Efficacy and Safety of Testosterone Replacement in Testicular Cancer Survivors With Treatment-Influenced Hypogonadism: A Systematic Review.

OBJECTIVE: The objective is to evaluate the efficacy and safety of testosterone supplementation in testicular cancer survivors with treatment-related hypogonadism. DATA SOURCES: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and used Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus to obtain data in June of 2024. STUDY SELECTION AND DATA EXTRACTION: Analyses evaluating testosterone supplementation in testicular cancer survivors with treatment-induced hypogonadism were included. Any analyses not assessing supplementation in this population or deemed unretrievable were excluded. DATA SYNTHESIS: Ten analyses were included for analysis. A total of 332 bilateral or unilateral testicular cancer survivors with treatment-influenced hypogonadism were reviewed, with 238 patients receiving testosterone replacement. Eight of the 10 analyses assessed participants without poor quality-of-life (QOL) metrics, metabolic factors, and bone mineral density (BMD) at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation. Two analyses evaluated participants with poor QOL metrics or BMD at baseline and showed improvements in QOL or BMD with testosterone supplementation. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism. CONCLUSIONS: The results suggest testosterone replacement may be beneficial in patients with impaired QOL metrics, metabolic factors, and BMD at baseline; the results also suggest that routine supplementation for all individuals in this patient population lacks efficacy.

Phenobarbital Dosing for the Treatment of Alcohol Withdrawal Syndrome: A Review of the Literature.

Objective: To determine the most appropriate phenobarbital dosing regimen by evaluating the safety and efficacy of the drug when specifically used in alcohol withdrawal syndrome (AWS). Data sources: A comprehensive literary search was conducted using PubMed and bibliographic mining in October 2023. Study selection and data extraction: An established monotherapy phenobarbital regimen needed to be established within the article to be included in analysis. Location of implementation was not a deterrent to evaluation, nor was the route of phenobarbital administration. Data synthesis: Six publications were evaluated in this review, and two main phenobarbital dosing regimens emerged. While fix-based dosing strategies and weight-based dosing strategies resulted, the dosing within the regimens resulted in the same or relatively similar doses employed, respectively. Each of the studies had a statistically significant decrease in their primary outcome being studied, and the use of phenobarbital as monotherapy was proven to improve AWS symptoms, significantly decrease intensive care unit and hospital length of stay, decrease the use of adjunctive medications, decrease the use of a ventilator, and prevent seizures. Conclusions: Despite benzodiazepines having been the clinical first-line therapy for AWS, research shows that the pharmacokinetic stability and clinical benefits of phenobarbital are in support creation of phenobarbital protocols, as monotherapy, in hospitals or institutions for patients with AWS.

Evaluation of Anticonvulsant-Induced Leukocytosis: A Review of Evidence for Carbamazepine, Lamotrigine, and Phenobarbital.

Objective: The objective was to determine the incidence of leukocytosis associated with carbamazepine, lamotrigine, and phenobarbital. Data sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Embase, and Google Scholar through June 2023 using the following search terminology: "leukocytosis/chemically induced"[MeSH Terms] AND ("Anticonvulsants"[MeSH Terms] OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "anticonvulsant"[All Fields] OR "anticonvulsion"[All Fields] OR "anticonvulsive"[All Fields] OR "anticonvulsives"[All Fields]) OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "antiepileptic"[All Fields] OR "antiepileptics"[All Fields])). Study selection and data extraction: Thirteen reports were included from 64 potential results of our literature review following the application of inclusion and exclusion criteria: 7 of the reports involved carbamazepine, 4 of the reports involved lamotrigine, and 2 of the reports involved phenobarbital. Data synthesis: Drug-induced leukocytosis is commonly a diagnosis of exclusion and is a phenomenon that has numerous ramifications to patients and clinicians at the bedside, including mandating a full infectious evaluation, the identification of confounding variables, and the eventual discontinuation of the offending agent. Despite several medications and medication classes possessing this adverse drug effect, an evaluation of the specific clinical presentation and management strategies for drug-induced leukocytosis associated with anticonvulsant medications has not been elucidated in the literature. Conclusions: Clinicians should be judicious when evaluating leukocytosis in patients on potentially precipitating medications, including carbamazepine, lamotrigine, and phenobarbital.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Anticoagulation Strategies in the Management of Lemierre Syndrome: A Systematic Review of the Literature.

