Impact of a pharmacy resident on a transitions of care rotation for inpatients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program.

A novel pharmacy residency rotation was created to meet the needs of patients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program but not yet discharged from the inpatient setting. This service resulted in a high number of antimicrobial stewardship interventions identified and accepted by the primary team(s).

Outcomes associated with empiric cefepime for bloodstream infections caused by ceftriaxone-resistant, cefepime-susceptible Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. METHODS: This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. RESULTS: Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016). CONCLUSION: Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Opportunities for antibiotic stewardship in emergency department or hospitalized patients with asymptomatic bacteriuria: identifying risk factors for antibiotic treatment.

Antibiotic treatment of asymptomatic bacteriuria (ASB) is considered inappropriate and may lead to adverse events. This 2-center, retrospective cohort study including emergency department or inpatient adults identified pyuria (odds ratio, 2.43; 95% confidence interval, 1.17-5.01; P = .02) as the only independent risk factor for antibiotic treatment of ASB.

A Case Report of May-Thurner Syndrome Identified on Abdominal Ultrasound.

May-Thurner syndrome (MTS) is most commonly caused by the compression of the left iliac vein by the right iliac artery against the lumbar spine, which leads to the development of a partial or occlusive deep venous thrombosis (DVT).1 Diagnosis begins with a duplex ultrasound of the lower extremities to evaluate for a femoropopliteal thrombus, and in high-risk patients where a more proximal DVT is suspected and the DVT ultrasound is negative, a computed tomography venogram (CTV) or magnetic resonance venogram (MRV) is performed.1,3 In this case report, a patient presented to the emergency department (ED) with two days of left lower extremity pain and swelling. Initial lower extremity DVT ultrasound was negative, so a CTV was ordered and revealed a thrombus in the left common iliac vein with overlying compression by the right common iliac artery, suggesting the diagnosis of May-Thurner syndrome (Figure 1). Afterwards, a point-of-care ultrasound (POCUS) was performed at bedside to evaluate the caval and iliac arteries and the findings were consistent with the CTV (Figure 2, 3, 4). If the POCUS was performed prior to the CTV, the patient may have been spared the radiation exposure from CT, as well as the risks of intravenous (IV) contrast required for a venogram. Therefore, in high risk patients in whom a negative DVT ultrasound will prompt advanced imaging with CTV or MRV, I propose the addition of a lower abdominal ultrasound using a curvilinear probe to assess the caval and iliac arteries prior to obtaining a CTV or MRV. Topics: May-Thurner Syndrome, leg swelling, POCUS, ultrasound, deep venous thrombosis.

A Case Report of Aortic Dissection Involving the Aortic Root, Left Common Carotid Artery, and Iliac Arteries.

Acute aortic dissection is a life-threatening event caused by separation of the aortic layers that requires prompt management and surgical consultation. We present the case of a 53-year-old male who developed acute, severe chest pain radiating to his back at a community hospital and was transferred to a tertiary center for definitive surgical management. The patient's aortic dissection was diagnosed via computed tomography angiography. He was started on rate-control and blood pressure medications, and was admitted emergently to the operating room. Emergency physicians should obtain immediate surgical consultation, promptly start medications for rate and blood pressure control, and administer analgesia in order to stabilize their patient and decrease the shear forces that would further propagate an aortic dissection. Topics: Aortic dissection, cardiothoracic surgery, vascular surgery, hypertensive emergency, aorta.

Long Noncoding RNA NIHCOLE Promotes Ligation Efficiency of DNA Double-Strand Breaks in Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNA) are emerging as key players in cancer as parts of poorly understood molecular mechanisms. Here, we investigated lncRNAs that play a role in hepatocellular carcinoma (HCC) and identified NIHCOLE, a novel lncRNA induced in HCC with oncogenic potential and a role in the ligation efficiency of DNA double-stranded breaks (DSB). NIHCOLE expression was associated with poor prognosis and survival of HCC patients. Depletion of NIHCOLE from HCC cells led to impaired proliferation and increased apoptosis. NIHCOLE deficiency led to accumulation of DNA damage due to a specific decrease in the activity of the nonhomologous end-joining (NHEJ) pathway of DSB repair. DNA damage induction in NIHCOLE-depleted cells further decreased HCC cell growth. NIHCOLE was associated with DSB markers and recruited several molecules of the Ku70/Ku80 heterodimer. Further, NIHCOLE putative structural domains supported stable multimeric complexes formed by several NHEJ factors including Ku70/80, APLF, XRCC4, and DNA ligase IV. NHEJ reconstitution assays showed that NIHCOLE promoted the ligation efficiency of blunt-ended DSBs. Collectively, these data show that NIHCOLE serves as a scaffold and facilitator of NHEJ machinery and confers an advantage to HCC cells, which could be exploited as a targetable vulnerability. SIGNIFICANCE: This study characterizes the role of lncRNA NIHCOLE in DNA repair and cellular fitness in HCC, thus implicating it as a therapeutic target.See related commentary by Barcena-Varela and Lujambio, p. 4899.

Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk.

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days (P < 0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

EVALI: A Mimicker of COVID-19.

