The efficacy and safety of direct oral anticoagulants in the treatment of the acute phase of heparin-induced thrombocytopenia: A systematic review.

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: To investigate the safety and efficacy of direct oral anticoagulants (DOACs) in the treatment of the acute phase of heparin-induced thrombocytopenia (HIT). SUMMARY: A systematic review of the literature was conducted on PubMed, MEDLINE, Embase, and Web of Science Core Collection through July 2023. Search terms included "heparin-induced thrombocytopenia AND direct-oral-anticoagulants" in addition to a list of oral anticoagulants. Adult patients who used direct oral anticoagulants as the initial treatment for the acute phase of HIT were included. A total of 1,188 articles were initially identified, with 770 articles reviewed following removal of duplicates. Following the application of inclusion and exclusion criteria, 12 articles were ultimately included. Rivaroxaban was the most-utilized DOAC (28 patients), followed by apixaban (7 patients) and dabigatran (1 patient). All patients with thrombocytopenia demonstrated successful platelet recovery, with two patients presenting with normal platelet counts. One patient developed a deep venous thrombosis with no other new or recurrent thromboses. There were no reported clinically significant adverse events in any patient. Obstacles and deterrents to the use of the standards of care in the acute phase of HIT exist. Argatroban and bivalirudin require intravenous infusion and require close aPTT monitoring and dose adjustment. Fondaparinux requires injection and is contraindicated with body weight <50kg. DOACs would offer the novel ability for an oral treatment in the treatment of the acute phase HIT and allow for minimal monitoring and consistent dosing strategies. Therefore, DOACs are an intriguing choice for the treatment of the acute phase of HIT. CONCLUSION: Data from 12 publications and across 36 patients suggests that the use of DOACs in the acute phase of HIT may be a safe and efficacious treatment option with favorable ease of monitoring and management.

Examining an Interaction Between Plasma Exchange and Apixaban Resulting in an Acute Ischemic Stroke.

Objective: Therapeutic drug monitoring is not routinely considered necessary in patients undergoing plasma exchange; however, it is possible for serum concentrations of select medications to be impacted by this procedure. Case: We describe a 50-year-old patient who presented to our facility with new onset aphasia and right-sided weakness. Despite presenting with a National Institute of Health Stroke Severity (NIHSS) score of 23, the patient did not receive fibrinolytic therapy due to his being anticoagulated with apixaban for atrial fibrillation. The patient instead underwent an emergent thrombectomy which resulted in a post-operative Thrombolysis in Cerebral Infarction (TICI) score of 3. The patient had a significant past medical history including numerous previous strokes necessitating assistance with activities of daily living, atrial fibrillation, chronic kidney disease, and thrombocytopenic purpura, for which he was receiving twice weekly plasma exchange and immunomodulatory therapy. The patient's last plasma exchange session was approximately 24 hours prior to admission, leading us to hypothesize that the patient's plasma exchange may have been implicated in the removal of apixaban from the serum and precipitating a stroke. Discussion/Conclusions: Heterogeneity of data exists when evaluating the effect of plasma exchange on apixaban. Although the drug properties of apixaban, including its low volume of distribution and high plasma protein binding capacity, support the notion that it may be vulnerable to removal through plasma exchange, only one other case report has been published on this phenomenon.

Serotonin syndrome and neuroleptic malignant syndrome: A case report of intersecting symptomatology.

Introduction: Serotonin syndrome and neuroleptic malignant syndrome are caused by 2 distinct pathologies; however, the clinical presentation associated with both syndromes share many features. Methods: We describe a 56-year-old male patient who presented to our facility with seizures, leukocytosis, fevers, extremity hyperreflexia, and signs of autonomic dysfunction as evidenced by cardiovascular instability. The patient was noted to be taking vortioxetine, trazodone, lamotrigine, lurasidone, and carbidopa-levodopa as outpatient medications for his depression, an unspecified mood disorder, and Parkinson disease. Following a robust workup and failure of other therapies, all serotonergic and dopaminergic medications were held, and the patient was tried on cyproheptadine for serotonin syndrome, which led to the cessation of fevers. Bromocriptine was added to the regimen, which led to the resolution of the remainder of the patient's symptoms. Results: The overlapping symptomatology of several key diagnostic criteria for both serotonin syndrome and neuroleptic malignant syndrome as well as their nature as diagnoses of exclusion require an evaluation of the patient's aggregate improvement following targeted pharmacologic strategies for both syndromes. The efficacy of both cyproheptadine and bromocriptine when administered concomitantly support the concurrent pathologies. Discussion: Clinicians at the bedside must be cognizant of the potential for clinically relevant drug-drug interactions that may present with overlapping pathologies.

Methylxanthine Derivatives in the Treatment of Sinus Node Dysfunction: A Systematic Review.

While the chronotropic effects of theophylline and aminophylline are well-known, their clinical application in the treatment of sinus node dysfunction has not been established in a review. The purpose of this systematic review is to evaluate the efficacy and safety of methylxanthines in the treatment of bradyarrhythmias associated with sinus node dysfunction. A systematic review was conducted in accordance with PRISMA guidelines on Embase, PubMed, MEDLINE, Cochrane Central, Web of Science, SciELO, Korean Citation Index, Global Index Medicus, and CINAHL through June 2023. A total of 607 studies were identified through the literature search. After applying the inclusion and exclusion criteria, 14 studies were included in this review. The causes of bradyarrhythmias involving the sinoatrial node included acute cervical spinal cord injury, coronavirus disease of 2019, carotid sinus syncope, chronotropic incompetence, heart transplant, and chronic sinus node dysfunction. Theophylline and aminophylline were shown to be effective for increasing heart rate and reducing the reoccurrence of bradyarrhythmias. The data on symptom resolution was conflicting. While many case studies reported a resolution of symptoms, a randomized controlled trial reported no significant difference in symptom scores between the control, theophylline, and pacemaker groups in the treatment of sick sinus syndrome. The incidence of adverse effects was low across all study designs. The data suggests methylxanthines may be useful as an alternative or bridge to nonpharmacologic pacing; however, dosing has yet to be established for various indications. Overall, methylxanthines proved safe and effective as a pharmacologic therapy for bradyarrhythmic manifestations of sinus node dysfunction.

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review.

OBJECTIVE: The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions. DATA SOURCES: A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: "psilocybin" AND "mental-disease" OR "substance-dependence" AND "disease-therapy," in addition to other synonymous key words. STUDY SELECTION AND DATA EXTRACTION: Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review. DATA SYNTHESIS: The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients. CONCLUSIONS: Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.

Wernicke's Encephalopathy and Serotonin Syndrome: A Case Report of Overlapping Pathologies.

Objective: Acute encephalopathy is a common symptom encountered in critically ill patients and may be associated with Wernicke's encephalopathy (WE) or serotonin syndrome (SS). We describe a patient who presented with clinical manifestations of both WE and SS and who responded to treatment for both pathologies. Case: A 56-year-old male presented after being found unresponsive and in a questionable tonic-clonic state. Past medical history was significant for depression managed with fluoxetine 20 mg by mouth daily and alcohol use disorder. A physical exam revealed severe clonus in the bilateral lower extremities; diffuse hyperreflexia along with akinesia on the left upper extremity; ophthalmoplegia; and persistent tachycardia despite pharmacologic interventions. It was learned that the patient had been taking his fluoxetine 3 times per day rather than daily as prescribed. Oral cyproheptadine was administered at a 12 mg initial dose followed by 4 mg every 6 hours. A thiamine regimen of 500 mg intravenous (IV) every 8 hours in addition to folic acid 1 mg IV every 24 hours was initiated to treat WE. Physical symptoms of both WE and SS resolved within 48 hours, and the patient was ultimately discharged to home in stable condition. Discussion/Conclusions: The clinical diagnosis of both WE and SS in this case is supported by the Caine and Hunter criteria, respectively, as well as the resolution of symptoms with accepted treatment modalities for each. It is important for clinicians to be cognizant of potential overlapping pathologies when patients present with nonspecific symptoms, especially acute encephalopathy, in the intensive care unit.

