Contraindicated drug–drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States

Objectives Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. Methods This cross-sectional study included multiple year pooled data (2003–2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral antibacterial or antifungal agents were evaluated for potential drug–drug interaction (DDI) contraindications. Findings with relative standard error >30% or unweighted sample size <30 were not reported because these were deemed unreliable estimates. Results From 2003 to 2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence interval (CI), 0.29–0.74) in which a patient was prescribed an antimicrobial agent associated with a contraindicated DDI. The most prevalent antimicrobials with contraindicated combination among outpatients were simultaneous use of macrolide-containing products (erythromycin or clarithromycin) with statin medication–containing products (simvastatin or lovastatin) (841 864 visits, proportion = 1.91%; 95% CI, 0.96–2.86). The next most common combination was use of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06–0.32). Conclusions Providers should be aware of potential contraindicated DDIs when prescribing antibiotics, especially macrolides and fluoroquinolones

Identification of gender differences in ultrasound milestone assessments during emergency medicine residency training: a pilot study

Objectives: Prior literature suggests that incongruities between male and female resident's procedural competency may be explained by gender bias during the evaluation process. There are no known studies investigating gender differences in the assessment of ultrasound-based procedural skills among emergency medicine (EM) residents. The purpose of this study was to evaluate for gender differences in ultrasound milestone assessments among EM residents. Methods: This is a retrospective study including EM residents. Milestone assessment data were collected from a total of 3 Accreditation Council for Graduate Medical Education (ACGME) EM residency programs representing a 3-year period The outcome measures included mean milestone levels, milestone levels at baseline and graduation and differences in milestone achievement between female and male EM residents. An unpaired Student's t-test was used to compare milestone scores between female and male residents. Results: A total of 456 ultrasound milestone evaluations were collected from 91 EM residents (34 females [37%] and 57 males [63%]). No significant differences were noted in the overall mean milestone level between females (2.3 +/- 0.6) and males (2.2 +/- 0.6) (P=0.387). There were no significant differences noted in the ultrasound milestone level between females (0.8 +/- 0.6) and males (0.7 +/- 0.7) at baseline (P=0.754). Although it did not reach statistical significance (P=0.197), the increase in the mean ultrasound milestone level from baseline to graduation was greater in males (3.4 +/- 0.7) compared to females (3.1 +/- 0.7). Conclusion: Overall, there were no statistically significant differences in the mean ultrasound milestone levels between females and males. The rate of ultrasound milestone level achievement during EM residency training at our institution had a slight tendency to be higher for males than females in the observed residency programs; however, this also did not reach statistical significance. Possible gender bias while evaluating ultrasound milestone levels needs to be further studied on a larger scale.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Psychological and Genetic Predictors of Pain Tolerance

Previous studies have shown associations between genetic polymorphisms and pain tolerance, but psychological evaluations are seldom measured. The objective of this study was to determine the independent effects of demographic, psychological, and genetic predictors of cold noxious pain tolerance. Healthy subjects (n = 89) completed the Pain Catastrophizing Scale (PCS) and Fear of Pain Questionnaire (FPQ-III), underwent genotyping for candidate single nucleotide polymorphisms (SNPs), and completed a cold-pressor test in a 1-2 degrees C water bath for a maximum of 3 minutes. The primary outcome measure was pain tolerance, defined as the maximum duration of time subjects left their nondominant hand in the cold-water bath. Cox proportional hazards regression indicated that female sex, Asian race, and increasing PCS and FPQ-III scores were associated with lower pain tolerance. No candidate SNP was significantly associated with pain tolerance. Future genetic studies should include demographic and psychological variables as confounders in experimental pain models.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Performance of Ultrasound-guided Peripheral Nerve Blocks by Medical Students After One-day Training Session

Introduction Ultrasound-guided peripheral nerve blocks (USGPNB) are performed by various specialists and are excellent, non-addicting pain control techniques. Alternative pain management approaches are needed to combat opiate abuse. Medical students should be aware of alternative pain management therapies before they begin clinical practice. Objective Our objective was to determine if medical students can identify peripheral nerves under ultrasound and perform a USGPNB after a one-day hands-on training session. Methods This was a cross-sectional study at an academic medical center. The study participants were third-year medical students with minimal prior ultrasound experience. Students were given an introductory lecture highlighting the opiate epidemic and benefits of USGPNB prior to the workshop. The one-day hands-on educational workshop consisted of learning basic sonographic anatomy, indications for USGPNB, and practicing needle guidance under ultrasound guidance. After the educational workshop, students' procedural competency was assessed by ultrasound-trained emergency medicine clinicians. Results A total of 94 participants were included in this study. The average pre-test score was 68.4% (95% confidence interval [CI]; 65.4% to 71.4%). After the one-day educational workshop, the post-test score was 92.8% (95% CI; 90.8% to 94.8%). The average hands-on evaluation score was 84.4% (95% CI; 81.6% to 87.3%). All students agreed that this educational session is a good start to learning about USGPNB, and they felt comfortable identifying the peripheral nerves using ultrasound. On a confidence scale of one (low) through 10 (high), 83% (95% CI; 75.9% to 90.15%) rated their confidence as >= 6. All except one student either agreed that this educational session helped them understand how USGPNB could be integrated into acute pain management. The majority (84% [95% CI; 77% to 91%]) agreed that the session will change how they manage patients' acute pain in their future medical practice. Conclusion Medical students can learn the sonographic anatomy of peripheral nerves and techniques of USGPNB after a one-day educational session.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

Background: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. Objectives: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. Sources: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. Content: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. Implications: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Comparison of Morphine and Fentanyl For Pain Due to Traumatic Injury in the Emergency Department

Class of 2011 AbstractOBJECTIVES: To compare fixed equianalgesic doses of morphine and fentanyl with regard to analgesic response for patients who presented to the ED with moderate to severe pain. METHODS: A retrospective cohort study of clinical data obtained through patient medical record review. Median pain reduction on the numeric pain scale was compared between the morphine and fentanyl groups. Independent variables of interest included: Age, sex, weight, initial pain score, injury severity, triage severity and injury type. RESULTS: : Pain scores were reported to be worse in the fentanyl group, p= 0.0002. However pain reduction was similar between the groups; median (IQR) of 2 (1-3) and 2 (1-4) in the morphine and fentanyl groups respectively, p= 0.6707. Injuries were more severe in the fentanyl group; injury severity score (ISS) median (IQR) of 5 (1-9) and 9 (3-12), p=0.0312 and more patients in the fentanyl group required additional opioids within 30 min of their first ED opioid dose, 15 (18%) and 31 (37%), p=0.006. CONCLUSION: Patients in both the morphine and fentanyl groups received similar analgesic response. Patients in the fentanyl group had a higher severity of injury, received higher doses of opioids from the EMS, and required the second dose of opioid sooner than patients in the morphine group.This item is part of the Pharmacy Student Research Projects collection, made available by the College of Pharmacy and the University Libraries at the University of Arizona. For more information about items in this collection, please contact Jennifer Martin, Librarian and Clinical Instructor, Pharmacy Practice and Science, [email protected]

Evaluation of Therapy Prescribed for Uncomplicated Urinary Tract Infection in Patients in an Emergency Department

Class of 2012 AbstractSpecific Aims: 1• Determine the results of urine culture and susceptibility testing for patients with uncomplicated UTI at an emergency department 2• Determine empiric antibacterial agents prescribed for treatment of uncomplicated UTI in the emergency department 3• Compare pathogen susceptibility pattern specific for patients with uncomplicated UTI compared to the overall institution antibiogram Examine the use of cephalexin for uncomplicated UTI in emergency department patients Methods: A retrospective electronic medical records of adult female patients admitted to University Medical Center in Tucson, Arizona, emergency department with a diagnosis of uncomplicated urinary tract infection (UTI) between June 1, 2010 and May 31, 2011 were collected. Different aspects of uncomplicated urinary tract infection (UTI) were characterized, and prescriptions for empiric antibiotic treatment were recorded. Culture results and susceptibility reports as well as antibacterial treatment decisions were studied to evaluate types of pathogens and resistance patterns along with therapy prescribed. The data was managed and analyzed by using SAS. All data was tabulated and described using summary statistics. Main Results: The dominant isolate of the study population was E.coli (88%). Cephalexin was prescribed 76% of the time, nitrofurantoin 8.4%, ciprofloxacin 7.6%, and TMP/SMX 5% of the time. The susceptibility rate of ampicillin was 50%, cefazolin 91%, ciprofloxacin 98%, nitrofurantoin 92%, and TMP/SMX 76%. Conclusions: Our study revealed that the resistant rate of TMP/SMX exceeded 20%; however, ciprofloxacin and nitrofurntoin susceptibility remains high. Cephalexin was the most commonly prescribed treatment, but not included in the antimicrobial susceptibility test (AST) panel.This item is part of the Pharmacy Student Research Projects collection, made available by the College of Pharmacy and the University Libraries at the University of Arizona. For more information about items in this collection, please contact Jennifer Martin, Librarian and Clinical Instructor, Pharmacy Practice and Science, [email protected]