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Glioblastoma multiforme (GBM) is the most aggressive and prevalent form of brain cancer, with an expected survival of 12-15 months following diagnosis. GBM affects the glial cells of the central nervous system, which impairs regular brain function including memory, hearing, and vision. GBM has virtually no long-term survival even with treatment, requiring novel strategies to understand disease progression. Here, we identified a somatic mutation in OR2T7, a G-protein-coupled receptor (GPCR), that correlates with reduced progression-free survival for glioblastoma (log rank p-value = 0.05), suggesting a possible role in tumor progression. The mutation, D125V, occurred in 10% of 396 glioblastoma samples in The Cancer Genome Atlas, but not in any of the 2504 DNA sequences in the 1000 Genomes Project, suggesting that the mutation may have a deleterious functional effect. In addition, transcriptome analysis showed that the p38α mitogen-activated protein kinase (MAPK), c-Fos, c-Jun, and JunB proto-oncogenes, and putative tumor suppressors RhoB and caspase-14 were underexpressed in glioblastoma samples with the D125V mutation (false discovery rate 0.05). Molecular modeling and molecular dynamics simulations have provided preliminary structural insight and indicate a dynamic helical movement network that is influenced by the membrane-embedded, cytofacial-facing residue 125, demonstrating a possible obstruction of G-protein binding on the cytofacial exposed region. We show that the mutation impacts the "open" GPCR conformation, potentially affecting G

Background Undiagnosed atrial fibrillation (AF) exposes unsuspecting patients to elevated stroke risks. The optimal algorithm for identifying patients who should be screened for AF remains undetermined. The objective of this study is to determine the AF burden in an asymptomatic, at-risk population. We also sought to investigate potential predictors of undiagnosed AF. Methods This registry is a prospective observational study assessing continuous ECG monitoring in screening for AF using a wearable single lead 7-day continuous monitoring device. Patients included were asymptomatic individuals, at risk for AF as determined by either 1) ≥65 years of age with ≥1 high risk factor or; 2) ≥75 years of age and ≥2 moderate risk factors. A multivariable logistic regression was used to explore the predictive value of certain patient characteristics in identifying patients susceptible to have undiagnosed AF. Results Among the 942 patients included, 25 patients (2.7%) had evidence of AF detected. Only 8 patients had AF duration ≥24 h. History of perioperative AF (OR: 3.25, 95%CI: 1.08–9.79, p = 0.036), age over 85 (OR: 4.71, 95%CI: 1.31–16.92, p = 0.017) and absence of cardiovascular disease (CVD) (OR: 0.27, 95%CI: 0.10–0.76, p = 0.013) were found to be predictive of undiagnosed AF. Conclusion This study demonstrates the feasibility of office-based AF screening in at-risk population. The low rate of AF detection suggests that the optimal algorithm for identifying asymptomatic patients who would benefit from continuous screening remains unclear. Advanced age, history of perioperative AF and absence of CVD are variables that could be explored further.

An experiment was set up to determine whether some short, focused training could influence decision makers to take a more structured and process-based approach to project decision-making. The experiment also investigated the impact on project decision-making of the way a decision is framed by an authority figure, i.e. how a decision is influenced by an authority figure advocating a process-driven, neutral or an opinion/schedule-driven approach. The experiment was set up so that half of the participants watched three 15-min training videos before answering questions on decision-making scenarios for projects, and the other half just answered questions on the decision-making scenarios. 40% of participants (split across those who watched the training videos and those that only answered the decision-making scenario questions) had undergone some prior training on decision making. The results demonstrate that watching the training videos has an impact. The impact is greater when there has been no prior training; however, there is still impact in each case, albeit small for some. This implies that the benefits of 1 h of training prior to project decision-making is more valuable for those with no prior training, but still worthwhile for those with prior training. The results showed that framing by an authority figure has a strong influence on the participants’ responses, in terms of whether a process-based, neutral or opinion/intuition-based response was given.

Objectives Factors that influence decision of non–vitamin K antagonist oral anticoagulants (NOACs) use among older atrial fibrillation (AF) patients in long-term care (LTC) facilities have not been well studied. The aim of this study was to assess whether increased frailty influenced physicians to prescribe NOACs over warfarin. Design We retrospectively reviewed the electronic medical record (EMR) and pharmacy data of 25 LTC facilities in Ontario, Canada, in May 2015. The diagnosis of AF was ascertained from EMR and confirmed by complete chart review of a random sample of the cohort. A score of ≥2 on the Changes in Health, End-stage disease, Signs, and Symptoms (CHESS) scale was used as a surrogate marker of frailty. Measures Multivariable logistic regression model was used to assess whether a higher frailty score is associated with the use of NOACs in comparison to warfarin, independent of potential patient-level confounders. Setting and participants In total, 3378 active residents were assessed in 25 LTC facilities. All the residents were ≥65 years old. We identified 433 residents with AF; 273 (63%) AF residents were on anticoagulation therapy and included in the analysis. Results Residents were more often treated with NOACs (n = 159; 58%) in comparison to warfarin (n = 114; 42%). A CHESS score of ≥2 increased the odds of prescribing NOACs by 2.46 times [95% confidence interval (CI) 1.11, 5.49; P = .03] when adjusted for important patient-level factors. Patients with hypertension had a trend of increased NOAC prescriptions but did not reach statistical significance [odds ratio 2.1 (95% CI 0.91, 4.81), P = .08]. None of the patient-level factors were associated with NOAC prescriptions. Conclusions and Implications In this real world cohort of AF patients in LTC who are prescribed an oral anticoagulation therapy, a higher CHESS score (≥2) is associated with increased use of NOACs in comparison to warfarin.

The present study moved beyond trait reports of rumination, reflection, and meaning in life (presence and search) by examining within-person relationships between daily states of these constructs and well-being. Participants (N = 130) completed reports at the end of the day for 14 days. When analyzed together, daily rumination was negatively related to daily well-being whereas daily reflection was not (with one exception). In contrast, daily reflection was positively related to daily search for meaning in life, whereas rumination was not related to daily search for meaning in life. Reflection moderated the within-person relationships between rumination and well-being such that negative relationships between rumination and well-being were stronger at higher levels of reflection. In contrast, rumination had virtually no effect on search for meaning in life at higher levels of reflection. Lagged analyses found that daily reflection led to increases in daily positive deactivated affect (e.g., relaxation) and searching for meaning in life, and daily rumination led to increased presence of meaning in life the following day. These results highlight the importance of considering both reflection and rumination in studies of within-person variation and the value of considering within-person variability in understanding presence of and search for meaning in life.

Background Close to 1 in 5 patients admitted to a skilled nursing facility (SNF) are readmitted to the acute hospital within 30 days, and a substantial percentage are readmitted within 2 days of the SNF admission. These rapid returns to the hospital may provide insights for improving care transitions between the acute hospital and the SNF. Objectives To describe the characteristics of SNF to hospital transfers that occur within 48 hours and 30 days of SNF admission based on root cause analyses (RCAs) performed by SNF staff, and identify potential areas of focus for improving transitions between hospitals and SNFs. Design Trained staff from SNFs enrolled in a randomized, controlled clinical trial of the INTERACT (Interventions to Reduce Acute Care Transfers) quality improvement program performed retrospective RCAs on hospital transfers during a 12-month implementation period. Setting SNFs from across the United States. Participants 64 of 88 SNFs randomized to the intervention group submitted RCAs. Interventions SNFs were implementing the INTERACT quality improvement program. Measures Data were abstracted from the INTERACT Quality Improvement (QI) tool, a structured, retrospective RCA on hospital transfers. Results Among 4658 transfers for which data on the time between SNF admission and hospital transfer were available, 353 (8%) occurred within 48 hours of SNF admission, 524 (11%) 3 to 6 days after SNF admission, 1450 (31%) 7 to 29 days after SNF admission, and 2331 (50%) occurred 30 days or longer after admission. Comparisons between transfers that occurred within 48 hours and within 30 days of SNF admission to transfers that occurred 30 days or longer after SNF admission revealed several statistically significant differences between patient risk factors for transfer, symptoms and signs precipitating the transfers, and other characteristics of the transfers. Hospitalization in the last 30 days and year was significantly more common among those with rapid returns to the hospital. Shortness of breath was significantly more common among those transferred within 48 hours or 30 days, and falls, functional decline, suspected respiratory infection, and new urinary incontinence less common. SNF staff rated a higher proportion of transfers within 30 days versus 30 days or longer as potentially preventable (25.1% vs 21.5%, P = .005). Case descriptions derived from the QI tools of transfers back to the hospital within 48 hours of SNF admission illustrate several factors underlying these rapid returns to the hospital. Conclusion RCAs on transfers back to the hospital shortly after SNF admission provide insights into strategies that both hospitals and SNFs can consider in collaborative efforts to reduce potentially avoidable hospital readmissions.

Background Determining if a transfer of a skilled nursing facility (SNF) patient/resident to an acute hospital is potentially avoidable or preventable is challenging. Most previous research on potentially avoidable or preventable hospitalizations is based on diagnoses without in-depth root cause analysis (RCA), and few studies have examined SNF staff perspective on preventability of transfers. Objectives To examine factors associated with hospital transfers rated as potentially preventable versus nonpreventable by SNF staff. Design Trained staff from SNFs enrolled in a randomized controlled clinical trial of the INTERACT (Interventions to Reduce Acute Care Transfers) quality improvement program performed retrospective RCAs on hospital transfers during a 12-month implementation period. Setting SNFs from across the United States. Participants Sixty-four of 88 SNFs randomized to the intervention group submitted RCAs with a rating of whether the transfer was determined to be potentially preventable or nonpreventable. Interventions SNFs were implementing the INTERACT Quality Improvement (QI) program. Measures Data were abstracted from the INTERACT QI tool, a structured, retrospective RCA on hospital transfers. Results A total of 4527 RCAs with a rating of preventability were submitted during the 12-month implementation period, of which 1044 (23%) were rated as potentially preventable by SNF staff. In unadjusted univariate analyses, factors associated with ratings of potentially preventable included acute changes in condition of fever, decreased food or fluid intake, functional decline, shortness of breath, and new urinary incontinence; other factors included the clinician, resident, and/or family insisting on the transfer, transfers that occurred fewer than 30 days from SNF admission and that occurred on weekends, transfers ordered by a covering physician (as opposed to the primary physician), and transfers that resulted in an emergency department (ED) visit with return to the SNF. Factors associated with ratings of nonpreventable included on-site evaluation by a physician or other clinician, and transfers related to falls. Among factors precipitating the transfers, clinician and resident and/or family insistence on transfer, and transfers related to fever and falls remained significant in a multivariate analysis. There were no significant differences among characteristics of SNFs that rated a relatively high versus low proportion of transfers as potentially preventable. Conclusion SNF staff rated a substantial proportion of transfers as potentially preventable on retrospective RCAs. Factors associated with ratings of preventability, as well as illustrative case examples, provide important insights that can assist SNFs in focusing education and care process improvements in order to reduce unnecessary hospital transfers and their associated morbidity and costs.

Background The majority of patients receiving implantable cardioverter-defibrillator (ICD) implantation under current guidelines never develop sustained ventricular arrhythmia; therefore, better markers of risk for sustained ventricular tachycardia and/or ventricular fibrillation are needed. Objective The purpose of this study was to identify cardiac magnetic resonance arrhythmic risk predictors of ischemic cardiomyopathy before ICD implantation. Methods Forty-three subjects (mean age, 64.5 ± 11.9 years) with previous myocardial infarction who were referred for ICD implantation were evaluated by cardiac magnetic resonance imaging (MRI). The MRI protocol included left ventricular functional parameter assessment using steady-state free precession and late gadolinium enhancement MRI using inversion recovery fast gradient echo. Left ventricular functional parameters were measured using cardiac magnetic resonance software. Subjects were followed up for 6–46 months, and the events of appropriate ICD treatments (shocks and antitachycardia pacing) were recorded. Results Twenty-eight patients experienced 46 spontaneous episodes during a median follow-up duration of 30 months. The total myocardial infarct (MI) size (18.05 ± 11.44 g vs 38.83 ± 19.87 g; P = .0006), MI core (11.63 ± 7.14 g vs 24.12 ± 12.73 g; P = .0002), and infarct gray zone (6.43 ± 4.64 g vs 14.71 ± 7.65 g; P = .0004) were significantly larger in subjects who received appropriate ICD therapy than in those who did not experience an episode of ventricular tachycardia and/or ventricular fibrillation. Multivariate regression analyses for the infarct gray zone and MI core adjusted for New York Heart Association class, diabetes, and etiology (primary or secondary prevention) revealed that the gray zone and MI core were predictors of appropriate ICD therapies ( P = .0018 and P = .007, respectively). Conclusion The extent of MI scar may predict which patients would benefit most from ICD implantation.

This paper examines how the requirement for annual catch limits (ACLs) has been implemented for data-limited stocks in all federally-managed fisheries in the United States. The legal mandate to establish ACLs in the U.S. has spurred substantial scientific advances, including the development and adoption of at least 16 methods for establishing catch limits for data-limited fisheries. This study analyzed the assessment methods that form the basis of ACLs, those which determine the overfishing limits (OFLs) and the acceptable biological catches (ABCs). Nationally, 30% (150) of OFLs/ABCs are currently calculated using conventional data-rich assessment methods, 11% (59) using data-moderate methods, and 59% (295) using data-poor approaches. There is substantial variation in the proportion of stocks that are currently managed with data-rich versus data-limited methods across regions, and there are clear geographical patterns in the types and diversity of methods being utilized to calculate OFLs/ABCs. Data-poor methods are the most commonly used OFL/ABC-setting methods in the U.S., particularly in the Southeast, Atlantic highly migratory species (HMS), Pacific, and Western Pacific regions. The Southeast and Atlantic HMS regions use some form of catch scalar or an ABC of zero landings for each data-limited stock. The Pacific and North Pacific regions currently employ a higher diversity of data-limited methods than any other region; these include both data-moderate methods and data-poor methods. Regional disparities in data-limited method development and implementation are attributed to regional differences in the number of stocks being managed, the data types and lengths of the time series available, and the resources dedicated to data processing and stock assessment. Recommendations for improving management of data-limited stocks include establishing a complete inventory of all available data for each managed stock, dedicating resources and expertise to data-limited method development and evaluation, and developing a more streamlined assessment process to handle the expanded volume of stocks requiring ACLs.

