Impact of Piperacillin-Tazobactam Dosing in Septic Shock Patients Using Real-World Evidence: An Observational, Retrospective Cohort Study.

BACKGROUND: Sepsis and septic shock are associated with significant morbidity and mortality. Rapid initiation of appropriate antibiotic therapy is essential, as inadequate therapy early during septic shock has been shown to increase the risk of mortality. However, despite the importance of appropriate antibiotic initiation, in clinical practice, concerns for renal dysfunction frequently lead to antibiotic dose reduction, with scant evidence on the impact of this practice in septic shock patients. OBJECTIVE: The purpose if this article is to investigate the rate and impact of piperacillin-tazobactam dose adjustment in early phase septic shock patients using real-world electronic health record (EHR) data. METHODS: A multicenter, observational, retrospective cohort study was conducted of septic shock patients who received at least 48 hours of piperacillin-tazobactam therapy and concomitant receipt of norepinephrine. Subjects were stratified into 2 groups according to their cumulative 48-hour piperacillin-tazobactam dose: low piperacillin-tazobactam dosing (LOW; <27 g) group and normal piperacillin-tazobactam dosing (NORM; ≥27 g) group. To account for potential confounding variables, propensity score matching was used. The primary study outcome was 28-day norepinephrine-free days (NFD). RESULTS: In all, 1279 patients met study criteria. After propensity score matching (n = 608), the NORM group had more median NFD (23.9 days [interquartile range, IQR: 0-27] vs 13.6 days [IQR: 0-27], P = 0.021). The NORM group also had lower rates of in-hospital mortality/hospice disposition (25.9% [n = 79] vs 35.5% [n = 108]), P = 0.014). Other secondary outcomes were similar between the treatment groups. CONCLUSIONS AND RELEVANCE: In the propensity score-matched cohort, the NORM group had significantly more 28-day NFD. Piperacillin-tazobactam dose reduction in early phase septic shock is associated with worsened clinical outcomes. Clinicians should be vigilant to avoid piperacillin-tazobactam dose reduction in early phase septic shock.

Recent Updates in the Pharmacological Management of Sepsis and Septic Shock: A Systematic Review Focused on Fluid Resuscitation, Vasopressors, and Corticosteroids.

OBJECTIVE: Describe recent developments in the pharmacological management of sepsis and septic shock, focusing on fluid resuscitation, vasopressors, and corticosteroids. DATA SOURCES: A literature search limited to randomized controlled trials written in the English language reporting mortality and other clinically relevant outcomes that were published from July 1, 2016, to August 31, 2018, in patients aged ≥ 18 years. Titles and abstracts were reviewed for relevance. References for pertinent review articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant randomized controlled trials conducted in patients meeting the pre-defined inclusion criteria were considered for inclusion. DATA SYNTHESIS: From an initial search that identified 147 studies, 14 original research studies met inclusion criteria and were included in this review. Risk of bias (ROB) was assessed using the Revised Cochrane ROB assessment tool, with most included studies having a low ROB. Relevance to Patient Care and Clinical Practice: Sepsis and septic shock pose a significant burden on public health. Despite advances in our understanding of sepsis, mortality remains unacceptably high. Recent developments in the pharmacological management of septic shock have focused on determining optimal composition and dosage of fluid resuscitation, enhanced use of vasopressor therapy, and clarifying the role of corticosteroids. This systematic review will provide recommendations for application to practice focusing on recent research on these topics. CONCLUSIONS: Although recent developments in the pharmacological management of sepsis are encouraging, clinicians must be keen to utilize patient-specific factors to guide therapy and continue to strive to address the remaining unanswered questions.

Virtual site visits - an emerging option for experiential quality assurance.

BACKGROUND AND PURPOSE: Site visits are a valuable tool for experiential quality assurance. There is sparse literature regarding the use of a virtual modality for completion of site visits. This manuscript describes the experience of using of onsite and virtual site visits, including benefits and limitations of each approach, by two pharmacy experiential programs. EDUCATIONAL ACTIVITY AND SETTING: Each experiential program utilizes both virtual and onsite visits to assess site quality, provide preceptor development, and connect with sites and preceptors. Information gathered and documentation processes are similar for both institutions for both visit modalities. The two pharmacy institutions differ in size, geographical location, number of experiential sites, and experiential department structure. FINDINGS: Based on site evaluator feedback from the two institutions, both visit modalities achieved the goals of evaluating sites for quality, fostering relationships with preceptors, and affording opportunities to provide preceptor development. Positive features of virtual site visits were increased flexibility with scheduling, expanded participation and engagement, increased efficiency, and decreased cost. Drawbacks noted with virtual site visits were challenges touring the site, decreased ability to observe group dynamics and culture, and participant multi-tasking. SUMMARY: A virtual approach to completing experiential site visits achieved programmatic goals. Utilizing a combination of virtual and onsite visits may facilitate a customized approach to navigating the advantages and disadvantages of each modality.

Impact of frequency of spaced retrieval using repeat testing on asthma pharmacotherapy knowledge retention.

OBJECTIVE: "Test-enhanced learning" is a strategy utilized to impact knowledge retention. This study aimed to assess the effect of the frequency of spaced retrieval using repeat testing on knowledge depreciation in a Doctor of Pharmacy (PharmD) Program. METHODS: The study randomly assigned second-year pharmacy students to one of three retrieval practice groups: (1) two retrieval practice assessments (2 and 4 months after the course), (2) one retrieval practice assessment (4 months after the course), or (3) no retrieval practice. A final assessment was administered to all participants 6 months after the course. The retrieval assessments and final assessment consisted of five multiple-choice questions on asthma pharmacotherapy. RESULTS: In total, 94 participants were included in the study, with 32 in Group 1 and 31 in both Groups 2 and 3. All three groups performed similarly on the final assessment regardless of the frequency of spaced retrieval. While Group 1 scored numerically higher than Group 2 on the 4-month retrieval practice assessment and did not impact performance on the final assessment. In Group 1, final assessment scores were decreased compared to the two previous retrieval assessments. CONCLUSION: Regardless of the frequency of spaced retrieval following the academic course where asthma pharmacotherapy was initially learned, retrieval practice using multiple choice assessments, with the gap times of this study, did not impact asthma pharmacotherapy knowledge depreciation among second-year student pharmacists.

Design and Evaluation of an APPE Readiness Dashboard Tool.

OBJECTIVE: To describe the design and evaluation of a dashboard tool to assess the readiness for advanced pharmacy practice experiences (APPEs). METHODS: The investigators developed a dashboard tool for the appraisal of APPE readiness consisting of indicators of pharmacy student knowledge, skills, and noncognitive attributes. For the 2018-2019 and 2019-2020 rotation years, a panel of stakeholders used the dashboard to evaluate APPE readiness. Students deemed not ready (5 or more dashboard indicators) had a remediation experience before the APPEs. The investigators monitored the students who were deemed ready but at risk for substandard performance (3 or 4 indicators or completion of remediation experience) and tracked the incidence of substandard performance for all APPE students. The outcomes were presented using descriptive statistics. Performance of the tool between years was compared using the χ2 test. RESULTS: For 2 APPE rotation cycles, the investigators evaluated readiness in 499 students. A total of 3 students were deemed not ready, and 78 students were considered at risk for substandard performance. The tool predicted 52.1% of students who experienced a substandard performance. It had a negative predictive value of 93.6% and a positive predictive value of 38.5% for substandard performance. The predictive value was similar across the risk categories of knowledge, skills, and noncognitive attributes. CONCLUSION: A dashboard tool facilitating holistic evaluation of APPE readiness was helpful in identifying students who were not ready for APPEs or at risk for substandard performance. The next steps include refinement of the tool through the evaluation of characteristics of students who experienced substandard performance and were not identified by the tool.

A Monitoring and Early Intervention Program for At-Risk Students on Advanced Pharmacy Practice Experiences.

Objective. To describe a monitoring and early intervention process for students at risk of substandard performance on advanced pharmacy practice experiences (APPEs).Methods. Using a dashboard of key indicators, students with potential deficits in knowledge, skills, or noncognitive attributes were identified as at risk of substandard performance on APPEs and placed on a list of students to be monitored during the APPE year. Employing a traffic light-based approach, at-risk students were initially designated with a monitoring status of red. If no issues were identified, students were de-escalated to yellow status and, subsequently, to green status. Monitored students who had issues or received a substandard evaluation on APPEs had a deficit-specific action plan implemented.Results. For the 2018-2019 and 2019-2020 academic years, 87 of 499 students entering APPEs were monitored. Of those 87 students, 77 (88.5%) completed experiences successfully on the first attempt, but 66 (75.9%) did require extended higher-level (red or yellow) monitoring. Over these two years, 54 (62.1%) of the 87 students deemed at risk did not have a substandard performance on APPEs, with 26 in the 2018-2019 year and 28 in the 2019-2020 year.Conclusion. A student monitoring and early intervention process may be beneficial in assisting at-risk students to successfully complete APPEs.

