Mercy St. Vincent Medical Center

Careful consideration of statistical issues related to the choice of a sample size is critical for achieving meaningful results in research studies designed to evaluate diagnostic tests. When assessing the ability of a diagnostic test to screen for disease, the parameters sensitivity, specificity, and predictive values are of interest. Study sample size requirements can be calculated based on a clinically acceptable degree of precision, the hypothesized values of sensitivity and specificity, and the estimated prevalence of disease in the target population. The simple methods and tables in this paper guide the researcher when deciding how many subjects to sample in a study designed to estimate both the sensitivity and the specificity of a diagnostic test, given a specified precision and estimated disease prevalence.

BACKGROUND: In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. METHODS: In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS: Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). CONCLUSIONS: In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

BACKGROUND: Esophageal cancer is the sixth leading cause of cancer-related deaths and the eighth most common cancer worldwide with a 5-year survival rate of less than 25%. Here we report the incidence, risk factors and treatment options that are available currently, and moving into the future. METHODS: We retrospectively analyzed the Surveillance Epidemiology and End Results (SEER) database made available by the National Cancer Institute in the USA. Specifically we extracted data from the years 2004 - 2015. RESULTS: In total we identified 23,804 patients with esophageal adenocarcinoma and 13,919 patients with esophageal squamous cell carcinoma. Males were at an increased risk of developing both types of esophageal cancer when compared to females. Most cases of adenocarcinoma were diagnosed as poorly differentiated grade III (42%), and most cases of squamous cell carcinoma were diagnosed as moderately differentiated grade II (39.5%). The most common stage of presentation for both adenocarcinoma (36.9%) and squamous cell (26.8%) carcinoma was stage IV. The worst outcomes for adenocarcinoma were noted with grade III tumors (hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.44 - 1.68, P value: < 0.01), stage IV tumors (HR: 3.58, 95% CI: 3.33 - 3.85, P value: < 0.01) and those not treated with surgery (HR: 2.54, 95% CI: 2.44 - 2.65, P value: < 0.01). For squamous cell carcinoma, the worst outcomes were noted with grade III tumors (HR: 1.35, 95% CI: 1.23 - 1.49, P value: < 0.01), stage IV tumors (HR: 2.12, 95% CI: 1.94 - 2.32, P value: <0.01). CONCLUSIONS: The incidence of esophageal adenocarcinoma in the USA is steadily on the rise. Conversely, the incidence of squamous cell carcinoma has been continually declining. While white males had an increased incidence of both types of esophageal cancer, a higher proportion of African Americans suffered from squamous cell carcinoma. Despite the wide spread use of proton pump inhibitors, adenocarcinoma continues to be a major public health concern.

BACKGROUND: Dalbavancin, a novel lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing, is active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The efficacy of dalbavancin for treatment of skin and skin structure infections (SSSIs) was demonstrated in a phase 2 study. METHODS: In a phase 3 noninferiority study, patients with complicated SSSIs, including infections known or suspected to involve MRSA, were randomized (ratio, 2 : 1) in a double-blind manner to receive dalbavancin (1000 mg given intravenously on day 1 and 500 mg given intravenously on day 8) or linezolid (600 mg given intravenously or intravenously/orally every 12 h for 14 days). Efficacy was assessed by determining clinical and microbiological responses at the end of therapy and at the test-of-cure visit. Relapses were identified by additional follow-up approximately 1 month later. RESULTS: MRSA was identified in 51% of patients from whom a pathogen was isolated at baseline. Dalbavancin and linezolid demonstrated comparable clinical efficacy in the clinically evaluable population at the test-of-cure visit (88.9% and 91.2% success, respectively). The rate of clinical success at the end of therapy was >90% in both arms. Less than 1.0% of patients in either treatment arm experienced relapse after the test-of-cure visit. Both treatments yielded successful microbiological response in excess of 85% among microbiologically evaluable patients at end of therapy and at the test-of-cure visit for all pathogens combined, for all S. aureus strains, and for MRSA. Gastrointestinal symptoms were among the most common adverse events in both arms. A higher proportion of patients in the linezolid arm reported adverse events that were judged by the investigator to be probably/possibly related to treatment (dalbavancin arm, 25.4% of subjects; linezolid arm, 32.2% of subjects). CONCLUSIONS: Two doses of dalbavancin (1000 mg given on day 1 followed by 500 mg given on day 8) were as well tolerated and as effective as linezolid given twice daily for 14 days for the treatment of patients with complicated SSSI, including those infected with MRSA.