Objective Assess factors that influence both the patient and the physician in the setting of minor head injury in adults and the decision-making process around CT utilization. Methods This is a convenience sample survey study of adult minor head injury patients (GCS 15) and their physicians regarding factors influencing the decision to use CT to evaluate for intra-cranial haemorrhage. Once a head CT was ordered and before the results were known, both the patient and physician were given a one-page survey asking questions about their concern for injury and rationale for CT use. CT results and surveys were then recorded in a centralized database and analyzed. Results 584 subjects were enrolled over the 27-month study period. The rate of any intra-cranial haemorrhage was 3.3%. Both the physicians (6% pre-test estimate) and the patients (22% pre-test estimate) over-estimated risk for haemorrhage. Clinical decision rules were not met in 46% of cases where CT was used. Physicians listed an average of 5 factors from a list of 9 that influenced their decision to order CT. Patients listed an average of 1.7 factors influencing their decision to present to the Emergency Department for evaluation. Many patients felt cost (45%) and low risk stratification (34%) should weigh heavily in the decision to use CT. If asked to limit CT utilization, physicians were able to identify a group with less than 2% risk of injury. Conclusions Patients with low risk of intra-cranial injury continue to be evaluated by CT. Physician decision-making around the use of CT to evaluate minor head injury is multi-factorial. Shared decision-making between the patient and the physician in a low risk minor head injury encounter shows promise as a method to reduce CT utilization in this low risk cohort.

We are developing indicators for the emergence of science and technology (S&T) topics. To do so, we extract information from various S&T information resources. This paper compares alternative ways of consolidating messy sets of key terms [e.g., using Natural Language Processing on abstracts and titles, together with various keyword sets]. Our process includes combinations of stopword removal, fuzzy term matching, association rules, and term commonality weighting. We compare topic modeling to Principal Components Analysis for a test set of 4104 abstract records on Dye-Sensitized Solar Cells. Results suggest potential to enhance understanding regarding technological topics to help track technological emergence.

Jolt accentuation or exacerbation of a baseline headache with horizontal rotation of the neck is a physical finding believed to assess for meningeal irritation. We conducted a prospective observational study of neurologically intact emergency department (ED) patients undergoing lumbar puncture in 2 inner city academic EDs to validate the sensitivity and specificity of jolt accentuation and to assess the sensitivity and specificity of Kernig sign, Brudzinski sign, and nuchal rigidity, in predicting cerebrospinal fluid (CSF) pleocytosis in individuals being assessed for meningitis. Adult patients 18 years and older undergoing lumbar puncture between 2006 and 2009 were approached for consent. Exclusions included inability to consent and altered mental status. Physicians were asked to answer a questionnaire of physical examination findings before receiving CSF results. The primary outcome was the presence or absence of pleocytosis, defined as greater than or equal to 5 cells/high-power field in the fourth CSF tube. We calculated descriptive statistics and tests of diagnostic accuracy. A total of 230 patients consented for participation and had CSF white blood cell counts recorded. Forty-seven individuals (20%) had pleocytosis. A total of 197 patients had headache and were, hence, eligible for jolt accentuation assessment. For pleocytosis, the sensitivity of jolt accentuation was 21%, Kernig sign was 2%, Brudzinski sign was 2%, and nuchal rigidity was 13%. The specificity of jolt accentuation was 82%, Kernig sign was 97%, Brudzinski sign was 98%, and nuchal rigidity was 80%. Jolt accentuation in our cohort was poorly predictive of pleocytosis and insensitive. The presence of Kernig sign, Brudzinski sign, or nuchal rigidity has moderate positive but no negative predictive value for pleocytosis.

Background The safety and efficacy of dabigatran in the periprocedural period for patients undergoing atrial fibrillation ablation is not well established. We conducted a meta-analysis of the periprocedural use of dabigatran vs warfarin (with or without heparin bridging). Methods A literature search was performed using multiple databases. Outcomes were (1) major bleeding; (2) minor bleeding; and (3) thromboembolic events. Odds ratios (ORs) were reported for dichotomous variables. Results Eleven controlled studies (9 cohorts, 1 randomized controlled trial and 1 case-control study; 3841 patients) were identified. Dabigatran was used in 1463 patients, uninterrupted in 223 and held up to 36 hours in the remainder. No significant differences were noted in major bleeding rates between dabigatran and warfarin groups (1.9% vs 1.6%; OR, 1.04 [95% confidence interval (CI), 0.51-2.13]; P = 0.92). Cardiac tamponade was observed in 1.4% in dabigatran vs 1.1% in warfarin groups (OR, 1.1; 95% CI, 0.55-2.11; P = 0.82). Similar rates for dabigatran vs warfarin were reported for minor bleeding (3.8% vs 4.5%; OR, 0.85; 95% CI, 0.58-1.25; P = 0.40), hematoma (2% vs 2.7%; OR, 0.67; 95% CI, 0.41-1.08; P = 0.1), and thromboembolic events (0.6% vs 0.1%; OR, 2.51; 95% CI, 0.78-8.11; P = 0.12). Conclusions This meta-analysis suggests that dabigatran and warfarin have similar safety and efficacy overall for periprocedural anticoagulation in patients undergoing radiofrequency atrial fibrillation ablation. Signals were seen favouring dabigatran (for hematomas) and warfarin (for thromboembolic events), but neither was statistically significant because of low event rates. More high-quality data are required to definitively compare the 2 strategies.

Background The difficulties with gum elastic bougie (GEB) use in the emergency department (ED) have never been studied prospectively. Objectives To determine the most common difficulties associated with endotracheal intubation using a GEB in the ED. Methods We conducted a prospective, observational study of GEB practices in our two affiliated urban EDs with a 3-year residency training program and an annual census of 150,000 patients. Laryngoscopists performing a GEB-assisted intubation completed a structured data form after laryngoscopy, recording patient characteristics, grade of laryngeal view (using the modified Cormack-Lehane classification), reason for GEB use, and problems encountered. Data were analyzed using standard statistical methods and 95% confidence intervals. Results A GEB was used for 88 patients. The overall success rate was 70/88 (79.6%; 95% confidence interval [CI] 71.1–88.0%). The GEB failure rate of the first laryngoscopist was 25/88 (28.4%; 95% CI 21.0–40.3%), with the two most common reasons being: inability to insert the bougie past the hypopharynx in 13 (52%; 95% CI 32.4–71.6%) and inability to pass the endotracheal tube over the bougie in six (24%; 95% CI 7.3–40.7). Conclusions The GEB is a helpful rescue airway device, but emergency care providers should be aware that failure rates are relatively high at a teaching institution.