Pharmacy student self-assessment of strength of residency candidacy compared to clinical faculty.

INTRODUCTION: The purpose of this study was to compare student and faculty perceptions of strength of residency candidacy and to identify student preferences and perceptions that influence the process of being selected by a residency program beyond standard application materials. METHODS: A 31-item questionnaire was administered to third-year and fourth-year pharmacy students to collect information regarding factors deemed important for successful residency program candidacy. Global assessment of strength of residency candidacy was self-rated by students and a group of clinical faculty blinded to student responses. Interrater reliability for student-to-faculty and faculty-to-faculty perceptions of strength of residency candidacy was determined. RESULTS: Students generally reported good academic metrics and participation in a wide variety of scholarly activities deemed important in attaining a residency position. Students rated overall strength of residency candidacy as "above average" (n = 54, 37.2%), "average" (n = 60, 41.4%), and "below average" (n = 31, 21.3%), and self-perception increased with matriculation. Student self-assessment of strength of residency candidacy compared to faculty assessment showed poor agreement (mean [SD] kappa = 0.27 [0.08]). Faculty concordance in assessment of strength of residency candidacy was moderate (α = 0.55). CONCLUSIONS: Concordance in self-assessment of strength of residency candidacy of students compared to faculty was poor. In contrast, agreement among faculty was moderate with generally lower ratings compared to student self-rating, suggesting that students are overconfident in this regard. These findings support residency preparedness training in pharmacy curricula which should include formal assessment of strength of residency candidacy to identify gaps.

Rosiglitazone may assist with glycemic control in the ICU.

INTRODUCTION: Hyperglycemia is a frequent sequela of critical illness. Rosiglitazone is an oral hypoglycemic agent of the thiazolinedione class. Thiazolinediones are known to activate peroxisome proliferator-activated receptor gamma (PPAR-gamma) that decreases inflammation in humans and decreases shock induced by zymosan in mice. HYPOTHESIS: Rosiglitazone can assist with hyperglycemic control in the intensive care unit (ICU). METHODS: A hospital billing query identified patients prescribed rosiglitazone while in a major university ICU. Patients who received rosiglitazone as an outpatient prior to hospitalization were excluded. Glycemic control was determined by average daily blood glucose, 24-hour insulin dose, and number of patients requiring an insulin drip. Glycemic control was evaluated on days 0, 3, and 7. Student t test was used to compare means. Fisher exact testing was used to compare insulin regimen before and after starting rosiglitazone. RESULTS: 34 patients were identified. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score was 17.2 +/- 4.4. Sixty-five percent were male, 62% were preexisting diabetics. The mean daily blood glucose was 159 +/- 30 mg/dL on day 0, 146 +/- 37 mg/dL on day 3, and 140 +/- 33 mg/dL on day 7 (P < .03 vs day 0). The mean 24-hour insulin dose was 80.6 +/- 87.9 U on day 0, 72.2 +/- 73.4 U on day 3, and 46.3 +/- 57.2 U on day 7 (P < .003 vs day 0). There was 1 major hypoglycemic event. CONCLUSION: Rosiglitazone may assist glycemic control in the ICU. Despite recent concerns of cardiac safety, further research should be done to evaluate its potential as a short-term therapeutic agent in the ICU, given its anti-inflammatory and antishock profile.

A Task Force on Recruitment, Admissions, and Retention to Improve Pharmacy College Admissions Outcomes.

Objective. To create a task force on recruitment, admission, and retention, and assess pharmacy students' opinions and perceived value of the initiatives implemented. Methods. A task force on recruitment, admission, and retention was created at the University of Florida College of Pharmacy to build relationships between the college and incoming students and improve the admissions process. Admission and retention initiatives were implemented over a three-year period. All applicants who received an offer of admission, whether they accepted or declined, were invited to complete an online survey designed to solicit feedback on the admissions and retention initiatives. Results. The response rate to the survey was 80.3% in 2016 and 85.7% in 2017. The majority of students who responded reported that the admission and retention initiatives were helpful with regard to building connections with the college of pharmacy. In the three years after the task force implemented the admissions and retention initiatives, the admission yield (total number of students who accepted admission divided by the number offered admission) increased from 72.5% in 2015 to 79.5% in 2016 and 81.9% in 2017. Conclusion. Development of a task force specifically aimed to build relationships with students accepted to the college through strategic initiatives was instrumental in increasing admission yield and reducing the number of applicants who initially accepted an offer of admission and then chose not to attend the college.

The effects of a social media policy on pharmacy students' facebook security settings.

OBJECTIVE: To examine how students entering a doctor of pharmacy (PharmD) program used Facebook privacy settings before and after the college's social media policy was presented to them. METHODS: The Facebook profiles of all entering first-year pharmacy students across 4 campuses of a college of pharmacy were evaluated. Ten dichotomous variables of interest were viewed and recorded for each student's Facebook account at 3 time points: before the start of the semester, after presentation of the college's social media policy, and at the end of the semester. Data on whether a profile could be found and what portions of the profile were viewable also were collected. RESULTS: After introduction of the policy, a significant number of students increased their security settings (made information not visible to the public) related to Facebook walls, information pages, and links. CONCLUSIONS: Making pharmacy students aware of a college's social media policy had a positive impact on their behaviors regarding online security and privacy.

Differential expression of toll-like receptor genes: sepsis compared with sterile inflammation 1 day before sepsis diagnosis.

Toll-like receptors (TLRs) are critical components of innate immunity. This study was designed to evaluate differential expression of genes for TLR and associated signal transduction molecules in critically ill patients developing sepsis compared with those with sterile inflammation. Uninfected critically ill patients with systemic inflammatory response syndrome were prospectively followed daily for development of sepsis. They were divided into two groups and compared in a case-control manner: (a) preseptic patients (n = 45) who subsequently developed sepsis, and (b) uninfected systemic inflammatory response syndrome patients (n = 45) who remained uninfected. Whole blood RNA was collected (PAXGene tube) at study entry and 1, 2, and 3 days before clinical sepsis diagnosis (or time-matched uninfected control) and analyzed via Affymetrix Hg_U133 Plus 2.0 microarrays. Genes were considered differentially expressed if they met univariate significance controlled for multiple comparisons at P < 0.005. Differentially expressed probes were uploaded into the Database for Annotation, Visualization and Integrated Discovery. The TLR pathway (Kyoto Encyclopedia of Genes and Genomes-KEGG) significance was determined via Expression Analysis Systematic Explorer (EASE) scoring. A total of 2,974 Affymetrix probes representing 2,190 unique genes were differentially expressed 1 day before sepsis diagnosis. Thirty-six probes representing 25 genes were annotated to the TLR pathway (KEGG) via the Database for Annotation, Visualization and Integrated Discovery with an EASE score at P < 0.0004. Notable TLR genes demonstrating increased expression include TLR-4 (median, 1.43-fold change), TLR-5 (2.08-fold change), and MAPK14 (1.90-fold change). An additional 11 unique genes were manually annotated into the TLR pathway based on known relevance such as TLR-8 (1.54-fold change). The total 36 genes contained 28 showing increased expression and 8 showing decreased expression. Differential gene expression was noted for TLR receptors (eight genes), TLR intracellular signal transduction cascade molecules (27 genes), and TLR-related effector molecules (one gene). The TLR and downstream signaling genes are differentially expressed in critically ill patients developing sepsis compared with those with sterile inflammation. These expression differences occur before phenotypic-based diagnosis of clinical sepsis.

Community-acquired pneumonia: compliance with centers for Medicare and Medicaid services, national guidelines, and factors associated with outcome.

BACKGROUND: This study was performed to evaluate the impact of adherence to national guidelines for management of community-acquired pneumonia (CAP) on patient outcomes. METHODS: Compliance with published national guidelines was assessed. Mortality rate and length of hospital stay were determined. RESULTS: Patients who were administered antibiotics within 4 hours of admission had a shorter stay. Those treated at least 8 hours after admission had the highest mortality. Good compliance seen with 1998 guidelines of the Infectious Diseases Society of America declined substantially when 2000 Infectious Diseases Society of America guidelines were evaluated. Pediatric compliance was difficult to evaluate. Documentation of vaccination screening and administration was poor. CONCLUSION: Antibiotic therapy should be started within 4 hours in patients with CAP. Using the most recent CAP guidelines as a benchmark may lower compliance unless providers are reeducated. National consensus guidelines for pediatric patients should be developed. Hospitals should evaluate documentation of vaccine screening and administration and should implement programs to increase vaccination rates if needed.