Clinical and Economic Implications of Restrictions on Calcitonin Utilization in a Health System.

Background: Hypercalcemia is a relatively common problem that may require hospital admission based on severity. A treatment option for hypercalcemia is calcitonin given intramuscularly or subcutaneously. Purpose: In 2015, calcitonin was on our health system formulary, but due to a sharp rise in cost, restrictions were placed to ensure appropriate utilization. Intervention: These restrictions reserved calcitonin for patients with symptomatic hypercalcemia or severe hypercalcemia, which was defined as an ionized calcium of greater than 1.5 mmol/L and/or total/corrected calcium (Ca) of greater than 13 mg/dL. In addition to providing criteria for its use, calcitonin orders also had an automatic stop date of 24 hours to ensure no more than 2 doses were provided in a 24-hour period. After the initial 24 hours, a patient would have to be reviewed again before any further doses were ordered and administered. If the patient met criteria, an additional 2 doses could be given in the next 24 hours for a total maximum treatment of 4 doses over a 48-hour time frame. Results: An evaluation to assess health system-wide compliance of the usage of calcitonin restrictions regarding utilization, effectiveness, and cost was conducted. In the 2-month study time frame that was examined, there was a decrease in 66 vials of calcitonin that were dispensed. This represents a 43% reduction in usage and an estimated US $450,000 reduction in the total money spent for calcitonin annually. No notable differences in Ca reduction were identified between the groups. Conclusion: This evaluation revealed that putting health system-wide restrictions in use for a high-cost medication can have a major financial impact without compromising clinical efficacy.

Octreotide Added to a Proton Pump Inhibitor Versus a Proton Pump Inhibitor Alone in Nonvariceal Upper-Gastrointestinal Bleeds.

Background: Literature indicating clinically relevant benefits of an adjunctive somatostatin analog to standard therapies in nonvariceal upper-gastrointestinal bleeding (NVUGIB) is lacking. Objective: The primary objective of this study was to find the association between outcomes in patients with NVUGIB treated with octreotide and a proton pump inhibitor (PPI; combination group) compared with those treated with a PPI alone. Methods: We conducted a retrospective cohort study of adults admitted within a 5-hospital health care system with a NVUGIB treated with a PPI continuous infusion with or without an octreotide infusion. Notable exclusion criteria included varices, history of cirrhosis without endoscopy, or active gastrointestinal cancer. The primary outcome was association of combination treatment versus PPI alone with hospital length of stay (LOS). Results: A total of 180 patients were included (combination group: n = 90; PPI: n = 90). In univariate analyses, the median hospital and intensive care unit (ICU) LOS in the combination group versus PPI was 6.1 versus 4.9 days (P = 0.25) and 2.3 versus 1.9 days (P = 0.24), and rebleeding and mortality occurred in 9% versus 12% (P = 0.63) and 6.7% versus 5.6% (P = 1.00) of patients. Median units of packed red blood cells in the combination therapy versus PPI group was 3 vs 2 units (P = 0.43). After propensity score adjustment in multivariable analyses, hospital and ICU LOS, rebleeding, and mortality all remained nonsignificant. Conclusion and Relevance: Our study observed no difference in clinical end points. This suggests that octreotide provides no additional major clinical benefit in NVUGIB, and PPI therapy alone may be sufficient.

Breast cancer patient with everolimus-induced angioedema: A rare occurrence with potential for serious consequences.

Background The development of angioedema is a rare yet serious clinical event that may develop due to an adverse drug reaction. Rapid recognition and treatment of this adverse reaction is critical for optimal patient outcomes; however, prevention of this occurrence is preferred. Case report A 59-year-old woman presented to the emergency department with lingual angioedema caused by the addition of everolimus to her medication regimen. The patient improved after withdrawal of the offending agent and standard treatment. Early recognition by healthcare providers and management of everolimus-induced angioedema is vital for successful patient outcomes. This report increases awareness of everolimus as a potentially causative agent for the development of angioedema.

Emergency Department Management of a Myasthenia Gravis Patient with Community-Acquired Pneumonia: Does Initial Antibiotic Choice Lead to Cure or Crisis?

BACKGROUND: Myasthenic crisis is a rare, yet serious condition that carries a 3%-8% mortality rate. Although infection is a common cause of decompensation in myasthenia gravis, several antibiotics classes have also been associated with an exacerbation. Selecting antibiotics can be a daunting clinical task and, if chosen inappropriately, can carry significant deleterious consequences. Not only do clinicians have to focus on treating the underlying infection appropriately, but avoiding antibiotics that may potentiate a myasthenic crisis is also vital. CASE REPORT: An 85-year-old female with a history of myasthenia gravis presented to the emergency department (ED) with increasing generalized weakness and shortness of breath. Clinical work-up was consistent with a community-acquired pneumonia (CAP) diagnosis. Her medical history included a myasthenia gravis exacerbation shortly after receiving moxifloxacin for CAP. After reviewing the patient's allergies, as well as potential antibiotic triggers, the decision was made to treat with tigecycline. The patient responded well to tigecycline therapy and was deemed stable for discharge on day 4 of hospitalization. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Evaluation of the myasthenia gravis patient frequently originates in the ED. It is important for clinicians to be able to distinguish between an underlying illness and a myasthenic crisis. In the event of an infectious process causing clinical deterioration in a myasthenia patient, optimal antibiotic selection becomes paramount. This patient case highlights the addition of tigecycline to the armamentarium of therapies available to treat myasthenia gravis patients presenting to the emergency department with CAP.

Nitrofurantoin-induced hepatotoxicity: a rare yet serious complication.

Nitrofurantoin is a commonly prescribed antibiotic for the treatment of recurrent uncomplicated urinary tract infections. Its importance has been emphasized by the current international clinical practice guidelines for the management of uncomplicated cystitis. Since its introduction into clinical practice, nitrofurantoin has been associated with various adverse effects, including hepatotoxicity. We searched the English-language literature using PubMed and SCOPUS for the period 1961 through the end of February 2013. Key search terms included "nitrofurantoin AND hepatotoxicity" as well as "nitrofurantoin AND hepatitis." When studies or case reports were found, we assessed articles cited in those publications. A broad spectrum of liver toxicity associated with nitrofurantoin use has been reported, ranging from acute hepatitis, granulomatous reaction, cholestasis, or autoimmune-mediated hepatitis to chronic active hepatitis that could lead to cirrhosis or death. The mechanism of hepatotoxicity is poorly understood, but it is believed to be the result of an immunologic process or a direct cytotoxic reaction. It has been postulated that prolonged exposure to nitrofurantoin, female sex, advanced age, and reduced renal function increase the risk of developing hepatotoxicity. For the management of severe cases, corticosteroids have been used along with nitrofurantoin discontinuation. Because of mixed results, the utility of corticosteroids has not been proven and should be used judiciously. Given the severity and seriousness of the adverse effect of hepatotoxicity, clinicians should weigh the risks and benefits of nitrofurantoin before initiating therapy, especially in long-term prophylaxis in high-risk patients. Clinicians also should be well versed in recognizing and managing liver injury associated with nitrofurantoin.

Urine Discoloration Associated With Metronidazole: A Rare Occurrence.

Objective: To report a case of metronidazole-induced urine discoloration in a patient with Clostridium difficile sepsis. Case Summary: A 52-year old man was admitted with sepsis secondary to C difficile colitis, which developed after he had been recently treated with broad-spectrum antibiotics for community-acquired pneumonia. The C difficile infection was treated with metronidazole, and the patient subsequently developed cola-colored urine. When metronidazole was inadvertently stopped for 34 hours, the urine color returned to normal, but again darkened when the medication was restarted. The patient suffered no clinically adverse effects from the abnormal urine color. He completed the treatment course for colitis and was discharged to home. Discussion: Urine discoloration is a known side of metronidazole. However, it has been poorly reported in the literature, and many clinicians are unaware that it may happen. Here we report the case of a patient who developed dark urine while receiving treatment with metronidazole. Other potential causes of the urine discoloration were explored, including hemolysis, rhabdomyolysis, or adverse reactions to other medications, with no clear positive findings. An objective causality assessment (Naranjo probability scale) revealed that the urine discoloration was probably due to metronidazole. Conclusions: Metronidazole can cause urine discoloration without otherwise harming the patient. Clinicians should be aware of this potential side effect and provide reassurance to patients who develop abnormal urine that there are no clinically relevant adverse outcomes.

Pharmacists: an important resource to improve core measure performance.

In 2001, the Quality Initiative from the Department of Health and Human Services resulted in the development of a set of core measures focused on five patient populations. Although not part of the original list of providers able to document core measures involving medications, pharmacists were added to the list in November 2007. Within the set of core measures, there are 22 of 44 (50%) that are medication related. The authors' purpose is to describe the role of a pharmacist in meeting core measurements and provide an example of how a pharmacist is utilized at our institution.

Leveling Up: Evaluation of IV v. PO Linezolid Utilization and Cost after an Antimicrobial Stewardship Program Revision of IV to PO Conversion Criteria within a Healthcare System.

The CDC's Core Elements of an Antimicrobial Stewardship Program (ASP) lists intravenous (IV) to oral (PO) conversion as an important pharmacy-based intervention. However, despite the existence of a pharmacist-driven IV to PO conversion protocol, conversion rates within our healthcare system remained low. We aimed to evaluate the impact of a revision to the current conversion protocol on conversion rates, using linezolid as a marker due to its high PO bioavailability and high IV cost. This retrospective, observational study was conducted within a healthcare system composed of five adult acute care facilities. The conversion eligibility criteria were evaluated and revised on 30 November 2021. The pre-intervention period started February 2021 and ended November 2021. The post-intervention period was December 2021 to March 2022. The primary objective of this study was to establish if there was a difference in PO linezolid utilization reported as days of therapy per 1000 days present (DOT/1000 DP) between the pre- and post-intervention periods. IV linezolid utilization and cost savings were investigated as secondary objectives. The average DOT/1000 DP for IV linezolid decreased from 52.1 to 35.4 in the pre- and post-intervention periods, respectively (p < 0.01). Inversely, the average DOT/1000 DP for PO linezolid increased from 38.9 in the pre-intervention to 58.8 for the post-intervention period, p < 0.01. This mirrored an increase in the average percentage of PO use from 42.9 to 62.4% for the pre- and post-intervention periods, respectively (p < 0.01). A system-wide cost savings analysis showed projected total annual cost savings of USD 85,096.09 for the system, with monthly post-intervention savings of USD 7091.34. The pre-intervention average monthly spend on IV linezolid at the academic flagship hospital was USD 17,008.10, which decreased to USD 11,623.57 post-intervention; a 32% reduction. PO linezolid spend pre-intervention was USD 664.97 and increased to USD 965.20 post-intervention. The average monthly spend on IV linezolid for the four non-academic hospitals was USD 946.36 pre-intervention, which decreased to USD 348.99 post-intervention; a 63.1% reduction (p < 0.01). Simultaneously, the average monthly spend for PO linezolid was USD 45.66 pre-intervention and increased to USD 71.19 post-intervention (p = 0.03) This study shows the significant impact that an ASP intervention had on IV to PO conversion rates and subsequent spend. By revising criteria for IV to PO conversion, tracking and reporting results, and educating pharmacists, this led to significantly more PO linezolid use and reduced the overall cost in a large healthcare system.

Can't keep it SECRET: system evaluation of carbapenem restriction against empirical therapy.

Objectives: Carbapenems are appealing agents for empirical use given their broad spectrum of activity; however, selective use is vital in minimizing the risk for development of carbapenem-resistant pathogens. We aimed to examine the impact of carbapenem restriction criteria and a pre-authorization process on utilization and cost savings across a health system. Methods: This retrospective study was conducted across five adult hospitals. The pre-implementation period was 8 February 2020 to 30 April 2020 and the post-implementation period was 8 February 2022 to 30 April 2022. The primary outcome was to compare the number of orders for carbapenems between the study periods for both the intervention and non-intervention hospitals. Secondary outcomes included projected annual cost and an estimated cost-savings evaluation using a stratified analysis for the intervention and non-intervention facilities to account for more resource-limited settings. Results: The total number of carbapenem orders decreased between study periods at the intervention hospital (246 versus 61, P < 0.01). At the non-intervention hospitals, orders decreased, although not significantly (333 versus 279, P = 0.58). Meropenem orders decreased by 66% compared with 12% for the intervention and the non-intervention hospitals, respectively (P < 0.001). Annual estimated cost for all facilities was $255 561 in the pre-implementation period compared with $29 593 in the post-implementation period (P < 0.001). Using a stratified analysis to account for available resources, the estimated annual cost saving was $225 968 for the system. Conclusions: Implementation of carbapenem restriction at the intervention hospital decreased utilization and provided significant cost savings. Furthermore, resource-limited facilities can still experience significant cost savings using a stratified antimicrobial stewardship intervention approach.

Evaluation of Hospitalized Patients Receiving High versus Low-Dose Opioids for Non-Cancer Pain.

Limited studies suggest that opioid-related adverse effects (ORAEs) may worsen hospitalized patient outcomes, but there is insufficient data related to the impact of high-dose opioids compared to low-dose on adverse patient events. Given the paucity of data, our study aims to evaluate these ORAEs in the general hospitalized patient with non-cancer pain. A retrospective study of adult patients receiving opioids with a primary diagnoses of myocardial infarction, chronic obstructive pulmonary disease, heart failure, pneumonia, sepsis, or diabetes was conducted. Average oral morphine milligram equivalents (MMEs) administered over the entire LOS was collected, and patients were categorized as high-dose (≥50 MMEs/day) or low-dose (<50 MMEs/day). The primary composite endpoint was the incidence of ORAEs (naloxone use, decreased oxygen saturations, nausea/vomiting). Secondary outcomes included LOS, 30-day readmission, ORAEs with >100 MMEs/day. A total of 100 patients were included (n = 58 low-dose group; n = 42 high-dose group). For the primary outcome, more patients in the high-dose group experienced ORAEs (50% high-dose vs. 22.4% low-dose; p < 0.006). No statistically significant differences in LOS or 30-day readmission rates were identified between the groups. For patients receiving >100 MMEs/day, ORAEs occurred in 61% of patients. Hospitalized patients receiving high-dose opioids for non-cancer pain may have an increased incidence of ORAEs.

Pharmacist Transition-of-Care Services Improve Patient Satisfaction and Decrease Hospital Readmissions.

BACKGROUND: Pharmacists ability to directly impact patient satisfaction through increases in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys utilizing transitions-of-care (TOC) services is unclear. METHODS: Retrospective analysis of TOC patients from 07/01/2018 to 03/31/2019 was conducted. Intervention (INV) patients received pharmacist medication reconciliation and education prior to discharge and post-discharge telephone follow-up. All other patients served as control group (CON). Primary outcome: Evaluate impact of TOC services on HCAHPS scores for "Communication about Medicines" and "Care Transitions." Secondary outcomes: 30-day readmissions, quantification of prevented potential safety events, assessment of discharge prescriptions sent to the academic medical center outpatient pharmacy (MOP) for TOC patients. RESULTS: Of 1,728 patients screened, 414 patients met inclusion criteria (INV = 414, CON = 1314). A significant improvement (14.7%; p = <0.0001) in overall medication-related HCAHPS results was seen when comparing pre- vs post-implementation of the TOC service. Statistically significant increases for individual questions "staff told you what the medicine was for" (14.2%; p = 0.018), "staff describe possible effects" (21.2%; p = 0.004), and "understood the purpose of taking medications" (11.4%; p = 0.035) were observed. A non-significant decrease in 30-day readmission rates for the groups was observed (CON 16.4%, INV 13.3%; p = 0.133); however, an unplanned subgroup analysis evaluating impact of discharge phone calls on 30-day readmission rates revealed a significant reduction of 17.3% to 12.4% (p = 0.007). One hundred forty-three medication safety event(s) were potentially prevented by the TOC pharmacist. Lastly, 562 prescriptions were captured at the MOP as a result of the TOC initiative. CONCLUSIONS: Pharmacy-based TOC models can improve patient satisfaction, prevent hospital readmissions, and generate revenue.

Comparison of Nafcillin and Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia.

BACKGROUND: Traditionally, the antibiotic of choice for Methicillin-susceptible Staphylococcus aureus related blood stream infections (MSSA-BSI) are the antistaphylococcal penicillins. Cefazolin is considered an alternative agent, with recent evidence showing similar clinical efficacy. This study further evaluates the utility of nafcillin versus cefazolin in MSSA bacteremia including high disease burden sources of infection and its impact on treatment failure. METHODS: This retrospective study included patients admitted to Methodist LeBonheur Healthcare adult hospitals from 2011 to 2016. Patients were included if they received at least 3 days of either nafcillin or cefazolin and had a positive blood culture for MSSA. The primary objective was to evaluate rates of treatment failure between groups. Secondary outcomes included clinical and microbiological cure, MSSA-BSI associated readmissions, identification of risk factors for treatment failure including disease burden, in-hospital and 90 day mortality. RESULTS: A total of 277 patients were included (nafcillin n = 126; cefazolin n = 151). Treatment failure and microbiologic cure were similar between nafcillin and cefazolin (20.6% vs. 16.6%; 91.2% vs. 87.2%, respectively). Clinical cure was significantly higher in the cefazolin treatment arm (93.4 vs. 83.3%; P = 0.012). However, the total number of patients with high disease burden was greater in the nafcillin group (54.8% vs. 39.1%; P = 0.011). Higher rates of in-hospital mortality were observed in the nafcillin group (15.1% vs. 6%; P = 0.016). CONCLUSIONS: Our study observed significantly higher rates of clinical cure and reduced in-hospital mortality in patients who received cefazolin. Further analysis is warranted to evaluate the effectiveness of these agents and identifying predictors of treatment failure.

Inhaled corticosteroids should be initiated before discharge from the emergency department in patients with persistent asthma.

National and International Guidelines concur that inhaled corticosteroids (ICS) are the preferred long-term maintenance drug therapy for mild persistent asthma for all ages. For moderate and severe persistent asthma, ICS are essential to optimal management, often concurrent with other key therapies. Despite strong evidence and consensus guidelines, ICS are still underused. While some patients who are treated in the emergency department (ED) have intermittent asthma, most have persistent asthma and need ICS for optimum outcomes. Failure to initiate ICS at this critical juncture often results in subsequent lack of ICS therapy. Along with a short course of oral corticosteroids, ICS should be initiated before discharge from the ED in patients with persistent asthma. Although the NIH/NAEPP Expert Panel Report 3 suggests considering the prescription of ICS on discharge from the ED, The Global Initiative for Asthma (GINA) 2008 guidelines recommend initiation or continuation of ICS before patients are discharged from the ED. The initiation of ICS therapy by ED physicians is also encouraged in the emergency medicine literature over the past decade. Misdiagnosis of intermittent asthma is common; therefore, ICS therapy should be considered for ED patients with this diagnosis with reassessment in follow-up office visits. To help ensure adherence to ICS therapy, patient education regarding both airway inflammation (show airway models/colored pictures) and the strong evidence of efficacy is vital. Teaching ICS inhaler technique, environmental control, and giving a written action plan are essential. Lack of initiation of ICS with appropriate patient education before discharge from the ED in patients with persistent asthma is common but unfortunately associated with continued poor patient outcomes.

Comparison of three antimicrobial strategies in diabetic foot infections post-amputation.

BACKGROUND: The 2012 Infectious Disease Society of America (IDSA) guidelines recommend antimicrobial treatment of diabetic foot infections (DFIs) post-amputation, but the optimal route and duration are poorly defined. OBJECTIVE: The objective of this study was to determine whether the selection of a specific antimicrobial treatment modality affected hospital and patient outcomes. METHODS: This was a retrospective review of hospital admissions of adults admitted to ourhealthcare system with a primary diagnosis of DFIs post-amputation. The groups were separated into patients who received intravenous antimicrobials (IV), oral antimicrobials (PO), or no antimicrobials (NA). Outcomes included average length of stay among others. RESULTS: Of the 200 patients screened, 120 patients were included (IV n = 72; PO n = 20; NA n = 28). No statistically significant differences were identified in average LOS (IV = 9.97 ± 5.85, PO = 8.83 ± 7.37, NA = 9.33 ± 5.91 days; p = 0.73). However, post-operative (post-op) LOS was significantly shorter in the PO group (PO = 3.43 ± 2.56, IV = 7.34 ± 5.95, NA = 5.81 ± 4.18 days; p = 0.0001). CONCLUSION: The results of our study indicate that a PO antimicrobial treatment strategy post amputation for DFIs has the potential to decrease post-op LOS without increasing the risk of readmission. Based on the results of our study, we feel consideration should be given to transition to oral antimicrobials soon after amputation to facilitate discharge and decrease the utilization of intravenous antimicrobials.

Lorazepam versus chlordiazepoxide for the treatment of alcohol withdrawal syndrome and prevention of delirium tremens in general medicine ward patients.

Alcohol withdrawal syndrome (AWS) is a serious complication of abrupt alcohol cessation. Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening. Lorazepam (LOR) and chlordiazepoxide (CDE) are mainstays of therapy for AWS. Current literature lacks studies comparing outcomes between the two drugs for patients who are not in a de-addiction ward specifically for withdrawal treatment. The primary objective of the study was to determine the incidence rate of DT between the groups. Of 2112 patients screened, 142 met inclusion criteria (LOR = 74, CDE = 68). Baseline characteristics were similar between groups. No significant difference in the primary outcome of DT development was observed (7% LOR, 9% CDE; p = 0.76). No significant differences in cumulative doses of scheduled LOR or CDE were observed (LOR 14.6 ± 8 mg, CDE 15.4 ± 12; p = 0.64). However, significant differences were found in the amount of "as needed" (PRN) LOR required for the two groups (LOR 3.2 ± 4 mg, CDE 6.6 ± 13 mg; p = 0.03) and the amount of scheduled plus PRN LOR required (LOR 17.7 ± 10 mg, CDE 21.9 ± 14 mg; p = 0.04). Doses are reported in LOR equivalents. There were no observed differences in duration of treatment (LOR 3.6 ± 1.3 days, CDE 3.9 ± 2.1 days; p = 0.3) or length of stay (LOR 5.28 ± 3.8 days, CDE 4.73 ± 4.2 days p = 0.4). No adverse events related to BZD were noted in either group. Hospital outcomes did not differ between the groups, but patients treated with CDE may require more adjuvant therapy to control symptoms of AWS. Both agents appear equally effective at preventing the development of DT in those patients admitted to general medicine wards.