Assessing the Effect of a Medical Toxicologist in the Care of Rattlesnake‐envenomated Patients

Background

Rattlesnake envenomation is an important problem in the United States, and the management of these envenomations can be complex. Despite these complexities, however, the majority of such cases are managed without the involvement of a medical toxicologist. The primary objective of this study was to evaluate the impact of a medical toxicology service (MTS) on the length of stay (LOS) of such patients.

Methods

The authors conducted a retrospective study at six centers in California. Patients were included if they were admitted in the 2 years before the establishment of a MTS (pre‐MTS) or in the 2 years after the creation of a MTS (post‐MTS).

Results

A total of 300 subjects were included (169 pre‐MTS, 131 post MTS). Baseline characteristics between the pre‐MTS and post‐MTS groups were very similar. The creation of a MTS was associated with a significant reduction in the mean (95% confidence interval) LOS (69.5 [59.1–79.9] hours vs. 48.1 [41.4–54.8] hours). This reduced LOS was not associated with any statistically significant change in readmission rates.

Conclusion

Rattlesnake bite patients treated by a medical toxicologist have a significantly reduced LOS compared to those without direct involvement of a medical toxicologist.

     

Accuracy of Computed Tomography in Diagnosis of Intra‐abdominal Injuries in Stable Patients With Anterior Abdominal Stab Wounds: A Systematic Review and Meta‐analysis

Background

Workup for patients presenting to the emergency department (ED) following an anterior abdominal stab wound (AASW) has been debated since the 1960s. Experts agree that patients with peritonitis, evisceration, or hemodynamic instability should undergo immediate laparotomy (LAP); however, workup of stable, asymptomatic or nonperitoneal patients is not clearly defined.

Objectives

The objective was to evaluate the accuracy of computed tomography of abdomen and pelvis (CTAP) for diagnosis of intraabdominal injuries requiring therapeutic laparotomy (THER‐LAP) in ED patients with AASW. Is a negative CT scan without a period of observation sufficient to safely discharge a hemodynamically stable, asymptomatic AASW patient?

Methods

We searched PubMed, Embase, and Scopus from their inception until May 2017 for studies on ED patients with AASW. We defined the reference standard test as LAP for patients who were managed surgically and inpatient observation in those who were managed nonoperatively. In those who underwent LAP, THER‐LAP was considered as disease positive. We used the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS‐2) to evaluate the risk of bias and assess the applicability of the included studies. We attempted to compute the pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR–) using a random‐effects model with MetaDiSc software and calculate testing and treatment thresholds for CT scan applying the Pauker and Kassirer model.

Results

Seven studies were included encompassing 575 patients. The weighted prevalence of THER‐LAP was 34.3% (95% confidence interval [CI] = 30.5%–38.2%). Studies had variable quality and the inclusion criteria were not uniform. The operating characteristics of CT scan were as follows: sensitivity = 50% to 100%, specificity = 39% to 97%, LR+ = 1.0 to 15.7, and LR– = 0.07 to 1.0. The high heterogeneity (I² > 75%) of the operating characteristics of CT scan prevented pooling of the data and therefore the testing and treatment thresholds could not be estimated.

Discussion

The articles revealed a high prevalence (8.7%, 95% CI = 6.1%–12.2%) of injuries requiring THER‐LAP in patients with a negative CT scan and almost half (47%, 95% CI = 30%–64%) of those injuries involved the small bowel.

Conclusions

In stable AASW patients, a negative CT scan alone without an observation period is inadequate to exclude significant intraabdominal injuries.

     

Systematic Review and Meta‐analysis of Outcomes of Patients With Subsegmental Pulmonary Embolism With and Without Anticoagulation Treatment

Background

This systematic review addresses the controversy over the decision to anticoagulate patients with subsegmental pulmonary embolism (SSPE).

Methods

We searched Ovid MEDLINE, PubMed, Embase, the Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, Google Scholar, and bibliographies in March 2017. Two authors reviewed and retained papers with symptomatic patients who underwent computerized tomographic pulmonary angiography and had sufficient information to determine SSPE; decision to treat (or not) with systemic anticoagulation; and outcomes of bleeding, venous thromboembolism (VTE) recurrence, and death. Papers were assessed for selection and publication bias and heterogeneity, with Eggers and the inconsistency indexes (I²).

Results

From 1,512 papers screened, we included 14 studies comprising 15,563 patients for full‐length review and analysis. Pooled data demonstrated I² = 99% with an Eggers p < 0.001, suggesting significant publication bias. The pooled prevalence of SSPE was 4.6% (95% confidence interval [CI] = 1.8%–8.5%). The frequency of bleeding in SSPE patients treated with anticoagulation (n = 589) was 8.1% (95% CI = 2.8%–15.8%), with no available bleeding data in untreated patients (n = 126). The frequency of VTE recurrence within 90 days was 5.3% (95% CI = 1.6%–10.9%) for treated versus 3.9% (95% CI = 4.8%–13.4%) for untreated, while the frequency of death was 2.1% (95% CI = 3.4%–5.2%) for treated versus 3.0% (95% CI = 2.8%–8.6%) for untreated.

Conclusion

This systematic review highlights the lack of any clinical trial to make a clear inference about harm or benefit of anticoagulation for SSPE. Comparison of pooled data from uncontrolled outcome studies shows no increase in VTE recurrence or death rates for patients who were not anticoagulated. These data suggest clinical equipoise for decision to anticoagulate or not anticoagulate patients with SSPE. However, this inference is limited by small numbers, imprecision, and the lack of a controlled clinical trial.

     

Homelessness and Emergency Medicine: A Review of the Literature

Objectives

We aimed to synthesize the available evidence on the demographics, prevalence, clinical characteristics, and evidence‐based management of homeless persons in the emergency department (ED). Where appropriate, we highlight knowledge gaps and suggest directions for future research.

Methods

We conducted a systematic literature search following databases: PubMed, Ovid, and Google Scholar for articles published between January 1, 1990, and December 31, 2016. We supplemented this search by cross‐referencing bibliographies of the retrieved publications. Peer‐reviewed studies written in English and conducted in the United States that examined homelessness within the ED setting were included. We used a qualitative approach to synthesize the existing literature.

Results

Twenty‐eight studies were identified that met the inclusion criteria. Based on our study objectives and the available literature, we grouped articles examining homeless populations in the ED into four broad categories: 1) prevalence and sociodemographic characteristics of homeless ED visits, 2) ED utilization by homeless adults, 3) clinical characteristics of homeless ED visits, and 4) medical education and evidence‐based management of homeless ED patients.

Conclusion

Homelessness may be underrecognized in the ED setting. Homeless ED patients have distinct care needs and patterns of ED utilization that are unmet by the current disease‐oriented and episodic models of emergency medicine. More research is needed to determine the prevalence and characteristics of homelessness in the ED and to develop evidence‐based treatment strategies in caring for this vulnerable population.

     

Genes associated with venous thromboembolism in colorectal cancer patients

Essentials

• The underlying pathophysiological mechanisms behind cancer‐associated thrombosis are unknown.
• We compared expression profiles in tumor cells from patients with and without thrombosis.
• Tumors from patients with thrombosis showed significant differential gene expression profiles.
• Patients with thrombosis had a proinflammatory status and increased fibrin levels in the tumor.

Summary

Background

Venous thromboembolism (VTE) is a frequent complication in patients with cancer, and is associated with significant morbidity and mortality. However, the mechanisms behind cancer‐associated thrombosis are still incompletely understood.

Objectives

To identify novel genes that are associated with VTE in patients with colorectal cancer (CRC).

Methods

Twelve CRC patients with VTE were age‐matched and sex‐matched to 12 CRC patients without VTE. Tumor cells were isolated from surgical samples with laser capture microdissection approaches, and mRNA profiles were measured with next‐generation RNA sequencing.

Results

This approach led to the identification of new genes and pathways that might contribute to VTE in CRC patients. Application of ingenuity pathway analysis indicated significant links with inflammation, the methionine degradation pathway, and increased platelet function, which are all key processes in thrombus formation. Tumor samples of patients with VTE had a proinflammatory status and contained higher levels of fibrin and fibrin degradation products than samples of those without VTE.

Conclusion

This case–control study provides a proof‐of‐principle that tumor gene expression can discriminate between cancer patients with low and high risks of VTE. These findings may help to further unravel the pathogenesis of cancer‐related VTE. The identified genes could potentially be used as candidate biomarkers to select high‐risk CRC patients for thromboprophylaxis.

     

Venous thromboembolism in patients with liver diseases

Essentials

• Emerging evidence shows that patients with liver disease are not protected from thrombotic events.
• We assessed the risk of venous thromboembolism (VTE) in patients with liver disease.
• The presence of VTE resulted in an increase in mortality for patients with liver disease.
• Hospitalized patients with moderate‐severe liver disease had low risk of VTE during admission.

Summary

Background and Aims

Patients with liver disease were traditionally believed to be protected against development of blood clots, but some studies have shown a potential increased risk of venous thrombotic complications. We assessed the risk of venous thromboembolism (VTE) in patients with liver disease.

Methods

Data in discharge reports of patients with liver disease and control patients without liver disease were analyzed from the national inpatient sample. Incidence of VTE was compared in patients with mild, moderate‐severe or no liver disease, and the impact on in‐hospital mortality and length of stay was calculated.

Results

The overall incidence of VTE for patients with no liver disease, mild liver disease and moderate‐severe liver disease was 2.7, 2.4 and 0.9 per 100 patient discharges, respectively. In the presence of VTE, in‐hospital mortality was 10.8%, 5.8%, and 21.7% for the no liver disease, mild disease and moderate‐severe liver disease, respectively. The presence of VTE resulted in an increase in mortality for patients with no liver disease (OR, 1.16; 95% CI, 1.14–1.18) and moderate‐severe liver disease (OR, 1.63; CI 95%, 1.42–1.88).

Conclusions

Patients with moderate‐severe liver disease have a lower risk of VTE than those without liver disease. Development of thrombosis during admission increased the risk of in‐hospital mortality.

     

Venous thromboembolism in cancer patients receiving neoadjuvant chemotherapy: a systematic review and meta‐analysis

Essentials

• Cancer patients are at risk for venous thromboembolism (VTE).
• The risk of VTE in less advanced stage cancer on neoadjuvant chemotherapy is unclear.
• In over 7800 patients, we found a 7% pooled incidence of VTE during neoadjuvant therapy.
• Highest VTE rates were observed in patients with bladder and esophageal cancer.

Summary

Background

Venous thromboembolism (VTE) is a frequent complication in cancer patients receiving adjuvant treatment. The risk of VTE during neoadjuvant chemo‐radiotherapy remains unclear.

Objectives

This systematic review evaluated the incidence of VTE in patients with cancer receiving neoadjuvant treatment.

Methods

MEDLINE and EMBASE databases were searched from inception to October 2017. Search results were supplemented with screening of conference proceedings of the American Society of Clinical Oncology (2009–2016) and the International Society of Thrombosis and Haemostasis (2003–2016). Two review authors independently screened titles and abstracts, and extracted data onto standardized forms.

Results

Twenty‐eight cohort studies (7827 cancer patients, range 11 to 1398) were included. Twenty‐five had a retrospective design. Eighteen cohorts included patients with gastrointestinal cancer, representing over two‐thirds of the whole study population (n = 6002, 78%). In total, 508 of 7768 patients were diagnosed with at least one VTE during neoadjuvant treatment, for a pooled VTE incidence of 7% (95% CI, 5% to 10%) in the absence of substantial between‐study heterogeneity. Heterogeneity was not explained by site of cancer or study design characteristics. VTE presented as pulmonary embolism in 22% to 96% of cases (16 cohorts), and it was symptomatic in 22% to 100% of patients (11 cohorts). The highest VTE rates were observed in patients with bladder (10.6%) or esophageal (8.4%) cancer.

Conclusions

This review found a relatively high incidence of VTE in cancer patients receiving neoadjuvant therapy in the presence of some between‐study variation, which deserves further evaluation in prospective studies.

     

Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study

Essentials

• Chronic kidney disease (CKD) is associated with procoagulant and inflammatory biomarkers.
• We studied the association of CKD and venous thromboembolism (VTE) in a case‐cohort study.
• Factor VIII, D‐dimer and C‐reactive protein appeared to explain the association of CKD and VTE.
• Statin use was protective against VTE in those with and without CKD.

Summary

Background

Chronic kidney disease (CKD) is associated with venous thromboembolism (VTE) risk via unknown mechanisms. Whether factors associated with reduced VTE risk in the general population might also be associated with reduced VTE risk in CKD patients is unknown.

Objectives

To determine whether thrombosis biomarkers attenuate VTE risk, and whether factors associated with reduced VTE risk are similarly effective in CKD patients.

Methods

Baseline biomarkers were measured in a cohort (294 VTE cases; 939 non‐cases) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationwide prospective cohort study of 30 239 persons aged ≥45 years with 4.3 years of follow‐up. The hazard ratio (HR) of VTE per 10 mL min^?1 1.73 m^?2 decrease in estimated glomerular filtration rate (eGFR), and the percentage attenuation of this HR by each biomarker, were calculated. Associations of protective factors (physical activity, lower body mass index [BMI], and aspirin, warfarin and statin use) with VTE were estimated in those with and without CKD.

Results

The HR for VTE with lower eGFR was 1.13 (95% confidence interval [CI] 1.02–1.25), and VTE risk was attenuated by 23% (95% CI 5–100) by D‐dimer, by 100% (95% CI 50–100) by factor VIII, and by 15% (95% CI 2–84) by C‐reactive protein. Normal BMI was associated with lower VTE risk in those without CKD (HR 0.47, 95% CI 0.32–0.70), but not in those with CKD (HR 1.07, 95% CI 0.51–2.22). Statin use, physical activity and warfarin use were associated with lower VTE risk in both groups.

Conclusions

Procoagulant and inflammatory biomarkers mediated the association of eGFR with VTE. Higher physical activity, statin use and warfarin use mitigated VTE risk in those with CKD and those without CKD, but normal BMI did not mitigate VTE risk in CKD patients.

     

Risk stratification for the development of venous thromboembolism in hospitalized patients with cancer

Essentials

• The Khorana score is validated for risk of venous thromboembolism (VTE) in cancer outpatients.
• We conducted a multicenter analysis of medically hospitalized cancer patients.
• Patients with a higher Khorana score on admission were more likely to develop VTE.
• The Khorana score is predictive of in‐hospital, symptomatic VTE development.

Summary

Introduction

The Khorana score is a validated risk assessment score for estimating the risk of symptomatic venous thromboembolism (VTE) in outpatients with cancer. The objective of this study was to assess the Khorana score for predicting the development of VTE in cancer patients during hospital admission.

Methods

We conducted an analysis of consecutive, adult cancer patients hospitalized for medical reasons between January and June 2010 in three academic medical centers. Information on objectively diagnosed, symptomatic VTE during hospitalization, use of anticoagulant thromboprophylaxis (TP) and Khorana score variables at the time of admission was collected.

Results

A total of 1398 patients were included. Mean age was 62 years, 51.2% were male, and mean BMI was 25.9 kg m^?2. The most frequent reasons for hospitalization were chemotherapy administration (22.3%), followed by pain control and palliation (21.4%). The overall incidence of VTE was 2.9% (95% CI, 2.0–3.8%), occurring in 5.4% (95% CI, 1.9–8.9%) of the high‐, 3.2% (95% CI, 2.0–4.4%) of the intermediate‐ and 1.4% (95% CI, 0.3–2.6%), of the low‐risk groups. High‐risk patients were more likely than low‐risk patients to have VTE (OR, 3.9; 95% CI, 1.4–11.2).

Conclusion

The Khorana score is predictive of in‐hospital, symptomatic VTE development in cancer patients who are hospitalized for medical reasons and may be a useful tool for tailoring inpatient anticoagulant thromboprophylaxis.

     

Are Nonpharmacologic Pain Interventions Effective at Reducing Pain in Adult Patients Visiting the Emergency Department? A Systematic Review and Meta‐analysis

Objectives

Pain is a common complaint in the emergency department (ED). Its management currently depends heavily on pharmacologic treatment, but evidence suggests that nonpharmacologic interventions may be beneficial. The purpose of this systematic review and meta‐analysis was to assess whether nonpharmacologic interventions in the ED are effective in reducing pain.

Methods

We conducted a systematic review of the literature on all types of nonpharmacologic interventions in the ED with pain reduction as an outcome. We performed a qualitative summary of all studies meeting inclusion criteria and meta‐analysis of randomized controlled studies measuring postintervention changes in pain. Interventions were divided by type into five categories for more focused subanalyses.

Results

Fifty‐six studies met inclusion criteria for summary analysis. The most studied interventions were acupuncture (10 studies) and physical therapy (six studies). The type of pain most studied was musculoskeletal pain (34 studies). Most (42 studies) reported at least one improved outcome after intervention. Of these, 23 studies reported significantly reduced pain compared to control, 24 studies showed no difference, and nine studies had no control group. Meta‐analysis included 22 qualifying randomized controlled trials and had a global standardized mean difference of –0.46 (95% confidence interval = –0.66 to –0.27) in favor of nonpharmacologic interventions for reducing pain.

Conclusion

Nonpharmacologic interventions are often effective in reducing pain in the ED. However, most existing studies are small, warranting further investigation into their use for optimizing ED pain management.

     

Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation,predicts the risk of venous thromboembolism in cancer patients

Essentials

• Neutrophil extracellular traps (NETs) might play a role in cancer‐related coagulopathy.
• We determined NET biomarkers and followed cancer patients for venous thromboembolism (VTE).
• We found a constant association with VTE for citrullinated histone H3.
• Biomarkers of NET formation could reflect a novel pathomechanism of cancer‐related VTE.

Summary

Background

Neutrophil extracellular traps (NETs) are decondensed chromatin fibers that might play a role in the prothrombotic state of cancer patients.

Objectives

To investigate whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell‐free DNA (cfDNA) and nucleosomes predict venous thromboembolism (VTE) in cancer patients.

Patients/Methods

Nine‐hundred and forty‐six patients with newly diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients were followed for 2 years. VTE occurred in 89 patients; the cumulative 3‐month, 6‐month, 12‐month and 24‐month incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively.

Results

Patients with elevated H3Cit levels (> 75th percentile of its distribution, n = 236) experienced a higher cumulative incidence of VTE (2‐year risk of 14.5%) than patients with levels below this cut‐off (2‐year risk of 8.5%, n = 710). In a competing‐risk regression analysis, a 100 ng mL^?1 increase in H3Cit level was associated with a 13% relative increase in VTE risk (subdistribution hazard ratio [SHR] 1.13, 95% confidence interval [CI] 1.04–1.22). This association remained after adjustment for high VTE risk and very high VTE risk tumor sites, D‐dimer level, and soluble P‐selectin level (SHR 1.13, 95% CI 1.04–1.22). The association of elevated nucleosome and cfDNA levels with VTE risk was time‐dependent, with associations with a higher risk of VTE only during the first 3–6 months.

Conclusion

These data suggest that biomarkers of NET formation are associated with the occurrence of VTE in cancer patients, indicating a role of NETs in the pathogenesis of cancer‐associated thrombosis.

     

Physician Age and Performance on the American Board of Emergency Medicine ConCert Examination

Objective

This study was undertaken to expand on results from a 2014 study on the association between physician age and performance on the American Board of Emergency Medicine (ABEM) ConCert examination.

Methods

This was a retrospective, longitudinal growth study comparing performance on the ConCert examination and physicians’ ages at the time of examination. All examination attempts from 1990 to 2016 made by residency‐trained physicians were eligible for inclusion. Multilevel growth models were constructed to examine the relationship between age at time of examination and performance, controlling for physician characteristics.

Results

The study group included 15,533 examination attempts by 12,786 physicians. The mean (±SD) age of the physicians across all examination administrations was 45.02 (±5.18) years (range = 35 to 72 years). The mean (±SD) ConCert examination score across all administrations was 85.39 (±5.71; range = 51 to 100). Among first‐time ConCert examination takers, older age was associated with lower examination scores (r = –0.25, p < 0.0001). Across all examination attempts, age was negatively correlated to examination scores (r = –0.24; p < 0.0001).

Conclusions

After physician characteristics were controlled for, there was an association between advancing age and declining performance on the ABEM ConCert examination. This information may be important to the individual physician to develop targeted competency assessment and professional development.

     

Reliability of hemostasis biomarkers is affected by time‐dependent intra‐patient variability

Essentials

• Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE).
• Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied.
• Hemostasis biological parameters vary over a short time‐frame in VTE patients.
• Hemostasis biological parameters also vary over a short time‐frame in healthy controls.

Summary

Background

Previous studies have associated neutrophil‐derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers.

Objectives

We performed a 3‐year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells.

Patients/Methods

Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6 months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs).

Results and Conclusions

In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334–0.764) and 0.091 (95% CI, ?0.026–0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042–0.463) and 0.161 (CI 95%, 0.008–0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time‐frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra‐individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers’ variability is warranted.

     

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

     

Longitudinal increases in blood biomarkers of inflammation or cardiovascular disease and the incidence of venous thromboembolism

Essentials

• Inflammatory and cardiac diseases are associated with increased venous thromboembolism (VTE) risk.
• Our prospective study assessed rise in inflammatory or cardiac biomarkers and VTE risk.
• A greater 6‐year rise in N‐terminal natriuretic peptide is associated with increased VTE incidence.
• Volume overload or impending cardiac disease may contribute to VTE occurrence.

Summary

Background

We previously showed that participants in the population‐based Atherosclerosis Risk in Communities (ARIC) cohort with elevated levels of blood biomarkers of inflammation or cardiac disease were at increased risk of venous thromboembolism (VTE).

Objective

We hypothesized that ARIC participants with larger 6‐year increases in the levels of three biomarkers – C‐reactive protein (CRP), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and troponin T – would also have an increased subsequent risk of VTE.

Methods

We measured changes in the levels of these biomarkers in 9844 participants from 1990–1992 to 1996–1998, and then identified VTEs through 2015.

Results

A greater 6‐year rise in the level of NT‐proBNP, but not in that of CRP or troponin T, was significantly associated with increased VTE incidence over a median of 17.6 years of follow‐up. After adjustment for other VTE risk factors, those whose NT‐proBNP level rose from < 100 pg mL^?1 to ≥ 100 pg mL^?1 had a hazard ratio for VTE of 1.44 (95% confidence interval [CI] 1.15–1.80), as compared with the reference group with an NT‐proBNP level of < 100 pg mL^?1 at both times. This hazard ratio was slightly higher (1.66, 95% CI 1.19–2.31) during the first 10 years of follow‐up, but was attenuated (1.24, 95% CI 0.99–1.56) after adjustment for prevalent and incident coronary heart disease, heart failure, and atrial fibrillation.

Conclusions

The two most likely explanations for our results are that: (i) an increasing NT‐proBNP level reflects increasing subclinical volume overload and potentially increased venous stasis or subclinical PE that had gone unrecognized over time; or (ii) an increasing NT‐proBNP level is a risk marker for impending cardiac disease that places patients at risk of VTE.

     

Change in Care Transition Practice for Patients With Nonspecific Chest Pain After Emergency Department Evaluation 2006 to 2012

Objectives

From 2005 to 2010 health care financing shifts in the United States may have affected care transition practices for emergency department (ED) patients with nonspecific chest pain (CP) after ED evaluation. Despite being less acutely ill than those with myocardial infarction, these patients’ management can be challenging. The risk of missing acute coronary syndrome is considerable enough to often warrant admission. Diagnostic advances and reimbursement limitations on the use of inpatient admission are encouraging the use of alternative ED care transition practices. In the setting of these health care changes, we hypothesized that there is a decline in inpatient admission rates for patients with nonspecific CP after ED evaluation.

Methods

We retrospectively used the Nationwide ED Sample to quantify total and annual inpatient hospital admission rates from 2006 to 2012 for patients with a final ED diagnosis of nonspecific CP. We assessed the change in admission rates over time and stratified by facility characteristics including safety‐net hospital status, U.S. geographic region, urban/teaching status, trauma‐level designation, and hospital funding status.

Results

The admission rate for all patients with a final ED diagnosis of nonspecific CP declined from 19.2% in 2006 to 11.3% in 2012. Variability across regions was observed, while metropolitan teaching hospitals and trauma centers reflected lower admission rates.

Conclusion

There was a 41.1% decline in inpatient hospital admission for patients with nonspecific CP after ED evaluation. This reduction is temporally associated with national policy changes affecting reimbursement for inpatient admissions.

     

Fluid Resuscitation in Patients With Severe Burns: A Meta‐analysis of Randomized Controlled Trials

Objectives

Fluid resuscitation is the mainstay treatment to reconstitute intravascular volume and maintain end‐organ perfusion in patients with severe burns. The use of a hyperosmotic or isoosmotic solution in fluid resuscitation to manage myocardial depression and increased capillary permeability during burn shock has been debated. We conducted a systematic review and meta‐analysis to compare the efficacies of hyperosmotic and isoosmotic solutions in restoring hemodynamic stability after burn injuries.

Methods

PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry were searched. Randomized control trials evaluating the efficacy and safety of hyperosmotic and isoosmotic fluid resuscitation in patients with burn injuries were selected. Eligible trials were abstracted and assessed for the risk of bias by two reviewers and results of hemodynamic indicators in the included trials were analyzed.

Results

Ten trials including 502 participants were published between 1983 and 2013. Compared with isoosmotic group, the hyperosmotic group exhibited a significant decrease in the fluid load (vol/% total body surface area [TBSA]/weight) at 24 hours postinjury, with a mean difference of ?0.54 (95% confidence interval = ?0.92 to ?0.17). No differences were observed in the urine output, creatinine level, and mortality at 24 hours postinjury between groups.

Conclusions

Hyperosmotic fluid resuscitation appears to be an attractive choice for severe burns in terms of TBSA or burn depth. Further investigation is recommended before conclusive recommendation.

     

Mild antithrombin deficiency and risk of recurrent venous thromboembolism: results from the MEGA follow‐up study

Essentials

• Mild antithrombin deficiency may increase the risk of recurrent venous thromboembolism (VTE).
• In a cohort study, we stratified patients with VTE to various cut‐off antithrombin levels.
• A 1.6–3.7‐fold increased risk of recurrent VTE was observed in the lowest antithrombin categories.
• Mild antithrombin deficiency (activity < 5th percentile of normal) increases recurrent VTE risk.

Summary

Background

Mild antithrombin deficiency (previously defined as antithrombin activity below 70% or 80%) has been associated with a 2.4–3.5‐fold increased risk of recurrent venous thromboembolism (VTE). This finding may have implications for duration of antithrombotic therapy in VTE patients with mild antithrombin deficiency.

Objectives

To externally validate whether mild antithrombin deficiency is a risk factor for recurrent VTE.

Methods

In a population‐based cohort study, patients with a first VTE (n = 2357) were stratified according to percentile cut‐off antithrombin levels (< 5th [< 87%], 5–10th [87–92%], > 10th percentile [> 92%]) and functional antithrombin levels (< 70%, 70–80%, > 80%).

Results

During a median follow‐up of 7.4 years, 361 recurrent events occurred (incidence rate, 2.5/100 patient‐years). We observed an increased risk of recurrent VTE in the lowest antithrombin activity category (< 5th percentile; < 87%) as compared with antithrombin activity that was > 10th percentile (> 92%), with an adjusted hazard ratio (HR) of 1.5 (95%CI, 1.0–2.3). When analyses were stratified to antithrombin cut‐off criteria of< 70% vs. patients with antithrombin activity > 80%, the adjusted HR for venous recurrence was 3.7 (95% CI, 1.4–9.9). Mild antithrombin deficiency was able to predict recurrent VTE over at least 8 years of follow‐up and the association remained present when the population was stratified to the presence or absence of thrombosis risk factors. Restriction analyses, where patients who used anticoagulation at time of blood draw and those who reported drinking ≥ 5 glasses alcohol daily were excluded, did not materially affect these outcomes.

Conclusion

This study confirms that mild antithrombin deficiency is a risk factor for recurrent VTE.

     

Reduction in physical function in women after venous thromboembolism

Essentials

• The association of venous thromboembolism (VTE) with subsequent physical function remains unclear.
• We prospectively evaluated this relationship among women from the Nurses’ Health Studies.
• We found a decline in physical function over four years in women with incident VTE.
• This decline was somewhat greater among women specifically reporting a pulmonary embolism.

Summary

Background

Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function.

Objectives

To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses’ Health Study(NHS), ages 46–72 in 1992, and 84 304 women from the Nurses’ Health Study II(NHS II), ages 29–48 in 1993.

Methods

Physical function was measured by the Medical Outcomes Short Form‐36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4‐year follow‐up period using multivariable linear regression.

Results

We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable‐adjusted mean difference NHS, ?6.5 points [95% CI ?7.4, ?5.6] per 4 years; NHS II, ?3.8 [95% CI ?5.6, ?2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, ?7.4 [95% CI ?8.7, ?6.1]; NHS II, ?4.8 [95% CI ?6.8, ?2.8]), and was equivalent to 6.2 years of aging. Whereas longer‐term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow‐up compared to women without VTE.

Conclusions

In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.

     

Elevated plasma levels of P‐selectin glycoprotein ligand‐1‐positive microvesicles in patients with unprovoked venous thromboembolism

Essentials

• PSGL‐1⁺ microvesicles (MVs) may be important in venous thromboembolism (VTE).
• We measured plasma levels and parental origin of PSGL‐1⁺ MVs in patients with unprovoked VTE.
• VTE patients had higher plasma levels of PSGL‐1⁺ MVs than healthy controls.
• The PSGL‐1⁺ MVs originated mainly from monocytes and endothelial cells.

Summary

Background

Microvesicles (MVs) express antigens from their parental cells and have a highly procoagulant surface. Animal studies suggest that P‐selectin glycoprotein ligand‐1‐positive (PSGL‐1⁺) MVs play a role in the pathogenesis of venous thromboembolism (VTE).

Objective

The aim of this study was to determine plasma levels, the cellular origin and the morphological characteristics of PSGL‐1⁺ MVs in patients with unprovoked VTE.

Methods

We conducted a population‐based case–control study in 20 patients with a history of unprovoked VTE and 20 age‐ and sex‐matched healthy controls recruited from the general population. Plasma levels, the cellular origin and the morphological characteristics of PSGL‐1⁺ MVs were evaluated using flow cytometry, electron microscopy and confocal microscopy.

Results

Plasma levels of PSGL‐1⁺ MVs were associated with increased risk of VTE. The odds ratio per one standard deviation increase in PSGL‐1⁺ MVs was 3.11 (95% confidence interval [CI], 1.41–6.88) after adjustment for age and sex, and 2.88 (95% CI, 1.29–6.41) after further adjustment for body mass index. The PSGL‐1⁺ MVs originated mainly from monocytes and endothelial cells determined by double staining with markers of parental cells using flow cytometry and transmission electron microscopy. Scanning electron microscopy of PSGL‐1‐labeled plasma‐derived MVs displayed dominantly spherical vesicles that varied between 50 and 300 nm in diameter.

Conclusions

Increased plasma levels of PSGL‐1⁺ MVs are associated with the risk of unprovoked VTE. Large population‐based prospective studies are required to validate our findings.