, 34 negative for PE) and for 25 patients with fatal PE. RESULTS: Interobserver agreement (11 readers) for ECG score was good (Spearman r = 0.74). The ECG score showed significant positive relationship to systolic pulmonary arterial pressure (sPAP) in patients with PE (r = 0.387, p < 0.001), whereas no significant relationship was seen in patients without PE (r = - 0.08, p = 0.122). When patients were grouped by severity of pulmonary hypertension (low, moderate, severe), only patients with severe pulmonary hypertension from PE had a significantly higher ECG score (mean, 5.8 +/- 4.9). At a cutoff of 10 points, the ECG score was 23.5% (95% confidence interval [CI], 16 to 31%) sensitive and 97.7% (95% CI, 96 to 99%) specific for the recognition of severe pulmonary hypertension (sPAP > 50 mm Hg) secondary to PE. In 25 patients with fatal PE, the ECG score was 9.5 +/- 5.2. CONCLUSIONS: The derived ECG score increases with severity of pulmonary hypertension from PE, and a score > or = 10 is highly suggestive of severe pulmonary hypertension from PE.

Pulseless electrical activity with witnessed arrest as a predictor of sudden death from massive pulmonary embolism in outpatients.

BACKGROUND: the objective was to determine clinical characteristics that can quickly distinguish sudden death from massive pulmonary embolism (MPE) from other causes of sudden death. METHODS AND RESULTS: all medical examiner reports from Charlotte, NC from 1992 to 1999 (n=4926) were hand-searched for cases of sudden death which met the inclusion criteria: non-traumatic death, age 18-65 years, transported to an emergency department (ED), and autopsy performed. Supplemental data from ED and prehospital records were retrieved to complete documentation. Data were analyzed by univariate odds ratios (OR) followed by chi-square (chi(2)) recursive partitioning for decision tree construction. Three hundred eighty four cases met inclusion criteria; MPE was the second most frequent cause of cardiac arrest in this cohort (37/384, 9.6%). The mean age of subjects with MPE (40.2+/-11.1 years) was significantly lower compared with non-PE subjects (46.5+/-9.9 years). Pulseless electrical activity was observed as the initial arrest rhythm (primary PEA) in 52/384 (13.5%) subjects. Out of 52 subjects with primary PEA, 28 (53%) died from MPE. Odds ratio data indicated significant association of MPE with female gender, arrest witnessed by medical providers, presence of primary PEA, and return of spontaneous circulation. The most accurate decision rule to recognize MPE consisted of witnessed arrest+primary PEA. This rule generated sensitivity=67.6% and specificity=94.5% and yielded a posttest probability of MPE of 57%. CONCLUSIONS: outpatients with witnessed cardiac arrest and primary PEA carry a high probability of MPE.

Identification of prearrest clinical factors associated with outpatient fatal pulmonary embolism.

UNLABELLED: Massive pulmonary embolism (MPE) is an important cause of outpatient sudden death, and description of these patients is critical for identification and treatment. OBJECTIVE: To test whether MPE patients can be distinguished from patients suffering sudden death from other causes based on clinical, demographic, and historical data. The hypothesis was that MPE cases would be more likely to manifest components of a clinical triad of 1) overt dyspnea, 2) alteration of mental status or syncope, and 3) shock index (pulse divided by systolic blood pressure) >0.8. METHODS: Retrospective case-control study of medical examiner data from 1992 to 1999 including all patients with nontraumatic death, aged 18-65 years, transported to an emergency department, with autopsy-determined cause of death. Analysis was done by 95% confidence interval (95% CI) for difference in proportions and multivariate logistic regression for odds ratios. RESULTS: The MPE patients (n = 37) were younger than the control subjects (n = 347) (40.2 vs 46.5 years, unpaired t-test p < 0.001). At least two of the three components of the triad were present in 56.8% of MPE cases vs 3.5% of controls (95% CI for difference in proportions = 37.3% to 68.0%). Significant variables (and odds ratios) for MPE after multivariate analysis included: dyspnea (13.8), shock index >0.8 (23.6), immobilization or fracture (14.6), seen by a physician within two weeks (5.1), and African American female status (6.4). CONCLUSIONS: Patients in this community with fatal MPE were young with risk factors for pulmonary embolism, and commonly manifested components of a triad including: dyspnea, alteration of mental status/syncope, and shock prior to death.

Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial.

