Prognostic significance of early platelet dynamics in Staphylococcus aureus bacteremia.

BACKGROUND: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB). METHOD: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence. RESULTS: Among the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2-3 following SAB onset, and Day 4 was a determining point of platelet count trajectory and mortality. Mortality risk was 6% or less for those with normal platelet count by Day 4 regardless of whether they experienced thrombocytopenia on Day 1, but the risk increased to 16-21% for those who experienced thrombocytopenia on Day 4 regardless of whether they had normal platelet count on Day 1 or sustained thrombocytopenia. The duration of bacteremia was prolonged by one day (median 3 d vs. 2 d) for those with sustained thrombocytopenia compared to those without. CONCLUSION: Early platelet dynamics during SAB have prognostic significance and represent an early window for potential platelet-directed therapeutic interventions to improve outcome.

Cytokine measurements add value to clinical variables in predicting outcomes for Staphylococcus aureus bacteremia.

BACKGROUND: We demonstrated that an early dysregulated cytokine response [high interleukin-10 to tissue necrosis factor (IL-10/TNF) ratio] predicted poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). However, high interpatient variability in cytokine levels were observed. We grouped cytokine measurements in quartiles and assessed their additive value to clinical variables for predicting bacterial persistence and 30-day mortality in patients with SAB. METHODS: A multicenter observational study was conducted in hospitalized patients with SAB. Medical charts were reviewed for relevant information. Blood samples were obtained for cytokine measurements by ELISA: interferon-gamma (IFNγ), interleukin (IL-1ß, IL-6, IL-8, IL-10, IL-17) and tissue necrosis factor (TNF). Cytokine measurements were grouped into quartiles. Significant predictors for bacterial persistence and 30-day mortality were determined by multivariable logistic regression analysis. Area under the ROC curve (AUC) analysis was performed and predictive performance was compared between models with and without cytokine quartiles. RESULTS: Among 606 patients with SAB, a subset of patients (n = 239) had Day 1 cytokine measurements and clinical data collected; of those, 53 (22%) had persistent bacteremia. Accounting for septic shock, the addition of either IL-10 (AUC 0.708) or TNF (AUC 0.714) quartiles measured on Day 1 improved model performance for predicting bacterial persistence. All patients had Day 4 cytokine measurements; 52 patients (8.5%) died within 30-days of SAB onset. Inclusion of either IL-10 (AUC 0.873) or TNF (AUC 0.879) quartiles, but not both, measured on Day 4 to the significant clinical predictors (coronary artery disease, Pitt bacteremia score ≥ 4, and septic shock) improved model performance for mortality. CONCLUSIONS: IL-10 or TNF levels falling within the range in the upper quartiles, when combined with clinical variables, improved model performance for predicting outcomes, and may potentially be used to support aggressive management and biomarker-guided studies to evaluate the benefit of adjunctive immunotherapy for SAB in the future.

Factors associated with prompt recovery among hospitalised patients with coronavirus disease 2019.

BACKGROUND: Patients who survived hospitalisation for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalised patients who recovered promptly versus survived a prolonged course of illness because of COVID-19. METHODS: This was a retrospective study from March-August 2020 of hospitalised adults with COVID-19 which were grouped based on time to recovery: short (≤3 days), intermediate (4-10 days) and prolonged (>10 days). Recovery was defined as resolution of fever, tachypnea, hypotension, extubation and return of mental status at baseline. Multivariate analysis was used to evaluate factors associated with prompt recovery. RESULTS: Among 508 patients hospitalised for COVID-19, 401 (79%) survived. Of those, prompt recovery (within 3 days) was achieved in 43% (174/401), whereas 23% (92/401) recovered after a prolonged period of >10 days. Overall, median age was 64 years with 73% admitted from home and 25% from a skilled nursing facility. Predictors for prompt recovery upon admission included female sex (OR, 1.8; 95% CI, 1.1-2.7; P = .01), no fever (OR, 1.6; 95% CI, 1.1-2.6; P = .03), longer time from symptom onset to hospitalisation (OR, 1.1; 95% CI, 1.0-1.1; P = .001), no supplemental oxygen (OR, 1.9; 95% CI, 1.2-3.0; P = .004), no direct ICU admission (OR, 41.7; 95% CI, 2.4-740.4; P = .01) and absence of bacterial co-infections (OR, 2.5; 95% CI, 1.5-4.0, P = .0003). CONCLUSIONS: Our study provides relevant data that could help clinicians triage competing resources in health systems that are challenged by the ebb and flow of COVID-19 cases by identifying clinical features of COVID-19 patients who may require less intensive management including avoidance of unnecessary antibacterial therapy.

MicroRNA-mediated disruption of dendritogenesis during a critical period of development influences cognitive capacity later in life.

The prenatal period of cortical development is important for the establishment of neural circuitry and functional connectivity of the brain; however, the molecular mechanisms underlying this process remain unclear. Here we report that disruption of the actin-cytoskeletal network in the developing mouse prefrontal cortex alters dendritic morphogenesis and synapse formation, leading to enhanced formation of fear-related memory in adulthood. These effects are mediated by a brain-enriched microRNA, miR-9, through its negative regulation of diaphanous homologous protein 1 (Diap1), a key organizer of the actin cytoskeletal assembly. Our findings not only revealed important regulation of dendritogenesis and synaptogenesis during early brain development but also demonstrated a tight link between these early developmental events and cognitive functions later in life.

Do pharmacist employers prefer or require board certification?

OBJECTIVE: The pharmacy profession has promoted the value of board certification, yet the impact of board certification on employment opportunities for pharmacists is largely unknown. This study aims to report employer preferences for board certification as indicated on job listings. DESIGN: A national search for pharmacy job postings from November 16, 2018, to March 8, 2019 was performed by reviewing websites and attending conferences. For each listing, data on the status of required, preferred, or neither for board certification, type of specialty, and the practice setting were recorded. Employers listing a preference or requirement for board certification were asked to complete a questionnaire to ascertain reasons for requiring or preferring board certification. SETTING AND PARTICIPANTS: The study includes job listings from various non-community pharmacy employers. OUTCOME MEASURES: The outcome measures were to (1) assess if board certification is required/preferred by pharmacist employers, (2) determine if predominantly clinical versus nonclinical job listings include board certification as a requirement or preference, (3) differentiate practice area and specialty with regard to requirement or preference for board certification, and (4) evaluate reasons behind the requirement or preference. RESULTS: More employers did not prefer or require board certification compared with those who listed such preferences (51% vs. 49%). Employers of jobs with a predominantly clinical component were more likely to require or prefer board certification (53% vs. 27% [no clinical component]). The board certification most often requested was pharmacotherapy, followed by oncology and psychiatry. Most employers (98%) who prefer board certification and those who require board certification (79%) believe that credentialing verifies competence in a specialty practice (P = 0.03) and ensures acquisition of knowledge and skills within the specialized field (P = 0.03). CONCLUSION: More pharmacy employers do not require or prefer board certification. Employers are more likely to prefer or require board certification for predominantly clinical jobs.

Implementation and assessment of a pilot, community pharmacy-based, opioid pain medication management program.

OBJECTIVES: This study aimed to evaluate care gaps in risk- and harm-reduction strategies for patients prescribed opioids and to describe the implementation of a community pharmacy-based, pilot pain-management program. SETTING: The pilot program was established in a community pharmacy within an academic medical center. Patients enrolled were prescribed opioids for chronic pain by a rheumatology clinic. PRACTICE DESCRIPTION: The patients enrolled met 1 or more of the following criteria: they were prescribed more than 1 short-acting opioid; more than 90 morphine milligram equivalents/d; and more than 7 days' supply of medications for acute pain, including high-risk medication combinations. Comprehensive pain-medication assessments and pharmacist interventions were communicated to providers and implemented at follow-up. Data were analyzed using descriptive statistics. PRACTICE INNOVATION: A gap analysis was conducted by including 23 patients seen at the clinic over a 22-month period. The care gaps identified served as the basis for the pilot-program design. EVALUATION: Patients referred to the program were seen over a span of 1 to 2 visits; a total of 19 visits were documented. Pharmacists identified unaddressed issues with mood (68%). Recommendations made to the providers included additional adjuvant therapy (84%), dose adjustment (58%), and laboratory tests (74%). Naloxone was provided (58%), and education on naloxone use was provided at every visit. DISCUSSION: Untreated depression, anxiety, and insomnia were the most common problems identified by pharmacists. Pharmacists implemented and documented risk-reduction strategies and coprescribed naloxone more frequently compared with clinic providers. The program enhanced the pharmacists' ability to make safe and clinically appropriate decisions with regard to filling opioid prescriptions. CONCLUSION: The pilot program identified care gaps and provided an approach for engaging with patients and providers to optimize pain management, implement opioid risk-reduction strategies, and expand naloxone access.

Utility of qSOFA score in identifying patients at risk for poor outcome in Staphylococcus aureus bacteremia.

BACKGROUND: The prognostic capability of the quick Sequential Organ Failure Assessment (qSOFA) bedside scoring tool is uncertain in non-ICU patients with sepsis due to bacteremia given the low number of patients previously evaluated. METHODS: We performed a retrospective cohort study of adult hospitalized patients with Staphylococcus aureus bacteremia (SAB). Medical charts were reviewed to determine qSOFA score, systemic inflammatory response syndrome (SIRS) criteria, and Pitt bacteremia score (PBS) at initial presentation; their predictive values were compared for ICU admission within 48 h, ICU stay duration > 72 h, and 30-day mortality. RESULTS: Four hundred twenty-two patients were included; 22% had qSOFA score ≥2. Overall, mean age was 56y and 75% were male. More patients with qSOFA ≥2 had altered mentation (23% vs 5%, p < 0.0001), were infected with MRSA (42% vs 30%, p = 0.03), had endocarditis or pneumonia (29% vs 15%, p = 0.0028), and bacterial persistence ≥4d (34% vs 20%, p = 0.0039) compared to qSOFA <2 patients. Predictive performance based on AUROC was better (p < 0.0001) with qSOFA than SIRS criteria for all three outcomes, but similar to PBS ≥2. qSOFA≥2 was the strongest predictor for poor outcome by multivariable analysis and showed improved specificity but lower sensitivity than SIRS ≥2. CONCLUSIONS: qSOFA is a simple 3-variable bedside tool for use at the time of sepsis presentation that is more specific than SIRS and simpler to calculate than PBS in identifying septic patients at high risk for poor outcomes later confirmed to have S. aureus bacteremia.

Clinical Pharmacy Services in a Multidisciplinary Specialty Pain Clinic.

PURPOSE: To describe a model of clinical pharmacy services as part of a multidisciplinary specialty pain clinic by discussing (1) the role of a clinical pharmacist in a specialty setting, including clinical interventions implemented, and (2) how integration of a clinical pharmacist may translate into an improved patient care model for the management of chronic pain. METHODS: A retrospective chart review was conducted of pharmacist visits from October 1, 2013, to September 30, 2015, in a specialty pain clinic at an academic medical center in Los Angeles, California. Data were collected regarding medication-related problems (MRPs) identified by the pharmacist, interventions implemented to resolve the MRPs, and types of medication care coordination activities (MCCAs) performed by the pharmacist, such as responding to medication refill requests and insurance issues. Descriptive statistics were used. Institutional review board approval was obtained prior to initiating the study. RESULTS: At least 1 MRP was identified in 98.7% of the 380 visits. Problems identified by the clinical pharmacist were divided into 5 categories: medication refills needed (43%), medication appropriateness/effectiveness (18%), miscellaneous (17%), safety (16%), and nonadherence/patient variables (6%). Interventions focused on referral to appropriate providers, medication counseling, medication initiation, dose adjustment, and medication discontinuation. The most common MCCA was responding to refill requests. CONCLUSION: A clinical pharmacist can identify many MRPs and implement interventions in chronic pain management. Integration of clinical pharmacy services may improve practice management by facilitating the completion of MCCAs and increase access to patients' needs outside the clinic.

A Dysregulated Balance of Proinflammatory and Anti-Inflammatory Host Cytokine Response Early During Therapy Predicts Persistence and Mortality in Staphylococcus aureus Bacteremia.

OBJECTIVES: The contribution of individual immune response to Staphylococcus aureus bacteremia on outcome has not been well studied. The objective was to relate the host cytokine response to outcome of Staphylococcus aureus bacteremia. DESIGN: Prospective observational study. SETTING: Three U.S. university-affiliated medical centers. PATIENTS: Adult patients infected with Staphylococcus aureus bacteremia hospitalized between July 2012 and August 2014. INTERVENTIONS: Blood specimens were obtained at Staphylococcus aureus bacteremia onset and 72 hours after therapy initiation. Levels of tissue necrosis factor, interleukin-6, interleukin-8, interleukin-17A, and interleukin-10 were measured by enzyme-linked immunosorbent assay at each time point and compared between those with persistent bacteremia (≥ 4 d) and resolving bacteremia. Primary outcome was persistent bacteremia after 4 days of effective therapy. Secondary outcomes were 30-day mortality and 30-day recurrence. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included (mean age, 59 yr); of them, 33% had methicillin-resistant Staphylococcus aureus bacteremia. Forty-seven percent of the methicillin-resistant Staphylococcus aureus strains were staphylococcal cassette chromosome mec IV. Persistent bacteremia occurred in 24% of patients (47/196); they were more likely to die than resolving bacteremia group (28% vs 5%; p < 0.001). Compared with resolving bacteremia group, persistent bacteremia patients had higher initial median levels of tissue necrosis factor (44.73 vs 21.68 pg/mL; p < 0.001), interleukin-8 (124.76 vs 47.48 pg/mL; p = 0.028), and interleukin-10 (104.31 vs 29.72 pg/mL; p < 0.001). Despite 72 hours of treatment, levels remained higher for the persistent bacteremia group than for the resolving bacteremia group (tissue necrosis factor: 26.95 vs 18.38 pg/mL, p = 0.02; interleukin-8: 70.75 vs 27.86 pg/mL, p = 0.002; interleukin-6: 67.50 vs 21.81 pg/mL, p = 0.005; and interleukin-10: 30.98 vs 12.60 pg/mL, p < 0.001). Interleukin-17A levels were similar between groups at both time points. After controlling for confounding variables by multivariate analysis, interleukin-10/tissue necrosis factor ratio at 72 hours most significantly predicted persistence (odds ratio, 2.98; 95% CI, 1.39-6.39; p = 0.005) and mortality (odds ratio, 9.87; 95% CI, 2.64-36.91; p < 0.001) at values more than 1.00 and more than 2.56, respectively. CONCLUSIONS: Sustained elevation of interleukin-10/tissue necrosis factor ratio at 72 hours suggests a dysregulated immune response and may be used to guide management to improve outcomes.

Young adults with hemophilia in the U.S.: demographics, comorbidities, and health status.

Improvements in hemophilia care over the last several decades might lead to expectations of a near-normal quality of life for young adults with hemophilia. However, few published reports specifically examine health status indicators in this population. To remedy this knowledge gap, we examined the impact of hemophilia on physical and social functioning and quality of life among a national US cohort of 141 young men with hemophilia aged 18-34 years of age who received care at 10 geographically diverse, federally funded hemophilia treatment centers in 11 states between 2005 and 2013 and enrolled in the Hemophilia Utilization Group Studies. Indicators studied included educational achievement, employment status, insurance, health-related quality of life, and prevalence of the following comorbidities: pain, range of motion limitation, overweight/obesity, and viral status. The cohort was analyzed to compare those aged 18-24 to those aged 25-34 years. When compared to the general US adult population, this nationally representative cohort of young US adults with hemophilia experienced significant health and social burdens: more liver disease, joint damage, joint pain, and unemployment as well as lower high-school graduation rates. Nearly half were overweight or obese. Conversely, this cohort had higher levels of health insurance and equivalent mental health scores. While attention has typically focused on newborns, children, adolescents, and increasingly, on older persons with hemophilia, our findings suggest that a specific focus on young adults is warranted to determine the most effective interventions to improve health and functioning for this apparently vulnerable age group.

Risk of developing pneumonia is enhanced by the combined traits of fluoroquinolone resistance and type III secretion virulence in respiratory isolates of Pseudomonas aeruginosa.