Received from the Department of General Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio.EVOKED potentials (EPs) are the electrophysiologic responses of the nervous system to sensory or motor stimulation. 1,2Stimulating the nervous system initiates the transmission of neural signals that may be recorded as EPs from various points along the stimulated pathway. Intraoperative monitoring (IOM) of EP has gained popularity because EPs reflect the functional integrity of neural pathways in anesthetized patients undergoing surgical procedures that place nervous system structures in jeopardy. EPs monitored intraoperatively include somatosensory evoked potentials (SSEPs), brainstem auditory evoked potentials (BAEPs; also referred to as auditory brainstem responses), visual evoked potentials (VEPs), and motor evoked potentials. Additional EP modalities include dermatomal sensory evoked potentials, electrocochleography, and electromyography.Intraoperative EP changes may result from surgical injury or ischemia of the specific neural pathway, or they may be due to nonspecific physiologic or pharmacologic influences. Physiologic factors that may influence EPs include temperature, blood pressure, hematocrit, acid–base balance, and oxygen and carbon dioxide tensions. Anesthetic drugs and sedatives are the most common pharmacologic causes of nonspecific EP changes.This review discusses the physiologic and pharmacologic factors (including newer anesthetic agents and adjuncts) that influence sensory evoked potentials (SEPs), focussing on SSEPs, BAEPs, and VEPs. For ease of reference and to allow better comparisons between anesthetic agents, the discussion of anesthetic effects is separated from physiologic effects. The review intends to help clinicians recognize the important confounding perturbations so that intraoperative changes in SEPs can be interpreted optimally. It also aims to guide anesthetic planning so that reliable intraoperative EP monitoring can be accomplished during effective and safe anesthesia.The single cortical sensory evoked response has a low amplitude (1–2 μV) compared with the much larger electroencephalogram waves (50–100 μV). Therefore, the EP wave has to be extracted from concurrent spontaneous electroencephalogram activity by repetitive stimulation and computer-signal averaging techniques. 3The EP waveform consists of a series of peaks and valleys presented as a graph of voltage over time and described in terms of amplitude, latency, and morphology. For IOM, amplitude is commonly measured as the waves’ peak-to-peak voltage difference. Latency is the time from stimulus to the peak of the response. Interpeak latency is the interval between the peaks of interest (fig. 1).Evoked potential waves can have either negative or positive polarity. A negative wave occurring at a latency of approximately 20 ms would be indicated as N-20. Generally, negative waves are shown as upward deflections, while positive waves are shown as downward deflections. Evoked potentials can be of cortical or subcortical origin. Responses recorded by electrodes located within 3–4 cm of the neural generator are termed near-field potentials (e.g. , cortical SSEP waves recorded from scalp electrodes), whereas those recorded from electrodes farther from the neural generator are called far-field potentials (e.g. , BAEP recorded over the vertex). 4,5SEPs are also classified as short latency (&lt; 30 ms), intermediate latency (30–75 ms), or long latency (&gt; 75 ms). 6For the purposes of this review, SEPs are considered recordable when reproducible waveforms are reported. An anesthetic regimen is described as compatible with IOM when it results in consistently recordable waveforms. Reliability of SEPs refers to their ability to detect potentially injurious conditions intraoperatively.The SSEP represents the reproducible electrical activity of cortical and subcortical structures time-locked to a peripheral nerve stimulus. For perioperative applications, electrical impulses are commonly delivered to the median nerve or posterior tibial nerves using needle or surface electrodes. The impulse propagates peripherally (resulting in muscle twitches) and centrally via the peripheral nerve and the dorsal root to the spinal cord. The nerve cell body of the first-order neuron lies in the dorsal root ganglion. Impulses then ascend primarily in the dorsal column fibers of the spinal cord, which synapse (fig. 2) in the lower medulla near the nucleus gracilis and cuneatus, respectively. Axons of the second-order neurons cross the midline at the cervicomedullary junction, from where they regroup to form the medial lemniscus and synapse in the ventroposterior–lateral nucleus of the contralateral thalamus. Third-order neurons from the ventroposterior–lateral leave the thalamus and travel through the posterior limb of the internal capsule as the thalamocortical radiation to synapse in the primary somatosensory cortex in the postcentral gyrus of the parietal lobe. The spinocerebellar pathways, located anteriorly in the spinal cord, contribute to the rostral conduction of SSEP signals. Therefore, SSEPs can assess the sensory system from the peripheral nerves through the spinal cord and brainstem to the cerebral cortex.Somatosensory evoked potential waveform activity can be recorded at the popliteal fossa after posterior tibial nerve stimulation and at Erb's point above the clavicle after median nerve stimulation. Spinal potentials recorded over the cervical and lumbar spinous processes confirm the delivery of the stimulus to the central neural axis, after it is delivered in the arm or leg, respectively. The subcortical component of the SSEP is recorded over the second cervical vertebra as a negative deflection (N-14) 14 ms after median nerve stimulation. The earliest cortical (midlatency) component of the SSEP wave is generated by the primary somatosensory cortex and occurs approximately 20 ms after median nerve and 40 ms after posterior tibial nerve stimulation. Cortical SSEPs are recorded from scalp overlying the contralateral primary sensory cortex (fig. 3). A spinal sensory EP may be stimulated or recorded from epidural electrodes placed percutaneously or in the surgical field. The central conduction time (CCT) is the time needed for the signal to travel from the cervicomedullary junction to the contralateral cerebral cortex (CCT = N-20 to N-14 latency difference after median nerve stimulation).The subcortical SSEP recorded over the second cervical vertebra can be very useful intraoperatively because it is not very susceptible to anesthetic effects. 7Assuming an electromyography artifact is eliminated and technical problems are solved, the cervical response has a shorter acquisition time that allows faster feedback to the surgical team, which enhances its usefulness in surgical procedures that may jeopardize the spinal cord. The midlatency cortical SSEP is moderately sensitive to anesthetic depression, but clinically useful recordings can be obtained in most patients with modifications in anesthetic technique. Longer latency SSEP waves, which represent further neural processing of sensory inputs into the association cortex, are exquisitely sensitive to anesthetic drugs, and therefore, are not useful to monitor the integrity of the sensory pathway. 8Diagnostic criteria to evaluate intraoperative waveform changes diagnostic of spinal cord dysfunction have been difficult to establish. Latency changes of 7–10% and amplitude decreases of 45–50% may occur without changes in postoperative neurologic function. 9–11The criteria for determining which event-related changes 10should be considered significant are still empiric. 12In patients undergoing surgical correction of neuromuscular scoliosis, sensitivity and specificity of IOM in the detection of new postoperative neurologic deficits was maximized with the use of a 50% amplitude reduction criterion. 13An alternate criterion for sounding the alarm intraoperatively has been loss of cortical baseline amplitude greater than 30–40%. 14–16Most, however, consider a decrease in amplitude of 50% or greater, an increase in latency of 10% or greater, or both to be significant changes reflecting loss of integrity of a neural pathway, provided these changes are not caused by anesthetics or temperature. 17–20At least one study suggests that the use of amplitude criteria is associated with better sensitivity for detecting neurologic injury than latency criteria. 21General anesthesia has an inhibitory effect on neurotransmission and, therefore, on the EP. The effect of anesthetics is greater on synaptic transmission than on axonal conduction. 22For this reason, responses recorded from polysynaptic pathways (e.g. , cortical recordings) are affected by anesthesia to a much greater extent than those recorded from oligosynaptic pathways (e.g. , spinal cord and subcortical recordings). 23For example, VEPs (which represent cortical activity) are very sensitive to the effects of anesthetics while BAEPs (representing brainstem and subcortical activities) are the least sensitive to drug effects.All volatile anesthetics produce a dose-dependent increase in SSEP latency, an increase in CCT, and a decrease in amplitude 23–29(table 1). They may also cause morphologic changes, such as contraction of early cortical waveforms (N-20) into a simple monophasic wave under deep isoflurane 30,31or sevoflurane 32,33anesthesia (fig. 4). The later cortical waveform components are most sensitive to volatile anesthetics, with marked attenuation at concentrations exceeding 0.5 minimum alveolar concentration (MAC). 30Satisfactory monitoring of early cortical SSEPs is possible with 0.5–1.0 MAC halothane, enflurane, or isoflurane without nitrous oxide. 24,26At 0.67 MAC halothane or less, SSEPs were recordable in 96% of cases but only in 91% with higher concentrations. 34During deep (1.6 MAC) isoflurane anesthesia, however, the early cortical N-20 wave was recordable 35in 94%, and amplitude decreased severely (table 1). 30Yet, the later N-35 wave, which is also important in IOM, could only be recorded in 47%. 35The effect of volatile anesthetics on cortical SSEP amplitude is compounded by nitrous oxide. Increasing isoflurane concentration from 0.5 to 1.0 MAC in the presence of nitrous oxide resulted in a 75% decrease in the cortical SSEP (from 1.2 μV to 0.3 μV). 36The newer volatile anesthetics desflurane and sevoflurane affect SSEPs not unlike isoflurane but may permit the use of higher inhaled concentrations (table 1). Increases in cortical latency and decreases in amplitude occur at doses of 1.5 MAC sevoflurane and desflurane or less, with minimal effects on subcortical SSEP components. 37,38Desflurane up to 1.0 MAC without nitrous oxide is compatible with cortical median nerve SSEP monitoring during scoliosis surgery. 38Even at 1.5 MAC (without nitrous oxide), the amplitude of cortical SSEPs was preserved at 60% of baseline. 39However, nitrous oxide added to desflurane 40or sevoflurane 41severely depresses amplitude. At 1.7–2.5 MAC sevoflurane, a high-amplitude early cortical SSEP waveform is found with absence of all later waves. 32,33How volatile anesthetics differ quantitatively in their effects on the SSEP is not completely settled. Pathak et al. 26showed that halothane had a greater effect on both amplitude and latency of the SSEP at equipotent concentrations than either isoflurane or enflurane. On the other hand, Peterson et al. 24found that isoflurane and enflurane reduced SSEP amplitude and prolonged CCT more than halothane did. Sevoflurane and desflurane are associated with less amplitude reduction than isoflurane at a MAC range of 0.7–1.3. 29In contrast to their effects on the cortical SSEP, all volatile anesthetics, even at concentrations above 1.0 MAC, only minimally affect the subcortical waveform, resulting in high recordability 35and reliability (table 2).Nitrous oxide (60–70%) generally diminishes cortical SSEP amplitude by approximately 50% while leaving cortical latency and subcortical waves unaffected. 36,42Nitrous oxide potentiates the depressant effect of volatile anesthetics 24,41and most intravenous anesthetics, 12,43,44producing greater amplitude depression than an equipotent concentration of volatile anesthetics administered alone 24,45,46(table 1). For example, adding 50% (0.5 MAC) nitrous oxide to a fentanyl-based anesthetic resulted in a greater decrease in amplitude than adding 1% (0.8 MAC) isoflurane, especially in patients with abnormal preoperative SSEP. 25Likewise, during opioid-based anesthetics, nitrous oxide depressed cortical SSEP amplitude to a greater extent than did propofol when substituted for nitrous oxide. 