Infection and venous thromboembolism in patients undergoing colorectal surgery: what is the relationship?

BACKGROUND: There is evidence demonstrating an association between infection and venous thromboembolism. We recently identified this association in the postoperative setting; however, the temporal relationship between infection and venous thromboembolism is not well defined OBJECTIVE: We sought to determine the temporal relationship between venous thromboembolism and postoperative infectious complications in patients undergoing colorectal surgery. DESIGN, SETTING, AND PATIENTS: A retrospective cohort analysis was performed using data for patients undergoing colorectal surgery in the National Surgical Quality Improvement Project 2010 database. MAIN OUTCOME MEASURES: The primary outcome measures were the rate and timing of venous thromboembolism and postoperative infection among patients undergoing colorectal surgery during 30 postoperative days. RESULTS: Of 39,831 patients who underwent colorectal surgery, the overall rate of venous thromboembolism was 2.4% (n = 948); 729 (1.8%) patients were diagnosed with deep vein thrombosis, and 307 (0.77%) patients were diagnosed with pulmonary embolism. Eighty-eight (0.22%) patients were reported as developing both deep vein thrombosis and pulmonary embolism. Following colorectal surgery, the development of a urinary tract infection, pneumonia, organ space surgical site infection, or deep surgical site infection was associated with a significantly increased risk for venous thromboembolism. The majority (52%-85%) of venous thromboembolisms in this population occurred the same day or a median of 3.5 to 8 days following the diagnosis of infection. The approximate relative risk for developing any venous thromboembolism increased each day following the development of each type of infection (range, 0.40%-1.0%) in comparison with patients not developing an infection. LIMITATIONS: We are unable to account for differences in data collection, prophylaxis, and venous thromboembolism surveillance between hospitals in the database. Additionally, there is limited patient follow-up. CONCLUSIONS: These findings of a temporal association between infection and venous thromboembolism suggest a potential early indicator for using certain postoperative infectious complications as clinical warning signs that a patient is more likely to develop venous thromboembolism. Further studies into best practices for prevention are warranted

Efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute pain after orthopedic trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Orthopedic Trauma Association

OBJECTIVES: Fracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established. METHODS: Clinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The working group reached consensus on the final evidence-based recommendations. RESULTS: A total of 19 studies were identified for analysis. Not all outcomes identified as critically important were reported in all studies, and the outcome of pain control was too heterogenous to perform a meta-analysis. Nine studies reported on non-union (three randomized control trials), six of which reported no association with NSAIDs. The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively. Of studies reporting on pain control and reduction of opioids, the use of NSAIDs reduced pain and the need for opioids after traumatic fracture. One study reported on the outcome of acute kidney injury and found no association with NSAID use. CONCLUSIONS: In patients with traumatic fractures, NSAIDs appear to reduce post-trauma pain, reduce the need for opioids and have a small effect on non-union. We conditionally recommend the use of NSAIDs in patients suffering from traumatic fractures as the benefit appears to outweigh the small potential risks

Transcriptome Analysis of the Hippocampal CA1 Pyramidal Cell Region after Kainic Acid-Induced Status Epilepticus in Juvenile Rats

Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA)-induced status epilepticus (SE) in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed), and long-term potentiation (LTP; 18 genes changed). Also genes involved in Ca2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP), apolipoprotein E (apo E), cannabinoid type 1 receptor (CB1), Purkinje cell protein 4 (PEP-19), and interleukin 8 receptor (CXCR1), with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE). However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the juvenile age group

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Preventable Harm from Venous Thromboembolism (VTE) - A New Metric for Quality of Care