The Role of Dexmedetomidine in Paroxysmal Sympathetic Hyperactivity: A Systematic Review.

OBJECTIVE: The objective was to evaluate the efficacy and safety of dexmedetomidine in the treatment and prophylaxis of paroxysmal sympathetic hyperactivity (PSH). DATA SOURCES: A review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and queried Embase, MEDLINE (PubMed), Cochrane CENTRAL, Web of Science, SciELO, Korean Journal Index (Clarivate), Global Index Medicus, and CINAHL Plus for results through June 2023. STUDY SELECTION AND DATA EXTRACTION: Studies providing efficacy or safety data associated with dexmedetomidine with a reported diagnosis of PSH were included. Exclusion of studies in pediatric populations, without quantitative and qualitative outcome data, and not readily translatable to English was adhered to. DATA SYNTHESIS: Thirteen observational studies of 178 patients were included in the qualitative analysis. Reductions in PSH frequency or symptom severity were reported in 44 of 48 patients who received dexmedetomidine for acute treatment. Prophylactic use of dexmedetomidine was associated with reductions in PSH-Assessment Measure (PSH-AM) scores in postsurgical patients with traumatic brain injuries (TBIs). Adverse events associated with dexmedetomidine were either absent or reported as none. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review supports the safe and effective use of dexmedetomidine in the treatment and prophylaxis of PSH. Further investigation is required to determine optimal dosing strategies and the extent to which PSH etiology correlated to the efficacy of dexmedetomidine. CONCLUSIONS: The use of dexmedetomidine appears to be both efficacious and safe for the treatment and prevention of PSH in patients experiencing a TBI. Additional research is needed to elucidate dosing strategies, titration parameters, and duration of therapy.

An Evaluation of Tertiary Drug Resources' Consistency Regarding Drug-Drug Interactions Between Tricyclic Antidepressants and Herbal Supplements.

Background: Tertiary drug information resources are utilized frequently by health care providers. While pharmacists are uniquely trained and prepared to interpret the information available on these resources, including the results of drug-drug interaction evaluations, discrepancies between such resources pose a major concern for clinicians with regard to patient safety and medication regimen efficacy. It was postulated that drug-drug interaction evaluations between prescription medications and over-the-counter herbal supplements would be particularly problematic. Objective: The objective of this project was to distinguish the discrepancies between tertiary drug information resources in the setting of drug-drug interactions between tricyclic antidepressants (TCAs) and herbal supplements. Methods: The following medications and herbal supplements were evaluated on Lexicomp, Micromedex, and Medscape: amitriptyline, nortriptyline, doxepin, imipramine, desipramine, amoxapine, St. John's Wort, valerian root, ginkgo biloba, and ginseng. Results: While all of the tertiary drug information resources identified a significant reaction between each TCA and St. John's Wort due to the risk of serotonin syndrome, several other discrepancies were noted, with regard to both the severity of the interaction indicated and whether or not an interaction was identified. Conclusion: It is imperative that clinicians be aware of potential discrepancies between tertiary drug information resources, including the potential for variation in both the clinical interpretation of its severity and the recognition of an interaction.

Tricyclic Antidepressants in Nociceptive and Neuropathic Pain: A Review of Their Analgesic Properties in Combination With Opioids.

Objectives: To determine the efficacy and safety of commonly prescribed tricyclic antidepressants (TCAs) as analgesics for nociceptive and neuropathic pain in combination with opioids. Data Sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Scopus, and Web of Science using the following search terminology: "Amitriptyline" OR "Doxepin" OR "Desipramine" OR "Imipramine" OR "Nortriptyline" OR "Clomipramine" OR "Trimipramine" AND "Analgesia." Reports of adult patients who received any TCA as an adjunctive analgesic to opioids were included. Study Selection and Data Extraction: A total of 293 results were obtained from the initial database inquiries, following which exclusion criteria were applied and 6 articles were included in this review. Three of the reports detailed the use of TCAs in the perioperative setting, whereas the remaining 3 evaluated their effect on different etiologies of neuropathic pain. Data Synthesis: Tricyclic antidepressants were found to have modest, yet not insignificant, independent analgesic properties, although the ability to provide pain relief was relegated to a select few agents. Desipramine has the most data available for use in nociceptive, postoperative pain through its ability to potentiate and prolong the analgesic effects of opioids and was not associated with adverse drug effects. Conclusions: The efficacy of TCAs for neuropathic pain was not corroborated by this review, and the anticholinergic adverse effects associated with this drug class were found to be significant. Further research is needed to quantify the efficacy of TCAs in the management of nociceptive pain.

Pharmacologic Management of Central Fever: A Review of Evidence for Bromocriptine, Propranolol, and Baclofen.

Objective: The purpose of this review was to evaluate the clinical data supporting bromocriptine, propranolol, and baclofen in the pharmacologic management of central fever. Data Sources: A comprehensive literature review was performed between January 2018 and August 2022 using the following keywords: "central fever" NOT "fever" OR "infection" OR "infectious" AND "neurocritical" OR "neurology" AND "treatment" AND "medication" OR "medicine" OR "drug" OR "pharmaceutical." Study Selection and Data Extraction: A total of 6 case reports met specified inclusion criteria, with 2 reporting on each of the evaluated medications. Data Synthesis: Significant heterogeneity exists regarding dosing strategies and duration of treatment with these medications for the management of central fever. Although each medication demonstrated the ability to restore normothermia, the variation in underlying cause of the fever and lack of cross-over evaluation between different medications makes a definitive treatment strategy for any of these agents elusive. Conclusions: The development of a central fever has been associated with poor outcomes in patients who have suffered a critical neurologic injury. Although their exact mechanism for this indication has not been fully elucidated, anecdotal evidence seemingly supports the use of bromocriptine, propranolol, and baclofen.

Muscle relaxants as adjunctive analgesics in the perioperative setting: A review of the literature.

Patients undergoing surgical procedures are one of the few populations that still require substantial doses of opioid medications to provide analgesia, despite the best efforts of clinicians to integrate non-opioid adjunctive analgesics into practice. While many options exist with varying degrees of evidence, one drug class that deserves renewed consideration are muscle relaxants. Although these medications have differing mechanisms of action and require a more thorough evaluation of patient parameters prior to administration as opposed to other adjunctive analgesics, it is readily apparent by the results of this review that these agents may be able to mitigate pain and limit opioid usage. The objective of this review was to determine the efficacy and safety of adjunctive muscle relaxers for the purposes of analgesia in the perioperative setting.

Heparin infusions in aneurysmal subarachnoid hemorrhages: clinical considerations for use beyond anticoagulation.

INTRODUCTION: Patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH) may face a significant morbidity burden following the acute phase of their injury. Though commonly employed as an anticoagulant, heparin may have clinical utility related to its ability to mitigate the production of pro-inflammatory cytokines and chelate oxidized blood. AREAS COVERED: A comprehensive review of the literature was conducted on PubMed, MEDLINE, Scopus, Cumulative Index of Nursing and Allied Health Library and Web of Science with the assistance of a medical reference librarian from January 2018 to March 2022. Two pieces of literature were evaluated in this review, both of which sought to determine the either efficacy or safety of heparin infusions in patients following an aSAH. The small sample size and the heterogeneity of outcome data reported makes defining a role in therapy for heparin difficult; however, it may be reasonable to use lower weight-based doses and to target a lower aPTT goal when considering a heparin infusion in these patients. EXPERT OPINION: Many options beyond heparin infusions exist in the armamentarium for clinicians when managing aSAH patients. Additional research is required to elucidate therapeutic drug monitoring targets and dosing protocols.

