Tacrolimus toxicity due to enzyme inhibition from ritonavir.

Tacrolimus is commonly used for immunosuppression in patients following solid organ transplantation. For transplant patients with COVID-19 infection, early treatment is indicated due to the risk of progression to severe disease. However, the first line agent, nirmatrelvir/ritonavir, has multiple drug-drug interactions. We report a case of tacrolimus toxicity in a patient with a history of renal transplant due to enzyme inhibition related to nirmatrelvir/ritonavir. An 85-year-old woman with a history of multiple comorbidities presented to the emergency department (ED) with weakness, increasing confusion, poor oral intake, and inability to walk. She had been recently diagnosed with COVID-19 infection and was prescribed nirmatrelvir/ritonavir due to her underlying comorbidities and immune suppression. In the ED, she was dehydrated and had an acute kidney injury (creatinine 2.1 mg/dL, up from a baseline of 0.8 mg/dL). The tacrolimus concentration on initial labs was 143 ng/mL (5-20 ng/mL) and it continued to rise despite being held, to a peak of 189 ng/mL on hospital day 3. The patient was treated with phenytoin for enzyme induction and the tacrolimus concentration began to fall. She was discharged to a rehabilitation facility after a 17 day hospitalization. ED physicians must be cognizant of drug-drug interactions when prescribing nirmatrelvir/ritonavir and evaluating patients recently treated with the drug to identify toxicity due to these interactions.

Trends in naloxone prescribed at emergency department discharge: A national analysis (2012-2019).

BACKGROUND: While having access to naloxone is recommended for patients at risk for opioid overdose, little is known about trends in national naloxone prescribing rates in emergency departments (EDs) both for co-prescription with opioids and for patients who presented with opioid abuse or overdose. This study aims to evaluate the change in naloxone prescribing and opioid/naloxone co-prescribing at discharge using national data. METHODS: We conducted an IRB exempt retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey from 2012 to 2019. The primary outcome was trend in rate of naloxone prescribing at discharge from ED visits. We also computed the proportion of visits where naloxone was both administered in the ED and prescribed at discharge, where naloxone and opioids were co-prescribed at discharge, and where an opioid was administered during the ED visit and naloxone was prescribed at discharge. All data were summarized using descriptive statistics and Spearman's Rho (SR) or Pearson's correlation (PR) were used to describe trends. RESULTS: There was an estimated total of 250,365 patient visits where naloxone was prescribed at discharge with an increasing rate over time (0% of all ED visits in 2012 to 0.075% in 2019, p = 0.002). There were also increases in naloxone being both administered in the ED and prescribed at discharge (PC: 0.8, p = 0.02) as well as in naloxone and opioid co-prescribing (SR: 0.76, P = 0.03). There was an increase in utilization of opioids during the ED visit and naloxone prescribing at discharge for the same visit (SR: 0.80, p = 0.02). CONCLUSION: There are increases in naloxone prescribing at discharge, naloxone and opioid co-prescribing, and opioid utilization during the same visit where naloxone is prescribed at discharge. Future studies should be done to confirm such trends, and targeted interventions should be put into place to increase access to this life-saving antidote.

Pharmacotherapy in COVID-19; A narrative review for emergency providers.

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.

Impact of COVID-19 pandemic on emergency department substance use screens and overdose presentations.

BACKGROUND: The COVID-19 pandemic can exacerbate underlying substance use disorder and has impacted this vulnerable population in a variety of ways. There are limited data regarding how this pandemic has impacted emergency department (ED) patient presentations. METHODS: We extracted data on ED visits from the electronic health record (EHR) of a large healthcare system in the Washington, DC/Baltimore, MD metropolitan area. The dataset includes data from 7 hospitals on ED visits between 11/1/2019-6/30/2020. The health system utilizes a validated screening program for substance use, Screening, Brief Intervention, and Referral to Treatment (SBIRT), for ED patients who are clinically stable and willing to complete screening. We evaluated trends in patients with a positive SBIRT screen and those presenting with a clinical diagnosis of acute alcohol or substance intoxication/overdose before (11/1/19-2/29/2020-pre) and during the first wave of the COVID pandemic (3/1/2020-6/30/2020-post). Data were described using descriptive statistics. Bivariate analyses were conducted using chi-square test and two-sample t-tests. Interrupted time series analysis was used to evaluate the changes in the weekly trends with the start of the pandemic. RESULTS: There were 107,930 screens performed in the EDs during the study period (61,961 pre, 45,969 post). The population was primarily African American (64.7%) and female (57.1%). Positive SBIRT screens increased from 12.5% to 15.8% during COVID (p < 0.001). Alcohol intoxication presentations increased as a proportion of positive screens from 12.6% to 14.4% (p = 0.001). A higher percentage of screened patients reported problem drinking (AUDIT score ≥ 7) during the pandemic (2.4% pre vs 3.2% post, p < 0.001). Substance intoxication/overdoses among all screened increased from 2.1% to 3.1% (p < 0.001) and as a percentage of positive screens during the pandemic (16.8% to 20%, p < 0.001). The proportion of opioid vs. non-opioid overdoses remained unchanged before (67%) and during the pandemic (64%, p = 0.33). DISCUSSION: There was an increase in the proportion of positive SBIRT screens and visits for acute overdoses and intoxication during the first wave of the COVID-19 pandemic. Additional research should focus on mitigation strategies to address substance use during this vulnerable time.

An international perspective of out-of-hospital cardiac arrest and cardiopulmonary resuscitation during the COVID-19 pandemic.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) accounts for a substantial proportion of sudden cardiac events globally, with hundreds of thousands of cases reported annually in the United States. The mortality rate of patients who suffer OHCA remains high despite extensive utilization of resources. OBJECTIVES: We aim to describe the current landscape of OHCA during the COVID-19 pandemic and provide an overview of the logistical challenges and resuscitation protocols amongst emergency medical service (EMS) personnel. DISCUSSION: Recent studies in Italy, New York City, and France characterized a significant increase in OHCA incidence in conjunction with the arrival of the 2019 coronavirus disease (COVID-19) pandemic. The presence of the pandemic challenged existing protocols for field resuscitation of cardiac arrest patients as the pandemic necessitated prioritization of EMS personnel and other healthcare providers' safety through stringent personal protective equipment (PPE) requirements. Studies also characterized difficulties encountered by the first responder system during COVID-19, such as dispatcher overload, increased response times, and adherence to PPE requirements, superimposed on PPE shortages. The lack of guidance by governmental agencies and specialty organizations to provide unified safety protocols for resuscitation led to the development of different resuscitative protocols globally. CONCLUSIONS: The ongoing COVID-19 pandemic modified the approach of first responders to OHCA. With the rise in OCHA during the pandemic in several geographic regions and the risks of disease transmission with superimposed equipment shortages, novel noninvasive, adjunct tools, such as point of care ultrasound, warrant consideration. Further prehospital studies should be considered to optimize OHCA and resource management while minimizing risk to personnel.