12,47–49Intravenous anesthetics generally affect SSEPs less than inhaled anesthetics (table 3). This is easily seen from the fact that the human SSEP is preserved even at high doses of narcotics and barbiturates (table 3) but abolished at high volatile anesthetic concentrations. Intravenous agents only modestly affect early and intermediate (&lt; 40 ms for median nerve stimulation and &lt; 80 ms for posterior tibial nerve stimulation) SSEP components. Low doses of intravenous agents have minimal effects on SSEPs, whereas high doses of most agents cause slight to moderate decreases in amplitude and increases in latency. With very few exceptions, subcortical potentials are unaffected (table 3).Barbiturates produce a dose-dependent increase in latency and decrease in early cortical SSEP amplitude that does not preclude IOM. Changes in long-latency cortical waves are affected more than subcortical and midlatency waveforms. This is consistent with the notion that barbiturates, like volatile anesthetics, affect synaptic transmission more than axonal conduction. An induction dose of thiopental (5 mg/kg) increases latency 10–20% and decreases amplitude 20–30%, an effect that lasts less than 10 min. 43,50,51Similar changes occur with thiamylal. 40Even at much higher doses, such as those used for barbiturate coma, barbiturates allow recording of cortical SSEPs. 52–55Unlike the barbiturates, etomidate dramatically increases cortical SSEP amplitude (N-20), up to 400% above preinduction baseline in some patients. 50,43Subcortical amplitude is decreased by up to 50% (table 3). 50,56Etomidate is associated with a high incidence of myoclonic movements. 57Patients with familial myoclonic epilepsy are also known to have abnormally large EPs, 58especially noted during myoclonic jerking episodes. It is tempting to speculate that myoclonus is an indication that sensory signals are being synchronized (pathologically or by etomidate), which then result in enhanced SSEP amplitude. However, Kochs et al. 59observed amplitude enhancement after etomidate whether or not myoclonic movements occurred. Based on careful electrophysiologic experiments in cats, SSEP amplitude enhancement with etomidate is thought to result from an altered balance between inhibitory and excitatory influences at the level of the cerebral cortex, 60resulting in increased signal synchronization at the thalamic level. 56Like etomidate, ketamine increases cortical SSEP amplitude, with the maximum effect occurring within 2–10 min of bolus administration. 61No effect on cortical latency 61or subcortical waveforms 62was evident. However, the addition of nitrous oxide 44or 1.0 MAC enflurane 61to a ketamine background anesthetic depressed SSEP amplitude by approximately 50%. Ketamine, 3 mg/kg, followed by 2 mg · kg−1· h−1combined with 0.15 mg · kg−1· h−1midazolam and 60% nitrous oxide was compatible with satisfactory recordings during major spine surgery. 63Propofol's effect on SSEPs is similar to that of the barbiturates. This is important because propofol can be infused in anesthetic concentrations during prolonged central nervous system (CNS) surgery and still effect rapid emergence for timely postoperative neurologic assessment. A dose of 2.5 mg/kg propofol produced no changes in the amplitude of the cortical (N-20) and subcortical (N-14) waves after median nerve stimulation. 62Cortical latency and CCT increased by 8 and 20%, respectively. In scoliosis surgery, total intravenous anesthesia with propofol and sufentanil (table 3) prolonged cortical latency 10–15% and reduced the amplitude of the cortical posterior tibial nerve SSEP by 50%. However, SSEP waveforms stabilized within 30 min after anesthetic administration and were compatible with IOM. 48When used as a sedative hypnotic in combination with opioids, propofol reduces SSEP amplitude less than nitrous oxide or midazolam. Cortical SSEP amplitude is approximately 50% lower during sufentanil–nitrous oxide 47,48or alfentanil–nitrous oxide anesthesia 49compared with sufentanil-propofol-opioid–based regimens. 47,48Propofol was associated with higher cortical SSEP amplitude despite the use of anesthetic concentrations equivalent to nitrous oxide or sevoflurane. 64Average cortical SSEP amplitude was higher and within-patient amplitude variability was less during propofol–alfentanil than during nitrous oxide–alfentanil anesthesia. 49Amplitude was also greater than during midazolam–alfentanil anesthesia. 65The typical W-shaped morphology of the cortical posterior tibial nerve SSEP was better preserved with propofol than with midazolam.Benzodiazepines have only mild-to-moderate depressant effects on SSEPs (table 3). Diazepam, 0.1–0.25 mg/kg, produced mild and moderate decreases in N-20 and later wave cortical amplitude, respectively. Very long latency peaks (200–400 ms) were abolished. 66In a dose of 0.2–0.3 mg/kg, midazolam is associated with modest 67or no 43reduction in amplitude and slight prolongation of median nerve SSEP latency (table 3). Adding opioids 43,68or nitrous oxide 43to midazolam or propofol 65preserves the cortical SSEP better when compared to adding nitrous oxide or opioids to thiopental, etomidate, 43or ketamine. 44Benzodiazepines affect sensory pathways differentially. The significant decrease in the amplitude of the evoked electromyelogram response (a spinal cord response to somatosensory stimulation) after diazepam 69indicates a peripheral action. Conversely, sedative doses of midazolam (60–70 μg/kg), while leaving the early cortical waveform (N-20) unaffected, depress late cortical waves generated in the association cortex. 69This is consistent with the notion that sedative doses of benzodiazepines might blunt the emotional response to pain perception. 70Most authors report clinically unimportant changes in SSEP latency and amplitude after the administration of opioids, whether given in analgesic or anesthetic doses (table 3).McPherson et al. 50found minimal SSEP changes after 25 μg/kg fentanyl for induction of anesthesia in adults. A small increase (5–6%) in cortical median nerve SSEP latency and a variable decrease (0–30%) in amplitude resulted after 36–71 μg/kg fentanyl, which was compatible with IOM. 71No significant effects on SSEP from fentanyl up to 130 μg/kg were observed during hypothermic cardiopulmonary bypass. The effect of fentanyl was greater with boluses compared to a continuous infusion 72during maintenance of anesthesia.A bolus dose of 5 μg/kg sufentanil produced 5% increases in early cortical SSEP latency and a 15% increase in CCT. 73The 40% decrease in cortical amplitude did not interfere with waveform acquisition. 73Sufentanil, 0.5–1.0 μg/kg, followed by 0.25–0.5 μg · kg−1· h−1with 50% nitrous oxide and 0.5% isoflurane prompted a 50% reduction in cortical amplitude and a 5–10% increase in cortical latency and CCT but no changes in subcortical waves. 74Alfentanil is associated with only modest SSEP amplitude depression while leaving latency unchanged 43,75(table 3). Three doses of remifentanil (table 3) combined with 0.4 MAC isoflurane produced a 20–30% decrease in early cortical amplitude that was not dose dependant. By contrast, late cortical waves showed a 10–30% increase in amplitude. 76Compared with the combination of fentanyl and nitrous oxide, remifentanil reduces cortical amplitude less, with lower amplitude variability. 77Pathak et al. 72reported posterior tibial nerve SSEP latency to increase by approximately 10–15% and amplitude to decrease by 20% after induction of anesthesia with 0.25 mg/kg morphine. Amplitude continued to decrease to approximately 10% of control during subsequent morphine infusion. This study could not isolate the effect of morphine from residual effects of the barbiturate used for induction and the effect of a background nitrous oxide anesthetic, but it shows that this regimen is not desirable for IOM. As with fentanyl, the magnitude of morphine's effect was greater with bolus administration than with continuous infusion.The administration of subarachnoid meperidine produced a 60% decrease in cortical posterior tibial nerve SSEP amplitude and a 10% increase in latency. The response was abolished in 40% of patients. 78This is attributed to the local anesthetic-like effect of meperidine in blocking voltage-dependent sodium channels. In contrast, subarachnoid fentanyl (25 μg), 78morphine (20 μg/kg) combined with sufentanil (50 μg), 79or morphine alone (15 μg/kg) 80produced no significant changes in latency or amplitude of cortical posterior tibial nerve SSEPS in the awake or anesthetized states, nor did the lumbar epidural administration of 0.1 mg/kg diamorphine in adolescents undergoing corrective surgery for idiopathic scoliosis. 81Droperidol is an acceptable anesthetic adjunct with minimal effects of SSEPs. 8Clonidine, an α2receptor agonist, reduces anesthetic requirements. 82,83However, clonidine administered alone added to MAC isoflurane not latency or amplitude of the cortical SSEP. At a dose of 10 μg/kg, subcortical amplitude decreased by and latency increased can be used as an anesthetic without SSEP SSEP amplitude minimally at sedative isoflurane anesthesia, it effect on SSEP amplitude. patients undergoing spinal surgery, conditions for SSEP oxide anesthesia, does not affect human SSEPs. blocking drugs not influence SSEP, or they may waveform by the through of the electromyography at higher especially when EPs are at lower stimulation and higher local anesthetic of the sensory SSEPs. of the cortical evoked response to stimulation does subarachnoid the other hand, epidural administration of clonidine the SSEP on dose and The SSEP response to stimulation is abolished by epidural By contrast, because the nerve root is during epidural anesthesia, posterior tibial nerve stimulation can still an SSEP response. epidural anesthesia with was associated with decreased cortical amplitude and increased cortical SSEP latency, while 1% resulted in less into the lumbar epidural prolonged latency and decreased amplitude of posterior tibial nerve SSEPs, with only slight latency prolongation with administration of local anesthetics at higher concentrations is not to anesthesia in scoliosis surgery SSEPs are to be administered cortical SSEPs but is to interfere with IOM. administered at concentrations in patients anesthetized with sufentanil–nitrous dose (&lt; isoflurane further decreased amplitude of the cortical SSEP by approximately and produced a small latency of effects of anesthetics on waveform morphology and is reliable be for major anesthetic and anesthetic to assess the specificity and sensitivity of SEPs in the of neural injury to allow and much of the of anesthetic effects on SEPs were in patients or were obtained surgical on the nervous such as those presented in a for of the reliability of IOM in and neural injury during various to that an reproducible waveform (which to as during the anesthetic for to be with IOM. Anesthetic during which even a small of waveforms are not for IOM. are anesthetics that result in amplitude depression and latency prolongation on the that would the of SSEP changes and potentially either not detecting a or include volatile anesthetics alone at a dose greater than MAC and volatile anesthetics at greater than 0.5 MAC in combination with nitrous oxide (table 1). Therefore, volatile anesthetics alone at up to 1.0 MAC can be or sevoflurane may allow IOM at even higher intravenous anesthetic such as amplitude to be of (table 3). In however, intravenous anesthetic result in less amplitude and latency than volatile evoked potential waveform is to amplitude and to amplitude variability. the amplitude of the SSEP waveform, the more is it to baseline electrical and other confounding influences. Therefore, amplitude be one of the important of the intraoperative monitoring This is important when baseline amplitude is low and variability is as occurs in (&gt; patients and those with scoliosis, scoliosis, spinal spinal or other neurologic the negative between cortical SSEP amplitude and within-patient amplitude the possible SSEP amplitude be reduced cortical SSEP amplitude variability in patients undergoing spine surgery and amplitude. nitrous anesthesia, surgical stimulation may increase cortical amplitude by more than to amplitude variability. of propofol for nitrous oxide increases cortical SSEP amplitude by up to during an opioid-based nitrous oxide from the background anesthetic has been shown to cortical amplitude to IOM more of remifentanil for fentanyl and nitrous oxide during a isoflurane anesthetic also decreased SSEP waveform which nitrous oxide is to be used in in which amplitude to be it be used in combination with where it depresses amplitude the least with with or no effect on SSEPs, such as and opioids (table may also be effect allow lower doses of anesthetics to be with less depression of SSEP using agents known to increase the EP amplitude, such as etomidate or can be to use etomidate to IOM in patients with abnormally small SSEP waves due to preoperative administration of etomidate, mg/kg, followed by the infusion of mg · kg−1· waveforms and monitoring that would not have been increases in the amplitude of SSEP may represent an early of etomidate could interfere with early detection of et al. to detect intraoperative to spinal cord in patients in etomidate had been used to the SSEP that etomidate did not neural the volatile anesthetic concentration in an to IOM may be associated with Low concentrations of volatile anesthetics are used during IOM, and anesthesia may be to and consider using or that in the of anesthetic Adding etomidate or propofol is to nitrous oxide or volatile anesthetic concentrations when anesthetic is anesthetics are also used to control blood and and may to be substituted

