Triglyceride Concentrations and Their Relationship to Sedation Choice and Outcomes in Mechanically Ventilated Patients Receiving Propofol.

Rationale: Propofol is a first-line sedative agent in the intensive care unit (ICU) but may be associated with hypertriglyceridemia and pancreatitis. To date, the relationship between propofol-induced hypertriglyceridemia and pancreatitis, as well as clinician responses to propofol-induced hypertriglyceridemia, have not been comprehensively studied. Objectives: To assess the incidence of hypertriglyceridemia and pancreatitis in patients receiving continuous propofol infusions in the ICU and to describe the association between hypertriglyceridemia and the use of nonpropofol continuous sedative infusions. Methods: This was a retrospective observational cohort study conducted at three urban academic hospitals within a single health system. Findings were additionally validated using the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database containing data from a separate tertiary care hospital. Mechanically ventilated adult patients who received a continuous propofol infusion between 2016 and 2021 were included. The primary exposure was serum triglyceride concentration, and hypertriglyceridemia was defined as a triglyceride concentration greater than 400 mg/dl. Outcomes included new-onset pancreatitis as well as receipt of midazolam, dexmedetomidine, or ketamine after the triglyceride measurement. The incidence of pancreatitis was compared between groups using a Fisher's Exact test. Multivariable logistic regression was used to assess the association between dichotomized triglyceride concentration and alternative sedative use. Results: In the primary cohort of 7,037 patients, 1,724 (24.5%) had one or more triglyceride concentration measured. Of these, 1,365 (79.2%) had a maximum concentration of less than 400 mg/dl, and 359 (20.8%) had a maximum concentration of greater than 400 mg/dl. Compared with patients with low triglyceride concentrations, patients with high triglyceride concentrations were more likely to receive a continuous infusion of midazolam (37.0% vs. 16.4%; adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 2.2-4.4; P < 0.01), ketamine (22.8% vs. 6.9%; aOR, 3.5; 95% CI, 2.3-5.3; P < 0.01), and dexmedetomidine (57.7% vs. 46.6%; aOR, 1.5; 95% CI, 1.1-2.0; P < 0.01). Rates of midazolam infusion increased as triglyceride concentrations exceeded 500 mg/dl. Forty-four (0.6%) patients developed pancreatitis after propofol initiation, of which 4 (9.1%) were considered related to propofol-associated hypertriglyceridemia. Findings were similar in the MIMIC-IV cohort. Conclusions: Propofol-associated hypertriglyceridemia is relatively common in mechanically ventilated ICU patients who have triglycerides measured. Pancreatitis related to propofol-associated hypertriglyceridemia is rare. Patients who develop hypertriglyceridemia while receiving propofol are more likely to receive continuous infusions of other sedatives.

Safety and Efficacy Analysis of Apixaban Compared to Heparins in Hospitalized Non-Critically Ill COVID-19 Patients.

Purpose: Heparin-based regimens are recommended for anticoagulation in hospitalized patients with COVID-19 though a study reported similar mortality with apixaban in critically ill hospitalized COVID-19 patients. Our pilot study sought to determine the differences in all-cause mortality, venous thromboembolism (VTE), and bleeding events between apixaban and therapeutic heparin-based regimens in hospitalized non-critically ill COVID-19 patients. Methods: We conducted a retrospective analysis of non-critically ill COVID-19 patients aged ≥ 18 years admitted to 3 campuses of Montefiore Medical Center during the first (March 2020 to May 2020) and second (January 2021 to February 2021) COVID-19 surges, who received within 48 hours of admission and continued for ≥72 hours a therapeutic dose of low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or any apixaban dose for VTE prophylaxis. Outcomes data analyzed included mortality, suspected or imaging-confirmed VTE, and bleeding using a defined criteria. Results: Overall, 162 patients met eligibility for analysis. Baseline characteristics were similar between the 2 groups except liver and renal functions. Mortality occurred in 10 (13.3%) patients on apixaban and 23 (26.4%) patients on a heparin-based regimen (P = .059). Confirmed VTE events were not different between the groups (8% vs 13.8%, P = .359), but higher incidence of bleeding occurred in heparin-based group (4% vs 52.9%, P < .001). Conclusion: There were no differences in mortality or confirmed VTE between apixaban and heparin-based regimens except for more bleeding events with the heparins. This study highlights the utility of apixaban in COVID-19.

Prices, taxes and alcohol use: a systematic umbrella review.

AIM: To measure the impact of taxes and prices on alcohol use with particular attention to the different context of rising alcohol consumption in low- and middle-income countries. METHODS: Systematic review: we searched MEDLINE, Embase, EconLit and LILACS, grey literature, hand-searched five specialty journals and examined references of relevant studies. We considered all reviews that included studies that quantitatively examined the relationship between alcohol prices or taxes and alcohol use. At least two reviewers independently screened the articles and extracted the characteristics, methods and main results and assessed the quality of each included study. We identified 30 reviews. RESULTS: There was overwhelming evidence that higher alcohol prices and taxes were associated with lower total alcohol consumption and that price responsiveness varied by beverage type. Total own-price elasticities of alcohol demand were consistently negative and substantial enough to be policy meaningful; total own-price elasticities for beer, wine and spirits were found to be approximately -0.3, -0.6 and -0.65. Reviews generally concluded that higher taxes and prices were associated with lower heavy episodic drinking and heavy drinking, although the magnitude of these associations was generally unclear. Reviews provided no evidence that alcohol price responsiveness differed by socioeconomic status, mixed and contradictory evidence with respect to age and sex and limited evidence that price responsiveness in low- and middle-income countries was approximately the same as in high-income countries. CONCLUSIONS: Taxes are effective in reducing alcohol use. Moreover, increasing the price of alcohol by increasing taxes can also be expected to increase tax revenue, because the demand for alcohol is most certainly inelastic.

Determinants of Vancomycin Trough Concentration in Patients Receiving Continuous Veno-Venous Hemodialysis.

BACKGROUND: Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). OBJECTIVE: The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. RESULTS: A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. CONCLUSION AND RELEVANCE: Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

CE: Using Smart IV Infusion Pumps Outside of Patient Rooms.

ABSTRACT: The COVID-19 pandemic has created unique challenges for health care workers, who have demonstrated dedication, collaboration, and innovation in response. In this article, the authors describe an important nursing innovation they employed at Montefiore Medical Center in the Bronx, New York, during the spring 2020 COVID-19 surge: the relocation of smart IV infusion pumps outside of patient rooms. The goals of this innovation were to improve delivery of care, conserve personal protective equipment, limit the spread of the virus, and protect staff from exposure. The authors discuss the initial concerns that arose regarding the safety and efficacy of this practice; the research they conducted with other colleagues in nursing, pharmacy, infection control, and patient safety in the face of scant clinical literature relevant to the difficult circumstances the pandemic created; and the strategies they ultimately employed to ensure that this practice maintained safety and efficacy.

Phase 1 Combination Study of the CHK1 Inhibitor Prexasertib and the PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer and Other Solid Tumors.

PURPOSE: Checkpoint kinase 1 (CHK1) plays a central role in the response to replication stress through modulation of cell-cycle checkpoints and homologous recombination (HR) repair. In BRCA-deficient cancers with de novo or acquired PARP inhibitor resistance, the addition of the CHK1 inhibitor prexasertib to the PARP inhibitor olaparib compromises replication fork stability, as well as HR proficiency, allowing for sensitization to PARP inhibition. PATIENTS AND METHODS: This study followed a 3+3 design with a 7-day lead-in of olaparib alone, followed by 28-day cycles with prexasertib administered on days 1 and 15 in combination with an attenuated dose of olaparib on days 1-5 and 15-19. Pharmacokinetic blood samples were collected after olaparib alone and following combination therapy. Patients enrolled to the expansion phase of the study underwent paired tumor biopsies for pharmacodynamic (PD) assessments. RESULTS: Twenty-nine patients were treated. DLTs included grade 3 neutropenia and grade 3 febrile neutropenia. The MTD/recommended phase 2 dose (RP2D) was prexasertib at 70 mg/m2 i.v. with olaparib at 100 mg by mouth twice daily. Most common treatment-related adverse events included leukopenia (83%), neutropenia (86%), thrombocytopenia (66%), and anemia (72%). Four of 18 patients with BRCA1-mutant, PARP inhibitor-resistant, high-grade serous ovarian cancer (HGSOC) achieved partial responses. Paired tumor biopsies demonstrated reduction in RAD51 foci and increased expression of γ-H2AX, pKAP1, and pRPA after combination exposure. CONCLUSIONS: Prexasertib combined with olaparib has preliminary clinical activity in BRCA-mutant patients with HGSOC who have previously progressed on a PARP inhibitor. PD analyses show that prexasertib compromises HR with evidence of induction of DNA damage and replication stress.

Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit.

BACKGROUND: Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option. OBJECTIVE: The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used. RESULTS: A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; P = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; P < 0.01), with no change in agitation (64% vs 63%; P = 0.28). CONCLUSION AND RELEVANCE: Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.

Clinical Pharmacists: An Invaluable Part of the Coronavirus Disease 2019 Frontline Response.

Although coronavirus disease 2019 was first identified in December 2019, it rapidly spread and became a global pandemic. The number of patients infected with the novel coronavirus (severe acute respiratory syndrome coronavirus 2) rose rapidly in New York State, placing great stress on healthcare systems. The traditional roles and practices of healthcare providers were dramatically redefined to meet the demand to care for the large number of ill patients. While literature reports on the experiences of many frontline staff, there is a scarcity of reports on the role of clinical pharmacists during this crisis. We report the role of critical care clinical pharmacists at a large academic medical center in New York City during this pandemic. Effective crisis management required clinical pharmacists to employ a wide array of skills and knowledge. Areas included clinical expertise, education, data analysis, health informatics infrastructure, and inventory management in times of surging medication use and manufacturer shortages. Clinical pharmacists fulfilled an essential service during the coronavirus pandemic by working to ensure the best possible outcomes for the patients they served on the frontline.

Income inequalities in the risk of potentially avoidable hospitaliation and readmission for chronic obstructive pulmonary disease: a population data linkage analysis.

INTRODUCTION: Hospitalizations for ambulatory care sensitive conditions, of which chronic obstructive pulmonary disease (COPD) is among the most common, represent an indirect measure of the healthcare system to manage chronic disease. Research has pointed to disparities in various COPD-related outcomes between persons of lower versus higher income; however, few studies have examined the influence of patients' social context on potentially avoidable COPD admissions. OBJECTIVE: The research explores the use of linked population census and administrative health data to assess the influence of income inequalities on the risk of hospitalization and rehospitalization for COPD among Canadian adults. METHODS: This analysis utilizes data from the 2006 Census linked longitudinally to the 2006/07-2008/09 Discharge Abstract Database. Multiple logistic regressions were conducted to assess the independent influence of income inequality on the risks of hospitalization and of six-month readmission due to COPD among the population aged 30-69, controlling for age, sex, education and other sociodemographic characteristics. RESULTS: Compared with adults in the most affluent income quintile, the adjusted odds of COPD hospitalization were significantly greater in the 4th highest income quintile (OR: 1.38; 95%CI: 1.30-1.47), and peaked for those in the least affluent quintile (OR: 2.92; 95%CI: 2.77-3.09). Among individuals who had been hospitalized at least once for COPD in the study period, and compared with the most affluent group, the adjusted odds of readmission were highest in the least affluent group (OR: 1.39; 95%CI: 1.22-1.58). CONCLUSIONS: Despite Canada's system of universal coverage for physician and hospital care, a clear income gradient in the risk of being hospitalized and, to some extent, rehospitalized for COPD, is found. Income inequalities may be contributing to excess hospitalizations, reinforcing the importance of integrating social and economic issues in primary care to meet the ambulatory needs of this population.

Effectiveness of oral antibiotics for definitive therapy of non-Staphylococcal Gram-positive bacterial bloodstream infections.

BACKGROUND: Data on the effectiveness of definitive oral (PO) antibiotics for BSIs in preparation for discharge from hospital are lacking, particularly for Gram-positive bacterial BSIs (GP-BSI). The objective of this study was to determine rates of treatment failure based on bioavailability of PO antimicrobial agents used for GP-BSI. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to an academic medical center over a three-year period. Patients with a non-staphylococcal GP-BSI who received intravenous antibiotics and were then switched to PO antibiotics for at least a third of their treatment course were included. The cohort was stratified into high (⩾90%) and low (<90%) bioavailability groups. The primary endpoint was the proportion of patients experiencing clinical failure in each group. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal versus bacteriostatic PO agents, and organism. RESULTS: A total of 103 patients met criteria for inclusion, which failed to reach the a priori power calculation. Of the patients included, 26 received high bioavailability agents and 77 received low bioavailability agents. Infections originated largely from a pulmonary source (30%) and were caused primarily by streptococcal species (75%). Treatment failure rates were 19.2% in the high bioavailability group and 23.4% in the low bioavailability group (p = 0.66). Clinical failure stratified by subgroups also did not yield statistically significant differences. CONCLUSIONS: Clinical failure rates were similar among patients definitively treated with high or low bioavailability agents for GP-BSI, though the study was underpowered to detect such a difference.

Pediatric lateral neck infections - Computed tomography vs ultrasound on initial evaluation.

OBJECTIVE: Review the evaluation of children with a deep lateral neck infection and define the impact of initial imaging modality on outcomes and costs. METHOD: Case series, pediatric patients <18 years of age admitted to a tertiary care hospital with lateral neck infection between 01/01/14-05/31/16 as identified by ICD-9 and ICD-10 codes: 289.3 (lymphadenitis, unspecified), 682.1 (cellulitis and abscess of neck), 683 (acute lymphadenitis), I88.9 (nonspecific lymphadenitis, unspecified), L02.11 (cutaneous abscess of neck), L03.221 (cellulitis of neck), and L03.222 (acute lymphangitis of neck). Patients were divided into two groups based on initial imaging modality: primary ultrasound or primary computed tomography. Differences in length of stay, type and total number of imaging studies obtained, number of procedures, hospital readmission, and hospital cost were compared between cohorts. RESULTS: There were 40 (31%) primary ultrasound and 88 (69%) primary computed tomography patients (128 total). Median length of stay was 46 (IQR: 25,90) hours (1.9 days) for primary ultrasound and 63 (IQR: 39,88) hours (2.6 days) for primary computed tomography patients (p = 0.33). Drainage was performed in 48% of both groups. Additional imaging occurred in 17 (43%) primary ultrasound and 18 (20%) primary computed tomography patients (p = 0.02). Readmission occurred in 8 patients (6.3%). Retropharyngeal infection was encountered in 13 patients (10%); this was only discovered in patients who had a computed tomography performed. Median cost per primary ultrasound patients was $5363 (IQR: 3011, 7920) and $5992 (IQR: 3450, 8060) for primary computed tomography patients. CONCLUSIONS: The primary imaging modality (ultrasound or computed tomography) used to work-up children with a lateral neck infection did not impact length of stay or hospital cost. However, a significant subset had a coexisting retropharyngeal infection that was only identified on computed tomography. Future studies are needed to identify appropriate criteria for imaging in the work-up of lateral neck infections.

Time, Resident Involvement, and Supply Drive Cost Variability in Septoplasty with Turbinate Reduction.

Objective To determine factors that influence cost variability in septoplasty with inferior turbinate reduction. Study Design Case series with chart review. Setting Tertiary care hospital and affiliated ambulatory surgical center. Subjects and Methods Surgical costs were reviewed for adult patients undergoing septoplasty with inferior turbinate reduction between December 2014 and September 2017. Cases where additional procedures were performed were excluded. Operative supply costs, operative time, room time, and resident involvement were determined. Contribution of these factors to total costs and variability were analyzed. Results The study included 116 patients (mean age, 38 years) and 4 faculty surgeons. Total cost was primarily driven by operative time (74%), with a smaller portion of total cost arising from supplies (26%). Time cost ( P < .0001) and supply cost ( P = .006) varied significantly among surgeons. A resident was involved in 46.6% of cases. When subanalyzed by resident year, no-resident and senior resident (postgraduate years 4 and 5) cases had nearly identical mean times, while junior resident (postgraduate years 1-3) cases had mean times and operative time costs that were 39% greater ( P < .001). Conclusion For septoplasty with inferior turbinate reduction, the greatest driver of cost variation was operative time. Resident involvement correlated with increased time and cost. Supply costs had a much smaller impact. When subanalyzed by resident year, junior resident-involved cases were significantly longer than no-resident cases.