Quality Improvement Through Nurse-initiated Kaiser Sepsis Calculator at a County Hospital.

BACKGROUND AND OBJECTIVES: Suspected early onset sepsis drives most antibiotic use in the newborn nursery. The Kaiser Sepsis Calculator (KSC) is a validated tool that safely decreases laboratory evaluation and antibiotic administration in infants aged ≥34 weeks. Our quality improvement aim was a nurse-initiated, KSC-based program to decrease blood cultures (BCx) and complete blood counts (CBC) by 10% from March 2021 to October 2021 among chorioamnionitis-exposed infants born ≥35 weeks' gestation. A secondary aim was to decrease antibiotic administration by 10%. METHODS: The KSC was implemented for infants at University Health, a county hospital affiliate of the University of Texas Health Science Center San Antonio, with a level I nursery and level IV NICU. The multidisciplinary project included pediatric hospitalists, neonatologists, family practitioners, maternal-fetal medicine physicians, fellows, residents, and nurses. All infants born 6 months before (August 2020-January 2021) and 7 months after protocol implementation (March 2021-September 2021) were analyzed. RESULTS: A total of 53 chorioamnionitis-exposed infants were included from the preintervention period and 51 from the postintervention period. CBC utilization decreased from 96% to 27%, BCx utilization decreased from 98% to 37%, and antibiotic utilization fell from 25% to 16%. In no cases were antibiotics prescribed against the KSC, and to our knowledge, no early onset sepsis diagnoses or infection-related hospital readmissions were missed. CONCLUSIONS: The multidisciplinary implementation of the KSC led to a reduction in testing, exceeding our initial goal. A nurse-initiated protocol reduced BCx, CBC, and antibiotic utilization among chorioamnionitis-exposed infants.

Effects of modafinil and R-modafinil on brain stimulation reward thresholds: implications for their use in the treatment of psychostimulant dependence.

BACKGROUND: Modafinil and its enantiomer R-modafinil are approved for the treatment of various sleep disorders, and may also be efficacious in the treatment of psychostimulant abuse. However, the ability of modafinil and R-modafinil to alter brain reward function has not yet been assessed. PURPOSE: This study assessed the effects of modafinil and R-modafinil on brain reward function using the intracranial self-stimulation (ICSS) paradigm. STUDY DESIGN: Male Sprague-Dawley rats were trained to respond for ICSS using current-intensity threshold determination procedures. Changes in ICSS thresholds were then assessed following administration of modafinil and R-modafinil (50, 100, and 150 mg/kg), or cocaine (2.5 - 20 mg/kg) as a positive control. RESULTS: ICSS thresholds were reduced by modafinil at the 150 mg/kg dose, as well as by cocaine at the 10 and 20 mg/kg doses. R-modafinil only produced non-significant trends towards reducing ICSS thresholds. CONCLUSION: Modafinil and R-modafinil have limited effects on brain reward function in otherwise drug-naïve subjects. Additional assessments of these effects in the context of psychostimulant dependence are needed.

Differential Modulation of Thresholds for Intracranial Self-Stimulation by mGlu5 Positive and Negative Allosteric Modulators: Implications for Effects on Drug Self-Administration.

Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5) receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively) on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS). In addition, when acute effects were observed, we examined changes in ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials current-intensity threshold determination procedure. Acute administration of the selective mGlu5 NAMs MTEP (0, 0.3, 1, or 3 mg/kg) and fenobam (0, 3, 10, or 30 mg/kg) dose-dependently increased ICSS thresholds (∼70% at the highest dose tested), suggesting a deficit in brain reward function. Acute administration of the mGlu5 PAMs CDPPB (0, 10, 30, and 60 mg/kg) or ADX47273 (0, 10, 30, and 60 mg/kg) was without effect at any dose tested. When administered once daily for five consecutive days, the development of tolerance to the ability of threshold-elevating doses of MTEP and fenobam to increase ICSS thresholds was observed. We conclude that mGlu5 PAMs and NAMs differentially affect brain reward function, and that tolerance to the ability of mGlu5 NAMs to reduce brain reward function develops with repeated administration. These brain reward deficits should be taken into consideration when interpreting acute effects of mGlu5 NAMs on drug self-administration, and repeated administration of these ligands may be an effective method to reduce these deficits.