OBJECTIVE: Acute renal injury and failure (ARF) after cardiopulmonary bypass (CPB) has been linked to low on-pump hematocrit (hematocrit). We aimed to 1) elucidate if and how this relation is modulated by the duration of CPB (TCPB) and on-pump packed red blood cell transfusions and 2) to quantify the impact of post-CPB renal injury on operational outcome and resource utilization. DESIGN: Retrospective review. SETTING: A Northwest Ohio community hospital. PATIENTS: Adult coronary artery bypass surgery patients with CPB but no preoperative renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We quantified post-CPB renal injury via 1) the peak postoperative change in serum creatinine (Cr) level relative to pre-CPB values (%DeltaCr) and 2) ARF, defined as the coincidence of post-CPB Cr > or =2.1 mg/dL and >2 times pre-CPB Cr. The separate effects of lowest hematocrit, intraoperative packed RBC transfusions, and TCPB on %DeltaCr and ARF were derived via multivariate regression, overlapping quintile subgroup analyses, and propensity matching. Lowest hematocrit (22.0% +/- 4.6% sd), TCPB (94 +/- 35 mins), and pre-CPB Cr (1.01 +/- 0.23 mg/dL) varied widely. %DeltaCr varied substantially (24 +/- 57%), and ARF was documented in 89 patients (5.1%). Both %DeltaCr (p < .001) and ARF (p < .001) exhibited sigmoidal dose-dependent associations to lowest hematocrit that were 1) modulated by TCPB such that the renal injury was exacerbated as TCPB increased, 2) worse in patients with relatively elevated pre-CPB Cr (> or =1.2 mg/dL), and 3) worse with intraoperative packed red blood cell transfusions (n = 385; 21.9%), in comparison with patients at similar lowest hematocrit. Operative mortality (p < .01) and hospital stays (p < .001) were increased systematically and significantly as a function of increased post-CPB renal injury. CONCLUSIONS: CPB hemodilution to hematocrit <24% is associated with a systematically increased likelihood of renal injury (including ARF) and consequently worse operative outcomes. This effect is exacerbated when CPB is prolonged with intraoperative packed red blood cell transfusions and in patients with borderline renal function. Our data add to the concerns regarding the safety of currently accepted CPB practice guidelines.

