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

Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP)

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment

Time intervals and routes to diagnosis for lung cancer in 10 jurisdictions: cross-sectional study findings from the International Cancer Benchmarking Partnership (ICBP)

OBJECTIVE: Differences in time intervals to diagnosis and treatment between jurisdictions may contribute to previously reported differences in stage at diagnosis and survival. The International Cancer Benchmarking Partnership Module 4 reports the first international comparison of routes to diagnosis and time intervals from symptom onset until treatment start for patients with lung cancer. DESIGN: Newly diagnosed patients with lung cancer, their primary care physicians (PCPs) and cancer treatment specialists (CTSs) were surveyed in Victoria (Australia), Manitoba and Ontario (Canada), Northern Ireland, England, Scotland and Wales (UK), Denmark, Norway and Sweden. Using Wales as the reference jurisdiction, the 50th, 75th and 90th percentiles for intervals were compared using quantile regression adjusted for age, gender and comorbidity. PARTICIPANTS: Consecutive newly diagnosed patients with lung cancer, aged ≥40 years, diagnosed between October 2012 and March 2015 were identified through cancer registries. Of 10 203 eligible symptomatic patients contacted, 2631 (27.5%) responded and 2143 (21.0%) were included in the analysis. Data were also available from 1211 (56.6%) of their PCPs and 643 (37.0%) of their CTS. PRIMARY AND SECONDARY OUTCOME MEASURES: Interval lengths (days; primary), routes to diagnosis and symptoms (secondary). RESULTS: With the exception of Denmark (-49 days), in all other jurisdictions, the median adjusted total interval from symptom onset to treatment, for respondents diagnosed in 2012-2015, was similar to that of Wales (116 days). Denmark had shorter median adjusted primary care interval (-11 days) than Wales (20 days); Sweden had shorter (-20) and Manitoba longer (+40) median adjusted diagnostic intervals compared with Wales (45 days). Denmark (-13), Manitoba (-11), England (-9) and Northern Ireland (-4) had shorter median adjusted treatment intervals than Wales (43 days). The differences were greater for the 10% of patients who waited the longest. Based on overall trends, jurisdictions could be grouped into those with trends of reduced, longer and similar intervals to Wales. The proportion of patients diagnosed following presentation to the PCP ranged from 35% to 75%. CONCLUSION: There are differences between jurisdictions in interval to treatment, which are magnified in patients with lung cancer who wait the longest. The data could help jurisdictions develop more focused lung cancer policy and targeted clinical initiatives. Future analysis will explore if these differences in intervals impact on stage or survival

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

Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p \u3c 5 × 10 CONCLUSIONS: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. PATIENT SUMMARY: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer

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

Two-Item Fall Screening Tool Identifies Older Adults at Increased Risk of Falling after Emergency Department Visit

Introduction: Few emergency department (ED)-specific fall-risk screening tools exist. The goals of this study were to externally validate Tiedemann et al’s two-item, ED-specific fall screening tool and test handgrip strength to determine their ability to predict future falls. We hypothesized that both the two-item fall screening and handgrip strength would identify older adults at increased risk of falling.Methods: A convenience sample of patients ages 65 and older presenting to a single-center academic ED were enrolled. Patients were asked screening questions and had their handgrip strength measured during their ED visit. Patients were given one point if they answered “yes” to “Are you taking six or more medications?” and two points for answering “yes” to “Have you had two or more falls in the past year?” to give a cumulative score from 0 to 3. Participants had monthly follow- ups, via postcard questionnaires, for six months after their ED visit. We performed sensitivity and specificity analyses, and used likelihood ratios and frequencies to assess the relationship between risk factors and falls, fall-related injury, and death.Results: In this study, 247 participants were enrolled with 143 participants completing follow-up (58%). During the six-month follow-up period, 34% of participants had at least one fall and 30 patients died (12.1%). Fall rates for individual Tiedemann scores were 14.3%, 33.3%, 60.0% and 72.2% for scores of 0,1, 2 and 3, respectively. Low handgrip strength was associated with a higher proportion of falls (46.3%), but had poor sensitivity (52.1%).Conclusion: Handgrip strength was not sensitive in screening older adults for future falls. The Tiedemann rule differentiated older adults who were at high risk for future falls from low risk individuals, and can be considered by EDs wanting to screen older adults for future fall risk