OBJECTIVES: To determine the differential association of host characteristics, antimicrobial resistance, and type III secretion system virulence of Pseudomonas aeruginosa isolates with respiratory syndromes in hospitalized adult patients. DESIGN: Retrospective, cohort study. SETTING: Community teaching hospital. PATIENTS: Two hundred eighteen consecutive adult patients with respiratory culture positive for P. aeruginosa between January 2005 to January 2010. INTERVENTIONS: Medical charts were reviewed to obtain demographic, laboratory, radiographic, and clinical information. Isolates were assayed by polymerase chain reaction for genes encoding the type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randomly amplified polymorphic DNA analysis. Levofloxacin susceptibility was determined by broth microdilution. Patients were grouped by colonization, bronchitis, or pneumonia and were compared for differential risk of developing the clinical syndrome with respect to host and microbial characteristics. MEASUREMENTS AND MAIN RESULTS: Half of the study cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14% (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%, respectively. Host factors strongly associated with pneumonia development were residence in long-term care facility, healthcare-associated acquisition of P. aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score, presence of enteral feeding tube, mechanical ventilation, and recent history of pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug-resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause pneumonia than bronchitis or colonization, respectively. Analysis of host and microbial factors in a multivariate regression model yielded the combined traits of fluoroquinolone resistance and gene encoding the type III secretion system ExoU effector in P. aeruginosa as the single most significant predictor of pneumonia development. CONCLUSIONS: These results suggest that fluoroquinolone-resistant phenotype in a type III secretion system exoU strain background contributes toward the pathogenesis of P. aeruginosa in pneumonia.

Patients presenting to the hospital with MRSA pneumonia: differentiating characteristics and outcomes with empiric treatment.

BACKGROUND: Concern for MRSA in patients presented to the hospital with pneumonia may be overestimated leading to excessive prescribing of empiric anti-MRSA therapy. This study aims to identify at-risk patients and treatment outcomes. METHODS: Adults hospitalized during 2005-2011 with pneumonia diagnosed within 48 h of admission were included. Medical charts were retrospectively reviewed for relevant data. Patients with MRSA were matched 1:1 to those with non-MRSA pathogen or negative culture. A published risk scoring system for MRSA pneumonia was applied. RESULTS: 268 elderly patients were included, 134 patients in each group. Compared to non-MRSA group, MRSA patients presented more acutely ill (p < 0.0001) (pneumonia severity index score, 150 vs 93; vasopressor therapy, 34% vs 6%; ICU admission, 47% vs 13%; and mechanical ventilation, 35% vs 10%) and had worse outcomes (p < 0.0001) (time to reach clinical stability, 6 vs 2.5d; length of stay, 10 vs 5d; clinical failure, 28% vs 4%; 28-day mortality, 22% vs 3%). When applied to our patients, a published risk scoring scheme had 93% sensitivity but lacked specificity at 55%; 40% of medium-risk patients did not have MRSA. A history of MRSA infection or pneumonia differentiated the latter group. Most MRSA patients (66%, 88/134) were treated empirically (primarily vancomycin) but outcome was not improved by receipt of empiric therapy. CONCLUSIONS: Use of a published risk scoring scheme with additional variables from this study can potentially reduce overprescribing of anti-MRSA empiric therapy in patients presented to the hospital with pneumonia. Prospective studies evaluating the treatment benefit of non-vancomycin alternatives as empiric therapy are needed.

Association of hyponatremia to diuretic response and incidence of increased serum creatinine levels in hospitalized patients with acute decompensated heart failure.

OBJECTIVES: Although hyponatremia is a prognostic factor in acute heart failure (AHF), its influence on the acute clinical course of heart failure is unknown. Our objective was to evaluate the association of hyponatremia with diuretic response, renal function, and clinical outcomes in AHF. METHODS: A retrospective study included 499 hospitalized AHF patients treated with intravenous loop diuretics for ≥48 h. Patients were grouped by nadir sodium concentrations (normonatremic, NN) ≥135 mEq/l, (mild hyponatremia, MHN) 130-134 mEq/l, and (moderate to severe hyponatremia, MSHN) <130 mEq/l. Association to diuretic response and clinical outcome was assessed. RESULTS: The incidence of hyponatremia was 54% (36% MHN, 18% MSHN). Maximum diuretic dose (furosemide equivalents: NN 84 ± 132 mg/day vs. MHN 114 ± 165 mg/day vs. MSHN 249 ± 450 mg/day, p < 0.001) and incidence of diuretic regimen escalation (NN 11% vs. MHN 16% vs. MSHN 44%, p < 0.001) were significantly higher in patients experiencing hyponatremia. Hyponatremia was also associated with a higher incidence of acute increases in serum creatinine (NN 27% vs. MHN 45% vs. MSHN 63%, p < 0.001), greater increases in blood urea nitrogen, longer hospital stay, and higher mortality. Outcome disparities to NN patients were similar whether hyponatremia was acute or present upon admission. CONCLUSIONS: Acute or admission hyponatremia, especially <130 mEq/l, in AHF patients is associated with greater diuretic requirements, higher incidence of serum creatinine increases, and a poorer outcome. Alternative treatments warrant evaluation in these patients.

Genomics and transcriptomic alterations of the glutamate receptors in acute myeloid leukemia.

Glutamine and glutamate have been widely explored as potential therapeutic targets in acute myeloid leukemia (AML). In addition to its bioenergetic role in leukemia cell proliferation, L-glutamate is a neurotransmitter that acts on glutamate receptors. However, the role of glutamate receptors in AML is largely understudied. Here, we comprehensively analyze the genomic and transcriptomic alterations of glutamate receptor genes in AML using publicly available data. We investigated the frequency of mutations in the glutamate receptor genes and whether an association exist between the presence of these mutations and clinical and molecular characteristics or patient's clinical outcome. We also assessed the dysregulation of glutamate receptor gene expression in AML with and without mutations and whether gene dysregulation is associated with clinical outcomes. We found that 29 (14.5%) of 200 patients with AML had a mutation in at least one glutamate receptor gene. The DNMT3A mutations were significantly more frequent in patients with mutations in at least one glutamate receptor gene compared with patients without mutations (13 of 29 [44.8%] vs. 41 of 171 [23.9%], p value: 0.02). Notably, patients with mutations in at least one glutamate receptor gene survived shorter than patients without mutations; however, the results did not reach statistical significance (overall survival: 15.5 vs. 19.0 months; p value: 0.10). Mutations in the glutamate receptor genes were not associated with changes in gene expression and the transcriptomic levels of glutamate receptor genes were not associated with clinical outcome.

Evaluating Change in Student Pharmacists' Familiarity, Attitudes, Comfort, and Knowledge as a Result of Integrating Digital Health Topics Into a Case Conference Series: Cohort Study.

BACKGROUND: The use of technology in health care, often referred to as digital health, has expanded rapidly because of the need to provide remote care during the COVID-19 pandemic. In light of this rapid boom, it is clear that health care professionals need to be trained in these technologies in order to provide high-level care. Despite the growing number of technologies used across health care, digital health is not a commonly taught topic in health care curricula. Several pharmacy organizations have called attention to the need to teach digital health to student pharmacists; however, there is currently no consensus on best methods to do so. OBJECTIVE: The objective of this study was to determine if there was a significant change in student pharmacist scores on the Digital Health Familiarity, Attitudes, Comfort, and Knowledge Scale (DH-FACKS) after exposure to digital health topics in a yearlong discussion-based case conference series. METHODS: Student pharmacists' initial comfort, attitudes, and knowledge were gathered by a baseline DH-FACKS score at the beginning of the fall semester. Digital health concepts were integrated into a number of cases in the case conference course series throughout the academic year. The DH-FACKS was administered again to students after completion of the spring semester. Results were matched, scored, and analyzed to assess any difference in DH-FACKS scores. RESULTS: A total of 91 of 373 students completed both the pre- and postsurvey (response rate of 24%). Using a scale from 1 to 10, the mean student-reported knowledge of digital health increased from 4.5 (SD 2.5) before intervention to 6.6 (SD 1.6) after intervention (P<.001) and the mean self-reported comfort increased from 4.7 (SD 2.5) before intervention to 6.7 (SD 1.8) after intervention (P<.001). There was a significant increase in scores for all 4 elements of the DH-FACKS. The mean familiarity scores increased from 11.6 (SD 3.7) to 15.8 (SD 2.2), out of a maximum of 20 (P<.001). The mean attitudes scores increased from 15.6 (SD 2.1) to 16.5 (SD 1.9), out of a maximum of 20 (P=.001). The mean comfort scores increased from 10.1 (SD 3.9) to 14.8 (SD 3.1), out of a maximum of 20 (P<.001). The mean knowledge scores increased from 9.9 (SD 3.4) to 12.8 (SD 3.9), out of a maximum of 20 (P<.001). CONCLUSIONS: Including digital health topics in a case conference series is an effective and approachable way of providing education on important digital health concepts to students. Students experienced an increase in familiarity, attitudes, comfort, and knowledge after the yearlong intervention. As case-based discussions are an important component of most pharmacy and other medical curricula, this method can be easily applied by other programs that wish to give their students practice applying their knowledge of digital health to complex case-based scenarios.

Risk factors and outcome associated with coinfection with carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumanii: a descriptive analysis.

Background: Nearly 30% of patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) were previously shown to be coinfected with carbapenem-resistant Pseudomonas aeruginosa (CRPA) or Acinetobacter baumannii (CRAB). Infections caused by multiple carbapenem-resistant pathogens present significant challenge to infection control and therapeutic management. The study objective was to identify risk factors for acquisition of multiple carbapenem-resistant pathogens and associated outcomes. Methods: A descriptive analysis of adults infected with either CRKP alone or coinfected with CRPA or CRAB was performed. Patient groups were compared on demographics, clinical characteristics, treatment, and outcome. Results: 86 patients with CRKP monoinfection and 60 patients with coinfections were evaluated. Respiratory tract was the predominant infection site for coinfected patients involving mostly CRPA whereas urinary tract was the primary site for CRKP-only group. More coinfected patients were severely debilitated, had prior carbapenem exposure (37% vs 13%, p<0.001) and history of pneumonia in the past year (67% vs 41%, p<0.01). More coinfected patients required direct ICU admission (45% vs 27%, p=0.02) and had prolonged length of stay (median 15 vs 10 days, p<0.01) than the CRKP-only group but mortality rates (18% vs 16%) were similar. Conclusions: CRKP coinfection with another carbapenem-resistant pathogen adds significant morbidity and healthcare burden overall. Empiric therapy with reliable activity against both CRKP and carbapenem-resistant Pseudomonas aeruginosa may be prudent for at risk patients with pneumonia.

Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection.

Background: Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management. Methods: A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort. Results: 457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p < 0.0001), and were hospitalized within the past 30 days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p < 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum ß-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30 days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality. Conclusion: Patients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.

Features of the TCR repertoire associate with patients' clinical and molecular characteristics in acute myeloid leukemia.

Background: Allogeneic hematopoietic stem cell transplant remains the most effective strategy for patients with high-risk acute myeloid leukemia (AML). Leukemia-specific neoantigens presented by the major histocompatibility complexes (MHCs) are recognized by the T cell receptors (TCR) triggering the graft-versus-leukemia effect. A unique TCR signature is generated by a complex V(D)J rearrangement process to form TCR capable of binding to the peptide-MHC. The generated TCR repertoire undergoes dynamic changes with disease progression and treatment. Method: Here we applied two different computational tools (TRUST4 and MIXCR) to extract the TCR sequences from RNA-seq data from The Cancer Genome Atlas (TCGA) and examine the association between features of the TCR repertoire in adult patients with AML and their clinical and molecular characteristics. Results: We found that only ~30% of identified TCR CDR3s were shared by the two computational tools. Yet, patterns of TCR associations with patients' clinical and molecular characteristics based on data obtained from either tool were similar. The numbers of unique TCR clones were highly correlated with patients' white blood cell counts, bone marrow blast percentage, and peripheral blood blast percentage. Multivariable regressions of TCRA and TCRB median normalized number of unique clones with mutational status of AML patients using TRUST4 showed significant association of TCRA or TCRB with WT1 mutations, WBC count, %BM blast, and sex (adjusted in TCRB model). We observed a correlation between TCRA/B number of unique clones and the expression of T cells inhibitory signal genes (TIGIT, LAG3, CTLA-4) and foxp3, but not IL2RA, CD69 and TNFRSF9 suggestive of exhausted T cell phenotypes in AML. Conclusion: Benchmarking of computational tools is needed to increase the accuracy of the identified clones. The utilization of RNA-seq data enables identification of highly abundant TCRs and correlating these clones with patients' clinical and molecular characteristics. This study further supports the value of high-resolution TCR-Seq analyses to characterize the TCR repertoire in patients.

Hispanic ethnicity and the rs4880 variant in SOD2 are associated with elevated liver enzymes and bilirubin levels in children receiving asparaginase-containing chemotherapy for acute lymphoblastic leukemia.

Asparaginase is an integral component of acute lymphoblastic leukemia (ALL)3 treatment. Hepatotoxicity related to asparaginase is one of the most common treatment-related toxicities in ALL therapy. Hispanic children are at higher risk of developing ALL, and toxicities from ALL therapy. The rs4880 variant in the superoxide dismutase 2 (SOD2)4 gene, a critical mitochondrial enzyme that protects cells against oxidative stress, was found to be associated with increased incidence of asparaginase-related hepatotoxicity in adult cohort of largely White non-Hispanics patients with ALL. The risk genotype (rs4880-CC) is more frequent among adult Hispanic patients with ALL. To assess the prevalence of hepatotoxicity and risk genotype among pediatric patients with ALL, particularly of Hispanic ethnicity, we conducted a prospective study of 143 pediatric patients with ALL (62.2% Hispanic). Bilirubin and hepatic transaminase levels were collected at different times during multiagent therapy including asparaginase treatment. Germline DNA blood samples were genotyped for the SOD2 rs4880. We found that the frequency of hepatotoxicity and the rs4880-CC risk genotype are higher in Hispanic patients than non-Hispanic. Patients with the CC genotype exhibit higher bilirubin and hepatic transaminase levels compared with patients with the TT and CT genotypes. In a multivariate Cox analysis, Hispanic ethnicity was identified as a strong predictor of hepatotoxicity (hazard ratio [HR] = 1.9, 95% confidence interval [95% CI] 1.0-3.5, p = 0.05). Altogether, these findings demonstrate that hepatotoxicity is highly prevalent among Hispanic pediatric patients with ALL, and those with rs4880-CC genotype.

Prevalence of and incentives for board certification among hospital pharmacy departments in California.

PURPOSE: Board of Pharmacy Specialties (BPS) certification is endorsed to distinguish pharmacists for advanced practice areas, yet perceived value to stakeholders remains poorly described. This study characterized how board certification is integrated in hospital pharmacy departments across California. METHODS: A prospective, cross-sectional study was conducted in which a survey was administered to all hospital pharmacy directors in California between November 2019 and March 2020. Licensed institutions and corresponding pharmacy directors were identified from the California State Board of Pharmacy. The survey queried for institution and pharmacy director characteristics and if/how board certification was integrated. Multivariable logistic models identified predictors of institutions with at least 25% full-time board certified pharmacists and those that reward board certification. RESULTS: Surveys were completed by 29% of institutions. Most of these institutions were urban (81%) and nonteaching (57%), with fewer than 325 hospital beds (71%), and with fewer than 50 full-time pharmacist positions (86%). The majority reported that less than 25% of their pharmacists were board certified. Currently, 47% consider board certification during hiring and 38% reward board certified employees. Predictors of institutions with 25% or more board certified pharmacists included being a teaching institution (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.24-7.06), having 325 or more beds (OR, 7.17; 95% CI, 2.86-17.97), and having a pharmacy director who was previously or currently board certified (OR, 3.69; 95% CI, 1.46-9.35). Hospitals with 100 or more pharmacist positions predicted institutions that reward board certification (OR, 16.69; 95% CI, 1.78-156.86). CONCLUSION: Board certification was an employment preference for almost half of the hospital survey respondents in California. Institutions more likely to reward board certified pharmacists are larger, urban, and teaching hospitals and have pharmacy directors who have been board certified.