Impact of a Cost Visibility Tool in the Electronic Medical Record on Antibiotic Prescribing in an Academic Medical Center

Background:

Studies evaluating the impact of passive cost visibility tools on antibiotic prescribing are lacking.

Objective:

The objective of this study was to evaluate whether the implementation of a passive antibiotic cost visibility tool would impact antibiotic prescribing and decrease antibiotic spending.

Methods:

An efficiency and effectiveness initiative (EEI) was implemented in October 2012. To support the EEI, an antibiotic cost visibility tool was created in June 2013 displaying the relative cost of antibiotics. Using an observational study of interrupted time series design, 3 time frames were studied: pre EEI, post EEI, and post cost visibility tool implementation. The primary outcome was antibiotic cost per 1,000 patient days. Secondary outcomes included case mix index (CMI)–adjusted antibiotic cost per 1,000 patient days and utilization of the cost visibility tool.

Results:

Initiation of the EEI was associated with a $4,675 decrease in antibiotic cost per 1,000 patient days (P = .003), and costs continued to decrease in the months following EEI (P = .009). After implementation of the cost visibility tool, costs remained stable (P = .844). Despite CMI increasing over time, adjustment for CMI had no impact on the directionality or statistical significance of the results.

Conclusion:

Our study demonstrated a significant and sustained decrease in antibiotic cost per 1,000 patient days when focused medication cost reduction efforts were implemented, but passive cost visibility tool implementation was not associated with additional cost reduction. Antibiotic cost visibility tools may be of most benefit when prior medication cost reduction efforts are lacking or when an active intervention is incorporated.     

AT–1001: a high-affinity α3β4 nAChR ligand with novel nicotine-suppressive pharmacology

Background and Purpose

The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001.

Experimental Approach

Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.

Key Results

AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm.

Conclusions and Implications

These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications.     

Increasing Hospital Pharmacist Clinical Competence in Intensive Pharmacotherapeutics Using a Novel Pharmacist Clinical Educational Program

Background:

Intensive pharmacotherapeutics (IP) is the application of multiple evidence-based practices applied at a patient-specific level, creating the overall best treatment plan in medically complex patients. To practice at this level, a high level of clinical knowledge and competency is paramount.

Objective:

The goal of the pharmacist clinical educational program was to develop an engaging, challenging, and interactive program, which was concise but intense, to improve pharmacists’ clinical knowledge and critical thinking skills.

Methods:

A 12-week educational series was developed and successfully implemented. The primary outcome was a comparison of the proportion of accepted clinical interventions per total number of medication orders reviewed by hospital pharmacists during and after the pharmacist clinical educational program to a 3-month baseline. The secondary outcome was to anonymously gauge participant satisfaction with the program.

Results:

The proportion of accepted clinical interventions increased from 6.4% (at baseline) to 9.1% and 8.7% in the 3 months during and 3 months immediately after the educational program, respectively (P < .01). The overall acceptance rate for clinical interventions remained >90% for all periods. Approximately 94% of respondents (n = 16) indicated that the program met their educational needs.

Conclusions:

The development of a clinical educational program to engage, challenge, and incentivize pharmacists is an essential tool to elevate the practice of IP. By maximizing existing resources, programming can be provided in an efficient and cost-effective manner. As health systems continue to merge on a national level, the methods described here demonstrate a means to provide critical education for both clinical and organizational competency.     

Impact of a Regional Pharmacy Call Center on Telephone Access Metrics Within the Veterans Health Administration

Purpose:

To establish a cost-effective centralized pharmacy call center to serve the patients of Veterans Integrated Service Network (VISN) 11 that would meet established performance metrics.

Methods:

A pilot project began in August 2011 with the Indianapolis VA Medical Center (VAMC) and the Health Resource Center (HRC) in Topeka, Kansas. The Indianapolis VAMC used a first-call resolution business model consisting of pharmacy technicians receiving tier 1 phone calls that could be escalated to a tier 2 line that consisted of lead technicians and pharmacists, while the HRC utilized general telephone agents that would transfer unresolved calls to the primary facility. Pre- and post-VISN 11 Pharmacy Call Center performance metrics were compared for each of the 7 facilities in the network with the goals being monthly average abandoned call rate less than 5% and average speed to answer less than 30 seconds. Cost per call was also compared.

Results:

The average abandoned call rate for the network during the year prior to VISN 11 Pharmacy Call Center implementation (August 2010-July 2011) was 15.66% and decreased to 3% in July 2014. The average abandoned call rate decreased for each individual facility. In fiscal year 2014, the VISN 11 Pharmacy Call Center was operating at a cost of $4.35 per call while providing more services than the HRC, resulting in less workload being transferred back to the individual facilities.

Conclusion:

A centralized VISN pharmacy call center is a reasonable alternative to individual facility call centers or the HRC.     

Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor

Background and Purpose

Cannabidiol has been reported to act as an antagonist at cannabinoid CB₁ receptors. We hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative allosteric modulation of CB₁ receptors.

Experimental Approach

Internalization of CB₁ receptors, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB₁ receptors and in the STHdh ^Q7/Q7 cell model of striatal neurons endogenously expressing CB₁ receptors. Cells were treated with 2‐arachidonylglycerol or Δ⁹‐tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol.

Key Results

Cannabidiol reduced the efficacy and potency of 2‐arachidonylglycerol and Δ⁹‐tetrahydrocannabinol on PLCβ3‐ and ERK1/2‐dependent signalling in cells heterologously (HEK 293A) or endogenously (STHdh ^Q7/Q7) expressing CB₁ receptors. By reducing arrestin2 recruitment to CB₁ receptors, cannabidiol treatment prevented internalization of these receptors. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino terminus of the CB₁ receptor.

Conclusions and Implications

Cannabidiol behaved as a non‐competitive negative allosteric modulator of CB₁ receptors. Allosteric modulation, in conjunction with effects not mediated by CB₁ receptors, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB₁ receptors have the potential to treat CNS and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of these receptors.

Abbreviations

2‐AG

2‐arachidonyl glycerol

BRET_Eff

BRET efficiency

CBD

cannabidiol

FAAH

fatty acid amide hydrolase

NAM

negative allosteric modulator

THC

Δ⁹‐tetrahydrocannabinol

     

Oral cadmium exposure during rat pregnancy: assessment of transplacental micronutrient transport and steroidogenesis at term

Diet is the main source of cadmium (Cd) exposure. Gastrointestinal absorption increases during pregnancy. Cadmium accumulated in the placenta may interfere with nutrient transport to the foetus. Data on the potential of Cd to act as a steroid disruptor of pregnancy are limited. We evaluated the effects of oral Cd exposure during pregnancy on placental function in micronutrient transfer to the foetus and steroidogenesis in Wistar rats (regular 4‐day cyclers) that mated with unexposed males. Pregnant rats were randomly assigned to a Cd group exposed orally to 50 mg Cd l^–1 (CdCl₂xH₂O dissolved in demineralized water), ≈7.5 mg Cd kg^–1 a day, during 20 days of gestation and control (supplied with demineralized water). Non‐pregnant rats were treated under the same experimental conditions. On day 20, all of the rats were killed and samples were taken for element analyses (by electrothermal atomic absorption spectrometry). Progesterone and testosterone were measured in serum and placenta‐derived samples (by immunoenzymometric assay and/or enzyme‐linked immunosorbent assay). In the exposed rats, Cd increased in blood and organs, more in pregnant rats, and in placenta and foetus whereas zinc increased in liver. Iron decreased in maternal organs and in foetus, whereas zinc decreased in maternal kidney and placenta. Liver copper was lower and kidney copper higher in all pregnant vs. non‐pregnant rats. Steroids in serum and placenta did not change. In conclusion, oral Cd exposure during rat pregnancy does not affect progesterone and testosterone at term. Transplacental iron and zinc handover are disrupted, which may put at risk the maintenance of foetal nutrition and viability. Copyright © 2014 John Wiley & Sons, Ltd.     

Impact of dosing regimen of custirsen,an antisense oligonucleotide,on safety,tolerability and cardiac repolarization in healthy subjects

Aims

Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects.

Methods

Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated.

Results

AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration–effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience.

Conclusion

Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen.