Targeting the gut microbiome in the management of sepsis-associated encephalopathy.

Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.

The Digital Classroom: How to Leverage Social Media for Infectious Diseases Education.

Social media (SoMe) platforms have been increasingly used by infectious diseases (ID) learners and educators in recent years. This trend has only accelerated with the changes brought to our educational spaces by the coronavirus disease 2019 pandemic. Given the increasingly diverse SoMe landscape, educators may find themselves struggling with how to effectively use these tools. In this Viewpoint we describe how to use SoMe platforms (e.g., Twitter, podcasts, and open-access online content portals) in medical education, highlight medical education theories supporting their use, and discuss how educators can engage with these learning tools effectively. We focus on how these platforms harness key principles of adult learning and provide a guide for educators in the effective use of SoMe tools in educating ID learners. Finally, we suggest how to effectively interact with and leverage these increasingly important digital platforms.

Variability among Online Opioid Conversion Calculators Performing Common Palliative Care Conversions.

Introduction: Online opioid conversion calculators (OOCCs) are commonly used to aid conversion between opioids to overcome tolerance, reduce adverse effects, or challenges related to administration. The purpose of this study was to describe and characterize variability among OOCC used by health care practitioners when converting common opioids and doses encountered in the hospice and palliative care setting. Methods: We collected 58 quantitative surveys and performed sentiment analysis on 62 qualitative responses from adult learners primarily practicing in the palliative care setting and enrolled in an online palliative care Master of Science program through the University of Maryland, Baltimore, who were asked to perform opioid conversion calculations using realistic patient cases. Results: OOCC have substantial variability leading to a wide range of outputs, which may put patients at risk for opioid-related harm. Assessing participant sentiment toward OOCC showed most participants held a "Negative Sentiment" toward these calculators after the activity. Conclusion: Overall, findings reveal that given the same information, clinicians can come to widely different opioid doses and these differences can be amplified by OOCC. These differences can be particularly dangerous given the higher opioid doses commonly used in the palliative care setting. Considering the significant harm that can arise from an error when converting between opioids, clinicians should avoid the routine use of OOCC in real-world patient care settings. If an OOCC is used, organizations should endorse a specific calculator, provide training and education about the algorithm that supports the calculations, and encourage clinicians to use it only after their own manual calculation, which should be documented in the medical record.

A single dose of pre-operative pregabalin reduces post-operative opioid use after orthotopic liver transplantation.

Multimodal pain management strategies including pregabalin (PGB) have been shown to reduce pain and opioid use after many types of surgeries. This was a single-center, retrospective study aimed to determine whether a single pre-operative dose of PGB reduces opioid requirements and post-operative pain after orthotopic liver transplantation (OLT). Outcomes included the mean morphine milligram equivalents used; the proportion of patients with no pain documented; and the maximum level of pain documented within the first 24h and in the 24-72h following OLT. A total of 44 patients received PGB vs 57 who received standard of care. Baseline demographics were comparable between groups. Patients who received PGB required 70% and 54% less opioids within the first 24h and subsequent 24-72h post-OLT, respectively (p-values < .001). In the first 24h post-OLT, there were more patients with no documented pain, and fewer with severe pain in the PGB group, but these were not significant. A greater proportion in the PGB group reported a maximum of mild pain (p = .039). This study demonstrated that a single dose of pre-operative PGB significantly reduced opioid use in the first 72 h after OLT. Larger studies will help determine the safety and efficacy of PGB in this setting.

Pulmonary arterial hypertension in the emergency department: A focus on medication management.

Pulmonary arterial hypertension (PAH) is a chronic progressive incurable condition associated with a high degree of morbidity and mortality. With over five drug classes FDA approved in the last decade, the significant advancements in the pharmacologic management of PAH has improved long-term outcomes. Drug therapies have been developed to directly target the underlying pathogenesis of PAH including phosphodiesterase type-5 inhibitors (PDE-5i), endothelin-receptor antagonists (ERAs), guanylyl-cyclase inhibitors, prostacyclin analogues, and prostacyclin receptor agonists. Although these agents offer remarkable benefits, there are significant challenges with their use such as complexities in medication dosing, administration, and adverse effects. Given these consequences, PAH medications are classified as high-risk, and the transitions of care process to and from the hospital setting are a vulnerable area for medication errors in this population. Thus, it is crucial for the emergency department provider to appropriately identify, manage, and triage these patients through close collaboration with a multidisciplinary team to ensure safe and effective medication management for PAH patients in the acute care setting.

Using an Ordinal Approach to Compare Outcomes Between Vancomycin Versus Ceftaroline or Daptomycin in MRSA Bloodstream Infection.

INTRODUCTION: Vancomycin remains first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI); however, its toxicity and reported clinical failures are well established. Binary efficacy endpoints evaluating alternative anti-MRSA therapies leave clinicians deciphering between segregated clinical and safety outcomes and do not provide a comprehensive patient-centered picture of comparative therapies. This study aimed to apply a novel methodology, desirability of outcomes ranking (DOOR), to compare anti-MRSA therapies. METHODS: This was a single-centered, retrospective, cohort of adult patients with MRSA BSI that received vancomycin, daptomycin, or ceftaroline. A previously developed DOOR for S. aureus BSI was adjusted and applied to this cohort to compare vancomycin-treated versus daptomycin/ceftaroline-treated patients. The DOOR had five mutually exclusive ranks: (1) alive without treatment failure, infectious complications, or grade 4 adverse events (AEs); (2) alive with any one of treatment failure, infectious complications, or grade 4 AE; (3) alive with two of treatment failure, infectious complications, or grade 4 AE; (4) alive with all three treatment failure, infectious complications, or grade 4 AE; or (5) deceased. RESULTS: A total of 43 vancomycin-treated and 13 daptomycin/ceftaroline-treated patients were included. Baseline clinical characteristics were similar, except for higher median serum creatinine in the daptomycin/ceftaroline cohort (0.76 [IQR 0.57, 1.11] vs 1.36 [IQR 1.09, 1.91] mg/dL, P = 0.03). Patients in the daptomycin/ceftaroline cohort had a 92% probability of better outcome using DOOR methodology. Patients treated with daptomycin/ceftaroline experienced less MRSA BSI persistence (0% vs 13.9%), MRSA BSI recurrence (7.8% vs 25.6%), grade 4 AEs (23.1% vs 46.5%), and in-hospital mortality (0% vs 9.3%). CONCLUSIONS: Although limited by sample size, this study demonstrates the potential of DOOR to produce valuable, patient-centered results. Clinicians are encouraged to become familiar with appropriate use and interpretation of DOOR methodology as it will become an increasingly common endpoint in clinical trials.

Interventions to reduce polypharmacy and optimize medication use in older adults with cancer.

The use of polypharmacy and potentially inappropriate medications (PIMs) is an increasingly common, concerning public health issue in older adults, and a concurrent cancer diagnosis only further escalates the prevalence and complexity. Polypharmacy and PIM use has been associated with negative patient outcomes, including falls, chemotherapy toxicities and other adverse events, postoperative complications, frailty, functional impairment, and shortened survival. Despite the recognition of the harms, the prevalence of polypharmacy and PIM use continues to rise due to a lack of standardized identification and intervention methods. Efforts to reduce the prevalence have included use of explicit PIM screening tools (e.g., Beers criteria), comprehensive medication reviews, and deprescribing algorithms. However, these efforts are not widespread and the research on the effectiveness of such interventions is limited. To better understand what is known, this paper summarized available studies evaluating the effect of interventions on reducing the burden of polypharmacy/PIMs and provided recommendations to guide further practice models to reduce the negative consequences associated with polypharmacy and PIM use. Furthermore, we aim to establish a framework for clinical practice and to highlight areas for future intervention-based research to improve outcomes for older adults with cancer.

Clinical strategies for optimizing infusion center care through a pandemic.

The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic.

Intravenous Fluid Management in Critically Ill Adults: A Review.

TOPIC: This article reviews the management of intravenous fluids and the evaluation of volume status in critically ill adults. CLINICAL RELEVANCE: Intravenous fluid administration is one of the most common interventions in the intensive care unit. Critically ill patients have dynamic fluid requirements, making the management of fluid therapy challenging. New literature suggests that balanced salt solutions may be preferred in some patient populations. PURPOSE OF PAPER: The bedside critical care nurse must understand the properties of various intravenous fluids and their corresponding impact on human physiology. The nurse's clinical and laboratory assessments of each patient help define the goals of fluid therapy, which will in turn be used to determine the optimal patient-specific selection and dose of fluid for administration. Nurses serve a vital role in monitoring the safety and efficacy of intravenous fluid therapy. Although this intervention can be lifesaving, inappropriate use of fluids has the potential to yield detrimental effects. CONTENT COVERED: This article discusses fluid physiology and the goals of intravenous fluid therapy, compares the types of intravenous fluids (isotonic crystalloids, including 0.9% sodium chloride and balanced salt solutions; hypotonic and hypertonic crystalloids; and colloids) and their adverse effects and impact on hemodynamics, and describes the critical care nurse's essential role in selecting and monitoring intravenous fluid therapy.

"Capturing your audience": analysis of Twitter engagements between tweets linked with an educational infographic or a peer-reviewed journal article.

Information represented through conventional text may fall short of capturing the attention and promoting engagement with today's digital audience. Transforming text into visual tools, such as infographics, has emerged as a simplified method of delivering information to attract a broader audience and enhance information dissemination. The first step to evaluate the potential value of infographics is to quantify their appeal and engagement rates over conventional text. This retrospective pilot analysis sought to evaluate the difference between engagement rates for tweets containing an of infographic compared to tweets containing a link to a peer-reviewed journal article. A total of 752 tweets were published within the study period; of these, 40 tweets met inclusion criteria. When engagement rates were compared, there was an increase in median engagement rates for tweets containing an infographic compared to a tweet linked to a peer-reviewed article at 10.97% (IQR 3.47%) and 5.33% (IQR 3.17%), respectively. This pilot study provides insight on the potential impact for infographics to enhance engagement rate, which may subsequently correlate with an increase in audience reach and readership. Prospective studies are needed to validate the utility of infographics in promoting scholarship publicity, learner engagement, and as a transferable pedagogical tool to educate medical practitioners.

Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Potential Role of Direct Oral Anticoagulants in the Management of Heparin-induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare, potentially life-threatening condition secondary to unfractionated heparin or low molecular weight heparin exposure. This immune-mediated drug reaction manifests as thrombocytopenia with a paradoxical hypercoagulable state that can result in life-threatening thrombosis. It is imperative to ensure cessation of heparin-based products as soon as HIT is identified. Traditional treatment options include argatroban, bivalirudin, fondaparinux, and danaparoid with a transition to warfarin upon platelet recovery. These anticoagulants are notwithstanding limitations including parenteral administration and routine laboratory monitoring leading to prolonged hospitalizations, emphasizing the need for new therapies. Direct oral anticoagulants (DOACs) have been increasingly investigated for the management of HIT and may overcome the aforementioned challenges of current therapies. The objective of this narrative review is to summarize the current HIT guidelines, discuss limitations to contemporary treatment options, provide insight into the emerging evidence for the DOACs rivaroxaban, apixaban, and dabigatran, and conclude with a clinical summary for their use in this setting. The PubMed, Google Scholar, and MEDLINE databases were searched for peer-reviewed literature from January 1, 2012, to June 31, 2018. Twenty-seven articles met inclusion criteria for review: 1 prospective trial, 5 retrospective cohort studies, and 21 case reports totaling 104 patients treated with a DOAC for HIT. The DOACs prevented new and recurrent thrombosis in 98% (n=102) of cases, and bleeding complications occurred in 3% (n=3). While current literature remains limited, it is suggestive of a potential role of DOACs for HIT, which has led to their integration into the 2018 American Society Hematology Guidelines with a conditional recommendation.

Clinical pharmacology of oncology agents in older adults: A comprehensive review of how chronologic and functional age can influence treatment-related effects.

Unique challenges exist when managing older adults with cancer. Associations between cancer and age-related physiologic changes have a direct impact on pharmacokinetics and pharmacodynamics of cancer therapies and can affect drug dosing, dose intensity, efficacy, safety and quality of life. The breadth and depth of these issues, however, have not been fully evaluated because the majority of clinical trials have focused on a younger and healthier population. As a consequence, little information is available to support clinicians in making evidence-based decisions regarding treatment with cancer therapies in older adults, especially those over age 75. Prior clinical pharmacology reviews summarized the literature on how age-related physiologic changes can influence and affect conventional and targeted anti-cancer treatments. Our article provides an updated review with expanded information that includes small molecule kinase inhibitors, monoclonal antibodies, immunotherapies, hormonal, conventional, and miscellaneous agents. Additionally, our article integrates how functional age, determined by the geriatric assessment (GA), can also influence treatment-related effects and health outcomes. Broadening cancer therapy trials to capture not only chronologic age but also functional age would allow clinicians to better identify subsets of older adults who benefit from treatment versus those most vulnerable to morbidity and/or mortality.

The prevalence of major drug-drug interactions in older adults with cancer and the role of clinical decision support software.

OBJECTIVES: Drug-drug interactions (DDIs) represent an escalating concern for older adults attributed to polypharmacy, multi-morbidity and organ dysfunction. Few studies have evaluated the prevalence of major DDIs and the variability between DDI detection software which confuses management. MATERIALS AND METHODS: Prevalence of major DDIs was examined as a secondary analysis of outpatients aged ≥65 years. Demographic and clinical information was collected from electronic health records including age, sex, race, cancer type, comorbidities, and medications. All DDIs were screened by a clinical pharmacist using Lexi-Interact® and Micromedex®. Major DDIs were defined as Lexi-Interact® category D or X and/or Micromedex® category major or contraindication. Summary statistics of patient characteristics and DDIs were computed. RESULTS: Our cohort included 142 patients (mean age, 77.7 years; 56% women, 73% Caucasian). The mean medications was 9.8 including 6.7 prescriptions, 2.6 non-prescriptions, and 0.5 herbals. Lexi-Interact® identified 310 major DDIs in 69% of patients (n = 98) with an average of 2.2 DDIs per patient. Micromedex® identified 315 major DDIs in 61% of patients (n = 87) with an average of 2.2 DDIs per patient. DDIs mostly involved opioids, antiplatelets, electrolyte supplements, antiemetics, and antidepressants. Variability existed with the severity rating reporting of the clinical decision support software. CONCLUSIONS: There was a high prevalence of major DDIs in older adults with cancer. Utilizing clinical decision support software was beneficial for detecting DDIs however, variability existed with severity reporting. Future studies need to identify the relevant DDIs with clinical implications in order to optimize medication safety in this population.