OBJECTIVE: To determine the optimal anticoagulation strategy in patients diagnosed with Lemierre Syndrome (LS). DATA SOURCES: A systematic review in accordance with PRISMA guidelines was conducted using PubMed, MEDLINE, Scopus, ProQuest, and CINAHL from January to April 2020. Search terms included "Lemierre Syndrome" AND "anticoagulation" NOT "prophylaxis" OR "atrial fibrillation," in addition to a list of parenteral and oral anticoagulants. Adult patients who developed a clot and required systemic anticoagulation as a result of LS were included in this review. STUDY SELECTION AND DATA EXTRACTION: A total of 4180 records were initially identified, though following the removal of duplicates and nonrelevant entries, 216 full-text articles were reviewed for inclusion; 13 articles were ultimately included. DATA SYNTHESIS: The majority (11/14) of patients developed thromboses of the internal jugular veins, which corresponds to the pathophysiology of LS. Anticoagulation strategies were varied in the included literature, though 12/14 patients initially received a parenteral product. Two patients received a direct-acting oral anticoagulant (DOAC) following either intravenous heparin or subcutaneous enoxaparin and had outcomes similar to patients transitioned to warfarin. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Anticoagulation in LS is a clinical controversy because the thromboembolic events have rarely led to significant complications; thrombi typically resolve independently, and concerns for bleeding risks are well founded; however, this review indicates both the efficacy and safety of anticoagulation. CONCLUSIONS: Anticoagulation is both efficacious and safe in LS, including treatment using a DOAC. Although further studies are needed, clinicians should consider a duration of anticoagulation of 6 to 12 weeks.

The Role of Phosphodiesterase-5 Inhibitors in COVID-19: An Exploration of Literature From Similar Pathologies.

Coronavirus Disease 2019 (COVID-19) has had a devastating impact on the ability of highly trained healthcare providers to render sufficient care, due to both the significant demand on resources and the unique nature of this disease that make it resistant to traditional therapies. This review sought to determine the potential role of phosphodiesterase-5 inhibitors (PDE-5) in the management of COVID-19 by extrapolating relevant data and clinical studies from other related disease states, including acute respiratory distress syndrome, acute lung injury, and high altitude pulmonary edema. Following a literature search, 4 reports were analyzed and included in this review. While the heterogenicity of data and the small number of trials included limit the interpretation and applicability, it was consistently demonstrated that PDE-5 inhibitors lowered pulmonary arterial pressures. The overall benefit of these agents is seemingly dependent upon the etiology of the respiratory failure, which warrants expanded clinical investigation for COVID-19.

Pharmacological Management of Steroid-Induced Psychosis: A Review of Patient Cases.

Objective: To review the efficacy and safety of medications used in the management of steroid-induced psychosis. Data Sources: A comprehensive literature search was conducted using PubMed, MEDLINE, ProQuest, and Scopus between May and October 2020 using the following search terminology: "steroid-induced psychosis" OR "corticosteroid-induced psychosis." Study Selection and Data Extraction: Definitive cases, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, were included in this review. Geriatric patients >65 years of age, those with a confounding neurological condition such as a traumatic brain or spinal cord injury, or those with active malignancy were excluded. Data Synthesis: A total of 13 patient cases were included in this review, representing 8 male patients and 5 female patients. The mean age at symptom presentation was 42.5 years. Six patients presented with delusions, 5 presented with hallucinations, and 2 presented with both manifestations; 12 patients were managed with an antipsychotic, with haloperidol being the most commonly prescribed, followed by risperidone. One patient was managed with lithium and clonazepam alone. All patients returned to their psychological baseline upon the discontinuation or decreased dose of steroids in combination with Pharmacological intervention, though the time to resolution of symptoms varied significantly. No notable adverse drug events associated with treatments were reported. Conclusions: Steroid-induced psychosis is a serious adverse effect of corticosteroid therapy; however, management strategies that combine a dose reduction or elimination of steroids, in combination with an antipsychotic medication, are effective in resolving this syndrome.

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.

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.

Manganese Toxicity Associated With Total Parenteral Nutrition: A Review.

Objective: To review hypermanganesemia-induced toxicities in adult patients receiving parenteral nutrition (PN) therapy. Data Sources: A comprehensive literature review was conducted from June 2020 to May 2021 on PubMED, MEDLINE, Scopus, ProQuest, the Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Web of Science. Study Selection and Data Extraction: Keyword and Boolean phrase searches were conducted using the following terminology: "manganese" OR "manganesemia" OR "manganism" or "hypermanganesemia" AND "total parenteral nutrition" OR "PN" or "parenteral nutrition" AND "toxicity" OR "accumulation." Appropriate filters, including "humans" and "English" and NOT "reviews," were utilized on all databases to improve search outcomes. Data Synthesis: A total of 4 reports detailing hypermanganesemia in 57 patient encounters were included in this review. Significant heterogeneity exists with regard to the duration of manganese supplementation and the dose of manganese. Toxicity associated with manganese was observed in as few as 15 days. The dose of manganese, though likely governed by content in commercially available products, may regularly exceed the recommendations of clinical guidelines and should be limited to 55 µg/day. Select patients with underlying malignancy, those with significant and prolonged Vitamin D deficiency, or those who have acquired a SLC30A10 genetic mutation may be at an increased risk of developing manganese toxicity. Conclusions: Clinicians must be cognizant of the concentration of trace elements added to PN, as manganese, and perhaps other biometals, may accumulate when dosed above the recommended daily allowances.

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.