Polymethylmethacrylate (PMMA) has been used in orthopaedics since the 1940s. Despite the development and popularity of new biomaterials, PMMA remains popular. Although its basic components remain the same, small proprietary and environmental changes create variations in its properties. PMMA can serve as a spacer and as a delivery vehicle for antibiotics, and it can be placed to eliminate dead space. Endogenous and exogenous variables that affect its performance include component variables, air, temperature, and handling and mixing. PMMA is used in hip arthroplasty and vertebral augmentation, notably, vertebroplasty and kyphoplasty. Cardiopulmonary complications have been reported.

OBJECTIVES: Available D-dimer assays have low specificity and may increase radiographic testing for pulmonary embolism (PE). To help clinicians better target testing, this study sought to quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE. METHODS: This was a prospective, multicenter, observational study. Emergency department (ED) patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals (CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk were also calculated. RESULTS: A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were Hispanic, and 144 (3%) were of other race or ethnicity. The mean (+/-SD) age was 48 (+/-17) years. Overall, 1,903 (44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739, Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis; lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was protective. In contrast, several variables known to be associated with PE were not associated with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE, (inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under treatment). CONCLUSIONS: Many factors are associated with a positive D-dimer test. The effect of these factors on the usefulness of the test should be considered prior to ordering a D-dimer.

Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and 450 deaths annually in the United States. It also may predispose to development of asthma later in life. Annual epidemics occur from November to April, and virtually all infants are infected by age 2. Immunity is not durable; hence, reinfection occurs throughout life, although subsequent infections are nearly always mild. Certain populations (eg, premature infants, infants with chronic lung disease, and immunocompromised individuals) are at risk for severe morbidity and have higher risk of mortality. Infection is spread to the nose and eyes by large droplets and direct contact with secretions, and fomites may remain infectious for up to 12 hours. Nosocomial infection is common. The virus infects airway ciliated epithelial cells, spreading by the formation of syncytia. Cellular debris and inflammation cause airway obstruction, hyperinflation, localized atelectasis, wheezing, and impaired gas exchange. Both humoral and cellular immune response are critical to ending the acute infection, but wheezing and reactive airways may persist for as long as 5-10 years after acute infection. No cure exists for respiratory syncytial virus infection, but commonly employed palliative treatments include oxygen, inhaled beta(2) agonists, racemic epinephrine, dornase alfa, systemic and inhaled corticosteroids, inhaled ribavirin, and nasopharyngeal suctioning. Infants suffering severe lower airways disease may require mechanical ventilation. Prophylactic measures include rigorous infection control and administration of polyclonal (RSV-IGIV [respiratory syncytial virus - immunoglobulin intravenous]) and monoclonal (palivizumab) antibodies. The cost of the prophylactic antibody treatment is high; it is cost-effective for only the highest risk patients. Development of a vaccine remains far in the future. Application of evidence-based clinical practice guidelines is making both out-patient and in-patient therapy as effective and economical as possible.

