Pharmacist driven antibiotic redosing in the emergency department.

STUDY OBJECTIVE: Determine whether an expanded emergency medicine (EM) pharmacist scope of practice reduces the frequency of major delays in subsequent antibiotic administration in patients boarded in the emergency department (ED). METHODS: A pre-post, quasi-experimental study conducted from November 2019-March 2020 at a single-center tertiary academic medical center following the implementation of an expanded EM pharmacist scope of practice. Adult patients were included if they received an initial antibiotic dose in the ED and deemed to be high-risk. Subsequent antibiotic doses were reordered by EM pharmacists for up to 24-h after the initial order pending ED length of stay (LOS). The historical control group consisted of retrospective chart review of cases from the previous year. RESULTS: The study identified that of the 181 participants enrolled, major delays in subsequent antibiotic administration occurred in 13% of the intervention group and 48% of the control group (p < 0.01). When compared to the control group, the intervention group had a significant decrease in the number of delays among antibiotics dosed at 6-h (39% vs 13%) and 8-h (60% vs 8%) intervals. For antibiotics dosed at 12-h intervals, no statistically significant difference was observed between the control and intervention groups respectively (19% vs 5%). A statistically significant lower incidence of in-hospital mortality was observed in the intervention group (3% vs 11%, p = 0.02). In the intervention group, 97% of patients received subsequent antibiotic doses while boarded in the ED, compared to 65% in the control group (<0.01). CONCLUSION: Expanding EM pharmacist scope of practice was associated with a significant reduction in the frequency of major delays in subsequent antibiotic administration as well as a decreased incidence of hospital mortality.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Outcomes of two quality improvement implementation interventions for depression services in adults with substance use problems.

Background: Comorbid depression and substance use disorders (SUDs) are associated with poor health and social outcomes disproportionately affecting under-resourced communities.Objectives: To test the hypothesis that a coalition approach to collaborative care (CC) for depression would improve outcomes of hazardous drinking and behavioral health hospitalizations, relative to technical assistance, for individuals with comorbid substance use problems. Substance use problems were defined by meeting criteria for DSM-IV substance abuse or dependence, hazardous drinking by AUDIT-C, or treatment in a SUD program within the prior 6 months.Methods: Two depression CC implementation approaches were compared: Resources for Services (RS) provided expert technical support for CC toolkits to individual programs. Community engagement and planning (CEP) supported multi-sector coalitions in collaborating in planning, adapting, implementing and monitoring CC toolkits. One thousand eighteen individuals with depression (PHQ-8 ≥10) enrolled. Regression analyses estimated intervention effects in participants with comorbid substance use problems (n = 588, 281 females, 307 males). Substance use problems were defined by meeting criteria for DSM-IV substance abuse or dependence, hazardous drinking by AUDIT-C, or treatment in a SUD program within the prior 6 months.Results: There were no significant baseline differences by intervention status among participants with depression and substance use problems. Intervention effects on primary outcomes including depression were not significant at 6 months. Compared to RS, CEP significantly reduced alcohol consumption (CEP = 1.6, RS = 2.1, p = .038), probability of behavioral health hospitalizations (OR = 0.50, p = .036), and use of specialty mental health visits (IRR = 0.52, p = .027), while increasing use of faith-based depression services (IRR = 3.4, p = .001).Conclusions: Given feasibility and possible benefits, CEP should be considered a promising approach to implementing depression CC with potential benefits to adults with comorbid substance use problems.

Commentary: Applying the Community Partners in Care Approach to the Opioid Crisis.

Background: Given national concern over rising mortality from opioid use disorders (OUD) and challenges to increasing OUD treatment access, a coalition approach may hold promise to improve access and outcomes for diverse populations. We present considerations of a community-partnered working group on adapting the Community Partners in Care (CPIC) study and coalition approach to OUD. Method: During January 2016 through January 2017, academic, provider, consumer and policy stakeholders reviewed options to adapt CPIC's Resources for Services (RS) for individual program technical assistance and Community Engagement and Planning (CEP) for coalition support to OUD treatments, integrating stakeholder input into design options with estimated sample sizes. Findings: The working group recommended Community Reinforcement and Family Treatment (CRAFT) as a stakeholder-support intervention to facilitate uptake and adherence to Medications for Addiction Treatment (MAT). Recommended implementation interventions for MAT/CRAFT were expert technical assistance supplemented by organizational readiness, and CEP for coalition support with a Learning Collaborative. Power estimation suggests that to compare implementation intervention effects on abstinence would require a somewhat larger enrolled sample and 3-4 times the screening sample as CPIC, and for mortality, at least 5-10 times the enrolled sample as CPIC. Discussion: Stakeholders viewed the CPIC design and interventions as feasible and acceptable as community-wide approaches for addressing the opioid epidemic, but comparing impacts on mortality would require large, multi-site trials.

