Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study.

Background There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin. Methods Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality. Results Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively. Conclusion The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.

Severe palmar-plantar erythrodysesthesia and aplasia in an adult undergoing re-induction treatment with high-dose cytarabine for acute myelogenous leukemia: a possible drug interaction between posaconazole and cytarabine.

High-dose cytarabine is recommended for re-induction chemotherapy in patients less than 60 years of age with acute myelogenous leukemia. This case describes a patient receiving high-dose cytarabine for re-induction and subsequently developed tingling and numbness in her hands and feet followed by severe pain, swelling, and erythema consistent with a diagnosis of palmar-plantar erythrodysesthesia. Furthermore, the patient's hemoglobin, platelets, and neutrophils did not recover after over 30 days post high-dose cytarabine. The patient was concurrently receiving posaconazole for fungal prophylaxis which was initiated after the induction therapy. We speculate that posaconazole may inhibit the cytarabine efflux through P-glycoprotein inhibition leading to the patient's palmar-plantar erythrodysesthesia and subsequent aplasia. Future pharmacokinetic studies need to be conducted to ascertain if posaconazole does influence the pharmacokinetics of cytarabine.

U-47700: A Clinical Review of the Literature.

BACKGROUND: U-47700 is a synthetic opioid developed by The Upjohn Company in the 1970s, which has recently appeared in the news and medical literature due to its toxicity. Currently, there are no clinical trial data assessing the safety of U-47700. OBJECTIVE: To describe the signs and symptoms of ingestion, laboratory testing, and treatment modalities for U-47700 intoxication. DISCUSSION: We searched PubMed, Embase, Web of Science, and EBSCO for articles using the term "U-47700" and "47700." The following inclusion criteria were used: had to be in English; full text; must involve humans; must be either a randomized control trial, prospective trial, retrospective analysis, case series, or case report; and must include clinical findings at presentation. We identified and extracted data from relevant articles. Ten relevant articles were included with 16 patients. Patients that died after overdose with U-47700 typically presented to the hospital with pulmonary edema. Patients who survived an overdose presented with decreased mental status and decreased respiratory rate suggestive of an opioid toxidrome. Patients also commonly had tachycardia. Immunoassays failed to identify U-47700, and the identification of U-47700 required the use of chromatographic and spectral techniques. CONCLUSION: We report the first clinical review of U-47700 intoxication.

Gamer's Thrombosis: A Review of Published Reports.

Background: Thrombosis, well known as a condition of the elderly, is occurring in the otherwise healthy adolescent population. Immobility is a significant risk factor for venous thromboembolism (VTE), and adolescents who play video games are immobile for extended periods of time. Some are presenting with VTE. When other risk factors such as obesity are present, the risk of VTE formation increases. We provide a review of published case reports regarding gaming and thrombosis. Methods: We searched PubMed, Scopus, Web of Science, and EBSCO for articles published through July 2019, using the keywords "computer game thrombosis," "computer game pulmonary embolism," "computer game deep vein thrombosis," "video game thrombosis," "video game pulmonary embolism," and "video game deep vein thrombosis." Results: Of the 26 articles we identified, we included 12 articles in our review that report a total of 15 cases, of which 2 resulted in fatalities. Modifiable risk factors included cigarette use, being overweight, birth control use, and prolonged immobility. Anticoagulation was the principal treatment modality in patients presenting with gaming thrombosis. Conclusion: We strongly encourage screening gamers for possible VTEs if clinically warranted.

Treating Non-fentanyl-derived Synthetic Opioid Overdose with a Traditional Opioid Reversal Agent.

As the opioid crisis in the United States continues to grow, non-fentanyl-derived synthetic opioids (NSOs) are growing in both availability and popularity. NSO use comes with considerable risk including a high potential for both abuse and overdose. In this editorial, we review the consequences of overdose with the NSOs U-47700 and butyrfentanyl (BF) and the potential for the use of naloxone as a treatment for such instances. Naloxone administration was found to be successful in reversing opioid effects and re-establishing independent breathing in a patient taking U-47700 or BF. With a high rate of success in treating opioid overdose and a low chance of negatively affecting healthy non-dependent persons, naloxone is an ideal medication in these situations. We recommend the use of naloxone in cases of NSO opioid overdose and advocate for the increased availability of naloxone products to improve overdose outcomes nationwide.