E-cigarette or vaping product use-associated lung injury (EVALI) is a respiratory illness that has significant overlap with the symptoms of coronavirus disease 2019 (COVID-19). In the current pandemic, diagnosis of EVALI may be delayed because of anchoring bias when patients present with symptoms consistent with COVID-19. We present 3 cases of patients who were hospitalized with a presumed diagnosis of COVID-19 but were later diagnosed with EVALI.

Supporting the Quadruple Aim Using Simulation and Human Factors During COVID-19 Care.

The health care sector has made radical changes to hospital operations and care delivery in response to the coronavirus disease (COVID-19) pandemic. This article examines pragmatic applications of simulation and human factors to support the Quadruple Aim of health system performance during the COVID-19 era. First, patient safety is enhanced through development and testing of new technologies, equipment, and protocols using laboratory-based and in situ simulation. Second, population health is strengthened through virtual platforms that deliver telehealth and remote simulation that ensure readiness for personnel to deploy to new clinical units. Third, prevention of lost revenue occurs through usability testing of equipment and computer-based simulations to predict system performance and resilience. Finally, simulation supports health worker wellness and satisfaction by identifying optimal work conditions that maximize productivity while protecting staff through preparedness training. Leveraging simulation and human factors will support a resilient and sustainable response to the pandemic in a transformed health care landscape.

Diminishing returns, increasing risks: Impact of antibiotic duration of therapy on respiratory bacterial isolates in hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic.

In 829 hospital encounters for patients with COVID-19, 73.2% included orders for antibiotics; however, only 1.8% had respiratory cultures during the first 3 hospital days isolating bacteria. Case-control analysis of 30 patients and 96 controls found that each antibiotic day increased the risk of isolating multidrug-resistant gram-negative bacteria (MDR-GNB) in respiratory cultures by 6.5%.

The Ideal Hospital Discharge Summary: A Survey of U.S. Physicians.

BACKGROUND: Hospital discharge summaries enable communication between inpatient and outpatient physicians. Despite existing guidelines for discharge summaries, they are frequently suboptimal. OBJECTIVE: The aim of this study was to assess physicians' perspectives about discharge summaries and the differences between summaries' authors (hospitalists) and readers (primary care physicians [PCPs]). METHODS: A national survey of 1600 U.S. physicians was undertaken. Primary measures included physicians' preferences in discharge summary standardization, content, format, and audience. RESULTS: A total of 815 physicians responded (response rate = 51%). Eighty-nine percent agreed that discharge summaries "should have a standardized format." Most agreed that summaries should "document everything that was done, found, and recommended in the hospital" (64%) yet "only include details that are highly pertinent to the hospitalization" (66%). Although 74% perceived patients as an important audience of discharge summaries, only 43% agreed that summaries "should be written in language that patients…can easily understand," and 68% agreed that it "should be written solely for provider-to-provider communication." Compared with hospitalists, PCPs preferred comprehensive summaries (68% versus 59%, P = 0.002). More PCPs agreed that separate summaries should be created for patients and for provider-to-provider communication than hospitalists (60% versus 47%, P < 0.001). Compared with PCPs, more hospitalists believe that "hospitalists are too busy to prepare a high-quality discharge summary" (44% versus 23%, P < 0.001) and "PCPs have insufficient time to read an entire discharge summary" (60% versus 38%, P < 0.001). CONCLUSIONS: Physicians believe that discharge summaries should have a standardized format but do not agree on how comprehensive or in what format they should be. Efforts are necessary to build consensus toward the ideal discharge summary.

Jefferson Fracture and the Classification System for Atlas Fractures, A Case Report.

The Jefferson fracture classification system describes fractures of the atlas (first cervical vertebra or C1). Jefferson fractures with potential tears in the transverse ligament can cause cervical spine instability and can result in neurologic injury if not appropriately diagnosed and managed. We present the case of a 54-year-old man who fell head first with cervical spine tenderness and upper extremity paresthesias. The patient's Jefferson fracture was diagnosed via computed tomography. The patient was then treated non-operatively for his Jefferson fracture, and he had an unremarkable hospitalization. Emergency physicians should obtain surgical consultation and consider the possibility of ligamentous injury in patients suffering injury to the cervical spine. Topics: Trauma, orthopedics, neurosurgery, cervical fracture, Jefferson fracture.

Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient.

ABSTRACT: Following advances in blood typing and storage, whole blood transfusion became available for the treatment of casualties during World War I. While substantially utilized during World War II and the Korean War, whole blood transfusion declined during the Vietnam War as civilian centers transitioned to blood component therapies. Little evidence supported this shift, and recent conflicts in Iraq and Afghanistan have renewed interest in military and civilian applications of whole blood transfusion. Within the past two decades, civilian trauma centers have begun to study transfusion protocols based upon cold-stored, low anti-A/B titer type O whole blood for the treatment of severely injured civilian trauma patients. Early data suggests equivalent or improved resuscitation and hemostatic markers with whole blood transfusion when compared to balanced blood component therapy. Additional studies are taking place to define the optimal way to utilize low-titer type O whole blood in both prehospital and trauma center resuscitation of bleeding patients.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Proteomic Analysis of Infants Undergoing Cardiopulmonary Bypass Using Contemporary Ontological Tools.

BACKGROUND: Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation. Given recent advances in analytic tools for identifying protein-protein interactions in the plasma proteome, we hypothesized that an unbiased proteomic analysis would help identify networks of interacting proteins for further investigation in pediatric CPB. MATERIALS AND METHODS: Infants up to 1 y of age were enrolled. Plasma samples were collected at 0, 1, 4, and 24 h after CPB. Mass spectrometry was used to identify proteins undergoing changes in concentration after CPB, and STRING and ToppGene tools were used to identify biological networks. Two-dimensional difference gel electrophoresis identified changes in protein concentrations. Inflammatory markers were assessed by enzyme-linked immunosorbent assay at the same time points. RESULTS: Ten infants with cardiac anomalies requiring surgery and CPB were enrolled; no major complications were recorded (median age, 127.5 d; interquartile range, 181.25 d). Using two-dimensional difference gel electrophoresis, >1400 individual protein spots were observed, and 89 proteins demonstrated change in concentration >30% with P < 0.02 when comparing 1, 4, or 24 h to baseline. Among protein spots with significant changes in concentration after CPB, 29 were identified with mass spectrometry (33%). In our interrogation of functional associations among these differentially expressed proteins, our results were dominated by the acute phase response, coagulation, and cell signaling functional categories. Among cytokines analyzed by enzyme-linked immunosorbent assay, IL-2, IL-8, and IL-10 were elevated at 4 h but normalized by 24 h, whereas IL-6 was persistently elevated. CONCLUSIONS: Infants manifest a robust response to CPB that includes overlapping, complex pathways. Further investigation of interactions among immune, coagulation, and cell signaling systems may lead to novel therapeutics or biomarkers useful in the management of infants requiring CPB.

Evaluation of Inpatient Antimicrobial Regimens for Readmitted Outpatient Parenteral Antimicrobial Therapy Patients Receiving Daptomycin or Ertapenem for Ease of Administration.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) allows for long-course intravenous treatment of infections without lengthy hospital stays. Upon discharge, antimicrobial therapy may be broadened for "ease" of once-daily administration (EOA). Patients requiring subsequent readmission can be tailored to pre-OPAT regimens to minimize adverse effects. This study assessed continuation of EOA regimens upon hospital readmission during or immediately after OPAT. METHODS: This was a retrospective review of adults enrolled in OPAT and discharged on ertapenem or daptomycin for EOA, defined by the terms "convenience" or "EOA" in OPAT notes or by switching to ertapenem or daptomycin upon OPAT enrollment despite adequate therapy with narrower-spectrum agents. The primary outcome was the percentage of patients readmitted during or after their OPAT course and maintained on an EOA regimen. Secondary outcomes included inpatient therapy cost, rates of Clostridioides difficile infection, and adverse events. RESULTS: Of 188 patients receiving an OPAT EOA regimen, 71 were readmitted, representing 113 unique readmissions. Patients were mostly males (81%) aged 57 years. The EOA regimens were continued in 27% of hospital readmissions. The Infectious Diseases (ID) team was consulted in 48% of readmissions, and the Antimicrobial Stewardship Program (ASP) intervened in 26%. Combined, this resulted in de-escalation in 28% of cases. Clostridioides difficile infections and adverse events occurred in 7% and 12% of readmissions, respectively. The median acquisition cost of inpatient EOA regimens was $150 per readmission. CONCLUSIONS: The OPAT EOA regimens were continued in 27% of hospital readmissions indicating a role for improved indication documentation and collaboration between ID services, ASPs, and OPAT teams.

Clinical characteristics and treatment outcomes among respiratory syncytial virus (RSV)-infected hematologic malignancy and hematopoietic stem cell transplant recipients receiving palivizumab.

Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected hematologic malignancy patients at our institution based on limited published data. We conducted this retrospective study to evaluate clinical outcomes and mortality rates of RSV-infected hematologic malignancy patients from 2007 to 2016. A total of 67 patients (19 received palivizumab and 47 received supportive care) were identified. Palivizumab-treated patients had a significantly higher proportion of underlying ischemic heart disease, graft-versus-host-disease, hypogammaglobulinemia, and concomitant pulmonary infections. There were no significant differences in mortality rates or readmission rates between the two groups. The estimated odds ratio for death in patients receiving palivizumab after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p = .08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors associated with severity of illness, there was no difference in mortality among patients treated with palivizumab.

Submassive Central Saddle and Extensive Bilateral Pulmonary Embolism Presenting as Syncope Treated with Catheter-directed Therapy.

Massive and submassive pulmonary emboli (PE) are rare but potentially life-threatening medical conditions that necessitate immediate recognition and appropriate treatment. We report a 52-year-old man who was found to have a submassive central saddle and extensive bilateral PEs after experiencing a syncopal event and who had evidence of right heart strain and pulmonary hypertension. He was subsequently treated with catheter-assisted thrombectomy and pulmonary artery tissue plasminogen activator administration. This case report presents an outcome in a patient who received an innovative therapy that has not been well established in this subset of patients.