12-Month Cost Outcomes of Community Engagement Versus Technical Assistance for Depression Quality Improvement: A Partnered, Cluster Randomized, Comparative-Effectiveness Trial.

Objective: To compare community engagement and planning (CEP) for coalition support to implement depression quality improvement (QI) to resources for services (RS) effects on service-use costs over a 12-month period. Design: Matched health and community programs (N=93) were cluster-randomized within communities to CEP or RS. Setting: Two Los Angeles communities. Participants: Adults (N=1,013) with depressive symptoms (Patient Health Questionnaire (PHQ-8) ≥10); 85% African American and Latino. Interventions: CEP and RS to support programs in depression QI. Main Outcome Measures: Intervention training and service-use costs over 12 months. Results: CEP planning and training costs were almost 3 times higher than RS, largely due to greater CEP provider training participation vs RS, with no significant differences in 12-month service-use costs. Conclusions: Compared with RS, CEP had higher planning and training costs with similar service-use costs.

Maintaining Internal Validity in Community Partnered Participatory Research: Experience from the Community Partners in Care Study.

Objective: With internal validity being a central goal of designed experiments, we seek to elucidate how community partnered participatory research (CPPR) impacts the internal validity of public health comparative-effectiveness research. Methods: Community Partners in Care (CPIC), a study comparing a community-coalition intervention to direct technical assistance for disseminating depression care to vulnerable populations, is used to illustrate design choices developed with attention to core CPPR principles. The study-design process is reviewed retrospectively and evaluated based on the resulting covariate balance across intervention arms and on broader peer-review assessments. Contributions of the CPIC Council and the study's design committee are highlighted. Results: CPPR principles contributed to building consensus around the use of randomization, creating a sampling frame, specifying geographic boundaries delimiting the scope of the investigation, grouping similar programs into pairs or other small blocks of units, collaboratively choosing random-number-generator seeds to determine randomized intervention assignments, and addressing logistical constraints in field operations. Study protocols yielded samples that were well-balanced on background characteristics across intervention arms. CPIC has been recognized for scientific merit, has drawn attention from policymakers, and has fueled ongoing research collaborations. Conclusions: Creative and collaborative fulfillment of CPPR principles reinforced the internal validity of CPIC, strengthening the study's scientific rigor by engaging complementary areas of knowledge and expertise among members of the investigative team.

Comparative Effectiveness of Coalitions Versus Technical Assistance for Depression Quality Improvement in Persons with Multiple Chronic Conditions.

Significance: Prior research suggests that Community Engagement and Planning (CEP) for coalition support compared with Resources for Services (RS) for program technical assistance to implement depression quality improvement programs improves 6- and 12-month client mental-health related quality of life (MHRQL); however, effects for clients with multiple chronic medical conditions (MCC) are unknown. Objective: To explore effectiveness of CEP vs RS in MCC and non-MCC subgroups. Design: Secondary analyses of a cluster-randomized trial. Setting: 93 health care and community-based programs in two neighborhoods. Participants: Of 4,440 clients screened, 1,322 depressed (Patient Health Questionnaire, PHQ8) provided contact information, 1,246 enrolled and 1,018 (548 with ≥3 MCC) completed baseline, 6- or 12-month surveys. Intervention: CEP or RS for implementing depression quality improvement programs. Outcomes and Analyses: Primary: depression (PHQ9 <10), poor MHRQL (Short Form Health Survey, SF-12<40); Secondary: mental wellness, good physical health, behavioral health hospitalization, chronic homelessness risk, work/workloss days, services use at 6 and 12 months. End-point regressions were used to estimate intervention effects on outcomes for subgroups with ≥3 MCC, non-MCC, and intervention-by-MCC interactions (exploratory). Results: Among MCC clients at 6 months, CEP vs RS lowered likelihoods of depression and poor MHRQL; increased likelihood of mental wellness; reduced work-loss days among employed and likelihoods of ≥4 behavioral-health hospitalization nights and chronic homelessness risk, while increasing faith-based and park community center depression services; and at 12 months, likelihood of good physical health and park community center depression services use (each P<.05). There were no significant interactions or primary outcome effects for non-MCC. Conclusions: CEP was more effective than RS in improving 6-month primary outcomes among depressed MCC clients, without significant interactions.

