Documenting limited health literacy in a clinical setting.

Objective: Health literacy is important in lung cancer care, where treatments and symptoms are difficult to navigate. This study aims to describe how a single-item measure of health literacy can facilitate health literacy system capacity. Methods: Data include retrospective medical records from 456 patients with lung cancer. Limited or adequate health literacy was based on participant response to the Single Item Literacy Screener (SILS). Data were collected over a 12-month period following diagnosis for each patient. Results: One-third of patients had limited health literacy; they were more likely to have lung cancers of stage IIIB or higher and greater median levels of depression based on the PHQ-9 questionnaire. Patients with limited health literacy were also more likely to have at least one emergency department visit or unplanned hospitalization and had these visits sooner. Conclusion: These data document need for interventions to buffer the association between limited health literacy and poor health outcomes. Innovation: Routine intake screens should include the SILS to measure health literacy among lung cancer patients. New models that address health literacy at the organizational and patient levels can be implemented in health care settings using the SILS.

Implementation of a Palliative Oncology Tumor Board.

CONTEXT: The integration of palliative care into standard oncologic care has been shown to improve multiple outcomes in patients with advanced cancer. Ideal methods for integrating these disciplines is an ongoing area of discussion. One method of integration is a palliative oncology tumor board (POTB). OBJECTIVES: To describe the implementation of a POTB in a community cancer center as a method of integrating oncology and palliative care by providing a forum for multidisciplinary discussion of complex cases. METHODS: During development of the POTB, multiple influencing factors and barriers were considered including the setting of implementation, culture prior to implementation, design elements, engagement of stakeholders, and evaluation of implementation. The focus of this POTB was to address the identified communication gap between inpatient and outpatient care teams. Two complex hospitalized oncology patients were selected to be discussed weekly. RESULTS: Conferences were attended by an average of 23 individuals. The highest proportion of attendees were members of oncology support services (including nurse navigators, social workers, chaplains, dietitians, financial counselors; OSS; 31%), followed by medical oncology (25%). The most common theme of discussion was methods of communication with patient and/or family (68% of cases). Thirty days after presentation, a total of 50 new referrals were placed to inpatient palliative care, OSS, and outpatient palliative care and 11 new advance care plans were documented in the electronic medical record. CONCLUSION: This paper describes a sustainable method to implement a POTB in a community cancer center setting, which is one method of integrating palliative care into standard oncologic care.

Anticancer Therapy at the End of Life: Lessons From a Community Cancer Institute.

INTRODUCTION: Studies have shown aggressive cancer care at the end of life is associated with decreased quality of life, decreased median survival, and increased cost of care. This study describes the patients most likely to receive systemic anticancer therapy at the end of life in a community cancer institute. MATERIALS AND METHODS: We performed a retrospective cohort study of 201 patients who received systemic anticancer therapy in our institution and died between July 2016 and April 2017. Data collected included primary malignancy, hospice enrollment, healthcare utilization, Oncology Care Model (OCM) enrollment, and clinical assessments at last office visit prior to a treatment decision before death. We defined our outcome variable as the receipt of anticancer treatment in the last 14 days of a patient's life. We evaluated 20 clinical exposure variables with respect to the outcome classes. Risk ratios along with their associated confidence intervals and P values were calculated. Significance was determined using the Benjamini-Hochberg procedure to account for multiple testing. RESULTS: Of the 201 patients who died of cancer, 36 (17%) received anticancer therapy within the last 14 days of life. Several risk factors were significantly positively associated with receiving anticancer therapy at the end of life including hospitalization within 30 days of end of life, number of hospitalizations per patient (≥2), death in hospital, enrollment in OCM, and a diagnosis of hematologic malignancy. CONCLUSION: Our findings demonstrate those enrolled in the OCM and those with hematologic malignancies have a higher risk of receiving anticancer therapy in the last 14 days of life. These observations highlight the need for better identifying the needs of high-risk patients and providing good quality care throughout the disease trajectory to better align end-of-life care with patients' wishes.

Patterns of Support Service, Emergency Department, and Hospital Utilization in Patients with Advanced Cancer: A Descriptive Study.

CONTEXT: Palliative care in oncology provides multiple benefits, however access to specialty palliative clinicians is limited in community cancer centers. Individual support services are more often available, but little is known on the utilization and impact of these services. OBJECTIVES: To describe the utilization of outpatient support services in the advanced cancer population and the association with ED and hospital use in a community setting. METHODS: A retrospective chart review of 314 patients with advanced cancer of lung, gastrointestinal, genitourinary, and gynecologic origin was conducted. Data collected included demographics, descriptive data, type and number of support services (symptom management, nurse navigator, social worker, nutrition, financial counselor, chaplain, and oncology clinical counselor) within 90 days of diagnosis and descriptions of ED visits/hospitalizations within 12 months of diagnosis. Support services were available to patients by referral. RESULTS: 29.6% of patients were deceased within 6 months and were considered to have severe disease. Patients with severe disease had a significantly greater mean number of support services than patients with non-severe disease (8.9 vs 6.0, p=0.001) and had a greater mean number of visits per year to the ED (6.4 vs 1.8, p<0.001). A greater proportion of patients with severe disease had palliative consultations (48.9% vs 21.7%, p<0.001), but 65.5% of palliative consultations occurred after an ED or hospital visit. CONCLUSION: Our data demonstrated that advanced cancer patients with severe disease had increased healthcare utilization in all areas measured. Despite high utilization, outpatient support services used in a reactive manner were not effective in reducing ED or hospital visits.

Methylphenidate restores novel object recognition in DARPP-32 knockout mice.

Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate.

MK-801 produces a deficit in sucrose preference that is reversed by clozapine, D-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia?

Currently prescribed antipsychotics attenuate the positive symptoms of schizophrenia but fail or only mildly improve negative symptoms. The present study aimed to establish an animal model of negative symptoms by examining the effects of the NMDA receptor antagonist MK-801 on sucrose preference. We sought to validate the model by examining the effects of clozapine and D-serine, for which there are positive clinical data regarding their effects on negative symptoms, and haloperidol which is clinically ineffective. We extended our analysis by examining CDPPB, an mGlu5 receptor positive allosteric modulator. Acute MK-801 produced effects indicative of a shift in the hedonic experience of sucrose not confounded by disruptions in motor abilities or taste as revealed by: 1) a decrease in sucrose intake at low concentrations (0.8% or 1.2%), but no effect on water, 2) an increase in consumption for higher (7%) sucrose concentrations, reflecting a shift to the right in the concentration-consumption curve, and 3) no effect on quinine intake. Sub-chronic clozapine and acute d-serine attenuated the MK-801-induced deficit in 1.2% sucrose consumption, whereas sub-chronic haloperidol (0.02 mg/kg) did not. Finally, acute treatment with CDPPB also attenuated this deficit. These data suggest that this model may be useful for identifying novel agents that improve negative symptoms, and that compounds which enhance NMDA receptor function, such as mGlu5 receptor PAMs, may have clinical utility in this regard.

Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus.

In the search for strategies to treat schizophrenia, attention has focused on enhancing NMDA receptor function. In vitro experiments show that metabotropic glutamate 5 receptor (mGluR5) activation enhances NMDA receptor activity, and in vivo experiments indicate that mGluR5 positive allosteric modulators (PAMs) are effective in preclinical assays measuring antipsychotic potential and cognition. Here we characterized the dose-effect function of CDPPB (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide), an mGluR5 PAM, on novel object recognition memory in unimpaired Wistar Hannover rats (0, 10 or 30 mg/kg CDPPB) and animals with an MK-801-induced deficit (0, 3, 10, or 30 mg/kg CDPPB). In each experiment compound was given 30 min prior to the first exposure in order to affect acquisition/consolidation of the memory. In both cases, an inverted-U-shaped dose-effect function was observed, with lower doses improving recognition but higher doses having no effect. We then examined the effects of CDPPB (0, 3, 10, or 30 mg/kg) on markers of synaptic plasticity in prefrontal cortex and hippocampus, focusing on the expression and phosphorylation status of proteins involved in NMDA related signaling, including the NMDA receptor subunits NR1 and NR2B, the AMPA receptor subunit GluR1, alphaCa((2+))/CaM dependent Ser-Thr kinases II (alphaCaMKII), and the transcription factor CREB. Expression and phosphorylation of many of these proteins, particularly in the prefrontal cortex, were also characterized by an inverted-U-shaped dose-effect function. Taken together, these findings show that mGluR5 activation enhances NMDA receptor function and markers of neuronal plasticity commensurate with improvements in recognition memory. However, the effects of CDPPB are heavily dependent on dose, with higher doses being ineffective in improving recognition memory and producing downstream effects consistent with heightened NMDA receptor activation. These findings may have important implications for the development of mGluR5 PAMs to treat schizophrenia.

The behavioral and neurochemical effects of a novel D-amino acid oxidase inhibitor compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and D-serine.

Multiple studies indicate that N-methyl-D-aspartate (NMDA) receptor hypofunction underlies some of the deficits associated with schizophrenia. One approach for improving NMDA receptor function is to enhance occupancy of the glycine modulatory site on the NMDA receptor by increasing the availability of the endogenous coagonists D-serine. Here, we characterized a novel D-amino acid oxidase (DAAO) inhibitor, compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and compared it with D-serine. Compound 8 is a moderately potent inhibitor of human (IC(50), 145 nM) and rat (IC(50), 114 nM) DAAO in vitro. In rats, compound 8 (200 mg/kg) decreased kidney DAAO activity by approximately 96% and brain DAAO activity by approximately 80%. This marked decrease in DAAO activity resulted in a significant (p < 0.001) elevation in both plasma (220% of control) and cerebrospinal fluid (CSF; 175% of control) D-serine concentration. However, compound 8 failed to significantly influence amphetamine-induced psychomotor activity, nucleus accumbens dopamine release, or an MK-801 (dizocilpine maleate)-induced deficit in novel object recognition in rats. In contrast, high doses of D-serine attenuated both amphetamine-induced psychomotor activity and dopamine release and also improved performance in novel object recognition. Behaviorally efficacious doses of D-serine (1280 mg/kg) increased CSF levels of D-serine 40-fold above that achieved by the maximal dose of compound 8. These findings demonstrate that pharmacological inhibition of DAAO significantly increases D-serine concentration in the periphery and central nervous system. However, acute inhibition of DAAO appears not to be sufficient to increase D-serine to concentrations required to produce antipsychotic and cognitive enhancing effects similar to those observed after administration of high doses of exogenous D-serine.

Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome.

This study assessed social behavior in a mouse model of Fragile X syndrome (FXS), the Fmr1 (tm1Cgr) or Fmr1 "knockout" (KO) mouse. Both the KO and wild-type (WT) mice preferred to be near a novel conspecific than to be alone. However, during the initial interaction with a novel conspecific, (1) a greater proportion of the KO mice exhibited high levels of grooming; and (2) the average duration of nose contact with the stimulus mouse was significantly shorter for the KO mice, both indicative of increased arousal and/or anxiety. Both groups exhibited a robust novelty preference when the novel animal was a "preferred" mouse. However, when the novel mouse was a "nonpreferred" animal, both groups showed a diminished novelty preference but this effect was more pronounced for the WT mice. This blunted negative reaction of the KO mice to a nonpreferred animal may indicate that they were less proficient than controls in distinguishing between positive and negative social interactions. These findings provide support for the use of this animal model to study the autistic features of FXS and autism spectrum disorders.