Rationale-Group II metabotropic glutamate receptor (mGluR) agonists represent a novel approach to the treatment of schizophrenia. Inasmuch as the peptide neurotransmitter Nacetylaspartylglutamate (NAAG) activates these receptors, NAAG peptidase inhibitors conceptually represent a parallel path toward development of new antipsychotic drugs. While group II agonists are effective in several animal models of schizophrenia, they are reported to lack efficacy in moderating the effects of phencyclidine (PCP) on prepulse inhibition of acoustic startle in animal models of sensory processing deficits found in this disorder.Objective-The objective of this study was to re-examine the efficacy of a group II metabotropic glutamate agonist and NAAG peptidase inhibitors in prepulse inhibition models of schizophrenia across two strains of mice.Methods-The method used was an assay to determine the efficacy of these drugs in moderating the reduction in prepulse inhibition of acoustic startle in mice treated with PCP and Damphetamine.Results-The group II agonist LY354740 (5 and 10 mg/kg) moderated the effects of PCP on prepulse inhibition of acoustic startle in DBA/2 but not C57BL/6 mice. In contrast, two NAAG peptidase inhibitors, ZJ43 (150 mg/kg) and 2-PMPA (50, 100, and 150 mg/kg), did not significantly affect the PCP-induced reduction in prepulse inhibition in either strain.Conclusions-These data demonstrate that the efficacy of group II agonists in this model of sensory motor processing is strain-specific in mice. The difference between the effects of the
Introduction
Automated specialty palliative care consultation (SPC) has been proposed as an intervention to improve patient-centered care in the intensive care unit (ICU). Existing automated SPC trigger criteria are designed to identify patients at highest risk of in-hospital death. We sought to evaluate common mortality-based SPC triggers and determine whether these triggers reflect actual use of SPC consultation. We additionally aimed to characterize the population of patients who receive SPC without meeting mortality-based triggers.
Methods
We conducted a retrospective cohort study of all adult ICU admissions from 2012–2017 at an academic medical center with five subspecialty ICUs to determine the sensitivity and specificity of the five most common SPC triggers for predicting receipt of SPC. Among ICU admissions receiving SPC, we assessed differences in patients who met any SPC trigger compared to those who met none.
Results
Of 48,744 eligible admissions, 1,965 (4.03%) received SPC; 979 (49.82%) of consultations met at least 1 trigger. The sensitivity and specificity for any trigger predicting SPC was 49.82% and 79.61%, respectively. Patients who met no triggers but received SPC were younger (62.71 years vs 66.58 years, mean difference (MD) 3.87 years (95% confidence interval (CI) 2.44–5.30) p<0.001), had longer ICU length of stay (11.43 days vs 8.42 days, MD -3.01 days (95% CI -4.30 –-1.72) p<0.001), and had a lower rate of in-hospital death (48.68% vs 58.12%, p<0.001).
Conclusion
Mortality-based triggers for specialty palliative care poorly reflect actual use of SPC in the ICU. Reliance on such triggers may unintentionally overlook an important population of patients with clinician-identified palliative care needs.
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