Importance of decision support implementation in emergency department vancomycin dosing

INTRODUCTION: The emergency department (ED) plays a critical role in the management of life-threatening infection. Prior data suggest that ED vancomycin dosing is frequently inappropriate. The objective is to assess the impact of an electronic medical record (EMR) intervention designed to improve vancomycin dosing accuracy, on vancomycin dosing and clinical outcomes in critically ill ED patients. METHODS: Retrospective before-after cohort study of all patients (n=278) treated with vancomycin in a 60,000-visit Midwestern academic ED (March 2008 and April 2011) and admitted to an intensive care unit. The primary outcome was the proportion of vancomycin doses defined as “appropriate” based on recorded actual body weight. We also evaluated secondary outcomes of mortality and length of stay. RESULTS: The EMR dose calculation tool was associated with an increase in mean vancomycin dose ([14.1±5.0] vs. [16.5±5.7] mg/kg, p<0.001) and a 10.3% absolute improvement in first-dose appropriateness (34.3% vs. 24.0%, p=0.07). After controlling for age, gender, methicillin-resistant staphylococcus aureus infection, and Acute Physiology and Chronic Health Evaluation II score, 28-day in-hospital mortality (odds ratio OR 1.72; 95% CI [0.76–3.88], p=0.12) was not affected. CONCLUSION: A computerized decision-support tool is associated with an increase in mean vancomycin dose in critically ill ED patients, but not with a statistically significant increase in therapeutic vancomycin doses. The impact of decision-support tools should be further explored to optimize compliance with accepted antibiotic guidelines and to potentially affect clinical outcome

Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated US Healthcare Personnel: A Prospective Cohort Study

OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of european ancestry

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P &lt; 1 7 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 7 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 7 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P 64 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Importance of Decision Support Implementation in Emergency Department Vancomycin Dosing

Introduction: The emergency department (ED) plays a critical role in the management of life-threatening infection. Prior data suggest that ED vancomycin dosing is frequently inappropriate.The objective is to assess the impact of an electronic medical record (EMR) intervention designed to improve vancomycin dosing accuracy, on vancomycin dosing and clinical outcomes in critically ill ED patients.Methods: Retrospective before-after cohort study of all patients (n=278) treated with vancomycin in a 60,000-visit Midwestern academic ED (March 2008 and April 2011) and admitted to an intensive care unit. The primary outcome was the proportion of vancomycin doses defined as “appropriate” based on recorded actual body weight. We also evaluated secondary outcomes of mortality and length of stay.Results: The EMR dose calculation tool was associated with an increase in mean vancomycin dose ([14.1±5.0] vs. [16.5±5.7] mg/kg, p&lt;0.001) and a 10.3% absolute improvement in first-dose appropriateness (34.3% vs. 24.0%, p=0.07). After controlling for age, gender, methicillin-resistant staphylococcus aureus (MRSA) infection, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, 28-day in-hospital mortality (odds ratio OR 1.72; 95% CI [0.76-3.88], p=0.12) was not affected.Conclusion: A computerized decision-support tool is associated with an increase in mean vancomycin dose in critically ill ED patients, but not with a statistically significant increase in therapeutic vancomycin doses. The impact of decision-support tools should be further explored to optimize compliance with accepted antibiotic guidelines and to potentially affect clinical outcome

Antimicrobial Therapy for Pneumonia in the Emergency Department: The Impact of Clinical Pharmacists on Appropriateness

Introduction: Pneumonia impacts over four million people annually and is the leading cause of infectious disease-related hospitalization and mortality in the United States. Appropriate empiric antimicrobial therapy decreases hospital length of stay and improves mortality. The objective of our study was to test the hypothesis that the presence of an emergency medicine (EM) clinical pharmacist improves the timing and appropriateness of empiric antimicrobial therapy for community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). Methods: This was a retrospective observational cohort study of all emergency department (ED) patients presenting to a Midwest 60,000-visit academic ED from July 1, 2008, to March 1, 2016, who presented to the ED with pneumonia and received antimicrobial therapy. The treatment group consisted of patients who presented during the hours an EM pharmacist was present in the ED (Monday-Friday, 0900–1800). The control group included patients presenting during the hours when an EM clinical pharmacist was not physically present in the ED (Monday–Friday, 1800–0900, Saturday/Sunday 0000–2400 day). We defined appropriate empiric antimicrobial therapy using the Infectious Diseases Society of America consensus guidelines on the management of CAP, and management of HCAP. Results: A total of 406 patients were included in the final analysis (103 treatment patients and 303 control patients). During the hours the EM pharmacist was present, patients were significantly more likely to receive appropriate empiric antimicrobial therapy (58.3% vs. 38.3%; p<0.001). Regardless of pneumonia type, patients seen while an EM pharmacist was present were significantly more likely to receive appropriate antimicrobial therapy (CAP, 77.7% vs. 52.9% p=0.008, HCAP, 47.7% vs. 28.8%, p=0.005). There were no significant differences in clinical outcomes. Conclusion: The presence of an EM clinical pharmacist significantly increases the likelihood of appropriate empiric antimicrobial therapy for patients presenting to the ED with pneumonia

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer