Enhancing implementation of the I-PASS Handoff Tool Using a Provider Handoff Task Force at a Comprehensive Cancer Center.

BACKGROUND: Communication failures are among the most common causes of harmful medical errors. At one Comprehensive Cancer Center, patient handoffs varied among services. The authors describe the implementation and results of an Organization-wide project to improve handoffs and implement an evidence-based handoff tool across all inpatient services. METHODS: The research team created a task force composed of members from 22 hospital services-advanced practice providers (APPs), trainees, some faculty members, electronic health record (EHR) staff, education and training specialists, and nocturnal providers. Over two years, the task force expanded to include consulting services and Anesthesiology. Factors contributing to ineffective handoffs were identified and organized into categories. The EHR I-PASS tool was used to standardize handoff documentation. Training was provided to staff on its use, and compliance was monitored using a customized dashboard. I-PASS champions in each service were responsible for the rollout of I-PASS in their respective services. The data were reported quarterly to the Quality Assessment and Performance Improvement (QAPI) governing committee. Provider handoff perception was assessed through the biennial Institution-wide safety culture survey. RESULTS: All fellows, residents, APPs, and physician assistants were trained in the use of I-PASS, either online or in person. Adherence to the I-PASS written tool improved from 41.6% in 2019 to 70.5% in 2022 (p < 0.05), with improvements seen in most services. The frequency of updating I-PASS elements and the action list in the handoff tool also increased over time. The handoff favorability score on the safety culture survey improved from 38% in 2018 to 59% in 2022. CONCLUSION: The implementation approach developed by the Provider Handoff Task Force led to increased use of the I-PASS EHR tool and improved safety culture survey handoff favorability.

Borrelia burgdorferi, the Lyme disease spirochete, possesses genetically-encoded responses to doxycycline, but not to amoxicillin.

Some species of bacteria respond to antibiotic stresses by altering their transcription profiles, in order to produce proteins that provide protection against the antibiotic. Understanding these compensatory mechanisms allows for informed treatment strategies, and could lead to the development of improved therapeutics. To this end, studies were performed to determine whether Borrelia burgdorferi, the spirochetal agent of Lyme disease, also exhibits genetically-encoded responses to the commonly prescribed antibiotics doxycycline and amoxicillin. After culturing for 24 h in a sublethal concentration of doxycycline, there were significant increases in a substantial number of transcripts for proteins that are involved with translation. In contrast, incubation with a sublethal concentration of amoxicillin did not lead to significant changes in levels of any bacterial transcript. We conclude that B. burgdorferi has a mechanism(s) that detects translational inhibition by doxycycline, and increases production of mRNAs for proteins involved with translation machinery in an attempt to compensate for that stress.

Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions.

Food effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80-1.25), increased exposure (AUC ratio ≥1.25), or decreased exposure (AUC ratio ≤0.8). Drugs with significantly increased exposure FE (AUC ratio ≥2.0; N=14) were BCS Class 2 or 4, while drugs with significantly decreased exposure FE (AUC ratio ≤0.5; N=2) were BCS Class 1/3 or 3. The lack of FE was aligned with the lack of a pH-dependent DDI for all 7 BCS Class 1 or 3 drugs as expected. For the 13 BCS Class 2 or 4 weak base drugs with an increased exposure FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). Among the 16 BCS Class 2 or 4 weak base drugs with no FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). FE appears to have limited correlation with BCS classes except for BCS Class 1 drugs, confirming that multiple physiological mechanisms can impact FE. Lack of FE does not indicate absence of pH-dependent DDI for BCS Class 2 or 4 drugs. Graphical Abstract.

Moving Forward to Nurture Workforce Resilience in Crisis.

As the CEO of a firm that helps organizations improve performance through culture and learning, and as someone who has spent the past 12 years coaching thousands of individual leaders, staff members, and physicians at hundreds of hospitals and health systems, I have seen both the positive effects of resilience and the negative effects of a lack of resilience. During the COVID-19 pandemic, I and my team have worked with organizations to find ways to help their distressed employees take better care of themselves and, in turn, help their patients as our collective recovery continues.

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19.

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation. End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: -3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: -13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2-17 year olds receiving LAIV was 48.6% (95% CI: -4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.

National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: Evidence of sub-optimal practice.

A survey of laboratory testing capabilities for systemic fungal pathogens was undertaken in the UK, to identify where improved compliance with published standards and guidelines is required and to inform antifungal stewardship (AFS). The survey captured information from laboratories in the UK on diagnostic capacity for invasive fungal diseases (IFD), including identification, serology, molecular diagnostics and susceptibility testing. The survey was circulated in March 2017 through key networks. Of 154 laboratories providing diagnostic mycology services in the UK, 80 (52%) responded to the survey. Results indicated that 85% of respondents identified fungal isolates from high risk patients to species level, and that many laboratories (78%) could access local susceptibility testing for yeasts, whereas 17% could for Aspergillus species. However, direct microscopy was only used in 49% as a first line investigation on samples where it would be appropriate. A low number of respondents identified yeasts cultured from intravascular line tips to species level (63%) and even fewer fully identified urine isolates from critically ill patients (42%) or the immunocompromised (39%). Less than half of respondents advised therapeutic drug monitoring (TDM) for flucytosine. Few laboratories had access to local ß-glucan (4%) or galactomannan (20%) testing. The survey highlights that the current level of fungal diagnostics in the UK is below accepted best practice with an urgent need to improve across many diagnostic areas including the timely accessibility of fungal biomarkers, susceptibility testing and provision of TDM testing. Improvements are important to facilitate the delivery of diagnostic driven AFS strategies as well as appropriate management of IFD.

Pharmacokinetics, pharmacodynamics and pharmacogenetics associated with nonsteroidal anti-inflammatory drugs and opioids in pediatric cancer patients.

INTRODUCTION: Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer. Areas covered: Analgesics commonly used to treat pediatric patients with malignancy patterned after the World Health Organization's 'analgesic ladder' for cancer pain management. Expert opinion: Addressing pain management safely and effectively in pediatric patients with cancer will require advances in both drug development, to increase the armament of analgesics available for children, and our pharmacologic understanding of those analgesics in current use. However, performing the necessary types of studies to develop new analgesics, or gain knowledge of existing therapy, within a population that is relatively small, diverse, and who experience pain originating from a variety of sources, is a tremendous challenge.

The imperative of culture: a quantitative analysis of the impact of culture on workforce engagement, patient experience, physician engagement, value-based purchasing, and turnover.

Current uncertainty for the future of the health care landscape is placing an increasing amount of pressure on leadership teams to be prepared to steer their organization forward in a number of potential directions. It is commonly recognized among health care leaders that culture will either enable or disable organizational success. However, very few studies empirically link culture to health care-specific performance outcomes. Nearly every health care organization in the US specifies its cultural aspirations through mission and vision statements and values. Ambitions of patient-centeredness, care for the community, workplace of choice, and world-class quality are frequently cited; yet, little definitive research exists to quantify the importance of building high-performing cultures. Our study examined the impact of cultural attributes defined by a culture index (Cronbach's alpha = 0.88) on corresponding performance with key health care measures. We mapped results of the culture index across data sets, compared results, and evaluated variations in performance among key indicators for leaders. Organizations that perform in the top quartile for our culture index statistically significantly outperformed those in the bottom quartile on all but one key performance indicator tested. The culture top quartile organizations outperformed every domain for employee engagement, physician engagement, patient experience, and overall value-based purchasing performance with statistical significance. Culture index top quartile performers also had a 3.4% lower turnover rate than the bottom quartile performers. Finally, culture index top quartile performers earned an additional 1% on value-based purchasing. Our findings demonstrate a meaningful connection between performance in the culture index and organizational performance. To best impact these key performance outcomes, health care leaders should pay attention to culture and actively steer workforce engagement in attributes that represent the culture index, such as treating patients as valued customers, having congruency between employee and organizational values, promoting employee pride, and encouraging the feeling that being a member of the organization is rewarding, in order to leverage culture as a competitive advantage.

What Can Be Learned from Recent New Drug Applications? A Systematic Review of Drug Interaction Data for Drugs Approved by the US FDA in 2015.

As a follow up to previous reviews, the aim of the present analysis was to systematically examine all drug metabolism, transport, pharmacokinetics (PK), and drug-drug interaction (DDI) data available in the 33 new drug applications (NDAs) approved by the Food and Drug Administration (FDA) in 2015, using the University of Washington Drug Interaction Database, and to highlight the significant findings. In vitro, a majority of the new molecular entities (NMEs) were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. In vivo, 95 clinical DDI studies displayed positive PK interactions, with an area under the curve (AUC) ratio ≥ 1.25 for inhibition or ≤ 0.8 for induction. When NMEs were considered as victim drugs, 21 NMEs had at least one positive clinical DDI, with three NMEs shown to be sensitive substrates of CYP3A (AUC ratio ≥ 5 when coadministered with strong inhibitors): cobimetinib, isavuconazole (the active metabolite of prodrug isavuconazonium sulfate), and ivabradine. As perpetrators, nine NMEs showed positive inhibition and three NMEs showed positive induction, with some of these interactions involving both enzymes and transporters. The most significant changes for inhibition and induction were observed with rolapitant, a moderate inhibitor of CYP2D6 and lumacaftor, a strong inducer of CYP3A. Physiologically based pharmacokinetics simulations and pharmacogenetics studies were used for six and eight NMEs, respectively, to inform dosing recommendations. The effects of hepatic or renal impairment on the drugs' PK were also evaluated to support drug administration in these specific populations.

Population pharmacokinetic-pharmacodynamic modelling to describe the effects of paracetamol and N-acetylcysteine on the international normalized ratio.

Paracetamol is one of the most common pharmaceutical agents taken in self-poisonings, and can increase the prothrombin time (PT) through liver injury, and in overdose without hepatic injury by reducing functional factor VII. PT is a measure of hepatic injury used to predict and monitor hepatotoxicity, reported as the international normalized ratio (INR). The antidote for paracetamol poisoning, N-acetylcysteine (NAC), has been reported to have an effect on the PT. This analysis included patients from a retrospective case series, a prospective inception cohort of paracetamol and psychotropic (control) overdoses, and a cross-over clinical trial. A population pharmacokinetic-pharmacodynamic model describing the pharmacodynamic effects of paracetamol and NAC on the INR was developed in Phoenix NLME. The dataset included 172 patients; the median age was 22 years (range 13-71 years). A one-compartment model with first-order input and linear disposition best described paracetamol pharmacokinetics. The population mean estimate of the concentration that induced a response halfway between the baseline and maximal pharmacological effect of paracetamol was 1302 µmol/L (242), the maximum effect of paracetamol was 0.534 (202; from baseline) and the maximum effect of NAC was 0.325 (9.03; from baseline). Both paracetamol and NAC contributed a pharmacological effect to the elevation of INR. The estimated paracetamol concentration that induced a response halfway between the baseline and maximal pharmacological effect was within the range of plasma paracetamol values studied, fivefold greater than the maximum therapeutic concentration, suggesting that an elevated INR would not be expected within the therapeutic range. Simulated 24 and 48 g paracetamol overdoses with NAC administration produced INR values (50th percentile) that reached the upper limit of, or exceeded, the reference range.

Covariates of intravenous paracetamol pharmacokinetics in adults.

BACKGROUND: Pharmacokinetic estimates for intravenous paracetamol in individual adult cohorts are different to a certain extent, and understanding the covariates of these differences may guide dose individualization. In order to assess covariate effects of intravenous paracetamol disposition in adults, pharmacokinetic data on discrete studies were pooled. METHODS: This pooled analysis was based on 7 studies, resulting in 2755 time-concentration observations in 189 adults (mean age 46 SD 23 years; weight 73 SD 13 kg) given intravenous paracetamol. The effects of size, age, pregnancy and other clinical settings (intensive care, high dependency, orthopaedic or abdominal surgery) on clearance and volume of distribution were explored using non-linear mixed effects models. RESULTS: Paracetamol disposition was best described using normal fat mass (NFM) with allometric scaling as a size descriptor. A three-compartment linear disposition model revealed that the population parameter estimates (between subject variability,%) were central volume (V1) 24.6 (55.5%) L/70 kg with peripheral volumes of distribution V2 23.1 (49.6%) L/70 kg and V3 30.6 (78.9%) L/70 kg. Clearance (CL) was 16.7 (24.6%) L/h/70 kg and inter-compartment clearances were Q2 67.3 (25.7%) L/h/70 kg and Q3 2.04 (71.3%) L/h/70 kg. Clearance and V2 decreased only slightly with age. Sex differences in clearance were minor and of no significance. Clearance, relative to median values, was increased during pregnancy (F(PREG) = 1.14) and decreased during abdominal surgery (F(ABDCL) = 0.715). Patients undergoing orthopaedic surgery had a reduced V2 (F(ORTHOV) = 0.649), while those in intensive care had increased V2 (F(ICV) = 1.51). CONCLUSIONS: Size and age are important covariates for paracetamol pharmacokinetics explaining approximately 40% of clearance and V2 variability. Dose individualization in adult subpopulations would achieve little benefit in the scenarios explored.

Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients.

Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the postoperative period. 53 patients were included in the dataset; 28 were men, median age (range) 60 years (33-87), median weight (range) 74 kg (54-129). Patients received 1, 1.5 or 2 g of intravenous acetaminophen every 4-6 h. Plasma and urine samples were collected at various intervals for up to 6 days after surgery. Simultaneous modelling of parent acetaminophen and its metabolites was conducted in Phoenix(®) NLME™ to estimate pharmacokinetic parameters. The population mean estimate (CV%) for central (plasma) volume of distribution of parent acetaminophen (VC) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (VT) was 50.9 (2.96) L, and intercompartmental clearance (Q) was 77.5 (9.29) L/h. The population mean (CV%) metabolic clearances for glucuronidation (CLPG) was 8.92 (3.25) L/h, sulfation (CLPS) was 0.903 (3.47) L/h, and oxidation (CLPO) was 0.533 (7.90) L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CLRP) was 0.137 (5.46) L/h, acetaminophen glucuronide (CLRG) was 3.81 (6.71) L/h, acetaminophen sulfate (CLRS) was 3.13 (4.32) L/h, and acetaminophen cysteine + mercapturate (CLRO) was 3.51 (9.98) L/h. Age was found to be a significant covariate on the formation of acetaminophen glucuronide, and renal function (estimated as creatinine clearance) on the urinary excretion of acetaminophen glucuronide.

The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery.

BACKGROUND: Intravenous (IV) paracetamol is commonly used in the postoperative period for the treatment of mild to moderate pain. The main pathways for paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim of this study was to describe the pharmacokinetics of IV paracetamol and its metabolites in adult patients after major abdominal surgery. METHODS: Twenty patients were given 1 g of paracetamol by IV infusion at induction of anesthesia (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72 hours (Interval 2). Plasma and urine samples were collected for up to 8 hours after infusion for both intervals. The samples were analyzed by high-performance liquid chromatography to determine the amount of paracetamol and its metabolites. The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent-metabolite model with linear disposition, to obtain the estimates for volume of distribution, metabolic and urinary clearance. RESULTS: Mean (95% confidence interval) metabolic clearance to paracetamol glucuronide increased from 0.06 (0.05-0.08) to 0.14 (0.11-0.18) L · h⁻¹ · kg⁻¹, P value <0.001 and urinary clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L · h⁻¹ · kg⁻¹, P value 0.002. The mean (95% confidence interval) volume of distribution of paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L · kg⁻¹, P value 0.032. CONCLUSIONS: After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of paracetamol glucuronidation.

Innovations in performance management.

In FY09, as a result of an initiative to improve net income, reduce expenses, and enhance revenue cycle processes, in which leaders' goals were tied to the financial performance of the organization, Baptist Health Care achieved: A $17 million increase in net operating income. A $9.2 million reduction in operating costs. Patient satisfaction levels in the 97th percentile. A coding accuracy rate of 99 percent. A more than $1 million increase in point-of-service collections.