Current clinical practice in many emergency departments (EDs) includes checking a type and screen blood test (TS) for Rhesus (Rh) status on all pregnant patients presenting with vaginal bleeding or abdominal pain. The test is expensive, and awaiting results may delay disposition.To determine if there is a subset of pregnant women who reliably know their blood type and for whom a TS blood test to determine Rh status can be safely omitted or deferred.A prospective study at two associated urban academic centers with an annual ED census of 150,000 patients was performed between January 2007 and June 2008. Pregnant patients who had a TS obtained as part of their ED evaluation were enrolled. Subjects completed a standardized data form that requested demographic information and were asked to select "no," "maybe," or "yes, definitely" if they knew their blood type. Standard descriptive statistics with 95% confidence intervals were performed.There were 319 pregnant women enrolled in the study. Among the 106 subjects that reported "yes, definitely" they knew their blood type, 103 (97.2%; 95% confidence interval [CI] 94.0-100%]) identified their correct blood type and 105 (99.1%; 95% CI 97.2-100%) identified their correct Rh status. None of these subjects selected a positive Rh when they were in fact a negative Rh. All 14 (13.2%) subjects with a negative Rh status identified themselves as having a negative Rh.Pregnant women reporting that "yes, definitely" they know their blood type, are reliable. Deferring TS testing test may be reasonable.

Background: The gum elastic bougie (GEB) is a rescue airway device commonly found in the emergency department (ED). However, data documenting its efficacy are lacking in the emergency medicine literature. Study Objectives: To determine the success rate of endotracheal intubation using a GEB and the reliability of “palpable clicks” and “hold-up” in the ED setting. Methods: The GEB was introduced at our two affiliated urban EDs with a 3-year residency training program and an annual census of 150,000. Physicians were trained in the use of the GEB before initiation of the study. Over the course of 1 year, we conducted a prospective, observational study of GEB practices in the ED. The study population included all adult patients on whom intubation was attempted with a GEB. All emergency physicians attempting intubation completed a structured data form after laryngoscopy, recording patient characteristics, grade of laryngeal view (using the modified Cormack-Lehane classification), and presence of “palpable clicks” and “hold-up.” Indications for GEB use in our ED include a difficult or rescue airway and for training purposes. Data were analyzed using standard statistical methods and 95% confidence intervals. Results: In our study period, there were 26 patients on whom intubation was attempted with a GEB. The overall success rate was 20/26 (76.9%; 95% confidence interval [CI] 60.7–93.1%). Among cases where the GEB was used for training purposes (all grade 1 or 2a laryngeal view), six of seven (85.7%) intubations were successful. When the GEB was used for clinically indicated purposes, 14 of 19 (73.7%; 95% CI 53.9–93.5%) intubations were successful. Palpable clicks were appreciated in 11/20 successful intubations (sensitivity 55.0%; 95% CI 33.2–76.8%); there was one false positive (specificity 80%; 95% CI 40.9–98.2%). Of 20 successful intubations, hold-up was deferred in five cases; of 15 remaining cases, hold-up was appreciated in 5/15 (sensitivity 33.3%; 95% CI 9.5–57.2%); there were no false positives (specificity 100%; 95% CI 60.7–100%). Conclusions: In our ED setting, the GEB had a success rate of 73.7% when utilized as a rescue airway after failed attempts. The characteristics of “palpable clicks” and “hold-up” were unreliable.

Background Medicare incentivizes the reduction of hospitalizations of nursing facility (NF) residents. The effects of these incentives on resident safety have not been examined. Objective Examine safety indicators in NFs participating in a randomized, controlled trial of the INTERACT Quality Improvement Program. Design Secondary analysis of a randomized trial in which intervention NFs exhibited a statistically nonsignificant reduction in hospitalizations. Setting NFs with adequate on-site medical, radiography, laboratory, and pharmacy services, and capability for online training and data input were eligible. Participants 264 NFs randomized into intervention and comparison groups stratified by previous INTERACT use and self-reported hospital readmission rates. Intervention NFs randomized to the intervention group received INTERACT materials, access to online training and a series of training webinars, feedback on hospitalization rates and root-cause analysis data, and monthly telephonic support. Measures Minimum data set (MDS) data for unintentional weight loss, malnutrition, hip fracture, pneumonia, wound infection, septicemia, urinary tract infection, and falls with injury for the intervention year and the year prior; unintentional weight loss, dehydration, changes in rates of falls, pressure ulcers, severe pain, and unexpected deaths obtained from the NFs participating in the intervention through monthly telephone calls. Results No adverse effects on resident safety, and no significant differences in safety indicators between intervention and comparison group NFs were identified, with 1 exception. Intervention NFs with high levels of INTERACT tool use reported significantly lower rates of severe pain. Conclusions/Implications Resident safety was not compromised during implementation of a quality improvement program designed to reduce unnecessary hospitalization of NF residents.

This paper explores visualizations of document collections, which we call topic maps. Our topic maps are based on a topic model of the document collection, where the topic model is used to determine the semantic content of each document. Using two collections of search results, we show how topic maps reveal the semantic structure of a collection and visually communicate the diversity of content in the collection. We describe techniques for assessing the validity and accuracy of topic maps, and discuss the challenge of producing useful two-dimensional maps of documents.

The steady state bifurcation structure of the double-gyre wind-driven ocean circulation is examined in a shallow water model where the upper layer is allowed to outcrop at the sea surface. In addition to the classical jet-up and jet-down multiple equilibria, we find a new regime in which one of the equilibrium solutions has a large outcropping region in the subpolar gyre. Time dependent simulations show that the outcropping solution equilibrates to a stable periodic orbit with a period of 8 months. Co-existing with the periodic solution is a stable steady state solution without outcropping. A numerical scheme that has the unique advantage of being differentiable while still allowing layers to outcrop at the sea surface is used for the analysis. In contrast, standard schemes for solving layered models with outcropping are non-differentiable and have an ill-defined Jacobian making them unsuitable for solution using Newton’s method. As such, our new scheme expands the applicability of numerical bifurcation techniques to an important class of ocean models whose bifurcation structure had hitherto remained unexplored.

Out-of-hospital cardiac arrest (OOHCA) treatment produces dismal recovery rates. Newer, directed therapies such as thrombolysis may be best considered if possible etiologies can be assessed immediately. We conducted a prospective, pilot, feasibility study of on-scene physician assessments in non-traumatic OOHCA. Physicians responded to the scene and reported likelihood of thromboembolic etiology based on detailed history and physical assessments. Included were 136/148 OOHCAs during the 6-month study period; median age was 69.5 years and 72% were men. Physicians judged 103/136 (76%) of arrests to be of thromboembolic etiology and would have recommended thrombolytic bolus in 83/136 (61%). Among 19 instances of physician-reported contraindications, 17 (90%) were not true contraindications. Median age was lower in the group recommended for thrombolysis. Thromboembolic etiology as judged by on-scene physicians was common and physicians recommended thrombolytic bolus commonly. Contraindications were highly overestimated. These data may be useful in the consideration of innovative, directed therapies such as thrombolysis in attempts to improve outcomes from OOHCA.

At the time of this writing, it has been 2 months since Newtown. We have each mourned from a distance, imagining the heartbreak. We have asked ourselves what we would have done were this our community, our school, our child. We have formed opinions about what may or may not have stopped this tragedy. And we have each quietly recalled other tragedies that we have witnessed. Now it is time, as individuals and as a specialty, to take action to decrease the likelihood of future deaths.... Language: en

Kinetic plasma simulations based on direct integration of the Vlasov equations are characterized by very low noise, but become numerically intensive in more than one spatial dimension. A set of less costly numerical strategies are presented in which a full Vlasov kinetic description is maintained only along one “dominant” spatial coordinate, with the perpendicular dimensions modeled by reduced moment-based methods. A simple initial-value simulation is use to test the algorithm and simulations of current-driven double layers and electron holes in the auroral ionosphere are used to illustrate the application of such methods to current research studies.

Objectives The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia. Background ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT). Methods We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset=9% and rate stability=10 ms; V > A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee. Results One hundred forty-nine patients had a history of sustained VT or VF. Mean age (± SD) was 60 ± 13 years; 83% were male, and mean ejection fraction was 35 ± 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio=0.47, P = .011). High-energy shocks were reduced from 0.58 ± 4.23 shocks/patient/month in the control group to 0.04 ± 0.15 shocks/patient/month in the enhanced group ( P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes). Conclusions Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT.

Individuals affected with tuberous sclerosis complex (TSC) develop cortical tubers characterized by disorganized cytoarchitecture and morphologically abnormal cell types, such as dysplastic neurons (DNs) and giant cells (GCs). As part of ongoing cDNA array analysis to study the molecular pathogenesis of tuber formation, we detected increased expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, a cell adhesion molecule (CAM) that functions in cytokine signaling, in tubers. Western and immunohistochemical analyses revealed that ICAM-1 protein was selectively expressed in tubers, but was only minimally expressed in control cortex, adjacent nontuberal cortex, or in non-TSC focal cortical dysplasia. Increased expression of ICAM-1 was found in mice in which the Tsc1 gene was conditionally inactivated in astrocytes. Expression of molecules involved in ICAM-1 activation and cytokine signaling were increased in tubers, including tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappaB). Numerous CD68-immunoreactive macrophages were observed clustered around GCs further supporting an inflammatory response in tubers. Expression of caspase 8 and Fas support cytokine activation and detection of TUNEL reactivity suggests ongoing cell death in tubers. Specific alterations in ICAM-1, TNF-alpha, NF-kappaB1, and MAPK expression coupled with the detection of numerous CD68-immunoreactive macrophages suggests activation of proinflammatory cytokine signaling pathways in tubers that may culminate in cell death.

Study objectives The optimal timing of discharge from the emergency department (ED) after pediatric procedural sedation and analgesia has not been well studied. Because concern about delayed adverse effects commonly delays discharge after sedation, we attempted to establish the timing of adverse effects in our cohort of procedural sedations. Methods We analyzed data from a prospectively generated database comprising consecutive sedation events throughout a 2-year period. We determined the timing of serious (eg, hypoxia, stridor, hypotension) and other adverse effects from final medication administration and calculated adverse effect risk ratios in relation to sedation characteristics. Results In 1,341 sedation events, there were 184 (13.7%) adverse effects, of which 159 (11.9%) were serious. The median age of children with and without adverse effects was similar (64 months in both groups). Most adverse effects occurred during the procedure (92%) rather than after the procedure (8%). Serious adverse effects occurred a median of 2 minutes after final medication dose (range –106 to +40 minutes). One hypoxic episode occurred each at 26, 30, and 40 minutes after final medication administration; all were repeated occurrences in children who had experienced previous hypoxia during the expected peak drug effect. Conclusion Adverse effects were common; however, serious adverse effects rarely occurred after 25 minutes from the final medication administration. Those that did occur this late were all preceded by a separate similar adverse effect during the expected peak drug effect, which suggests that when similar medication regimens are used, discharge from the ED may be safe at approximately 30 minutes after final sedation medication administration if no adverse effects have occurred.

OBJECTIVES The aim of this study was to compare the effectiveness of the implantable cardioverter defibrillator (ICD) and medical strategies for prevention of arrhythmic events and death. BACKGROUND The ICD is a potential strategy to reduce mortality in patients at risk of sudden death. METHODS The MEDLINE, EMBASE, and Cochrane Library electronic databases were searched from January 1966 to April 2002. All published randomized controlled trials comparing ICD implantation with medical therapy were reviewed. Four independent reviewers extracted data on all-cause mortality, nonarrhythmic death, and arrhythmic death using a standardized protocol. RESULTS Nine studies including over 5,000 patients were synthesized using both fixed-effects and random-effects models. The primary and secondary prevention trials showed a significant benefit of the ICD with respect to arrhythmic death, with relative risks (RR) of 0.34 and 0.50, respectively (both p < 0.001). The mortality benefit of the ICD was entirely attributable to a reduction in arrhythmic death (all trials: p < 0.00001). Whereas the secondary prevention trials exhibited a robust decrease in all-cause ICD mortality (RR 0.75; p < 0.001), the pooled primary prevention trials demonstrated decreased all-cause ICD mortality (RR 0.66; p < 0.05) which was dependent on selected individual trials. The disparity in ICD-related mortality reductions in the primary prevention trials was related to variability in the incidence of arrhythmic death between individual studies. CONCLUSIONS Although the ICD decreases the risk of arrhythmic death, its impact on all-cause mortality is related to the underlying risk of arrhythmia-related death relative to competing causes. Given the cost of the device strategy, policies of targeted intervention based on the future risk of arrhythmia are warranted.

This study used a device (DDD implantable cardioverter defibrillator [ICD]) capable of delivering pacing and shock therapies to restore normal sinus rhythm in patients with atrial tachycardias or atrial fibrillation (AF). The purpose of this study was to assess the effect of the device on patient-perceived, health-related quality of life (QOL).The DDD ICD was implanted in 267 patients with drug refractory, symptomatic AF from 45 centers across Europe, the United States, and Canada. Patients completed self-reported, validated QOL assessments at baseline and at 3- and 6-month follow-up visits (The Medical Outcomes Short Form 36 [SF-36] and the Symptom Checklist [SCL]).The mean age of the study group was 62 +/- 12 years, and 73% of the patients were male. A total of 150 patients completed SF-36 assessments, and 138 patients completed SCL assessments at all 3 times. Baseline scores were more impaired (P.05) on most SF-36 scales compared with norms for a general population, but were similar to a comparison group of patients with AF who were referred to tertiary care centers. The role-physical, physical functioning, vitality, mental health, and social functioning scales all improved significantly with time (all P.04). Similarly, symptom frequency and severity (SCL) also improved significantly from baseline to 6 months (both P.01). Shock therapy was delivered in 86 of the 150 patients (57%) with complete SF-36 evaluations. There was no evidence that receiving shocks decreased the relative improvement in QOL associated with implantation of the device.In a 6-month period, QOL improves after implantation of a DDD ICD with atrial shock and pacing therapies. These improvements were not attenuated by receipt of shocks.

Background The primary aim of this study was to compare quality-of-life outcome between patients randomized to implantable cardioverter defibrillator (ICD) therapy and patients randomized to amiodarone treatment in the Canadian Implantable Defibrillator Study (CIDS). A secondary aim was to evaluate the effects on quality-of-life outcomes of receiving shocks from the device. Methods Quality of life was assessed in 317 English-speaking participants by use of the Rand Corporation's 38-item Mental Health Inventory (MHI) and the Nottingham Health Profile (NHP). Assessments were done in the hospital at baseline and with mailed questionnaires after 2, 6, and 12 months of follow-up. Sixty-two percent of patients completed the follow-up assessments at 6 and 12 months. Results Repeated measures analysis of variance revealed significant time by treatment group interaction effect on total MHI and the psychological distress and psychological well-being sub-scales, and on 5 of the 7 NHP scales (energy, physical mobility, emotional reactions, sleep disturbance, and lifestyle impairment) (P

The study of the Israel–Palestine conflict is a live laboratory for political geographers and this is reflected in a number of studies undertaken by Saul Cohen during his career. Despite the recent collapse of the Israel–Palestine peace process, the ongoing attempts at conflict resolution continue to focus on the territorial dimensions of the conflict. All attempts to configure State territories which are acceptable to both sides must take account not only of the tangible dimensions of boundary demarcation and strategic sites, but also the symbolic aspects of territory and the way in which such territories are part of the process through which national identities are constructed and maintained. Notions of territorial partition remain much the same as they were prior to the establishment of the State of Israel in 1948. However, the changing demographic and settlement realities that have emerged during this period have resulted in the creation of new facts on the ground which must constantly be re-fed into the negotiation process at any given time.

Background The impact of atrial fibrillation (AF) and its treatment on health-related quality of life (QOL) is not well understood. We assessed QOL in patients with symptomatic AF participating in the Canadian Trial of Atrial Fibrillation. Methods Self-report QOL questionnaires including the Short-Form-36 (SF-36), symptom checklist (SCL) and AF Severity Scale (AFSS) were completed at baseline and 3, and 12 months after randomization. Results The study group was aged 65 ± 10 years and 59% were male. By design, 50% of patients were randomized to amiodarone (n = 132), 25% to sotalol (n = 66), and 25% to propafenone (n = 66). Most patients had normal left ventricular function (89%). Physical (41.9 ± 9.3 to 43.7 ± 9.2, P =.001) and mental health (47.5 ± 10.5 to 49.0 ± 9.8, P =.023) summary measures from the SF-36 improved significantly from baseline to 3 months. Arrhythmia symptom frequency and severity (SCL) also improved markedly from baseline to 3 months (symptom frequency 20.4 ± 9.4 to 16.2 ± 9.5 and symptom severity 16.7 ± 8.2 to 12.9 ± 7.4, both P

The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.

Panic disorder is a common condition that includes symptoms that may masquerade as a primary cardiovascular disorder. In addition, many patients with cardiovascular disease may also have panic disorder. To date, no definitive pathophysiological mechanism for panic disorder has been found; however, there are several hypotheses in the literature. Patients with syndrome X, coronary artery disease and/or palpitations, in addition to panic disorder all present to cardiologists. However, many patients go undiagnosed and ultimately place large costs on the health care system as a result. Panic disorder is a treatable condition, and cardiologists could easily identify patients with panic disorder and initiate appropriate therapy and/or referral.

Notions of territory and space have become more common in the writings of political scientists in recent years. Notwithstanding, there is a tendency not to cite the works of political geographers. Due to the power asymetry within the social sciences, political geographers have a greater need to publish within political science journals and to cite the works of political scientists than the reverse. Notwithstanding, much of the political science work on territory is quantitative and descriptive as contrasted with the conceptual advances which have been made within political geography. There is room for increased cross-disciplinary dialogue between the disciplines and a need to understand territory as a dynamic factor in its own right, rather than simply as a special compartment within which political dynamics take place.

Peter C. Wyer, MD Michael D. Brown, MD, MSc David H. Newman, MD Brian H. Rowe, MD, MSc From the Department of Medicine, Columbia University College of Physicians, New York, NY (Wyer); the Department of Epidemiology and Emergency Medicine, Michigan State University, Grand Rapids, MI (Brown); the Department of Medicine, St. Luke’s/Roosevelt Hospital System, New York, NY (Newman) and the Division of Emergency Medicine, Capital Health Authority, Department of Public Health Services, University of Alberta, Edmonton, Alberta, Canada (Rowe).

I recall the day a woman from the Office of Physician Misconduct explained to our faculty what it means to be cited by the state. Like police in the rearview mirror, her presence rattled me. When asked for an example, she was swift and certain, recounting a tale of ketamine administration in a head-injured patient. The physician involved lost his license. Reversals of conventionalmedical wisdom are common, a fact cemented byPrasad et al in a landmark 2013 article and memorialized by Sidney Burwell, who mused that half of what medical students are taught will, within 10 years, be revealed aswrong.The danger of ketamine in head injury, for instance, has been recently and elegantly deconstructed: there is none. Physicians agree almost universally on the veracity of Burwell’s dictum, though perhaps only in theory. In reality everyone wants change but nobody likes it. For physicians, whose authority is derived in large part from heirloom knowledge and experience, collectedwisdom is the foundation of our expertise. Reversals challenge the core of medical authority and personal accomplishment by suggesting expertise is not just impermanent but also often false. Medicine humbles. In this issue of Annals, we are humbled again by Claveau et al, who offer a study challenging the age-old teaching that acute afterload reduction in the setting of aortic stenosis is perilous. Although limited by observational design, the report is nonetheless more valid and reproducible than any relevant data set of which I am aware. Virtually all assertions I could find suggesting danger with nitroglycerin in the setting of aortic stenosis were either physiologic or unreferenced. I have routinely taught trainees to be wary of aortic stenosis in acute pulmonary edema. Despite being slightly esoteric (or perhaps because of it), the teaching has been a staple of my bedside arsenal. I recall the certainty and

Purpose: To investigate the validity of the 25% and 15% rules in manual exposure selection. Methods: The mAs required to produce a constant film density of 1.5 was determined over the X-ray tube potential range 50–150 kV for different thicknesses of water, under grid and no grid conditions. Results: The mAs change is an exponential function with depth and is dependent upon the attenuation coefficient. The 25% rule assumes a constant attenuation coefficient with a half value layer (HVL) equal to 3 cm. The results indicate that for non-grid work at low X-ray tube potentials and for grid work at higher tube potentials the 25% rule is applicable. The 15% rule implies an inverse power relationship between mAs and tube potential, the power term being 5. The results indicate that for both grid and no grid conditions the 15% rule is obeyed only over the tube potential range 50–100 kV and for thicknesses up to 15 cm. Discussion: The 25% and 15% rules have provided useful practical guidelines for exposure factor selection. It is shown that they are applicable to some but not all radiographic situations.

