Focused use of drug screening in overdose patients increases impact on management.

UNLABELLED: Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. STUDY OBJECTIVES: Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. METHODS: Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. RESULTS: A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. CONCLUSIONS: In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED

Patients' understanding of blood tests and attitudes to HIV screening in the emergency department of a Swiss teaching hospital: a cross-sectional observational study.

BACKGROUND: In Switzerland, patients may undergo "blood tests" without being informed what these are screening for. Inadequate doctor-patient communication may result in patient misunderstanding. We examined what patients in the emergency department (ED) believed they had been screened for and explored their attitudes to routine (non-targeted) human immunodeficiency virus (HIV) screening. METHODS: Between 1st October 2012 and 28th February 2013, a questionnaire-based survey was conducted among patients aged 16-70 years old presenting to the ED of Lausanne University Hospital. Patients were asked: (1) if they believed they had been screened for HIV; (2) if they agreed in principle to routine HIV screening and (3) if they agreed to be HIV tested during their current ED visit. RESULTS: Of 466 eligible patients, 411 (88%) agreed to participate. Mean age was 46 ± 16 years; 192 patients (47%) were women; 366 (89%) were Swiss or European; 113 (27%) believed they had been screened for HIV, the proportion increasing with age (p ≤0.01), 297 (72%) agreed in principle with routine HIV testing in the ED, and 138 patients (34%) agreed to be HIV tested during their current ED visit. CONCLUSION: In this ED population, 27% believed incorrectly they had been screened for HIV. Over 70% agreed in principle with routine HIV testing and 34% agreed to be tested during their current visit. These results demonstrate willingness among patients concerning routine HIV testing in the ED and highlight a need for improved doctor-patient communication about what a blood test specifically screens for

Red cell distribution width and mortality in acute heart failure patients with preserved and reduced ejection fraction.

Elevated red blood cell distribution width (RDW) is a valid predictor of outcome in acute heart failure (AHF). It is unknown whether elevated RDW remains predictive in AHF patients with either preserved left ventricular ejection fraction (LVEF) ≥50% or reduced LVEF (<50%). Prospective local registry including 402 consecutive hospitalized AHF patients without acute coronary syndrome or need of intensive care. The primary outcome was all-cause mortality (ACM) at 1 year after admission. Demographic and clinical data derive from admission, echocardiographic examinations (n = 269; 67%) from hospitalization. The Cox proportional hazard model including all patients (P < 0.001) was adjusted for age, gender, and RDW quartiles. Independent predictors of 1-year ACM were cardiogenic shock (HR 2.86; CI: 1.3-6.4), male sex (HR 1.9; CI: 1.2-2.9), high RDW quartile (HR 1.66; CI: 1.02-2.8), chronic HF (HR 1.61; CI: 1.05-2.5), valvular heart disease (HR 1.61; CI: 1.09-2.4), increased diastolic blood pressure (HR 1.02 per mmHg; CI: 1.01-1.03), increasing age (HR 1.04 by year; CI: 1.02-1.07), platelet count (HR 1.002 per G/l; CI: 1.0-1.004), systolic blood pressure (HR 0.99 per mmHg; CI: 0.98-0.99), and weight (HR 0.98 per kg; CI: 0.97-0.99). A total of 114 patients (28.4%) died within the first year; ACM of all patients increased with quartiles of rising RDW (χ(2) 18; P < 0.001). ACM was not different between RDW quartiles of patients with reduced LVEF (n = 153; χ(2) 6.6; P = 0.084). In AHF with LVEF ≥50% the probability of ACM increased with rising RDW (n = 116; χ(2) 9.9; P = 0.0195). High RDW is associated with increased ACM in AHF patients with preserved but not with reduced LVEF in this study population

Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias

Background Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. Patients and methods We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeon's affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. Results Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). Conclusions This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortalit

Predictors and Implications of Early Clinical Stability in Patients Hospitalized for Moderately Severe Community-Acquired Pneumonia.

Assessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP). To describe the predictors and the outcomes of early clinical stability. We did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested. Younger age (OR 0.98, 95% CI 0.96-0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94-0.98), lower respiratory rate (OR 0.94, 95% CI 0.90-0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40-0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69-0.98) and signs or symptoms (OR 0.78, 95% CI 0.68-0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p<0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0-10.0 vs. 10.0 days, IQR 7.0-15.0, p<0.001). Patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny

Salmeterol for the prevention of high-altitude pulmonary edema.

BACKGROUND: Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models. METHODS: In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition. RESULTS: Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P<0.001). CONCLUSIONS: Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

A significant challenge in chemistry is to rationally reproduce the functional potency of a protein in a small molecule, which is cheaper to manufacture, non-immunogenic, and also both stable and bioavailable. Synthetic peptides corresponding to small bioactive protein surfaces do not form stable structures in water and do not exhibit the functional potencies of proteins. Here we describe a novel approach to growing small molecules with protein-like potencies from a functionally important amino acid of a protein. A 77-residue human inflammatory protein (complement C3a) important in innate immunity is rationally transformed to equipotent small molecules, using peptide surrogates that incorporate a turn-inducing heterocycle with correctly positioned hydrogen-bond-accepting atoms. Small molecule agonists (molecular weigh

Clinician miscalibration of survival estimate in hypothermic cardiac arrest: HOPE-estimated survival probabilities in extreme cases.

Patients with hypothermic cardiac arrest may survive with an excellent outcome after extracorporeal life support rewarming (ECLSR). The HOPE (Hypothermia Outcome Prediction after ECLS) score is recommended to guide the in-hospital decision on whether or not to initiate ECLSR in patients in cardiac arrest following accidental hypothermia. We aimed to assess the HOPE-estimated survival probabilities for a set of survivors of hypothermic cardiac arrest who had extreme values for the variables included in the HOPE score. Survivors were identified and selected through a systematic literature review including case reports. We calculated the HOPE score for each patient who presented extraordinary clinical parameters. We identified 12 such survivors. The HOPE-estimated survival probability was ≥10% for all (n = 11) patients for whom we were able to calculate the HOPE score. Our study confirms the robustness of the HOPE score for outliers and thus further confirms its external validity. These cases also confirm that hypothermic cardiac arrest is a fundamentally different entity than normothermic cardiac arrest. Using HOPE for extreme cases may support the proper calibration of a clinician's prognosis and therapeutic decision based on the survival chances of patients with accidental hypothermic cardiac arrest