Optimizing Patient Outcomes with PD-1/PD-L1 Immune Checkpoint Inhibitors for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

The rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) now includes two agents, pembrolizumab and atezolizumab, approved for first-line treatment of advanced non-small cell lung cancer (aNSCLC) as monotherapy or as part of chemoimmunotherapy. This review summarizes the clinical evidence supporting these indications, with a focus on strategies to optimize patient outcomes. These strategies include patient and tumor factors, adverse-effect profiles, pharmacokinetic and pharmacodynamic drug interactions, and quality of life and cost-effectiveness considerations. We performed a systematic literature search of the PubMed, Scopus, and Google Scholar databases, as well as a search of the conference proceedings of the American Society of Clinical Oncology, European Society for Medical Oncology, and American Association for Cancer Research (through August 31, 2019). The addition of ICIs to conventional chemotherapy as first-line treatment against aNSCLC is now part of the standard of care options. However, even though ICIs may be cost-effective in patients with aNSCLC, high drug and other associated costs can still be a barrier to treatment for patients. Moreover, the adverse-effect profiles of ICIs differ significantly from conventional chemotherapy, and some immune-related adverse effects may have a lasting impact on quality of life. Therefore, in adhering to a patient-centered model of care, clinicians should be mindful of patient- and treatment-specific factors when considering therapeutic options for patients with aNSCLC. Although the role of the immune system in cancer progression and regression has not been fully elucidated, the full clinical potential of immunotherapeutics in the treatment of cancer likely remains to be unleashed.

The Road to a Hypoglycemic Care Model.

Hypoglycemia is a modifiable condition that causes mortality and readmission rates to increase in a hospital setting. The condition is worsened by its complications, quick onset, and an absence of a protocol mapped out by hospitals. This complication does not come from one origin, but rather from a range of barriers. Research from a variety of sources, such as those found from the American Diabetes Association, have shown great promises in ways to treat and prevent hypoglycemia that are of importance to highlight for practitioners in the inpatient setting.

An Unnecessary Pain: Using Pharmacogenetics for Statin-related Skeletal Muscle Toxicity.

Statins are an important class of medications in reducing the risk of cardiovascular events as well as overall mortality. However, a well-known adverse effect of statins is skeletal muscle toxicity, which may lead to abrupt discontinuation of the statin. In turn, patients may miss out on the benefits of statin therapy. An important factor to consider is a patient's solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism status. Herein, an overview of the pharmacogenetics of SLCO1B1 is provided as well as recommendations for use in practice.

Putting Out the Fire: The Relationship of Pharmacogenetics and Proton Pump Inhibitors for the Treatment of Gastroesophageal Reflux Disease.

Proton pump inhibitors (PPIs) are a mainstay treatment for gastroesophageal reflux disease (GERD) and are mainly metabolized by CYP2C19 in the liver. However, several polymorphisms of CYP2C19 exist that affect the metabolism of PPIs. Due to the large variability of PPI pharmacokinetics among the polymorphisms, this has implications in the management of patients with refractory GERD who may be potentially undertreated. Herein, we discuss the role of CYP2C19 and its relation to PPI therapy, particularly in those with GERD.

The Relationship of UGT2B15 Pharmacogenetics and Lorazepam for Anxiety.

Anxiety affects over 260 million people worldwide. Benzodiazepines are a class of agents used in combination with other therapies for the management of anxiety. Lorazepam is a commonly prescribed benzodiazepine metabolized by uridine 5'-diphosphate-glucuronosyltransferases. Herein, we discuss recent findings regarding the pharmacogenetics of uridine 5'-diphosphate-glucuronosyltransferase 2B15 (UGT2B15), lorazepam, and its role in the treatment of anxiety.

Evaluation of Factors which Influence Mortality in Gram-positive Bacteremia in Hemodialysis Patients.

Vascular access infection is one of the major contributors to hemodialysis (HD) patient morbidity and mortality. There is a paucity of consensus guidelines on vancomycin use in the HD population. The primary objective of this study was to determine if vancomycin serum concentrations were associated with positive outcomes in HD patients with Gram-positive bacteremia. A retrospective cohort study conducted at a 443-bed tertiary teaching county hospital from January 1, 2010 to January 1, 2016 was performed. Patients aged 18-89, with chronic renal failure on hemodialysis who presented with positive blood cultures with Gram-positive bacteria and received intravenous vancomycin for at least 24 hours were evaluated. A multivariate analysis was utilized comparing factors related to outcomes including Simplified Acute Physiology Score II (SAPS II), loading dose, 30-day mortality and vancomycin serum concentrations. A total of 139 patients were obtained, 90 of whom had documented pre-dialysis serum vancomycin concentrations. A multivariate analysis showed that a lower SAPS II score [OR 1.220 (95% CI: 1.086-1.370, p < 0.0001)], a higher loading dose/kg [OR 0.7911 (0.6302-0.9929, p = 0.0239)], and pre-dialysis concentrations between 15 and 20 mcg/mL [0.05437 (95% CI: 0.0033-0.8891, p = 0.0099)] were associated with decreased mortality (overall multivariate model, p < 0.0001). When patient acuity and loading dosing are taken into account, pre-dialysis vancomycin serum concentrations between 15 and 20 mcg/mL were associated with decreased mortality in Gram-positive bacteremic intermittent HD patients. Further prospective studies are needed to assess whether targeting a pre-dialysis serum vancomycin concentration of 15-20 mcg/mL can improve mortality.

A Review of the Opioid Analgesic Benzhydrocodone-Acetaminophen.

There is an undeniable opioid crisis in the United States that has caused significant negative consequences including many lives lost due to opioid overdoses. Currently, researchers are searching for alternatives for pain management as well as developing abuse-deterrent agents. In February 2018, the Food and Drug Administration (FDA) approved benzhydrocodone and acetaminophen (Apadaz™) for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and where alternative treatments are inadequate. This article looks further into this oral opioid prodrug and assesses its clinical pharmacology, pharmacokinetics, clinical trials and safety considerations that led to approval. Even though this prodrug provides a novel approach to analgesia, it was not classified as an abuse-deterrent agent and therefore still has the potential for abuse and misuse. This new agent potentially runs a higher risk of augmenting the opioid crisis rather than curtailing it. Innovative approaches to discover opioid alternatives are warranted.

Correction to: Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis.

Unfortunately, ≥ was found missing between scores and 20 in conclusion section of the online published article. The original article was corrected.

Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis.

BACKGROUND: Critically ill patients display altered pharmacokinetics and pharmacodynamics and are more likely to be infected with more resistant pathogens. Beta-lactam antibiotics exhibit time-dependent pharmacodynamics; therefore, it is postulated that continuous infusion (CI) may optimize these parameters. OBJECTIVE: To perform a systematic review and meta-analysis of the available literature comparing CI versus intermittent bolus (IB) of beta-lactam antibiotics in critically ill adult patients with respiratory infections to determine if clinical benefits exist. METHODS: PubMed, EMBASE, and Web of Science were searched. Thirteen randomized controlled trials were included in the meta-analyses of clinical cure and/or mortality. Four retrospective studies reporting clinical cure and/or mortality, and 11 studies that reported pharmacokinetic/pharmacodynamic parameters were included in the systematic review. RESULTS: The majority of patients in both groups maintained the percentage of time the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) targets throughout the treatment, with differences favoring CI being more prevalent when the MIC of the offending pathogen increased. CI of beta-lactam antibiotics in critically ill adult patients with respiratory infections significantly improved clinical cure rates when compared to IB (risk ratio [RR] 1.177; 95% CI 1.065-1.300). No significant differences in mortality rates were seen when patients were treated with either dosing modality (RR 0.845; 95% CI 0.644-1.108). CONCLUSIONS: CI of beta-lactam antibiotics is associated with better cure rates and higher %fT > MIC when administered to critically ill patients with respiratory infections, but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections.

AH-7921: A review of previously published reports.

AH-7921 is a synthetic opioid that was developed in the early 1970s. It has resulted in several fatal and nonfatal intoxications, despite not having approval from the US Food and Drug Administration. To date, AH-7921 is listed as a schedule I drug, and there have been no clinical trials exploring the safety of AH-7921. Herein, we provide an analysis of existing case reports available in the literature regarding AH-7921. We searched PubMed, Scopus, Web of Science, and EBSCO for articles (up until December 2017) using the terms "AH-7921" and "AH7921." In total, 48 articles were identified, and 5 articles were included in our review. A total of 14 cases were found, of which 13 resulted in fatalities. The oral route of administration was reported in two cases, and most cases reported use of concomitant pharmaceutical agents. Pulmonary edema was the most common finding postmortem among deceased cases, with nine of the cases having heavier lungs. Overall, fatalities occurred with low and high concentrations of AH-7921 in the femoral blood. We strongly encourage toxicology screenings for this novel opioid to be included when an overdose of an opioid of unknown nature is suggested.

Pain Perception and the Opioid Receptor Delta 1.

Genetic factors play an integral role in the perception of pain, and studies have only recently begun to explore the degree to which these factors affect clinical decisions. The process of prescribing opioids is greatly influenced by an individual's pain perception, which can vary based on several factors including genetic variation. Opioid receptor delta 1 (OPRD1) plays a significant role in the perception of both pain and its relief via opioids, and it shows significant variability between individuals. Herein, we discuss the nature of the OPRD1 receptor and the value of further research into its effects, particularly in the realm of pain management.

Proposal for a Pharmacogenetic Decision Algorithm.

Personalized medicine is playing an ever-increasing role in patient care. Over the past decade, awareness of the role of pharmacogenetics and its benefits is leading to its growing acceptance among providers. Though providers are using pharmacogenetics in practice, the decision-making process of when to use this tool can be ambiguous. Herein, we propose an algorithm to help guide providers on when to use pharmacogenetics for patient care.

The Current Landscape of Marijuana and Pharmacogenetics.

The treatment of medical conditions with cannabis and cannabinoid compounds is advancing. Although there are numerous reports related to the genetic variations of the cannabinoid receptor, a lack of studies that examine the relationship between other pharmacogenetic markers and health outcomes currently exists. Herein, we advocate for the legalization of marijuana in the United States in order to perform more randomized controlled trials to help elucidate the role of other pharmacogenetic targets and cannabis for use in clinical practice.

Update on targeted therapies for advanced non-small cell lung cancer: nivolumab in context.

While the initial treatment of non-small cell lung cancer (NSCLC) usually relies on surgical resection followed by systemic cytotoxic chemotherapy and/or radiation therapy, recent advances in understanding of NSCLC biology and immunology have spurred the development of numerous targeted therapies. In particular, a class of immune modulatory drugs targeting the immune checkpoint pathways has demonstrated remarkable durable remissions in a select minority of advanced NSCLC patients, potentially heralding the elusive "cancer cure". This review focuses on the clinical evidence for one of these agents, nivolumab, and clarifies the role of this drug in the context of the other targeted therapies currently available for the treatment of NSCLC. We also discuss the impact of nivolumab on patient quality of life and health economics.

To Dab or Not to Dab: Rising Concerns Regarding the Toxicity of Cannabis Concentrates.

Cannabis use is steadily rising in the United States. As the popularity of marijuana rises, new varieties of cannabis-related products are becoming available. Dabs are cannabis concentrates gaining notoriety for their significant amounts of tetrahydrocannabinol (THC) that are ultimately vaporized and inhaled for their effect. Herein, we provide an overview of recent cases of dabbing to bring awareness to the clinicians, of the significant adverse effects associated with dabs including psychosis, neurotoxicity, and cardiotoxicity.