BACKGROUND: Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance. OBJECTIVE: Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE. METHODS: Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low-molecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5 days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36(®) Physical Component Summary (PCS) score < 30 at 90-day follow-up. RESULTS: Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5 days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90 days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P = 0.017). CONCLUSIONS: Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.

D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography.

BACKGROUND: Increasing the threshold to define a positive D-dimer could reduce unnecessary computed tomographic pulmonary angiography (CTPA) for a suspected pulmonary embolism (PE) but might increase rates of a missed PE and missed pneumonia, the most common non-thromboembolic diagnosis seen on CTPA. OBJECTIVE: Measure the effect of doubling the standard D-dimer threshold for 'PE unlikely' Revised Geneva (RGS) or Wells' scores on the exclusion rate, frequency and size of a missed PE and missed pneumonia. METHODS: Patients evaluated for a suspected PE with 64-channel CTPA were prospectively enrolled from emergency departments (EDs) and inpatient units of four hospitals. Pretest probability data were collected in real time and the D-dimer was measured in a central laboratory. Criterion standard was CPTA interpretation by two independent radiologists combined with clinical outcome at 30 days. RESULTS: Of 678 patients enrolled, 126 (19%) were PE+ and 93 (14%) had pneumonia. Use of either Wells' ≤ 4 or RGS ≤ 6 produced similar results. For example, with RGS ≤ 6 and standard threshold (< 500 ng mL(-1)), D-dimer was negative in 110/678 (16%), and 4/110 were PE+ (posterior probability 3.8%) and 9/110 (8.2%) had pneumonia. With RGS ≤ 6 and a threshold < 1000 ng mL(-1) , D-dimer was negative in 208/678 (31%) and 11/208 (5.3%) were PE+, but 10/11 missed PEs were subsegmental and none had concomitant DVT. Pneumonia was found in 12/208 (5.4%) with RGS ≤ 6 and D-dimer < 1000 ng mL(-1). CONCLUSIONS: Doubling the threshold for a positive D-dimer with a PE unlikely pretest probability could reduce CTPA scanning with a slightly increased risk of missed isolated subsegmental PE, and no increase in rate of missed pneumonia.

European and American suspected and confirmed pulmonary embolism populations: comparison and analysis.

BACKGROUND: If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location. OBJECTIVE: To determine possible causes and potential clinical consequences of these PE prevalence differences. METHODS: Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE-suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European- and US-suspected PE populations in ED. RESULTS: European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE-mortality rate (3.4% vs. 0.7%). CONCLUSIONS: Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

Prospective multicenter assessment of interobserver agreement for radiologist interpretation of multidetector computerized tomographic angiography for pulmonary embolism.

BACKGROUND: Emergency physicians rely on the interpretation of radiologists to diagnose and exclude pulmonary embolism (PE) on the basis of computerized tomographic pulmonary angiography (CTPA). Few data exist regarding the interobserver reliability of this endpoint. OBJECTIVE: To quantify the degree of agreement in CTPA interpretation between four academic hospitals and an independent reference reading (IRR) laboratory. METHODS: Hospitalized and emergency department patients who had one predefined symptom and sign of PE and underwent 64-slice CTPA were enrolled from four academic hospitals. CTPA results as interpreted by board-certified radiologists from the hospitals were compared against those from the IRR laboratory. CTPAs were read as indeterminate, PE(-) or PE(+), and percentage obstruction was computed by the IRR laboratory, using a published method. Agreement was calculated with weighted Cohen's kappa. RESULTS: We enrolled 492 subjects (63% female, age 54 +/- 1 years, and 16.7% PE(+) at the site hospitals). Overall agreement was 429/492 (87.2%; 95% confidence interval 83.9-90.0). We observed 13 cases (2.6%) of complete discordance, where one reading was PE(+) and the other reading was PE(-). Weighted agreement was 92.3%, with kappa = 0.75. The median percentage obstruction for all patients was 9% (25th-75th percentile interquartile range: 5% to -30%). For CTPAs interpreted at the site hospitals as PE(-) or indeterminate but read as PE(+) by the IRR laboratory, the median of percentage obstruction was 6% (4-7%). CONCLUSION: We found in this sample a good level of agreement, with a weighted kappa of 0.75, but with 2.6% of patients having total discordance. Overall, a large proportion of clots were distal or minimally occlusive clots.

Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.

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 < 50 years, pulse < 100 beats min(-1), SaO(2) >or= 95%, 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 <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.