Review of Nonformulary Medication Approvals in an Academic Medical Center.

BACKGROUND: The Joint Commission requires hospitals to formally review formulary medications at least annually based on new clinical information. Although review of nonformulary medication (NFM) use is not required, frequent and inappropriate use of NFMs has the potential to increase hospital costs, negatively affect quality of care, and increase medication errors. Limited resources may restrict an institution's ability to review NFM use in addition to the required annual formulary review. NFM use at Brigham and Women's Hospital (BWH) was reviewed to provide insight on how to best direct an NFM review that is both effective and efficient. How an NFM review may negatively affect cost, quality of care, and medication errors is also inferred. METHODS: All approved NFM requests between 2009 and 2012 from Brigham and Women's Hospital's computerized provider order entry system were extracted and categorized according to the American Hospital Formulary Service (AHFS) Pharmacologic-Therapeutic Classification System. RESULTS: Of the 15,356,016 new medication orders, there were 223,266 NFM approvals for 433 unique NFMs. NFMs were categorized into 91 AHFS, 14 combination, and 4 "Others" classes. Twenty-five AHFS Classes accounted for approximately the top 90% of all NFM approvals, and the top 2 NFMs in each class accounted for a majority of the NFM approvals. CONCLUSION: Only a few classes of medications and a few medications within each class accounted for most of the NFM use at BWH. Targeting review of the most frequently used NFMs in each class may be a feasible strategy to reviewing NFMs annually that is both effective and efficient in optimizing formulary benefits.

Community Partners in Care: 6-Month Outcomes of Two Quality Improvement Depression Care Interventions in Male Participants.

OBJECTIVE: Limited data exist on approaches to improve depression services for men in under-resourced communities. This article explores this issue using a sub-analysis of male participants in Community Partners in Care (CPIC). DESIGN: Community partnered, cluster, randomized trial. SETTING: Hollywood-Metropolitan and South Los Angeles, California. PARTICIPANTS: 423 adult male clients with modified depression (PHQ-8 score≥10). INTERVENTIONS: Depression collaborative care implementation using community engagement and planning (CEP) across programs compared with the more-traditional individual program, technical assistance (Resources for Services, RS). MAIN OUTCOME MEASURES: Depressive symptoms (PHQ-8 score), mental health-related quality of life (MHRQL), mental wellness, services utilization and settings. RESULTS: At screening, levels of probable depression were moderate to high (17.5%-47.1%) among men across services sectors. Intervention effects on primary outcomes (PHQ-8 score and MHRQL) did not differ. Men in CEP compared with RS had improved mental wellness (OR 1.85, 95% CI 1.00-3.42) and reduced hospitalizations (OR .40, 95% CI .16-.98), with fewer mental health specialty medication visits (IRR 0.33, 95% CI .15-.69), and a trend toward greater faith-based depression visits (IRR 2.89, 95% CI .99-8.45). CONCLUSIONS: Exploratory sub-analyses suggest that high rates of mainly minority men in under-resourced communities have high prevalence of depression. A multi-sector coalition approach may hold promise for improving community-prioritized outcomes, such as mental wellness and reduced hospitalizations for men, meriting further development of this approach for future research and program design.

12-month outcomes of community engagement versus technical assistance to implement depression collaborative care: a partnered, cluster, randomized, comparative effectiveness trial.