Cannabidiol in refractory status epilepticus: A review of clinical experiences.

OBJECTIVE: To summarize and evaluate clinical experiences with refractory status epilepticus in which cannabidiol (CBD) was utilized for cessation of seizure activity. METHODS: A comprehensive literature review was performed on PubMED, MEDLINE, Scopus, and CINAHL between May - June 2022 with the assistance of a medical reference librarian using the following search terms: "Cannabidiol" [MAJR], "Status Epilepticus" [MAJR], "New-Onset Refractory Status Epilepticus", and "cannabidiol." Reports that provided dosing regimens and patient outcomes were included. RESULTS: Thirty-two articles were screened. Five articles were selected for inclusion in this review and detailed the clinical courses of 11 patients. Five of the 11 patients received CBD during the chronic epilepsy stage, while the remaining 6 received it during a period of acute status epilepticus. Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation. CONCLUSIONS: CBD may provide a potentially efficacious and safe management strategy in refractory status epilepticus, including patients with new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. A potential for drug-drug interactions between CBD and anti-epileptic drugs warrants judicious monitoring. Additional research is necessary to determine a definitive dosing strategy for this agent.

Seizures Associated With Bone Density Conservation Agents.

Objective: The purpose of this review is to discuss the existing literature regarding patients who have experienced seizures after administration of a bone density conservation agent (BDCA). Data Sources: A comprehensive literature review was performed between September and October 2021 using the following keywords: osteoporosis/drug therapy, seizures/chemically induced, hypercalcemia, hypocalcemia, osteoporosis, seizure risk, osteoclast medication, seizures, bisphosphonates, risedronate, zoledronic acid, pamidronate, denosumab, Prolia, Xgeva, calcitonin, BDCAs. Study Selection and Data Extraction: A total of 90 articles were identified, but only 6 articles met prespecified inclusion and exclusion criteria. These articles included 4 case reports, 1 case series, and 1 retrospective cohort study. Data Synthesis: Two case reports and 1 case series described the occurrence of seizures with the use of zoledronic acid. One case report described the occurrence of seizures with the use of alendronate, 1 retrospective cohort study with the use of denosumab, and 1 case report with the use of calcitonin. The articles displayed a variety of contributing factors that could have caused seizures including those with a prior history of seizures, calcium or vitamin D deficiency prior to starting therapy, a history of gastrectomy impairing glucose homeostasis, or concurrent infection. Conclusion: While there is not a direct link to BDCA causing seizures, the hypocalcemic effect may be severe enough in some patients to precipitate a seizure. The correction of underlying conditions and electrolyte disturbances should be addressed before initiating a BDCA. Further studies are needed to better explore the relationship between BDCA and seizures.

Clinical considerations for rapid administration of undiluted or minimally diluted levetiracetam bolus doses.

INTRODUCTION: The ability to administer medications via rapid intravenous bolus has the potential to allow for the rapid attainment of therapeutic drug levels and to limit the amount of unnecessary fluid volumes infused. The purpose of this review was to evaluate the efficacy and safety of undiluted or minimally diluted levetiracetam bolus doses. AREAS COVERED: A total of six pieces of the literature were evaluated in this review. Doses of up to 4,500 mg of intravenous levetiracetam were found to be both efficacious and safe when administered undiluted or minimally diluted in either a peripheral or central line. Product concentrations of levetiracetam ranged from 50 mg/mL to 100 mg/mL, with volumes ranging from 10 to 30 mL. Maintenance doses of up to 1,500 mg twice daily were demonstrated to be both efficacious and safe when administered undiluted or minimally diluted. Injection site pain and agitation were the most commonly reported adverse drug effects. EXPERT OPINION: Although hospitals and clinicians must be judicious with regard to training and the safety concerns of bolus intravenous push doses, and will need to address numerous logistical concerns, this practice is supported by practice guidelines and should be readily employed.

Dosing Considerations for Combination Antistaphylococcal ß-Lactam and Glyco/lipopeptide Salvage Therapy for Resistant Gram-Positive Infections: A Systematic Review.

OBJECTIVE: The objective of this systematic review is to evaluate dosing regimens of combination salvage regimens used as part of infectious disease pharmacotherapy. DATA SOURCES: A systematic review was conducted on PubMed, MEDLINE, Scopus, ProQuest Central, and CINAHL through March 2021 using the following terminology: "combination" OR "Seesaw" OR "see-saw" OR "salvage" AND "infection" OR "resistant infection" OR "Gram-positive" AND "beta-lactam" OR "cephalosporin" OR "carbapenem" OR "monobactam" OR "glycopeptide" OR "lipopeptide." STUDY SELECTION AND DATA EXTRACTION: Following the application of inclusion and exclusion criteria, 8 pieces of literature were ultimately included in this review. DATA SYNTHESIS: Vancomycin in combination with another agent was most commonly prescribed as initial or empirical therapy. The most common combination salvage therapy regimen consisted of daptomycin in doses up to 12 mg/kg IV every 24 hours with ceftaroline 200 to 600 mg IV every 8 to 12 hours. Although the duration of combination salvage therapy varied drastically, blood culture clearance was typically observed within 24 hours. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Antimicrobial-resistant Gram-positive organisms have posed an emergent threat to antimicrobial stewardship initiatives. Utilizing either a glycopeptide or lipopeptide antibiotic in combination with an antistaphylococcal ß-lactam antibiotic has demonstrated efficacy in treating resistant bacteria. This work describes the heterogeneity of dosing regimens and seeks to define an optimal dose, duration, and combination of antibiotics. CONCLUSIONS: Combination salvage therapy has demonstrated efficacy and safety in treatment of resistant Gram-positive infections. It appears the combination of daptomycin and ceftaroline can clear resistant infections expeditiously.

Hypermanganesemia-Induced Cerebral Toxicity Mimicking an Acute Ischemic Stroke: A Case Report and Review of Overlapping Pathologies.

Objective: To review and consider risk factors associated with the accumulation of and toxicity from manganese in patients receiving total parenteral nutrition (TPN). Case Summary: A 66-year-old female presented to the emergency department with right facial and arm weakness that initiated 1 hour prior to admission. Past medical history includes oral cancer with chronic aspiration and gastroparesis secondary to chemotherapy, TPN for 9 months, and a previous episode of right facial and arm parasthesias due to hypertensive emergency 4 years prior. The patient was assigned a National Institutes of Health Stroke Scale score of 6, cleared of an intracranial hemorrhage on imaging, and was administered tPA (tissue plasminogen activator) for an acute ischemic stroke after managing her hypertension to <185/110 mm Hg. Resolution of symptoms occurred within 24 hours. A magnetic resonance imaging of the patient's brain 24-hours post-tPA indicated an increased signal density in the globus pallidus, which in turn is linked with encephalopathy and has been described as a marker for hypermanganesemia. Discussion: Manganese is an essential trace element with a critical role in numerous physiologic functions. Though readily obtained from dietary sources and rarely causing issue, manganese provided to patients via TPN may result in toxicities. Though the presentation of neurotoxicities associated with TPN-delivered manganese has been previously documented, the clinical presentation of toxicity has never mimicked an acute ischemic stroke. Conclusion: Though an evaluation of overlapping pathologies is warranted, this patient's clinical presentation of manganese toxicity mimicked an acute ischemic stroke and resulted in the administration of a fibrinolytic. A more comprehensive appreciation of the implications of trace elements is demanded of clinicians.

Remdesivir and Coronavirus Disease 2019 (COVID-19): Essential Questions and Answers for Pharmacists and Pharmacy Technicians.

Objective: To conduct a review of the investigational drug remdesivir and its therapeutic potential for treatment of COVID-19, in the form of a series of questions and answers. The purpose of the review is to narrow gaps in knowledge, clarify concepts, and to investigate research advancements for health care professionals. Data Sources: From June 2020 to August 2020, we conducted comprehensive searches of MEDLINE-PubMed, Scopus, and Google Scholar databases with no time limitations. Search terms were included that contained the terms "remdesivir," "COVID-19," "novel coronavirus" and "evidence," "therapy," "safety," "effectiveness," "efficacy," "clinical trial." Study Selection and Data Extraction: The sources of information include all publicly available data from previously published research reports. Reports must have at least one reference to remdesivir as a treatment modality for COVID-19 with no specified outcomes. Data Synthesis: Major research findings on the efficacy and safety of remdesivir are summarized in tabular format and presented in chronological order. Results of this review reveal remdesivir to be an effective therapy in specific clinical contexts; however, in several areas, available data are insufficient to support evidence-based guidance for remdesivir in the treatment of COVID-19. Conclusions: Clinical trials on remdesivir are ongoing, yet questions remain and further research is needed as to the selection of patients, effectiveness, and duration of treatment in the use of remdesivir for treatment of COVID-19.

Thiamine Dosing for the Treatment of Alcohol-Induced Wernicke's Encephalopathy: A Review of the Literature.

Objective: To determine the most appropriate thiamine replacement regimen by evaluating safety and efficacy of the drug specific to alcohol-induced Wernicke's encephalopathy (WE). Data Sources: A comprehensive literature search was conducted using PubMed, MEDLINE, Scopus, and ProQuest between January and August 2020 using the following keyword and Boolean search terminology: "thiamine" AND "alcohol" AND (encephalopathy OR korsakoff). Study Selection and Data Extraction: Randomized control trials; prospective, observational, and retrospective cohort analyses; and case reports and series were included in this evaluation. A confirmed diagnosis of alcohol-induced WE and treatment with parenteral or intramuscular (IM) thiamine were required for inclusion. Data Synthesis: Six publications composed of 138 patients were evaluated in this review, in which a wide variety of thiamine supplementation strategies were employed. Clinical diagnostic criteria varied significantly between publications. Doses ranged from 100 to 1500 mg intravenous thiamine and up to 300 mg IM thiamine, with no apparent difference in patient outcomes. All patients who received thiamine experienced symptom improvement, and adverse drug events were minimal. Conclusions: Despite the clinical controversy regarding the appropriate thiamine supplementation regimen, the heterogeneity of published works combined with symptom resolution across the gamut of dosing strategies makes a definitive consensus elusive. Clinicians should continue to provide parenteral or IM thiamine in doses of ≥100 mg to patients with confirmed alcohol-induced WE.

A Comparison of Tertiary Drug Resources' Consistency Regarding Drug-Drug Interactions of Adjunctive Analgesics.

Background: Health care providers routinely rely on tertiary drug information resources to affirm knowledge or proactively verify the safety and efficacy of medications. Though all patient care areas are affected, the reliability of these resources is perhaps nowhere as poignant as it is in high-acuity settings, including the emergency department and the intensive care unit. As providers seek to identify adjunctive analgesics for acute pain in these areas, they must be able to rely on the integrity to whichever resource their institution has granted access. Objective: To determine the congruency of drug-drug interaction information found on 3 tertiary drug resources. Methods: A drug-drug interaction analysis was conducted on Micromedex, Lexicomp, and Medscape. Adjunctive analgesics included dexmedetomidine and ketamine, which were compared with the intravenous opioid products morphine, fentanyl, and hydromorphone. Results: Significant discrepancies were appreciated with regard to the severity of drug-drug interactions. In addition, the heterogeneity in which reaction severity and likelihood are described by each respective resource makes direct comparisons difficult. Interaction warnings for dexmedetomidine and fentanyl included a "major interaction" from Micromedex, whereas Lexicomp did not identify a risk and Medscape only recommended increased monitoring on the grounds of respiratory and central nervous system depression. Conclusions: Health care providers must remain vigilant when reviewing tertiary drug information resources. Pharmacists possess the training and skills necessary to assist interdisciplinary medical teams in providing optimal patient care through evaluating and applying the information gleaned from these resources.