One-dimensional Vlasov equations are solved numerically for conditions appropriate to the ionospheric F-region during the initial stages of HF-radiation modification experiments at two altitudes: one at the critical altitude, the other approximately 1.5 km lower. Numerical simulations of wave growth and saturation with self-consistent evolution of particle distributions are run past the point at which a statistically steady state is reached. At the critical altitude the wave turbulence is dominated by coherent collapsing wave packets or ‘cavitons’ and at the lower altitude by a combination of coherent (strong) and incoherent (weak) turbulence. Our results are consistent with the predictions of Hanssen et al. [Journal of Geophysical Research, 97, 12,073 (1992)]. Semi-open boundary conditions, in which a small fraction of the hot electrons generated by interactions with the strong localized caviton fields are replaced by electrons from the cool background distribution, are employed to model a heated region of finite length that is large compared to the simulation domain. The resultant steady-state electron distributions are characterized by power-law tails of hot electrons superposed on an approximately Maxwellian bulk distribution. The Langmuir-wave dissipation spectra are found to be in good agreement with predictions based on linear Landau damping on the nonthermal electron tails.

Morning peaks in the circadian variation of sustained ventricular tachycardia (VT) may reflect the contribution of sympathetic activation to onset of VT. We hypothesized that adrenergic blockade would eliminate this morning peak. Fifty-four patients using a defibrillator had 1114 time-stamped episodes of VT requiring therapy with a device: 1012 episodes with and 102 episodes without antiadrenergic medications. Nine patients had episodes both with and without antiadrenergic medication and were examined separately. In patients taking antiadrenergic agents, data fitted to a harmonic regression model revealed a morning peak at 9:00 AM (R2= 0.542; p < 0.05), with a secondary peak at 4 PM. Those not receiving antiadrenergic therapy had a similar morning peak. Antiadrenergic agents as used in standard clinical practice do not prevent circadian variation in onset of VT. This variation may be mediated by systems other than adrenergic receptor-linked activation or may reflect inadequacy of adrenergic blockade in standard clinical dosing.

Objectives. We sought to determine the electrophysiologic mechanisms explaining the efficacy of combination therapy with dl-sotalol and a type Ia drug in the treatment of ventricular tachycardia (VT).Background. Combination antiarrhythmic drug therapy with low dose dl-sotalol plus a type Ia antiarrhythmic agent has been shown to prevent spontaneous and induced VT. The mechanisms underlying the efficacy of this drug combination have not been fully elucidated.Methods. We studied 32 patients with spontaneous sustained VT by using programmed electrical stimulation in the drug-free condition and after treatment with dl-sotalol (average dose [mean ± SE] 151 ± 8 mg/day) and a class Ia agent (quinidine, 1,337 ± 59 mg/day, or procainamide, 2,083 ± 327 mg/day). Sustained VT was induced in all patients at baseline study, and induction was reattempted during drug therapy. Monophasic action potential duration at 90% repolarization (APD90) and ventricular effective refractory period (ERP) were recorded with use of a contact electrode.Results. Ventricular ERP increased from 258 ± 4 ms at baseline to 310 ± 6 ms at a 600-ms drive cycle length (DCL600) with treatment (p < 0.001). APD90increased from 288 ± 6 ms by +10.1% at DCL600 and from 267 ± 7 ms by +13.3% at a 400-ms drive cycle length (DCL400) (p < 0.001). Paced QRS duration increased from 141 ± 3 to 158 ± 6 ms at DCL400 (p < 0.05).At baseline, the shortest achieved coupling interval between successive propagated extrastimuli decreased progressively with respect to the first extrastimulus, following double and triple extrastimuli, at both DCL600 (−14.0% and −20.0%, respectively) and at DCL400 (−16.4% and −22.4%, respectively). This “peeling back” of refractoriness was attenuated on therapy with sotalol plus a class Ia antiarrhythmic agent to −6.7% and −10.5% (DCL600, p < 0.05), and −8.1%, −9.5% (DCL400, p < 0.05), for double and triple extrastimuli, respectively. The absolute prolongation of functional refractory periods by the drug combination increased with successive extrastimuli, from 55 ± 6 ms for the V1V2interval to 75 ± 6 ms for V2V3and 67 ± 6 ms for V3V4at DCL600, and from 51 ± 5 ms for V1V2to 69 ± 6 ms for V2V3and 74 ± 7 ms for V3V4at DCL400 (p < 0.001).Conclusions. The combination of low dose sotalol and a class Ia agent greatly prolongs refractoriness. The magnitude of the effect increases at shorter coupling intervals.(J Am Coll Cardiol 1997;29:100–5)>

is: Metlay JP, Kapoor WN, Fine MJ. Does this patient have community-acquired pneumonia? Diagnosing pneumonia by history and physical examination. JAMA. 1997;278: 1440-1445. The Annals’ EBEM editors assisted in the preparation of the abstract of this rational clinical examination review, as well asof this rational clinical examination review, as well as selection of the Evidence-Based Medicine Teaching Points. OBJECTIVE To evaluate the validity of diagnosing pneumonia using various aspects of the history and physical examination. DATA SOURCES The authors searched English-language medical literature using MEDLINE from 1966 through October 1995. They cite a specific MEDLINE search strategy that is not detailed in the article but is available on request from the authors. STUDY SELECTION The authors used a 3-step approach to select studies. After the initial retrieval (MEDLINE search and potentially eligible articles recognized through review of the article reference lists), the authors excluded articles that focused on hospital-acquired pneumonia, pediatric pneumonia, or AIDS-related pneumonia. They then excluded nonoriginal data and studies of patients younger than 16 years, with known immunosuppression, or with nosocomial infections. Last, the remaining eligible articles were evaluated by an author using a methodologic filter assigning a level of evidence ranging from I to V. Only articles qualified as level I (primary, prospective study of the accuracy or precision of the clinical examination in community-acquired Volume 46, no. 5 : November 2005 pneumonia enrollingO50 consecutive subjects) were used in the main analyses. DATA EXTRACTION AND ANALYSIS The authors calculated likelihood ratios (LRs) for the presence or absence of distinct clinical findings and included in the results only findings associated with pneumonia in at least 1 study, using a 2-tailed c or Fischer exact test with P\.05. MAIN RESULTS There were no studies that examined interobserver variability for the precision of the symptoms and signs of communityacquired pneumonia. Analogous work cited by the authors revealed considerable interobserver variation in the recording of symptoms. One study examined interobserver agreement for physical examination findings in patients with a variety of respiratory conditions. The 3 most reliable findings, dullness to percussion, wheezes, and crackles, had agreement values ranging from 72% to 79%, with k values from 0.41 to 0.52. The accuracy of the clinical history in the diagnosis of community-acquired pneumonia is addressed by 4 studies. The symptoms (Table 1) with the highest positive LR (LR(C)) include a history of fever (LR(C)=2.1), cough (LR(C)=1.8), chills (LR(C)=1.7), and night sweats (LR(C)=1.7), whereas rhinorrhea and sore throat had negative LRs of (LR( )=2.4 and 1.5), respectively. One study demonstrated a reduction in the odds of pneumonia if the patient had a history of asthma (LR( )=3.8 [see teaching point]). The pooled and individual results for accuracy of the physical examination are shown in Table 2. The prediction rule described by Diehr et al yields an LR(C) 1.5 to 14.0 and an LR( ) 0.22 to 0.82 for the diagnosis of pneumonia. Singal et al demonstrate probabilities of pneumonia ranging from 4% to 49%, depending on the number of findings present. Heckerling et al showed a maximum probability of pneumonia of 50% if all 5 of their clinical predictors were fulfilled. CONCLUSIONS There is significant interobserver variability in elucidating the presence or absence of individual findings on chest examination of patients with respiratory illness. The use of any Annals of Emergency Medicine 465 EBEM/Rational Clinical Examination Abstract individual symptom or sign to guide the diagnosis of community-acquired pneumonia is lacking suitable test characteristics. There is not enough evidence to rule in or out the diagnosis of community-acquired pneumonia based on any individual symptom or sign of the patient. Decision rules exist for community-acquired pneumonia that take into account the signs and symptoms of the patient and render a lesser or greater likelihood of pneumonia. However, there is again no combination of symptoms or signs, whether present or absent, that reliably confirms or rules out the diagnosis of pneumonia. Rational Clinical Examination Author Contact Michael J. Fine, MD, MSc Center for Health Equity Research and Promotion Veterans Affairs Pittsburgh Healthcare System Pittsburgh, PA E-mail finemj@msx.upmc.edu COMMENTARY: CLINICAL IMPLICATION Pneumonia is the leading infectious cause of death and seventh leading cause of all deaths in the United States. Mortality rates of hospitalized and outpatients with pneumonia exceed 5%, whereas patients requiring admission to the ICU have rates as high as 37%. With a prevalence of approximately 4 million cases per year, emergency physicians diagnose and treat community-acquired pneumonia regularly. As the authors of the rational clinical examination explain, the importance of accurately diagnosing pneumonia is paramount in choosing the appropriate treatment regimens, reducing health care costs, and, more important, decreasing the morbidity and mortality from pneumonia in our population. In their rational clinical examination series, Metlay et al present results of numerous studies to evaluate the utility of the clinical examination in diagnosing pneumonia, including elements from the patient’s medical history, signs from the physical examination, and prediction decision rules.The authors concluded that there were no single items in the clinical examination whose presence or absence would reliably rule in or rule out the diagnosis of pneumonia without the use of radiography. The decision to proceed to radiography in a patient suspected of having pneumonia should be driven by the probability of the disease, the sensitivity and specificity of the Table 1. LRs for pneumonia based on individual medical history findings. Symptoms Positive LR (LRC) Negative LR (LR ) Fever 2.1 0.7 Cough 1.8 0.31 Chills 1.7 0.85 Night sweats 1.7 0.83 Asthma 0.1 3.8 Rhinorrhea 0.78 2.4 Sore throat 0.76 1.5 466 Annals of Emergency Medicine diagnostic test, the costs and dangers of the test, and the threshold to treat. The inaccuracy of the clinical examination suggests that emergency physicians should maintain a low threshold to obtain chest radiography in patients with possible pneumonia. Although chest radiography is not 100% sensitive and interpretation may exhibit variable interobserver agreement, it is an inexpensive and safe test. Moreover, it may be the closest modality physicians have to a convenient and accessible reference standard in the current diagnosis of pneumonia. TAKE HOME MESSAGE Although a few select history and physical examination factors appear to be contributory in a patient suspected of having pneumonia, no single finding or combination of findings is able to rule in or rule out the diagnosis. Therefore, physicians should maintain a low threshold for chest radiography to aid in the diagnosis of pneumonia when clinical suspicion indicates it. EBEM Commentator Contact Adam J. Rosh, MD Department of Emergency Medicine New York University/Bellevue Hospital New York, NY E-mail rosha01@med.nyu.edu EBEM TEACHING POINT Inverted LRs. The LR of a positive test represents the ratio of the proportion of true positives to the proportion of false positives. By convention, we think of these ‘‘positive LRs’’ as being greater than 1.0, and we think of a potentially useful diagnostic test as having a positive LR of greater than or equal to 10. In other words, it is roughly 10 times more likely that a positive test represents a true (correct) result than a false (incorrect) result. It is also possible, however, that the proportion of false positives will be greater than the corresponding proportion of true positives. Although this will not yield the result we expect to see because the number will be less than 1.0, it offers valuable information. In this rational clinical examination, for instance, in the setting of possible pneumonia a history of asthma is associated with a positive LR of 0.1, which informs clinicians that patients with a history of asthma are one tenth as likely to demonstrate Table 2. LRs for pneumonia based on physical examination findings. Signs Positive LR (LRC) Negative LR (LR ) Any vital sign abnormality 1.2–4.4 0.5–0.8 Any chest finding 1.3 0.57 Crackles 1.6–2.7 0.9 Egophony 8.6 0.96 Dullness to percussion 4.3 0.93 Decreased breath sounds 2.6 0.64 Asymmetric respirations Infinity 0.95 Volume 46, no. 5 : November 2005 EBEM/Rational Clinical Examination Abstract pneumonia on a chest radiograph (a true positive) than not (a false positive). Stated in its inverse, patients with asthma are 10 times more likely to have a normal chest radiograph result than one that demonstrates pneumonia. Although this is not the information expected from a positive LR, it is clearly valuable information. Therefore, understanding the underlying meaning of the LR allows us to infer important information from the statistic, regardless of whether it is above or below 1.0. REFERENCES 1. Fletcher CM. The problem of observer variation in medical diagnosis with special reference to chest diseases. Method Inform Med. 1964;3:98-103. 2. Cochrane AL, Chapman PJ, Oldham PD. Observers’ errors in taking medical histories. Lancet. 1951;1:1007-1008. 3. Spiteri MA, Cook DG, Clarke SW. Reliability of eliciting physical signs in examination of the chest. Lancet. 1988;1:873-875. 4. Diehr P, Wood RW, Bushyhead J, et al. Prediction of pneumonia in outpatients with acute cough: a statistical approach. J Chronic Dis. 1984;37:215-225. 5. Singal BM, Hedges JR, Radack KL. Decision rules and clinical prediction of pneumonia: evaluation of low-yield criteria. Ann Emerg Med. 1989;18:13-20.