BACKGROUND: Depression collaborative care implementation using community engagement and planning (CEP) across programs improves 6-month client outcomes in minority communities, compared with technical assistance to individual programs (resources for services [RS]). However, 12-month outcomes are unknown. OBJECTIVE: To compare effects of CEP and RS on mental health-related quality of life (MHRQL) and use of services among depressed clients at 12 months. DESIGN: Matched health and community programs (n = 93) in 2 communities randomly assigned to receive CEP or RS. (ClinicalTrials.gov: NCT01699789). MEASUREMENTS: Self-reported MHRQL and services use at baseline, 6 months, and 12 months. SETTING: Los Angeles, California. PATIENTS: 1018 adults with depressive symptoms (8-item Patient Health Questionnaire score ≥10), 88% of whom were an ethnic minority. INTERVENTION: CEP and RS to implement depression collaborative care. MEASUREMENTS: The primary outcome was poor MHRQL (12-item mental health composite score ≤40) at baseline, 6 months, and 12 months; the secondary outcome was use of services at 12 months. RESULTS: At 6 months, the finding that CEP outperformed RS to reduce poor MHRQL was significant but sensitive to underlying statistical assumptions. At 12 months, some analyses suggested that CEP was advantageous to MHRQL, whereas others did not confirm a significant difference favoring CEP. The finding that CEP reduced behavioral health hospitalizations at 6 months was less evident at 12 months and was sensitive to underlying statistical assumptions. Other services use did not significantly differ between interventions at 12 months. LIMITATION: Data are self-reported, and findings are sensitive to modeling assumptions. CONCLUSION: In contrast to 6-month results, no consistent effects of CEP on reducing the likelihood of poor MHRQL and behavioral health hospitalizations were found at 12 months. Still, given the needs of underresourced communities, the favorable profile of CEP, and the lack of evidence-based alternatives, CEP remains a viable strategy for policymakers and communities to consider. PRIMARY FUNDING SOURCE: National Institute of Mental Health, Robert Wood Johnson Foundation, California Community Foundation, National Library of Medicine, and National Institutes of Health/National Center for Advancing Translational Science for the UCLA Clinical and Translational Science Institute.

Explaining the determinants of first phase HIV decay dynamics through the effects of stage-dependent drug action.

A recent investigation of the effect of different antiretroviral drug classes on first phase dynamics of HIV RNA plasma virus levels has indicated that drugs acting at stages closer to viral production, such as the integrase inhibitor raltegravir, can produce a steeper first phase decay slope that may not be due to drug efficacy. Moreover it was found that for most drug classes the first phase transitions from a faster (phase IA) to a slightly slower decay region (phase IB) before the start of the usual second phase. Neither of these effects has been explained to date. We use a mathematical model that incorporates the different stages of the HIV viral life cycle in CD4+ T cells: viral entry, reverse transcription, integration, and viral production, to investigate the intracellular HIV mechanisms responsible for these complex plasma virus decay dynamics. We find differences in the phase IA slope across drug classes arise from a higher death rate of cells when they enter the productively infected stage post-integration, with a half-life of approximately 8 hours in this stage, whereas cells in earlier stages of the infection cycle have half-lives similar to uninfected cells. This implies any immune clearance is predominantly limited to the productive infection stage. We also show that the slowing of phase IA to phase IB at day 2 to 4 of monotherapy, depending on drug class, is a result of new rounds of infection. The level at which this slowing occurs is a better indicator of drug efficacy than the slope of the initial decay.

Influence of the Thermal Environment on Work Rate and Physiological Strain during a UCI World Tour Multistage Cycling Race.

PURPOSE: This study aimed to characterize the thermal and cardiovascular strain of professional cyclists during the 2019 Tour Down Under and determine the associations between thermal indices and power output, and physiological strain. METHODS: Gastrointestinal temperature ( Tgi ), heart rate (HR), and power output were recorded during the six stages (129-151.5 km) of the Tour Down Under in ≤22 male participants. Thermal indices included dry-bulb, black-globe, wet-bulb, and wet-bulb-globe (WBGT) temperature; relative humidity (RH), Heat Index; Humidex; and universal thermal climate index. The heat stress index (HSI), which reflects human heat strain, was also calculated. RESULTS: Dry-bulb temperature was 23°C-37°C, and RH was 18%-72% (WBGT: 21°C-29°C). Mean Tgi was 38.2°C-38.5°C, and mean peak Tgi was 38.9°C-39.4°C, both highest values recorded during stage 3 (WBGT: 27°C). Peak individual Tgi was ≥40.0°C in three stages and ≥39.5°C in 14%-33% of cyclists in five stages. Mean HR was 131-147 bpm (68%-77% of peak), with the highest mean recorded in stage 3 ( P ≤ 0.005). Mean power output was 180-249 W, with the highest mean recorded during stage 4 ( P < 0.001; 21°C WBGT). The thermal indices most strongly correlated with power output were black-globe temperature ( r = -0.778), RH ( r = 0.768), universal thermal climate index ( r = -0.762), and WBGT ( r = -0.745; all P < 0.001). Mean Tgi was correlated with wet-bulb temperature ( r = 0.495), HSI ( r = 0.464), and Humidex ( r = 0.314; all P < 0.05), whereas mean HR was most strongly correlated with HSI ( r = 0.720), along with Tgi ( r = 0.599) and power output ( r = 0.539; all P < 0.05). CONCLUSIONS: Peak Tgi reached 40.0°C in some cyclists, although most remained <39.5°C with an HR of ~73% of peak. Power output was correlated with several thermal indices, primarily influenced by temperature, whereas Tgi and HR were associated with the HSI, which has potential for sport-specific heat policy development.

Cardiac Safety of Clonidine and Quetiapine in Post-Cardiac Surgery Intensive Care Unit Patients.

Background: Clonidine and quetiapine are frequently used medications in the cardiac surgery intensive care unit (ICU). Objective: The purpose of this study is to assess the impact of clonidine compared to quetiapine on cardiac safety outcomes in adult cardiac surgery ICU patients. Methods: This was a single-center, retrospective observational analysis at a tertiary care, academic medical center. Results: One hundred and sixty-one cardiac surgery patients who were administered clonidine or quetiapine during their ICU stay were included between June 2015 and May 2017. The major endpoint of this study was a cardiac safety composite of bradycardia, hypotension, and QTc prolongation. Minor endpoints included ICU and hospital length of stay, and in-hospital mortality. There were 115 patients included in the clonidine arm and 46 patients in the quetiapine arm. There was no difference between groups with regard to the major endpoint (30.43% vs 33.15%; P < .8). There was a shorter ICU and hospital length of stay in the clonidine arm compared to quetiapine P < .0001. All other endpoints were not statistically significant. Conclusion: Patients who received clonidine tended to have undergone less complex procedures, be younger, and have a lower APACHE II score than patients who received quetiapine. The incidence of composite cardiac safety outcomes was not different in clonidine compared to quetiapine in cardiac surgery ICU patients.

Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy.

PURPOSE: The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea/vomiting (CINV) among lung cancer patients receiving multi-day chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting. METHODS: The Georgia Cancer Specialists electronic medical records database was used to retrospectively identify lung cancer patients who received multi-day cisplatin or carboplatin regimens with ondansetron or palonosetron on day 1 between April 1, 2006 and July 31, 2009. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea/vomiting), CPT codes (dehydration), rescue medications, nausea/vomiting hospitalizations, and/or antiemetic therapy after last chemotherapy administration of the cycle. Risk for uncontrolled CINV, up to 7 days after last chemotherapy administration, was analyzed at cycle level using logistic regression with regressors of gender, age, number of chemotherapy administration days, Charlson comorbidity index, cancer type, multicancer diagnoses, and chemotherapy regimen. RESULTS: A total of 209 palonosetron and 153 ondansetron patients (702 and 515 cycles, respectively) met the inclusion criteria. Palonosetron patients were significantly older (mean 67.9 versus 63.9 years; P < 0.0001), with no significant difference in gender, baseline comorbidity score, or multicancer diagnosis. Palonosetron cycles had 63% lower risk for uncontrolled CINV events versus ondansetron cycles [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.25-0.54; P < 0.0001]. Sub-analysis by chemotherapy supported overall analysis (cisplatin OR 0.09; 95% CI 0.04-0.25; P < 0.0001; carboplatin OR 0.46; 95% CI 0.30-0.70; P = 0.0003). CONCLUSION: In this retrospective analysis of lung cancer patients, multi-day chemotherapy cycles administered with palonosetron on day 1 were associated with a significantly lower risk for uncontrolled CINV events versus ondansetron-initiated chemotherapy cycles.

Practical approach to clinical controversies in glycemic control for hospitalized surgical patients.

The importance of glycemic management in surgical patient populations stems from an association between hyperglycemia and increased rates of surgical site infections, sepsis, and mortality. Various guidelines provide recommendations regarding target glucose concentrations, but all stress the importance of avoiding hypoglycemia as well. Within the surgical patient population, glycemic targets may vary further depending on the surgical service, such as cardiac surgery, neurosurgery, or reconstructive burn surgery. Glycemic management in critically ill surgical patients is achieved primarily through the use of intravenous insulin infusion protocols. These protocols can include fixed protocols, multiplication factor protocols, and computerized algorithms. In contrast, noncritically ill surgical patients are generally managed through the utilization of subcutaneous insulin with a combination of basal, bolus, and sliding scale insulin. Insulin protocols should be effective at maintaining glucose concentrations within the specified target range with minimal hypoglycemic events. Monitoring glucose concentrations while on either an intravenous or subcutaneous insulin protocol is essential. Point-of-care testing is the primary method for monitoring glucose concentrations in both critically ill and noncritically ill surgical patients and allows for adjustment of the insulin regimen. As patients move between units and to the outpatient setting, ensuring adequate follow-up is essential to maintaining control of hyperglycemia.

Evaluation of a Clinical Pharmacist-Led Automated Dispensing Cabinet Stewardship Program at a Tertiary Academic Medical Center.

BACKGROUND: There is little guidance regarding the best methodology or frequency to optimize automated dispensing cabinets. Clinical pharmacists are in the unique position to make decisions regarding automated dispensing cabinet inventory to best serve their specific patient population. OBJECTIVE: The purpose of this evaluation was to determine if automated dispensing cabinet optimization by clinical pharmacists would affect the number of dispenses from central pharmacy, number of stockouts, and inventory cost. METHODS: A retrospective analysis was completed to evaluate the quantity of medications dispensed from a central pharmacy department over 2 separate 2-month periods, with optimization of automated dispensing cabinets occurring in between. The differences in quantity of medications dispensed and redispensed, as well as the number of stockouts and inventory cost on all automated dispensing cabinets, were compared pre- and postintervention. RESULTS: There were 1132 medication additions, 262 medication removals, and 167 medication par level adjustments. Medications dispensed from central pharmacy were decreased by 12% from the preintervention group to the postintervention group. The number of stockouts per cabinet per day also decreased from 0.75 to 0.61 in the pre- and postintervention groups, respectively. The inventory-at-par cost level was decreased by 15%. CONCLUSION AND RELEVANCE: Automated dispensing cabinet optimization by clinical pharmacists led to increased medication availability on inpatient units and decreased the number of dispenses from central pharmacy. Simple yet meaningful interventions can be taken to improve multiple medication distribution metrics simultaneously.

Generation of three induced pluripotent stem cell (iPSC) lines from a patient with developmental epileptic encephalopathy due to the pathogenic KCNA2 variant c.869T>G; p.Leu290Arg (NUIGi052-A, NUIGi052-B, NUIGi052-C).

De novo pathogenic variants in KCNA2 are implicated in causing a spectrum of human neurological disorders, in particular developmental and epileptic encephalopathies. KCNA2 encodes the voltage-gated delayed rectifier potassium channel Kv1.2, which is vital in regulating neuronal membrane potential and repolarization. In this study, we generated three iPSC lines with non-integrating Sendai viral vectors from dermal fibroblasts of an 11-year old female patient harboring the KCNA2 c.869T>G (p.Leu290Arg) pathogenic variant. The iPSC lines were validated with standardized procedures including the targeted mutation, free of transgene integration, SNP karyotyping, pluripotent gene expression, and differentiation capacity into three embryonic germ layers.

Complementary Pharmacokinetic Profiles of Netupitant and Palonosetron Support the Rationale for Their Oral Fixed Combination for the Prevention of Chemotherapy-Induced Nausea and Vomiting.

NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1-3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%-87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656-2257 L and 483-679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate-to-low systemic clearances and long half-lives (cancer patients: netupitant, 19.5-20.8 L/h and 56.0-93.8 hours; palonosetron: 7.0-11.3 L/h and 43.8-65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%-93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance.