Effects of steroid stewardship on glycemic control in acute exacerbations of chronic obstructive pulmonary disease patients.

INTRODUCTION: The adverse effects of corticosteroids are dose-dependent, and guidance is to use the lowest effective dose in most disease states. The study facility recently reported a steroid stewardship program that reduced steroid dosing in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients by 50%. The purpose of this post-hoc analysis was to evaluate the effect of this intervention on glycemic control in hospitalized AECOPD before and after cohorts. METHODS: This was a retrospective post-hoc review of hospitalized patients in a before and after study design (n = 27 in each group). The primary endpoint was the proportion of glucose readings >180 mg/dL. Baseline characteristics, mean glucose levels, and corrective insulin were also collected. Continuous variables were compared with a Student's t-test (or Mann-Whitney U where appropriate) and nominal variables with a chi-square test in R Studio. RESULTS: There was a significantly higher proportion of glucose >180 mg/dL readings in the pre-intervention cohort: 38% vs. 25% (p = 0.007). The mean glucose levels were numerically lower post-intervention but did not reach statistical significance (160 mg/dL vs. 145 mg/dL, p = 0.27) both in diabetics (192 mg/dL vs. 181 mg/dl, p = 0.69) and non-diabetics (142 mg/dL vs. 125 mg/dL, p = 0.08). The use of correctional insulin was similar: a median of 25 units vs. 24.5 units (p = 0.92). CONCLUSION: A stewardship program focused on steroid reduction in AECOPD significantly lowered the proportion of hyperglycemic readings but did not significantly affect mean glucose and corrective insulin usage while hospitalized.

Implementation of a novel learning experience in scientific writing, publishing, and peer review into a first year pharmacy practice residency.

BACKGROUND: Pharmacists with competency in writing, publishing, and peer review are essential to continue advancing the pharmacy profession, but structured training of these skills may vary. OBJECTIVE: The authors set out to implement and assess the impact of a structured learning experience into a postgraduate year 1 pharmacy residency training program that provides tangible experience in the processes of scientific writing, publishing, and peer reviewing. METHODS: A quarterly pharmacy newsletter process was augmented to include an editorial board that consisted of residency trained pharmacists with varying levels of experience in scientific writing, publishing, and peer reviewing. The process was designed to provide a structured writing learning experience, to reinforce important concepts and terminology, and to simulate the process of submitting a manuscript to a peer-reviewed publication. Impact of the learning experience on quality of article submissions was assessed by comparing first quarter and last quarter writing submission scores for residents between 2017 and 2020. RESULTS: A statistically significant difference was observed in both raw scores (27 vs. 42.5 points out of 50 points possible, P < 0.05) and the proportion of pass or fail when comparing writing submission scores from the first quarter of the learning experience to submission scores from the last quarter (25% passing rate vs. 83% passing rate, P = 0.007). CONCLUSION: This novel learning experience was successfully integrated into a quarterly pharmacy newsletter and resulted in improved writing scores. This structured writing learning experience can be readily integrated into pharmacy residency training programs, and it provides hands-on training in scientific writing, publishing, and peer review for both residents and preceptors.

A multifaceted stewardship intervention helps curb steroid overprescribing in hospitalized patients with acute exacerbations of COPD.

PURPOSE: Corticosteroid overprescribing is well documented in real-world practice. There is currently no evidence to guide best practices for steroid stewardship. The aim of this study was to assess the effects of a 3-part stewardship intervention strategy on inpatient steroid prescribing in patients with acute exacerbations of COPD (AECOPD). SUMMARY: Investigators implemented a 3-part stewardship initiative consisting of (1) an anonymous survey for providers on steroid prescribing in a simplified case of AECOPD, (2) face-to-face education and review of survey results, and (3) prospective audit and feedback from a clinical pharmacist. This was a quasi-experimental before-and-after study evaluating hospitalized adults diagnosed with AECOPD in two 12-month study periods before (April 2019-March 2020) and after (May 2020-April 2021) implementation. The primary outcome was mean inpatient steroid dosing. Secondary outcomes were duration of therapy, length of stay (LOS), 30-day readmissions, 30-day mortality, and incidence of hyperglycemia. Per power analysis, there were 27 patients per cohort. The interventions resulted in a significant reduction in prednisone equivalents during hospitalization: 118 mg vs 53 mg (P = 0.0003). This decrease was similar in ICU (160 mg vs 61 mg, P = 0.008) and non-ICU (102 mg vs 49 mg, P = 0.004) locations. There was no significant difference in duration of therapy (8 days vs 7 days, P = 0.44), length of stay (3.3 days vs 3.9 days, P = 0.21), 30-day mortality (4% vs 7%, P = 0.55), 30-day readmissions (15% vs 7%, P = 0.39), or rate of hyperglycemia (48% vs 44%, P = 0.78). CONCLUSION: A multifaceted stewardship intervention significantly reduced steroid dosing in hospitalized AECOPD patients. This reduction was not associated with known deleterious effects.

Impact of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) on Food Content During Esophagogastroduodenoscopy (EGD).

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have delayed gastric emptying properties; however, the impact on esophagogastroduodenoscopy (EGD) visualization is unknown. OBJECTIVE: This study examines the impact of GLP-1RA use on EGD visualization and gastric content retention. METHODS: This was a retrospective cohort study with matched controls. The primary endpoint was the odds of retained food documented during EGD. Secondary endpoints included incidence of lavage and need for repeat EGD due to poor visualization and were compared using Fisher exact test. Analyses were performed in R Studio. RESULTS: There were 59 patients in the cohort prescribed a GLP-1RA with 118 matched controls. Food retention was documented with 4 patients (6.8%) in the GLP-1RA cohort versus 2 patients (1.7%) in the control group (odds ratio [OR] 4.22 [95% CI 0.87-20.34]). No difference was observed in the need for lavage during EGD or in the need for repeat EGD attributed to poor visualization. CONCLUSION AND RELEVANCE: This study addresses a previously uninvestigated question in clinical practice. GLP-1RA did not significantly increase odds of retained food on EGD. Although a numerical difference was observed, it did not reach statistical difference. No cases required repeat EGD due to poor visualization, and no change to EGD pre-procedure instructions were warranted at the study facility.

Transitioning From Consult-Based to Automatic Pharmacy-Driven Vancomycin Management: Results From a Single, Primary Care Center.

OBJECTIVE: The transition to area under the curve (AUC) vancomycin monitoring requires substantial updates in pharmacy policies and procedures. The study facility was tasked with transitioning from a consult-based collaborative agreement to an automatic pharmacist management policy on all intravenous (IV) vancomycin orders. The purpose of this quality assessment (QA) study was to evaluate the effectiveness of this transition. METHODS: The primary outcome was the proportion of patients with pharmacist assessment of pharmacokinetics and dosing with documentation in IV vancomycin treated patients from January-June 2020. Secondary outcomes included the proportion of AUC24 levels within therapeutic range, the incidence of acute kidney injury (AKI) and treatment failures in patients treated ≥72 hours compared to a historical, trough-based cohort. RESULTS: There were 88 patients in the QA analysis with 100% having a pharmacist assessment with documentation. There were 34 patients treated ≥72 hours in the AUC group, 36 in the trough-based group. AUC24 fell within desired range in 45% of monitored patients. Rates of AKI (9% vs 11%, p = 0.75) and treatment failures were similar (3% vs 0%, p = 0.3). CONCLUSION: The transition from consult-based to an automatic pharmacy management agreement was successful with similar safety and efficacy compared to a historical trough-based cohort.

Efficacy and Safety of Vancomycin Therapy After the Transition to AUC/MIC Monitoring in a Primary Facility.

BACKGROUND: New guidance recommends area under the curve/minimum inhibitory concentration (AUC/MIC) instead of trough-based monitoring for vancomycin therapy. While this transition has demonstrated improved safety and efficacy in large, tertiary centers, this has not been assessed in the primary hospital setting. OBJECTIVE: The primary objectives were to evaluate the efficacy and safety of AUC/MIC monitoring in inpatient veterans treated with intravenous vancomycin for ≥72 hours compared to a historical cohort of trough-based monitoring. METHODS: This was a retrospective, quasi-experimental study over 2 five-month study periods. Efficacy was evaluated by comparing clinical failure rates as defined by a persistent fever, clinical deterioration, or escalation of gram-positive therapy. Safety was determined by the incidence of acute kidney injury (AKI) defined by an acute increase in serum creatinine ≥0.3 mg/dL over 48 hours. RESULTS: 25 patients met the criteria in the before group and 19 in the after group. Efficacy was equivalent between groups; no patients exhibited clinical failure of vancomycin therapy. In the before group, 2 patients (8%) met defined criteria for AKI, while none in the after group experienced AKI (P = 0.21). Total vancomycin exposure was similar between groups (P = 0.56). CONCLUSION: AUC-based monitoring was equally efficacious as trough-based monitoring with similarly low rates of AKI.

Deinduction of P-glycoprotein resulting in delayed viral response during hepatitis C treatment.

WHAT IS KNOWN AND OBJECTIVE: Drug-drug interactions can involve inhibition or induction of cell membrane transporters. Deinduction occurs after an inducing agent is stopped. CASE SUMMARY: This case describes suspected P-glycoprotein (P-gp) deinduction by carbamazepine resulting in a slow viral response during treatment of chronic hepatitis C virus (HCV) infection. Evidence of deinduction occurred beyond clearance of carbamazepine and resulted in extension of HCV treatment. WHAT IS NEW: The understanding of the role P-gp transport plays in drug elimination is relatively new and evidence of P-gp deinduction is variable. CONCLUSION: Clinicians should consider deinduction when starting and stopping medications involving strong inducers of P-gp transport proteins.

Provider perceptions on steroid dosing in AECOPD: Laying the groundwork for steroid stewardship.

INTRODUCTION: Steroid overprescribing is well documented in acute exacerbations of COPD (AECOPD). Given the myriad of unwanted side effects of corticosteroids, facilities should implement steroid stewardship efforts. The objective of this project was to evaluate the prescribing habits of steroids in AECOPD for needs assessment and to tailor interventions in a single centre. METHODS: A questionnaire was developed to evaluate practices and beliefs around steroid dosing in a simplified case of uncomplicated AECOPD. There were 31 total responders: 12 inpatient clinicians, 9 medical residents and 10 emergency department (ED) clinicians. All steroid dosing was converted to prednisone equivalents for reporting. Subgroup analysis was conducted between provider groups. RESULTS: Initial dosing ranged from 40 to 625 mg/day with only four responders (13%) selecting 40 mg/day. Dosing was not significantly different in newer providers ≤4 years' experience: mean 215 mg versus >4 years' experience: mean 312 mg (P = 0.23). Less experienced providers selected shorter treatment durations: median 5 days (IQR 5,6) versus 8.5 days (IQR 6,10.5) (P = 0.015). ED providers selected higher doses than non-ED providers: 447 mg versus 208 mg (P = 0.003). Most responders (81%) selected IV agents over oral steroids. The majority (65%) stated dosing choices were based on prescribing habits/clinical experience, while 36% felt their selections were based on current evidence. Five (16%) of responders correctly identified consensus treatment guidelines and the majority (77%) reported being "very likely" or "somewhat likely" to prescribe lower doses. CONCLUSION: Baseline knowledge was a significant barrier to guideline utilisation. Education will need to focus on the evidence behind using lower doses, oral agents and disease severity.

Steroid-Induced Sleep Disturbance and Delirium: A Focused Review for Critically Ill Patients.

OBJECTIVE: Insomnia and delirium have gained much attention since the publication of recent guidelines for the management in critically ill adults. Neurologic effects such as sleep disturbance, psychosis, and delirium are commonly cited adverse effects (AEs) of corticosteroids. Steroid use is considered a modifiable risk factor in intensive care unit patients; however, reported mechanisms are often lacking. This focused review will specifically evaluate the effects of steroids on sleep deprivation, psychosis, delirium, and what is known about these effects in a critically ill population. OBSERVATIONS: The medical literature proposes 3 pathways primarily responsible for neurocognitive AEs of steroids: behavior changes through modification of the hypothalamic-pituitary-adrenal axis, changes in natural sleep-wake cycles, and hyperarousal caused by modification in neuroinhibitory pathways. Initial search fields produced 285 articles. Case reports, reviews, letters, and articles pertaining to primary care or palliative populations were excluded, leaving 8 relevant articles for inclusion. CONCLUSIONS: Although steroid therapy often cannot be altered in the critically ill population, research showed that steroid overuse is common in intensive care units. Minimizing dosage and duration are important ways clinicians can mitigate AEs.

Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital.

OBJECTIVE: Consensus guidelines for vancomycin monitoring now recommend area under the curve (AUC) calculations for optimal vancomycin efficacy and safety. This will be a major practice change for many facilities. Implementation guidance is available but has not been reported in smaller, primary care hospitals. The objective of this study was to measure the uptake of AUC monitoring implementation in a rural facility. METHODS: This is a gap analysis evaluating the appropriateness of vancomycin levels tests after the April 1, 2019 transition. All vancomycin levels between April 2019 and June 2019 after the go-live date were included with no exclusions in a retrospective chart review. The primary outcome was the proportion of levels in the appropriate time frame: peaks 1 to 2 hours after infusion with troughs at least 1 half-life after initial dose and prior to the next dose. Secondary outcomes included reasons identified for inappropriate levels and the proportion of AUC24 calculations within therapeutic range (400-600 mg.h/L). Descriptive statistics were used to measure the scope and outcomes of this transition. RESULTS: The transition was effective with 97% of cases utilizing AUC-based methods. There were 65 vancomycin levels in the 3-month study period with 86% deemed appropriate. Of the 9 inappropriate levels, 4 had to be repeated for accurate monitoring. There were 28 two-level couplets used for AUC24 calculations, 17 (61%) fell within therapeutic range. CONCLUSION: Implementation strategies for the AUC transition described in tertiary medical centers can be successfully utilized in primary facilities.

Enzymatic deinduction phenomenon and clinical implications with a focus on direct-acting oral anticoagulants.

: The aim of the study was to describe the deinduction process and clinically relevant cases reported in the medical literature. Performed PubMed database search for key words 'enzymatic deinduction'. Findings are summarized. Although many unwanted drug interactions occur from the additive effects of combined medications or through competition at binding sites, some interactions occur because of alterations in homeostasis of natural metabolizing pathways. Enzymatic induction is a natural process in which normal metabolizing enzymes are increased because of RNA signaling from xenobiotics. Strong inducing medications can lead to decreased serum levels of other drugs, which are metabolized through these substrates; notably the direct-acting oral anticoagulants are affected. What is less understood, however, is the process of enzymatic deinduction and the clinically relevant sequela of overlooking this interaction. Providers should be aware of enzymatic deinduction and the potentially severe adverse effects of this phenomenon.

Acetazolamide Causes Worsening Acidosis in Uncompensated COPD Exacerbations: Increased Awareness Needed for Patient Safety.

BACKGROUND: Acetazolamide has been studied extensively in post-hypercapnic alkalosis as a tool to facilitate ventilator weaning in chronic obstructive pulmonary disease (COPD). It has also been utilized to facilitate respiratory drive in nonmechanically ventilated patients with COPD. Although this is generally a forgiving intervention, providers must carefully select patients for this medication, as it can cause severe acidosis and deterioration of clinical status in severe COPD cases. The present report describes two cases of patients who developed worsening acidosis and hypercapnia after receiving acetazolamide in acute respiratory failure. CASE REPORT: Case 1 was a 72-year-old obese male with COPD who was dependent on supplemental oxygen and presented to the emergency department (ED) with acute on chronic hypercapnic respiratory failure. He was given a one-time dose of acetazolamide in the ED for "respiratory failure made worse by severe metabolic alkalosis." His arterial blood gas (ABG) worsened overnight, accompanied by decreased mental status: pH 7.32, paCO2 82 mm Hg, paO2 50 mm Hg, HCO3 41.7 mmol/L, FiO2 32% to pH 7.21, paCO2 91.7 mm Hg, paO2 59 mm Hg, HCO3 36.6 mmol/L, and FiO2 32%. Case 2 was a 62-year-old male with COPD who was dependent on supplemental oxygen and presented to the ED with acute on chronic hypercapnic respiratory failure. He was given acetazolamide in the ED with similar results: ABG on presentation pH 7.37, paCO2 79.3 mm Hg, paO2 77.6 mm Hg, HCO3 45.5 mmol/L, and FiO2 32%. The next morning, ABG was pH 7.29, paCO2 79 mm Hg, paO2 77 mm Hg, HCO3 45.5 mmol/L, and FiO2 32%. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acetazolamide given early in the uncompensated setting can worsen acidosis and potentiate clinical deterioration.

An obscure case of using apixaban anti-Xa levels in a morbidly obese patient who was nil per os with enterocutaneous fistula.

: Apixaban anti-Xa levels have been introduced to monitor apixaban activity. Presented is a fundamental use of anti-Xa monitoring in questionable absorption in enterocutaneous fistula. A 57-year-old morbidly obese male (150 kg, BMI 42.5) presented to the emergency department with deep venous thromboses and pulmonary embolisms. He also had high-output enterocutaneous fistula managed with an abdominal collection device, total parental nutrition therapy, and nil per os status. He was able to take some oral (PO) medications; however, he reported finding whole capsules in his collection device. He refused enoxaparin injections for venous thromboembolism treatment. The decision was made to load with apixaban therapy with anti-Xa monitoring. After two 10-mg doses, peak apixaban anti-Xa level was 146 ng/ml which fell within on-therapy levels in the AMPLIFY study, prothrombin time 18 s, partial thromboplastin time 35.5 s, international normalized ration 1.5. Monitoring was an important factor in this patient with questionable absorption and further complicated by his morbid obesity which has not been adequately studied in clinical trials.

Implementation of the Procalcitonin Assay in a Rural Hospital.

Objective: Most positive studies in procalcitonin (PCT) utilization were done in large, tertiary medical centers. Furthermore, there is a paucity of data describing the implementation process. This article is the first to describe in detail the implementation process and initial outcomes after 6 months of PCT testing in a rural, 65-bed, primary hospital. Methods: Education before and during PCT implementation as well as facility rollout are described. Initial outcomes were assessed using a before and after quasi-experimental study design comparing 2 identical 6-month time periods: May to October 2016 and May to October 2017. Antibiotic consumption is described with days of therapy (DOT) per 1000 patient days (PD). Antimicrobial purchasing costs, admission rates, and length of stay (LOS) are also compared. Results: Antimicrobial consumption was variable with the greatest reduction at 6 months: 856 DOT/1000 PD before versus 576 DOT/1000 PD after (P < .0001). Admission rates and LOS were unaffected. There was no associated savings in antibiotic purchasing costs: $114 189.79 before and $139 829.26 after (difference +$25 639.47). Conclusion: Although implementation of PCT testing is feasible in a rural health care facility, after 6 months, it was associated with a marginal decrease in antibiotic consumption with no decrease in admission rates, LOS, or antibiotic cost savings.

Administration of four-factor prothrombin complex concentrate for a life-threatening bleed in a Jehovah's Witness patient.

: Life-threatening bleeds are medical emergencies that require time-sensitive decision making. Patients of the Jehovah's Witness faith can present a challenging conundrum when their beliefs conflict with modern treatment options for haemorrhage. Providers may not be aware of the grades of acceptance of the newer products outside of packed red blood cells. Researchers present a case of using four-factor prothrombin complex concentrate in a Jehovah's Witness patient in a life-threatening gastrointestinal haemorrhage along with a brief review of the literature.

Psychiatric outcomes in operatively compared with non-operatively managed patients with facial trauma: Is there a difference?

Patients who sustain facial injury and who require an operation may be at greater risk for developing psychological distress and maladaptive coping. The purpose of this study was to examine psychological responses in adult victims of facial trauma after operation. A consecutive group of adult patients attending specialist outpatient clinics after facial trauma were evaluated for psychological distress. The subjects were divided into two groups based on whether their facial injuries were managed operatively or conservatively. The primary predictor variable in this study was surgical intervention. The main outcome variable was Hospital Anxiety and Depression Scale (HADS) scores. Chi-squared, Mann Whitney U-test, and multiple regression analysis were used to analyse data. The sample consisted of 102 subjects; 71 patients had been managed operatively and 31 patients treated non-operatively. Psychometric scores suggestive of anxiety were present in 21% (n = 15) of the operatively managed group compared with 13% (n = 4) of the non-operatively managed group of patients. The prevalence of depression was comparable between both groups (14% compared with 13%). The median anxiety subscale scores for the operatively managed group when compared with the conservatively managed group of patients were significantly higher (6.6 compared with 4.4, p = 0.02); however, differences in the depression subscale scores did not reach statistical significance (6.2 compared with 4.6, p = 0.06). This study shows an association between anxiety disorders and operative interventions in patients with facial trauma (HADS-A, ß = 2.2, p = 0.04). Similar rates of depression were found in the surgically and conservatively managed patients.

Unlinked memory helper responses promote long-lasting humoral alloimmunity.

Essential help for long-lived alloantibody responses is theoretically provided only by CD4 T cells that recognize target alloantigen, processed and presented by the allospecific B cell. We demonstrate that in an alloresponse to multiple MHC disparities, cognate help for class-switched alloantibody may also be provided by CD4 T cells specific for a second "helper" alloantigen. This response was much shorter-lived than when help was provided conventionally, by Th cell recognition of target alloantigen. Nevertheless, long-lasting humoral alloimmunity developed when T cell memory against the helper alloantigen was first generated. Costimulatory blockade abrogated alloantibody produced through naive Th cell recognition of target alloantigen but, crucially, blockade was ineffective when help was provided by memory responses to the accessory helper alloantigen. These results suggest that memory Th cell responses against previously encountered graft alloantigen may be the dominant mechanism for providing help to generate new specificities of alloantibody in transplant patients receiving immunosuppression.