Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

INTRODUCTION: There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS: A total of 449 consecutive patients were included in this retrospective analysis. RESULTS: No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION: For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.

Medication Safety Events After Acute Myocardial Infarction Among Veterans Treated at VA Versus Non-VA Hospitals.

INTRODUCTION: Fragmentation of health care across systems can contribute to mistakes in prescribing and filling medications among patients treated for myocardial infarction (MI). We sought to compare omissions, duplications, and delays in outpatient medications used for secondary prevention among veterans treated for MI at Veterans Affairs (VA) versus non-VA hospitals. METHODS: We utilized national VA and Centers for Medicare and Medicaid Services data (2012-2018) to identify veterans 65 years or older hospitalized for MI and measured the use of outpatient medications for secondary prevention in the 30 days after MI among those treated at VA versus non-VA hospitals. RESULTS: A total of 118,456 veterans experiencing MI were included; of which 102,209 were hospitalized at non-VA hospitals. An omission in any medication class occurred more frequently among veterans treated at non-VA versus VA hospitals (82.8% vs 67.8%, P < 0.001). In multivariable modeling, the odds of omissions in any medication class were higher among those treated at non-VA versus VA hospitals (odds ratio: 3.04; 95% CI: 2.88-3.20). Duplications occurred more frequently in veterans treated at non-VA versus VA hospitals: 1.9% versus 1.6% had 1 or more for non-VA versus VA hospitals ( P < 0.001). Veterans treated at non-VA hospitals were more likely to have delays of 3 days or more in prescription fills after hospital discharge (88.4% vs 70.6% across all classes, P < 0.001). CONCLUSIONS: Omissions, duplications, and delays in outpatient prescribing of secondary prevention medications were more common among 118,456 veterans treated at non-VA versus VA hospitals for MI. Interventions aimed at improving care transitions and optimizing medication use among veterans treated at non-VA hospitals should be implemented.

Impact of race and ethnicity on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

Non-Hispanic Black patients are disproportionally affected by multiple myeloma (MM) and whether efficacy outcomes after autologous stem cell transplant (ASCT) differ by race and ethnicity remains an area of active investigation. This study included 449 patients enriched with a large proportion of non-Hispanic Black patients and sought to highlight the impact of race and ethnicity on outcomes after HDT-ASCT for patients with newly diagnosed MM. We found induction chemotherapy followed by high-dose therapy-ASCT and maintenance chemotherapy is associated with long-term PFS and OS, regardless of race or ethnicity.

Comparison of Outcomes in Neonates Receiving Cefepime or Ceftazidime.

OBJECTIVES: Cefepime and ceftazidime are alternatives to cefotaxime for management of Gram-negative infections in neonates. The objective was to evaluate neonatal outcomes when receiving cefepime or ceftazidime. METHODS: This was a single center, retrospective analysis of neonates exposed to at least 24 hours of cefepime or ceftazidime between June 1, 2018, and June 1, 2021. The primary outcome was incidence of culture-positive, late-onset sepsis after initial exposure. Secondary outcomes included culture-negative, respiratory, urinary tract, and resistant infections; necrotizing enterocolitis; length of stay; age at discharge; mortality; and adverse effects. RESULTS: A total of 105 neonates were included (cefepime, n = 50; ceftazidime, n = 55). Baseline characteristics were similar except more cumulative days of antibiotics (25.0 [IQR, 9.3-47.0] versus 9.0 [IQR, 4.0-23.5], p = 0.01), central line days (11.0 [IQR, 6.0-40.0] versus 6.5 [IQR, 0.0-11.5], p = 0.001), and ventilator days (13.0 [IQR, 2.3-48.0] versus 4.0 [IQR, 0.0-25.0], p = 0.02) were found in the cefepime group than in the ceftazidime group. There was no difference in culture-positive sepsis after the initial antibiotic course (8.0% versus 3.6%, p = 0.42). Statistical differences were seen in select secondary outcomes including treated respiratory infections (16.0% versus 1.8%, p = 0.01), length of stay greater than 30 days (72.0% versus 50.9%, p = 0.03), and mortality (26.0% versus 9.1%, p = 0.02). These differences were not observed in analyses adjusted for ventilator days. CONCLUSIONS: This analysis found no difference in culture-positive sepsis in neonates exposed to cefepime versus ceftazidime. Moreover, there were no differences in secondary outcomes in adjusted analyses. Further research is needed to assess neonatal outcomes in a larger analysis.

Risk factors for predicting extended-spectrum ß-lactamase-producing Enterobacterales (ESBLE) infections in non-urinary isolates.

Background: With increases in antimicrobial resistance, it is crucial that patients receive appropriate antimicrobial therapy in a timely manner. Advancements in rapid diagnostics offer the ability to identify resistant organisms quickly. However, this technology is not always accessible and relies on correct specimen collection. While awaiting new microbiology methods, it may be beneficial to identify risk factors associated with common types of resistance. Specifically, extended-spectrum ß-lactamase-producing Enterobacterales (ESBLE) are a rising threat globally. Objective: The primary objective of this retrospective case-control analysis was to identify factors associated with non-urinary ESBLE versus non-ESBLE infections. Design/Methods: Patient cultures were randomly selected based on type of culture (blood, bacterial, or exudate) and organism (E. coli, K. pneumoniae, or K. oxytoca) to provide a 1:1 ratio of ESBLE to non-ESBLE infections. Baseline demographics and potential risk factors (malignancy, cirrhosis, acute kidney injury (AKI), and diabetes) were collected for each patient encounter. Results: In the univariate analysis, risk factors that achieved a significant difference included cirrhosis, AKI, presence of urinary catheter, presence of center venous catheter, history of an ESBLE infection, hospital-acquired infection, and recent fluoroquinolone, cephalosporin, or beta-lactam use. The multivariate analysis showed that four factors were independently associated with an ESBLE infection: cirrhosis, urinary catheter, central venous catheter, and history of ESBLE. Having a history of an ESBLE had the highest adjusted odds ratio (aOR 12.49; 95% CI 4.71-33.15, P < .001) of the four factors. Conclusions: These results demonstrate that there may be benefit in incorporating select risk factors into clinical decision support tools to identify patients at highest risk of ESBLE infection.

Geographic distribution of United States clinical trial sites utilized for guideline changing studies of cholesterol management.

BACKGROUND: This study aimed to evaluate the geographic distribution of United States (US) clinical trial sites utilizedfor guideline changing studies of cholesterol management. METHODS: Randomized trials evaluating pharmacologic interventions for cholesterol treatment and reporting location data (ie, zip code of trial sites) were identified. Location data was abstracted from ClinicalTrials.gov. RESULTS: Half of US counties were over 30 miles from a study site and, social determinants of health were more favorable in counties with versus without clinical trial sites. CONCLUSIONS: Stakeholders such as regulatory bodies andtrial sponsors should incentivize and support infrastructure that would enable a larger number of US counties to be utilized for clinical trial sites. TRIAL REGISTRATION: Not applicable.

Effectiveness, Safety, and Cost Implications of Outpatient Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma.

BACKGROUND AND OBJECTIVE: Autologous hematopoietic stem cell transplant (aHCT) has become standard care for patients with multiple myeloma (MM). Outpatient aHCT with high-dose melphalan conditioning has reduced costs and length of hospital stay. This study aimed to highlight the effectiveness, safety, and cost implications of outpatient vs inpatient aHCT at a tertiary academic medical center, as well as the utility of growth factor use in these patients. PATIENTS AND METHODS: Using an institutional HCT database, a total of 100 patients undergoing aHCT for MM were identified; 50 patients who underwent aHCT in the outpatient setting (chemotherapy and stem cell infusion followed by inpatient admission if needed) were compared with 50 patients in the inpatient setting (chemotherapy and stem cell infusion followed by discharge to outpatient setting). Patients were excluded if the melphalan dose was less than 200 mg/m2. Outcomes assessed through retrospective chart review included time to engraftment, incidence of infection, febrile neutropenia, growth factor use, and total length of inpatient stay through day +100. RESULTS: Time to neutrophil and platelet engraftment was shorter in the outpatient group than in the inpatient group (14 vs 16 days and 19 vs 21 days, respectively; P < 0.001). Median length of hospital stay was also shorter in the outpatient group (8.5 vs 15.5 days, respectively; P < 0.001). Ninety percent of the outpatient group required admission for neutropenic fever, and 60% of these patients received growth factor support starting at a median of 9 days after stem cell infusion, for a median duration of 4 days. Compared to 16 patients who did not receive growth factor support, these patients had a significantly shorter time to neutrophil recovery (13 days with vs 15 days without growth factor, P = 0.02) and no difference in the total length of hospital stay (8 days with vs 10 days without growth factor, P = 0.43). CONCLUSION: For adult patients with MM undergoing aHCT, the outpatient setting is safe and reduces the total length of hospital stay and thus overall transplant costs. Growth factor support for patients with febrile neutropenia may not reduce length of stay for subsequent hospitalizations.

Impact of Race and Ethnicity on Severe Hypoglycemia Associated with Sulfonylurea Use for Type 2 Diabetes among Veterans.

Sulfonylureas are associated with hypoglycemia. Whether a racial/ethnic disparity in this safety outcome exists is unknown. We sought to assess the impact of race/ethnicity on severe hypoglycemia associated with sulfonylurea use for type 2 diabetes (T2D). Using Veterans Affairs and Medicare data, Veterans initially receiving metformin monotherapy for T2D between 2004 and 2006 were identified. Sulfonylurea use (either alone or via the addition of a prescription for a sulfonylurea to metformin) was captured and compared to remaining on metformin alone during the follow-up period (2007-2016). Hazard ratios (HR) and 95% confidence intervals (CI) from longitudinal competing risk Cox models were used to measure the association between sulfonylurea use and severe hypoglycemia defined as hospitalization for hypoglycemia. A total of 113,668 Veterans with T2D were included. A higher risk of severe hypoglycemia was associated with the receipt of sulfonylurea prescriptions versus remaining on metformin alone across all groups. The effect was largest among Hispanic Veterans (HR: 7.59, 95%CI:4.32-13.33), followed by Veterans in the other race/ethnicity cohort (HR: 4.57, 95%CI:2.50-8.36) and Non-Hispanic Black Veterans (HR: 3.67, 95%CI:2.78-4.85). The effect was smallest among Non-Hispanic White Veterans (HR: 3.11, 95%CI:2.77-3.48). In conclusion, a higher risk of severe hypoglycemia associated with sulfonylurea prescriptions was observed across all analyses. The relationship was most pronounced for Hispanic Veterans, who had nearly 8 times the risk of severe hypoglycemia with sulfonylureas versus remaining on metformin alone.

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study.

AIMS: To assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone. MATERIALS AND METHODS: This was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes. RESULTS: Switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively). CONCLUSIONS: Switching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.

First hepatitis B vaccine uptake in neonates prior to and during the COVID-19 pandemic.

INTRODUCTION: Routine vaccination for hepatitis B is recommended at birth, and most infants should be vaccinated within 24 h of life. Historically, vaccination rates have been less than ideal, and routine vaccination has been further complicated by the COVID-19 pandemic, with decreased uptake of many vaccines. This retrospective study assessed hepatitis B vaccination rates at birth before and after the start of the COVID-19 pandemic and explored the factors associated with lower vaccination rates. METHODS: Infants born at a single academic medical center in Charleston, South Carolina from November 1, 2018 through June 30, 2021 were identified. Infants were excluded if they died or received ≥ 7 days of systemic steroid therapy within the first 37 days of life. Maternal and infant baseline characteristics and uptake of the first hepatitis B vaccine during hospital admission were recorded. RESULTS: A total of 7808 infants were included in the final analysis, with an overall vaccine uptake of 91.6 %. Of the 3880 neonates in the pre-pandemic group, 3583 (92.3 %) were vaccinated, versus 3571 (90.9 %) of 3928 neonates in the pandemic group (rate difference = 1.4 %; 95 % confidence interval -2.8 % to 5.7 %, p = 0.52). Factors independently associated with lower vaccine uptake included being of non-Hispanic white race, born to a married mother, birth weight < 2 kg, and parental refusal of erythromycin eye ointment at birth. CONCLUSION: The COVID-19 pandemic did not significantly affect the uptake of inpatient neonatal hepatitis B vaccination. Several patient-specific factors were associated with suboptimal vaccination rates in this population.

Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience.

For patients with newly diagnosed multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT), hematopoietic stem cell mobilization can be affected by induction chemotherapy. In clinical trials, the addition of daratumumab (dara) to a triplet backbone lowered hematopoietic stem cell yield, necessitating the administration of plerixafor to achieve the desired yield for ASCT. Here we describe our experience of stem cell mobilization and collection after dara-based and non-dara-based induction regimens. This single-center retrospective analysis included patients with newly diagnosed MM who had received induction chemotherapy and were candidates for upfront HDT-ASCT. Based on the induction regimen used, patients were divided into 2 groups, RVd (lenalidomide, bortezomib, and dexamethasone) and DRVd (RVd with the addition of dara). Based on our institutional practice, patients received pegylated growth colony-stimulating factor (G-CSF) on day -3 (at 0900 hours) in combination with plerixafor on day -1 (at 2300 hours) as a preemptive mobilization strategy. Patients continued apheresis for 1 to 3 days until the goal dose of hematopoietic stem cells was collected (2.5 × 106 cells/kg for one ASCT and 5.0 × 106 cells/kg for 2 ASCTs). Patients with a suboptimal stem cell yield on day 1 received additional doses of plerixafor with or without G-CSF. A total of 101 patients with newly diagnosed MM who underwent mobilization between July 2021 and June 2022 were analyzed. The median patient age was 61 years (range, 36 to 80 years), and 51.5% of the cohort was female. Patients received a median of 5 (range, 2 to 12) cycles of induction chemotherapy, with a median of 4 (range, 2 to 12) cycles of DRVd and 6 (range, 3 to 12) cycles of RVd. The median number of CD34+ cells collected in the DRVd and the RVd groups was 6.54 × 106/kg and 6.78 × 106/kg, respectively. Target CD34+ stem cells were collected in a median of 1 day (range, 1 to 4 day) in each group. On average, more patients in the DRVd group compared to the RVd group received additional doses of plerixafor (51% versus 43%) and additional doses of GCSF (19% versus 14%) to achieve the target stem cell yield. There were no mobilization failures or grade 3+ mobilization-related adverse events reported in either group. The addition of daratumumab to the RVd induction regimen did not lead to any clinically significant differences in stem cell yield or number of collection days, provided that the patient received preemptive G-CSF and plerixafor. Patients with suboptimal collection on day 1 were able to collect adequate stem cells with additional doses of plerixafor with or without G-CSF.

Impact of Pharmacist-Driven Transitions of Care Interventions on Post-hospital Outcomes Among Patients With Coronary Artery Disease: A Systematic Review.

Background: Transitions of care (ToC) aim to provide continuity while preventing loss of information that may result in poor outcomes such as hospital readmission. Readmissions not only burden patients, they also increase costs. Given the high prevalence of coronary artery diseases (CAD) in the United States (US), patients with CAD often make up a significant portion of hospital readmissions. Objective: To conduct a systematic review evaluating the impact of pharmacist-driven ToC interventions on post-hospital outcomes for patients with CAD. Methods: MEDLINE, Scopus, and CINAHL were searched from database inception through 03/2020 using key words for CAD and pharmacists. Studies were included if they: (1) identified adults with CAD at US hospitals, (2) evaluated pharmacist-driven ToC interventions, and (3) assessed post-discharge outcomes. Outcomes were summarized qualitatively. Results: Of the 1612 citations identified, 11 met criteria for inclusion. Pharmacist-driven ToC interventions were multifaceted and frequently included medication reconciliation, medication counseling, post-discharge follow-up and initiatives to improve medication adherence. Hospital readmission and emergency room visits were numerically lower among patients receiving vs not receiving pharmacist-driven interventions, with statistically significant differences observed in 1 study. Secondary prevention measures and adherence tended to be more favorable in the pharmacist-driven intervention groups. Conclusion: Eleven studies of multifaceted, ToC interventions led by pharmacists were identified. Readmissions were numerically lower and secondary prevention measures and adherence were more favorable among patients receiving pharmacist-driven interventions. However, sufficiently powered studies are still required to confirm these benefits.

Impact of Cytogenetic Abnormalities, Induction and Maintenance Regimens on Outcomes After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma: A Decade-Long Real-World Experience.

Background: High-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) has become a standard of care for transplant eligible newly diagnosed multiple myeloma (NDMM) patients. While cytogenetic abnormalities have been shown to affect outcomes after HDT-ASCT in clinical trials, these trials often exclude or underrepresent elderly patients with comorbidities and those belonging to ethnic minorities. We describe our institutional experience highlighting the impact of high-risk cytogenetic abnormalities (HRCAs) on outcomes after HDT-ASCT for NDMM patients. Methods: A total of 449 patients with NDMM who underwent HDT-ASCT between February 2012 and August 2022 were included in this retrospective analysis. HRCAs included the presence of one or more of: deletion 17p, t(14;16), t(4;14), and amplification 1q. Survival analyses, including progression-free survival (PFS) and overall survival (OS), were performed using Kaplan-Meier estimator. Results: With a median follow-up of 29 (1 - 128) months for the entire patient population, the best overall response rate for the patients with HRCAs was lower compared to those with standard risk cytogenetics (90% vs. 96%; P = 0.01). Patients with HRCAs had an inferior PFS compared to patients with standard-risk cytogenetics (29 vs. 58 months; P < 0.001) without a difference in OS (70 months vs. not reached; P = 0.13). Conclusions: In a multivariable analysis adjusting for factors including age, race, and comorbidities, HRCAs, non-lenalidomide-based maintenance, non-proteasome inhibitor-based maintenance, and age greater than 65 were associated with inferior PFS. Amongst these factors, only non-lenalidomide-based maintenance was associated with inferior OS.

Evaluation of the impact of nasal colonization with methicillin-resistant Staphylococcus aureus on left ventricular assist device infections.

In this retrospective cohort study, we evaluated the predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs for the development of MRSA infections in patients with left ventricular assist devices. In 106 patients, the MRSA nasal swab had a negative predictive value of 92.9% demonstrating a potential role in antibiotic de-escalation.

Association between duration of antipseudomonal beta-lactam therapy and Clostridioides difficile infections in monomicrobial Enterobacterales bloodstream infections at an academic medical center.

Objective: To evaluate the effects early de-escalation of antipseudomonal ß-lactam (APBL) on 90-day CDI risk in Enterobacterales bloodstream infections (BSIs). Design: Retrospective cohort analysis. Setting: An academic medical center in South Carolina. Patients: We included patients aged >18 years with monomicrobial BSIs with Enterobacterales who received APBL between July 1, 2015, and June 30, 2020. Methods: Rates of CDI were compared between patients who received an APBL for >72 hours and <72 hours, followed by comparison between formulary APBLs utilized. Results: In total, 447 patients were included; 292 and 155 patients received APBL for < 72 hours and > 72 hours, respectively. The incidences of CDI for <72 hours compared to >72 hours were 2.4% and 6.5%, respectively (unadjusted hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.03-7.10; P = .04). This difference was not statistically significant in the adjusted model (HR, 2.66; 95% CI, 0.97-7.31; P = .06). Meropenem was associated with an increased risk of CDI when compared with all other formulary APBLs: 4 (26.7%) of 15 versus 13 (3.0%) of 432 (P < .001). Conclusions: Utilization of an APBL for >72 hours was associated with a statistically significant increase in the incidence of CDI in an unadjusted model and with a numerically higher CDI incidence in the adjusted model. Meropenem was the formulary APBL that carried the highest risk of CDI. The results of this study provide further evidence supporting active antimicrobial stewardship to reduce unnecessary broad-spectrum antibiotics in the effort to alleviate the burden that CDI imposes on the healthcare system.

Risk Factors for Antibiotic Resistant Urinary Pathogens in Patients Discharged From the Emergency Department.

Purpose: Urinary tract infections (UTIs) are one of the most common indications for antimicrobial use in the emergency department (ED). Appropriate empiric selection is crucial to ensure optimal care while limiting broad-spectrum antibiotic use. The primary objective of this study was to evaluate the relationship between patient-specific risk factors and drug resistant urinary pathogens in patients discharged from the ED and followed by Emergency Medicine Pharmacists (EMPs). Methods: This was a single-center, retrospective chart review of adult (≥18 years old) patients with positive urine cultures discharged from the ED. The association between risk factors and pathogen resistance to ≥1 classes of antibiotics was evaluated using multivariate logistic regression. Risk factors included the following: hospitalization within the previous 30 days, intravenous antibiotic use within 90 days, diabetes, clinical atherosclerotic cardiovascular disease, psychiatric disorder, dementia, current antibiotic use for any indication, previous lifetime history of UTIs, indwelling or intermittent catheterization, hemodialysis, previous lifetime history of a urologic procedure, urinary tract abnormality, immunosuppressive disease or medications, current residence in a nursing or rehabilitation facility, and history of a multidrug resistant organism (MDRO). Results: A total of 1018 patients were included. There was an increase in the odds of antibiotic resistance in patients with cystitis and ≥2 risk factors (Odds Ratio [OR] = 1.70, 95% CI = 1.24-2.32). In those with pyelonephritis, there was a non-significant increase in the odds of resistance for those with ≥2 risk factors (OR = 1.83, 95% CI = 0.98-3.42). Patients with pyelonephritis discharged on inappropriate antibiotics were more likely to return to the ED within 30 days (P = .03). Conclusions: For patients with cystitis discharged from the ED, those with ≥2 patient-specific risk factors had significantly increased odds of antibiotic resistance. Patients with pyelonephritis, but not cystitis, who were discharged on inappropriate antibiotics were more likely to return to the ED within 30 days. In conjunction with an EMP culture follow-up program, the identification of risk factors for antimicrobial resistance can be used to design more patient-specific empiric antibiotic selections.