Venous thromboembolism (VTE), comprised of deep venous thrombosis (DVT) and pulmonary embolism (PE), is an underappreciated public health concern. According to the United States’ Surgeon’s General “Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism,” VTE affects between 350,000-600,000 Americans each year, causing over 100,000 deaths annually. Even with overwhelming evidence of benefit, many hospitalized patients do not receive adequate VTE prophylaxis. The Agency for Healthcare Research and Quality (AHRQ) has called VTE prevention the number one strategy to improve patient safety in hospitals. As a consequence, many governmental agencies, accrediting bodies, and patient safety organizations have made improving VTE prophylaxis a priority and VTE is suggested as an ideal target for public reporting. However, VTE rates alone are not reliable as quality indicators. We suggest a more palatable and reliable measure of preventable harm from VTE. Chapter 1 shows how publicly reported VTE process and outcome measures fail to correlate and are not valid to benchmark hospitals. Chapter 2 explains how surveillance bias limits the role of VTE outcome reporting and offers a better solution- linking VTE process and outcome data into a single measure to define preventable harm. Chapter 3 summarizes published approaches to improve VTE prophylaxis for hospitalized patients. Chapter 4 offers perspectives on lessons learned while implementing a mandatory computerized clinical decision support tool to improve VTE prevention at our academic medical center. Chapters 5 and report data showing how our tool decreased preventable harm from VTE (using our definition) in adult trauma and medicine patients. Chapter 7 presents a real-world example of the feasibility of linking VTE prevention process and outcome measures. The work of this dissertation has already influenced national policy. By inclusion in The Centers for Medicare and Medicaid Services financial incentives programs for the “meaningful use” of certified electronic health record (EHR) technology to improve patient care. VTE-6 is defined as patients diagnosed with confirmed VTE who did not receive VTE prophylaxis" This definition followed our suggestion that “performance measures could link a process of care with adverse outcomes when defining incidences of preventable harm.” We posed the question; CMS now requires that all participating hospitals answer our query

Preventable Harm from Venous Thromboembolism (VTE) - A New Metric for Quality of Care

Venous thromboembolism (VTE), comprised of deep venous thrombosis (DVT) and pulmonary embolism (PE), is an underappreciated public health concern. According to the United States’ Surgeon’s General “Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism,” VTE affects between 350,000-600,000 Americans each year, causing over 100,000 deaths annually. Even with overwhelming evidence of benefit, many hospitalized patients do not receive adequate VTE prophylaxis. The Agency for Healthcare Research and Quality (AHRQ) has called VTE prevention the number one strategy to improve patient safety in hospitals. As a consequence, many governmental agencies, accrediting bodies, and patient safety organizations have made improving VTE prophylaxis a priority and VTE is suggested as an ideal target for public reporting. However, VTE rates alone are not reliable as quality indicators. We suggest a more palatable and reliable measure of preventable harm from VTE. Chapter 1 shows how publicly reported VTE process and outcome measures fail to correlate and are not valid to benchmark hospitals. Chapter 2 explains how surveillance bias limits the role of VTE outcome reporting and offers a better solution- linking VTE process and outcome data into a single measure to define preventable harm. Chapter 3 summarizes published approaches to improve VTE prophylaxis for hospitalized patients. Chapter 4 offers perspectives on lessons learned while implementing a mandatory computerized clinical decision support tool to improve VTE prevention at our academic medical center. Chapters 5 and report data showing how our tool decreased preventable harm from VTE (using our definition) in adult trauma and medicine patients. Chapter 7 presents a real-world example of the feasibility of linking VTE prevention process and outcome measures. The work of this dissertation has already influenced national policy. By inclusion in The Centers for Medicare and Medicaid Services financial incentives programs for the “meaningful use” of certified electronic health record (EHR) technology to improve patient care. VTE-6 is defined as patients diagnosed with confirmed VTE who did not receive VTE prophylaxis" This definition followed our suggestion that “performance measures could link a process of care with adverse outcomes when defining incidences of preventable harm.” We posed the question; CMS now requires that all participating hospitals answer our query

Practice, Policy, Public Reporting, & Patient Engagement: Learning from the Venous Thromboembolism Example

At the conclusion of this presentation, the participant will be able to: Review risk factors for and guidelines suggesting methods to prevent VTE in hospitalized patients Explain how a systems approach can improve prescription of VTE prophylaxis Examine the impact of surveillance bias on public reporting of DVT rates Discuss adopting missed VTE prophylaxis doses as a quality improvement targe