The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL ( sd 20) for lipid emulsion patients, and 2 mg/dL ( sd 18) for control patients ( p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients ( p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Effectiveness and Safety of Beta-Lactam Antibiotics with and without Therapeutic Drug Monitoring in Patients with Pseudomonas aeruginosa Pneumonia or Bloodstream Infection.

This objective of this study was to compare clinical outcomes in hospitalized patients with Pseudomonas aeruginosa pneumonia (PNA) or bloodstream infection (BSI) receiving beta-lactam antibiotic (BLA) infusions with and without the guidance of therapeutic drug monitoring (TDM). A retrospective, parallel cohort study was conducted at two academic medical centers between December 2015 and January 2020, UF Shands Gainesville, which uses BLA TDM for select patients (BLA TDM), and UF Health Jacksonville, which does not use BLA TDM (No-BLA TDM). All hospitalized adult patients with respiratory or blood culture positive for P. aeruginosa who met diagnosis criteria for lower respiratory tract infection with a positive P. aeruginosa respiratory culture and who received ≥48 h of intravenous BLA with in vitro susceptibility within 72 h of positive culture collection were included. The primary outcome was a composite of presumed treatment failure defined as the presence of any of the following from index-positive P. aeruginosa culture collection to the end of BLA therapy: all-cause mortality, escalation of and/or additional antimicrobial therapy for P. aeruginosa infection after 48 h of treatment with susceptible BLA due to worsening clinical status, or transfer to a higher level of care (i.e., the intensive care unit [ICU]). Analyses were adjusted for possible confounding with inverse probability of treatment weighting (IPTW). Two-hundred patients were included (BLA TDM, n = 95; No-BLA TDM, n = 105). In IPTW-adjusted analysis of the primary composite endpoint, BLA TDM demonstrated a significant decrease in presumed treatment failure compared to No-BLA TDM (adjusted odds ratio [aOR] 0.037, 95% confidence interval [CI] [0.013 to 0.107]; P < 0.001). BLA TDM had more 30-, 60- and 90-day infection-related readmissions ([aOR], 11.301, 95% CI (3.595 to 35.516); aOR 10.389, 95% CI [2.496 to 43.239], and aOR 24.970, 95% CI [6.703 to 93.028]) in IPTW analyses. For both unadjusted and IPTW-adjusted cohorts, there was no significant difference in hospital and ICU length of stay, adverse effects while on BLA, or microbiological eradication between BLA TDM and No-BLA TDM. In hospitalized adult patients with P. aeruginosa PNA or BSI, the use of TDM-guided BLA infusions decreased the odds of presumed treatment failure compared to patients receiving BLA infusions without TDM guidance. Future studies should evaluate BLA TDM impact on readmission.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature.

Objective: Recent literature suggests that intravenous (IV) administration may cause hypotension in hospitalized patients; data further suggest that this effect is most pronounced in the critically ill. The purpose of this review is to identify and evaluate current literature that addresses the incidence and implications of IV acetaminophen-induced hypotension. Data Sources: A literature search of MEDLINE, Cochrane, and EMBASE databases was performed (2002-2019) using the following terms: acetaminophen, paracetamol, intravenous, and hypotension. Abstracts and peer-reviewed publications were reviewed. Study Selection and Data Extraction: Relevant English-language studies conducted in humans evaluating the hemodynamic effects of IV acetaminophen were considered. Data Synthesis: A majority of the 19 studies included in this review identified a statistically significant drop in hemodynamic variables after the administration of 500 to 1000 mg IV acetaminophen as measured by changes in systolic blood pressure, diastolic blood pressure, or mean arterial pressure. Of the trials reporting vasopressor use, the authors found a significant increase in vasopressor requirements following IV acetaminophen administration. Relevance to Patient Care and Clinical Practice: This review represents the first comprehensive review of IV acetaminophen-induced hypotension. The findings raise the question of whether IV acetaminophen is an appropriate choice for inpatient pain or temperature management in the critically ill. Conclusions: Available evidence indicates that the administration of IV acetaminophen may be harmful in the critically ill. Additional monitoring is likely required when using IV acetaminophen in this specific population, particularly if a patient is hemodynamically unstable prior to administration.