OBJECTIVE: To determine whether the shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is a useful marker for significant injury in trauma patients. METHODS: A retrospective database analysis was used to relate the SI to the clinical measures: death within 24 hours, injury severity score (ISS) > or = 16, intensive care unit (ICU) stay > or = 1 day, and amount of blood transfused (BT) > or = 2 units. Consecutive trauma patients seen at one level I trauma center over a 24-month period were reviewed; excluded were patients not requiring trauma team consultation, or those with either incomplete records, severe head injury (Glasgow Coma Scale score < or = 8), or age < 14 years. The SI was calculated from ED admission vital signs. Receiver operating characteristic (ROC) curves were used to find the value of the SI that maximized the sum of sensitivity and specificity for predicting each measure, separately; a separate analysis was done to determine the optimal SI threshold for predicting any of the severity measures. RESULTS: 1,101 cases met study criteria. The optimal SI values (by ROC analysis) for predicting the severity measures were: 1.10 for death < 24 hours, 0.71 for ISS > or = 16, 0.77 for ICU > or = 1 day, and 0.85 for BT > or = 2 units. The optimal SI value (by ROC analysis) for any of the above measures was 0.83; use of this SI cutoff provided a sensitivity of 37% (95% CI 32-42%), a specificity of 83% (95% CI 80-87%), and a negative predictive value of 58% (95% CI 54-61%) for any measure. This SI threshold predicted between 24% fewer cases and 4% more cases of poor outcome than did the optimal thresholds HR and SBP, respectively. CONCLUSION: The optimal SI threshold performed similarly to the optimal threshold HR or SBP for prediction of injury severity.

BACKGROUND AND PURPOSE: EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy compared with established stent retrievers. METHODS: ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0-2) and all-cause mortality at 90 days. RESULTS: value, <0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was achieved in 76%, and mTICI ≥2b was 92.5%. The rate of first pass (mTICI ≥2b following a single pass) was 51.5%. The primary safety end point composite rate of symptomatic intracerebral hemorrhage or serious adverse device effects was 5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%, respectively. CONCLUSIONS: The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02488915.

A prospective study was performed in obese and nonobese patients undergoing lumbar spine surgery to report perioperative data and surgical outcomes. One hundred fifty-nine consecutive patients who underwent lumbar spine surgery by a single surgeon entered the study. Among 159 consecutive patients, 55 met the criteria for obesity (> 20% ideal body weight). The average weight was 226 lb in the obese group. There were 28 men and 27 women with ages ranging from 25 to 81 years, with a mean of 47.9 years. The diagnoses and procedures included 31% herniated nucleus pulposus with laminotomy and discectomy, 14% spinal stenosis with laminectomy, and 55% lumbar fusion procedures for other disorders. Twenty-nine percent had previous lumbar surgery that had failed. Results indicated that there were no significant differences between the obese and control groups in terms of duration of surgery (3.8 versus 3.2 h), blood loss (723 versus 605 ml), and duration of hospital stay (5.6 versus 5.8 days). The clinical results were 24% excellent, 40% good, 27% fair, and 9% poor in the obese group; and 27% excellent, 37% good, 19% fair, and 17% poor in the control group. This study found no significant differences between obese and control patients relative to blood loss, operative time, hospital stay, rate of complications, and functional outcome in lumbar spine surgery. Patient selection continues to be the most important factor in terms of operative success. We believe that lumbar spine surgery, including fusion, should not be withheld from obese patients who present with proper indications for surgery and fail an appropriate course of conservative treatment.

Motor evoked potentials (MEPs) have shown promise as a valuable tool for monitoring intraoperative motor tract function and reducing postoperative plegia. MEP monitoring has been reported to contribute to deficit prevention during resection of tumors adjacent to motor structures in the cerebral cortex and spine, and in detecting spinal ischemia during thoracic aortic reconstruction. Many commonly used anesthetic agents have long been known to depress MEP responses and reduce MEP specificity for motor injury detection. Although new stimulation techniques have broadened the spectrum of anesthetics that can be used during MEP monitoring, certain agents continue to have dose-dependent effects on MEP reliability. Understanding the effects of anesthetic agents and physiologic alterations on MEPs is imperative to increasing the acceptance and application of this technique in the prevention of intraoperative motor tract injury. This review is intended as an overview of the effects of anesthetics and physiology on the reproducibility of intraoperative myogenic MEP responses, rather than an analysis of the sensitivity and specificity of this monitoring method in the prevention of motor injury.

Emergency medicine (EM) program directors have expressed a desire for more evaluative data to be included in application materials. This is consistent with frustrations expressed by program directors of multiple specialties, but mostly by those in specialties with more competitive matches. Some of the concerns about traditional narrative letters of recommendation included lack of uniform information, lack of relative value given for interval grading, and a perception of ambiguity with regard to terminology. The Council of Emergency Medicine Residency Directors established a task force in 1995 that created a standardized letter of recommendation form. This form, to be completed by EM faculty, requests that objective, comparative, and narrative information be reported regarding the residency applicant.

The relationship between maternal mental health and infant development has been established in the literature. The Neonatal Intensive Care Unit (NICU) is a particularly challenging environment for new mothers as several natural processes are disrupted. The objective of this study is to elucidate protective factors and environmental deficits associated with the NICU. The experiences of forty-six (n = 46) mothers of infants admitted to a Level III NICU in the Midwestern United States, who responded to a related open-ended question, were analyzed thematically. Five themes related to the NICU environment emerged as being either stressful or helpful: (1) amount and quality of communication with medical staff, (2) bedside manner of medical staff, (3) feeling alienated from infant’s care, (4) support from other NICU mothers and families, and (5) NICU Physical Environment and Regulations. There is a need for medical staff training on awareness, communication, empathy, and other behaviors that might improve maternal (and parental) experiences in the NICU. The physical environment, including rules and regulations of the NICU, should be reexamined with family comfort in mind in addition to the clinical care of the infant.

Background Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice. Methods Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), mortality, and symptomatic intracranial hemorrhage (sICH). Results A total of 634patients were included. Mean age was 66.1±14.8 years and mean baseline NIH Stroke Scale (NIHSS) score was 17.4±6.7; 86.7% had an anterior circulation occlusion. Mean time from symptom onset to puncture and time to revascularization were 363.1±264.5 min and 78.8±49.6 min, respectively. 80.3% achieved TICI ≥2b. 90-day mRS ≤2 was achieved in 47.9%, compared with 51.4% when restricting the analysis to the anterior circulation and within 6 hours (similar to recent AHA/ASA guidelines), and 54.3% for those who achieved complete revascularization. The 90-day mortality rate was 19.8%. Independent predictors of clinical outcome included age, baseline NIHSS, use of balloon guide catheter, revascularization, and sICH. Conclusion The TRACK Registry results demonstrate the generalizability of the recent thrombectomy RCTs in real-world clinical practice. No differences in clinical and angiographic outcomes were shown between patients treated within the AHA/ASA guidelines and those treated outside the recommendations.

BACKGROUNDNovel therapeutic approaches are critically needed for Staphylococcus aureus bloodstream infections (BSIs), particularly for methicillin-resistant S. aureus (MRSA). Exebacase, a first-in-class antistaphylococcal lysin, is a direct lytic agent that is rapidly bacteriolytic, eradicates biofilms, and synergizes with antibiotics.METHODSIn this superiority-design study, we randomly assigned 121 patients with S. aureus BSI/endocarditis to receive a single dose of exebacase or placebo. All patients received standard-of-care antibiotics. The primary efficacy endpoint was clinical outcome (responder rate) on day 14.RESULTSClinical responder rates on day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics-alone groups, respectively (difference = 10.4, 90% CI [-6.3, 27.2], P = 0.31), and were 42.8 percentage points higher in the prespecified exploratory MRSA subgroup (74.1% vs. 31.3%, difference = 42.8, 90% CI [14.3, 71.4], ad hoc P = 0.01). Rates of adverse events (AEs) were similar in both groups. No AEs of hypersensitivity to exebacase were reported. Thirty-day all-cause mortality rates were 9.7% and 12.8% in the exebacase + antibiotics and antibiotics-alone groups, respectively, with a notable difference in MRSA patients (3.7% vs. 25.0%, difference = -21.3, 90% CI [-45.1, 2.5], ad hoc P = 0.06). Among MRSA patients in the United States, median length of stay was 4 days shorter and 30-day hospital readmission rates were 48% lower in the exebacase-treated group compared with antibiotics alone.CONCLUSIONThis study establishes proof of concept for exebacase and direct lytic agents as potential therapeutics and supports conduct of a confirmatory study focused on exebacase to treat MRSA BSIs.TRIAL REGISTRATIONClinicaltrials.gov NCT03163446.FUNDINGContraFect Corporation.

Atrial fibrillation (AF) is the most commonly seen arrhythmia in clinical practice. At present, few studies have been conducted centering on depression and anxiety in AF patients. Our aim in this systematic review is to use the relevant literature to (1) describe the prevalence of depression and anxiety in AF patients, (2) assess the impact that depression and anxiety have on illness perception in patients with AF, (3) provide evidence to support a hypothetical connection between the pathophysiology of AF and depression and anxiety, (4) evaluate the benefit of treatment of AF on depression and anxiety, and (5) give insight on medically managing a patient with AF and concomitant depression and anxiety.

OBJECTIVE: To estimate the incidence of false-positive findings of thoracic outlet syndrome (TOS) shoulder maneuvers, Adson's test (AT), costoclavicular maneuver (CCM), elevated arm stress test (EAST), and supraclavicular pressure (SCP) in healthy subjects. METHODS: A cross-sectional, observational study was performed in a medical school and affiliated emergency medicine residency program setting. Participants included healthy adult volunteers without symptoms of TOS. The shoulder maneuvers AT, CCM, EAST, and SCP were performed in randomized order for 30 sec, 30 sec, 3 min, and 30 sec, respectively. Pulse quality and the presence and timing of pain or paresthesias were assessed. RESULTS: 53 subjects were enrolled, including 27 women, aged 29.7 +/- 6.4 years (range 21-58 years). AT, CCM, EAST, and SCP resulted in an altered pulse in 11%, 11%, 62%, and 21%; pain in 0%, 0%, 21%, and 2%; and paresthesias in 11%, 15%, 36%, and 15% of cases, respectively. The following outcomes had reasonable false-positive rates (upper 95% confidence limit): pain with the AT (7%), CCM (7%), SCP (10%), or any 2 TOS shoulder maneuvers (10%); discontinuing the EAST because of symptoms (16%); or any symptom with 3 (13%) or 4 (7%) TOS shoulder maneuvers. CONCLUSIONS: In a study of TOS shoulder maneuvers in healthy subjects, the outcomes of pulse alteration or paresthesias were unreliable in general. However, TOS shoulder maneuvers have reasonably low false-positive rates when a positive outcome is defined as pain after AT, CCM, or SCP; discontinuation of the EAST secondary to pain; pain in the same arm with > or =2 maneuvers; or any symptom in the same arm with > or =3 maneuvers.