Evaluation of the protective effects of ß-blockers in the management of acute exacerbations of chronic obstructive pulmonary disease.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this study was to evaluate the association between early ß-blocker continuation and major inpatient events in patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This single centre, retrospective, investigational review board approved cohort study evaluated patients admitted for a primary diagnosis of AECOPD. Patients were evaluated based on early continuation of a ß-blocker whether a ß-blocker was initiated within 24 hours of admission and continued for at least 72 hours. Patients with AECOPD who did not receive ß-blockers were assigned to the control group. Major inpatient events were a composite outcome composed of arrhythmias, myocardial infarction (MI) and death. Safety data were collected on the incidences of bradycardia, bronchospasms and hypotension. RESULTS AND DISCUSSION: Of the 96 patients admitted for AECOPD, fifty-five patients were included in the early ß-blocker group and forty-one patients in the control group. Early ß-blocker utilization was associated with a significantly lower rate of major inpatient events compared with the control group (40% vs 80.5%; P < 0.001). Arrhythmias were significantly less common in the early ß-blocker group (30.9% vs 65.9%; P = 0.001); however, there were no significant differences in the rates of MI (9.1% vs 14.6%; P = 0.54), death (0 vs 0) or safety outcomes between groups. WHAT IS NEW AND CONCLUSION: ß-blocker therapy could result in a paradigm shift in managing chronic obstructive pulmonary disease patients from a true cardiopulmonary approach. This retrospective cohort study demonstrated early ß-blocker continuation in patients admitted for an AECOPD was associated with less major inpatient events, primarily arrhythmias.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective ß-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Safety and effectiveness of direct oral anticoagulants following ultrasound-assisted catheter directed thrombolysis for venous thromboembolism.

Ultrasound-assisted catheter-directed thrombolysis (USAT) is a novel approach for the treatment of venous thromboembolism (VTE) that is thought to be associated with a decreased risk of bleeding. Direct oral anticoagulants (DOACs) are approved for the treatment of VTE but have not been studied in a post-fibrinolysis setting. The intention of this retrospective observational study was to determine the safety and effectiveness of DOACs compared to the vitamin-K-antagonist (VKA) warfarin following USAT in patients with documented VTE. Included patients were aged 18 years or older who had documented VTE and received oral anticoagulation with either a DOAC or VKA following USAT. The primary outcome of this study was to compare the 90-day composite incidence of major and minor bleeding and recurrent VTE between patients receiving DOACs after USAT to those receiving VKA after USAT. Similar rates of bleeding and recurrent VTE were observed (4/42; 9.5% in the DOAC group versus 2/34; 5.9% in the VKA group). The use of DOAC therapy post-USAT for VTE was not associated with higher rates of 90-day major or minor bleeding or 90-day recurrent VTE.

Corrigendum: 2016 ACG Abstracts- Clinical Vignettes/Case Reports - Esophagus.

This corrects the article DOI: 10.1038/ajg.2016.368.

Evaluation of Neuroleptic Utilization in the Intensive Care Unit During Transitions of Care.

PURPOSE: The purpose of this study was to identify risk factors associated with inappropriate continuation of neuroleptics postdischarge from the intensive care unit (ICU) and hospital. MATERIALS AND METHODS: A retrospective chart review was performed including all patients greater than 18 years of age who received neuroleptic medications in an ICU. RESULTS: One hundred sixty-one patients were included during the 12- month study period. There were 85 (53%) patients discharged from the ICU with inappropriate continuation of a neuroleptic medication. There were 54 (34%) patients discharged from the hospital with inappropriate continuation of a neuroleptic medication. Patients were more likely to be discharged from the ICU with an inappropriate neuroleptic if they were prescribed multiple neuroleptics ( P = .02), did not have a urine drug screen collected at admission ( P = .023), or if trazodone was utilized in their therapy ( P = .004). Patients were more likely to be discharged from the hospital with a neuroleptic if they had multiple neuroleptic orders ( P = .0001) or if trazodone was utilized in their therapy ( P = .0023). CONCLUSION: Risk factors associated with the continuation of inappropriate neuroleptic medications upon discharge from the ICU or the hospital include multiple neuroleptic medications prescribed, the lack of a urine drug screen upon admission, and the utilization of trazodone.

Approach to the Complicated Alcohol Withdrawal Patient.

Alcohol withdrawal syndromes are common causes for admission to the intensive care unit. As many as one-fifth of the admitted patients have an alcohol-associated disorder. Identifying the benefit of the γ-aminobutyric acid (GABA) agonists has shifted toward methods to improve benzodiazepine (BZD) utilization. Literature validating this treatment approach in severe withdrawal, especially in the critical care setting, is limited, and extrapolation to this population may be dangerous. Multiple therapies have been suggested or utilized in the literature including continuous infusion of GABA agonists, ethanol, dexmedetomidine, antiepileptics, and antipsychotics, introducing a significant amount of variability into clinical practice. This variability in treatment approaches highlights the lack of uniformity and recommendations available for the treatment of severe refractory patients. In patients progressing to severe withdrawal, it may be warranted to escalate care with adjunctive or more aggressive therapies. Although multiple practices are commonly used, the evidence supporting their use after failing symptom-triggered or aggressive therapy with BZDs is virtually nonexistent. These patients commonly receive a multimodal approach, which varies substantially between providers and institutions. Further literature should be directed at the approach most likely to provide benefit when standard of care has failed.

Idarucizumab for Reversal of Dabigatran-Associated Bleeding: Misnomer or Miracle?

BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding. DISCUSSION: Although existing clinical studies show a rapid reversal of coagulation assays, these studies did not describe a corresponding improvement in mortality or rapid cessation of hemorrhage. It is questionable how heavily clinicians can rely upon the use of the surrogate endpoints in clinical studies, such as ecarin clotting time and dilute thrombin time. Another issue is whether patients exhibiting re-elevation of coagulation assays would benefit from an additional dose of idarucizumab, because this has not been studied. It is currently unclear if blood products must be given in addition to idarucizumab can be used as monotherapy. CONCLUSIONS: The initial data suggest a definite role for idarucizumab in treatment of bleeding associated with dabigatran. As more clinical practice experience is gained with the agent and the remaining data on its use are released, clinicians can better guide the clinical use of idarucizumab. At present, there is currently not enough evidence for idarucizumab to be used as monotherapy.

The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting.

BACKGROUND: The utilization of bolus-dose phenylephrine (PHE) has transitioned to the emergency department (ED) for the treatment of acutely hypotensive patients, despite a paucity of literature in this setting. METHODS: This was a single center retrospective chart review of the utilization of bolus-dosed PHE for acute hypotension in the ED at an academic non-forprofit hospital. The primary objective of this study is to report the frequency of patients that were initiated on a continuous vasopressor infusion (CVI) within 30 minutes after the first administration of bolus-dose PHE. Secondary objectives included an observational description of the impact of early preload expansion (fluids) on the initiation of CVIs in the setting of bolus-dose PHE in the ED. RESULTS: Seventy-three patients met inclusion criteria for analysis. The primary outcome, 46.5% (n = 34) of patients were initiated on a CVI within 30 minutes following bolus-dose PHE. Initial preload expansion (30 mL/kg of IV fluids) was found to be significantly disproportionate with 34.2% appropriately fluid challenged vs 65.8% (P = .0048). In addition, a significant decrease in the number of PHE bolus doses were required [1.5 vs 2.3 (P = .01)] in the adequately IVF challenged group. For secondary endpoints, PHE was most commonly indicated for peri-intubation hypotension (n = 52, 71.2%). Significant adverse events were documented for 15 (20.5%) patients, with bradycardia (n = 7; 9.6%) as the most common adverse event. CONCLUSIONS: Initial preload IVF expansion was found to be significantly disproportionate, and appears to be associated with an increase number of phenylephrine bolus doses in our study population.

A Stewardship Approach To Optimize Antimicrobial Therapy through Use of a Rapid Microarray Assay on Blood Cultures Positive for Gram-Negative Bacteria.

A Gram-negative (GN) blood culture microarray assay with an antimicrobial stewardship program (ASP) intervention was evaluated in 126 patients with GN bacteremia. The median time to optimal therapy was shorter in the postintervention group than in the preintervention group (49.3 h versus 38.5 h, respectively; P = 0.0199). ASP can utilize microarray technology to decrease the time to optimal antimicrobial therapy.

The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients.

INTRODUCTION: Thrombocytopenia in the intensive care unit (ICU) is a commonly experienced complication; the pathology is not always easily understood. Continuous renal replacement therapy (CRRT) provides a method to dialyze unstable critically ill patients. We hypothesized that CRRT may precipitate a form of thrombocytopenia. In trials thrombocytopenia occurred at rates as high as 70%. The etiology remains unknown and results in additional diagnostic workup, as well as possible drug therapy. The extent, duration and temporal relation of thrombocytopenia remain to be determined. OBJECTIVES: Identify a pattern in platelet fluctuations after the initiation of CRRT and its impact on health care. METHODS: A retrospective study was conducted in patients receiving CRRT for >24 h with no pre-existing thrombocytopenia. Patients initiated on CRRT had daily platelet counts monitored, and CRRT attributes and therapeutic interventions were collected. Platelets were assessed for time to nadir, degree of decline and time to return to baseline after discontinuation of CRRT. RESULTS: Forty-nine patients met inclusion criteria. Thirty-seven percent of patients receiving heparinoids were tested for heparin-induced thrombocytopenia (HIT), during CRRT, with 39% of these patients having therapy changed to non-heparinoid agents due to suspected HIT; no HIT antibodies were positive. Eleven patients (22%) receiving anticoagulants, prophylactically or therapeutically had them held for a drop in platelets. There was a mean decline in platelets of 48% with a mean of 4.6 days to the nadir. An average 2.48 days were observed until rebound to >150 × 10(3)/mm(3). Statistical analysis failed to identify any patient attributes that correlated with the probability of thrombocytopenia. CONCLUSION: CRRT appears to be associated with a drop in platelets within the first 5 days of therapy with an average decline of 48%. However, platelets appear to return to >150 × 10(3)/mm(3) after cessation of CRRT. This fluctuation should be considered in the setting of patients developing thrombocytopenia after initiation of CRRT.

Colorectal Endoscopic Submucosal Dissection: Past, Present, and Factors Impacting Future Dissemination.

First performed in the stomach for removal of localized gastric tumors, endoscopic submucosal dissection (ESD) has evolved into a technique that is increasingly being employed to resect colorectal lesions. As opposed to endoscopic mucosal resection (EMR), ESD allows the endoscopist to remove large specimens en bloc to provide accurate pathologic evaluation and lower local recurrence rates. ESD is an ideal technique for resection of lesions without lymph node metastases and is becoming the standard of care in Japan as outcomes data has proven it to be equally efficacious, less invasive, and inexpensive as compared with surgery; however, potential risk for complications is high and the procedure is currently not widely available in the Western world. As more interest, endoscopist training, and data supporting the technique's use mount, ESD will also likely become the standard of care in the Western world for resection of localized colorectal lesions.

Comparison of clevidipine vs nicardipine in the treatment of hypertensive urgency and emergency in critically ill patients.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Evidence has suggested that clevidipine may provide faster blood pressure (BP) reduction with less volume than nicardipine in stroke and cardiothoracic surgery patients, but its use in hypertensive crises has not been well established. The primary objective of this study was to compare the treatment success of clevidipine and nicardipine in hypertensive crisis. METHODS: This was a multicenter, retrospective cohort study including patients who received either clevidipine or nicardipine for treatment of hypertensive crisis. The primary outcome was the time from infusion start to attainment of goal BP, defined as the higher value of the guideline-directed 25% reduction in BP or the physician-ordered goal. Secondary outcomes were the time from infusion start to guideline-directed 25% reduction in BP, drug and total volume intake, the time from order entry to BP goal attainment, the number of BP and heart rate excursions, intensive care unit (ICU) length of stay, and study medication cost. RESULTS: In total, 182 patients were included in the study (103 receiving nicardipine and 79 receiving clevidipine). Time to goal BP was similar between the groups (35 vs 33 minutes for clevidipine vs nicardipine, respectively; P = 0.37). Time to guideline-directed 25% reduction was also similar (P = 0.42). Volume from study drug was significantly less with clevidipine (222 vs 518 mL; P = 0.01); however, the total volume received in the ICU was similar (3,370 vs 3,383 mL; P = 0.43). Percent time in the goal BP range was similar (43.1% vs 42.3%). The cost of clevidipine was $199.37 per vial (based on the average wholesale price as of June 2023). This cost was 682% higher than that for a bag of nicardipine. CONCLUSION: Time to goal BP was similar for clevidipine and nicardipine in this population. Any decreases in medication-associated volume with clevidipine were no longer evident when all volume sources were considered. These results show that clevidipine may not provide meaningful benefit in this heterogenous population. The difference in cost does not seem justified given the lack of improvement in clinically relevant outcomes.

Automated centrifugal microfluidic system for the preparation of adaptor-ligated sequencing libraries.

The intensive workload associated with the preparation of high-quality DNA libraries remains a key obstacle toward widespread deployment of sequencing technologies in remote and resource-limited areas. We describe the development of single-use microfluidic devices driven by an advanced pneumatic centrifugal microfluidic platform, the PowerBlade, to automate the preparation of Illumina-compatible libraries based on adaptor ligation methodology. The developed on-chip workflow includes enzymatic DNA fragmentation coupled to end-repair, adaptor ligation, first DNA cleanup, PCR amplification, and second DNA cleanup. This complex workflow was successfully integrated into simple thermoplastic microfluidic devices that are amenable to mass production with injection molding. The system was validated by preparing, on chip, libraries from a mixture of genomic DNA extracted from three common foodborne pathogens (Listeria monocytogenes, Escherichia coli and Salmonella enterica serovar Typhimurium) and comparing them with libraries made via a manual procedure. The two types of libraries were found to exhibit similar quality control metrics (including genome coverage, assembly, and relative abundances) and led to nearly uniform coverage independent of GC content. This microfluidic technology offers a time-saving and cost-effective alternative to manual procedures and robotic-based automation, making it suitable for deployment in remote environments where technical expertise and resources might be scarce. Specifically, it facilitates field practices that involve mid- to low-throughput sequencing, such as tasks related to foodborne pathogen detection, characterization, and microbial profiling.

Prevalence and lifetime risk of endoscopy-related complications among patients with inflammatory bowel disease.

BACKGROUND & AIMS: Few studies have analyzed the safety of endoscopy in patients with inflammatory bowel disease (IBD). We aimed to determine the prevalence of procedure-related complications among these patients, compared with the general population, and estimate the lifetime risk of colonoscopy-related complications. METHODS: We collected data on complications in 685 patients with IBD and 17,000 patients without IBD (controls) using an automated system to track all emergency department visits to the Beth Israel Deaconess Medical Center within 14 days of an endoscopic procedure, from March 1, 2007, to November 30, 2007. We reviewed charts of all IBD patients to determine health care use (telephone calls or visits to a gastroenterologist or primary care physician and visits to other emergency departments or hospitals) after endoscopy. The lifetime risk of procedure-related complications was estimated using a Markov Monte Carlo model. RESULTS: Rates of complications were 1.17% among patients with IBD and 0.96% among controls (P = .55). The chart review showed that 3.8% of the IBD cohort received medical care within 14 days of the endoscopic procedure. Based on a Markov Monte Carlo simulation model, the lifetime risk of complications after a surveillance colonoscopy protocol was 12.7% among patients with IBD and 2.0% in the general population undergoing screening colonoscopy (P < .001). CONCLUSIONS: Although the risk of adverse events after each endoscopic procedure was similar for patients with IBD and the general population, IBD patients have an increased lifetime risk of complications after colonoscopies. A higher percentage of patients with IBD also seek medical care after endoscopic procedures than controls.

Stewardship approach for optimizing antimicrobial therapy through use of a rapid microarray assay on blood cultures positive for Enterococcus species.

Enterococci are a major cause of bloodstream infections in hospitalized patients and have limited antimicrobial treatment options due to their many resistance mechanisms. Molecular technologies have significantly shortened the time to enterococcal isolate identification compared with conventional methods. We evaluated the impact of rapid organism identification and resistance detection with the Verigene Gram-positive blood culture microarray assay on clinical and economic outcomes for patients with enterococcal bacteremia. A single-center preintervention/postintervention quasiexperimental study compared inpatients with enterococcal bacteremia from 1 February 2012 to 9 September 2012 (preintervention period) and 10 September 2012 to 28 February 2013 (postintervention period). An infectious disease and/or critical care pharmacist was contacted with the microarray assay results, and effective antibiotics were recommended. The clinical and economic outcomes for 74 patients were assessed. The mean time to appropriate antimicrobial therapy was 23.4 h longer in the preintervention group than in the postintervention group (P = 0.0054). A nonsignificant decrease in the mean time to appropriate antimicrobial therapy was seen for patients infected with vancomycin-susceptible Enterococcus isolates (P = 0.1145). For patients with vancomycin-resistant Enterococcus bacteremia, the mean time to appropriate antimicrobial therapy was 31.1 h longer in the preintervention group than in the postintervention group (P < 0.0001). In the postintervention group, the hospital length of stay was significantly 21.7 days shorter (P = 0.0484) and mean hospital costs were $60,729 lower (P = 0.02) than in the preintervention group. The rates of attributed deaths in the two groups were not statistically different. Microarray technology, supported by pharmacy and microbiology departments, can decrease the time to appropriate antimicrobial therapy, the hospital length of stay, and health care costs.