One-Year All-Cause Mortality and Delivery of the Collaborative Chronic Care Model in General Mental Health Clinics.

OBJECTIVE: This study aimed to determine whether the evidence-based collaborative chronic care model (CCM) is associated with reduced all-cause mortality among adult patients treated in general mental health clinics. METHODS: Data came from a stepped-wedge, cluster-randomized CCM implementation trial across nine U.S. Department of Veterans Affairs medical centers. Survival analysis was used to estimate the relative effect of the treatment (N=5,570) compared with a control group (N=46,443) over 1 year. RESULTS: After adjustment for site-level and individual-level acute care utilization factors, analyses indicated that patients treated with the CCM experienced a reduction in all-cause mortality relative to patients in the control cohort (hazard ratio=0.76, 95% CI=0.60-0.95). CONCLUSIONS: This study is the first in which CCM has been shown to reduce all-cause mortality for patients treated in general mental health clinics. Care delivery models should be considered part of efforts to reduce the life expectancy gap between individuals with psychiatric conditions and those without such conditions.

Prevalence of dementia and mild cognitive impairment before incarceration.

BACKGROUND: Accumulating evidence indicates that behaviors in Alzheimer's disease and related dementias could result in incarceration. Yet, the proportion of persons diagnosed with dementia and mild cognitive impairment (MCI) before they were incarcerated is largely unknown. By leveraging a national sample of mid- to late-life adults who were incarcerated, we determined the prevalence of dementia and MCI before their incarceration. METHODS: In this current study, participants were Medicare-eligible U.S. veterans who transitioned from incarceration to the community in mid- to late-life from October 1, 2012, to September 30, 2018, after having been incarcerated for ≤10 consecutive years (N = 17,962). Medical claims data were used to determine clinical diagnoses of dementia and MCI up to three years before incarceration. Demographics, comorbidities, and duration of incarceration among those with dementia and MCI were compared to those with neither diagnosis. RESULTS: Participants were >97% male, 65% non-Hispanic white, 30% non-Hispanic black, and 3.3% had a diagnosis of either dementia (2.5%) or MCI (0.8%) before their most recent incarceration. Individuals with MCI or dementia diagnoses were older, were more likely to be non-Hispanic white, had more medical and psychiatric comorbidities, and experienced homelessness and traumatic brain injury at higher rates than those with neither diagnosis. Average duration of incarceration was significantly shorter among those with MCI (201.8 [±248.0] days) or dementia (312.8 [±548.3] days), as compared to those with neither diagnosis (497.0 [±692.7] days) (p < 0.001). CONCLUSIONS: These findings raise awareness of the proportion of incarcerated persons in the United States who have a diagnosis of MCI or dementia before they are incarcerated. Improved understanding of pathways linking cognitive impairment to incarceration in mid- to late-life are needed to inform appropriateness of incarceration, optimization of health care, and prevention of interpersonal harm in this medically vulnerable population.

Time course and heterogeneity of treatment effect of the collaborative chronic care model on psychiatric hospitalization rates: A survival analysis using routinely collected electronic medical records.

BACKGROUND: Health systems are undergoing widespread adoption of the collaborative chronic care model (CCM). Care structured around the CCM may reduce costly psychiatric hospitalizations. Little is known, however, about the time course or heterogeneity of treatment effects (HTE) for CCM on psychiatric hospitalization. RATIONALE: Assessment of CCM implementation support on psychiatric hospitalization might be more efficient if the timing were informed by an expected time course. Further, understanding HTE could help determine who should be referred for intervention. OBJECTIVES: (i) Estimate the trajectory of CCM effect on psychiatric hospitalization rates. (ii) Explore HTE for CCM across demographic and clinical characteristics. METHODS: Data from a stepped wedge CCM implementation trial were reanalyzed using 5 570 patients in CCM treatment and 46 443 patients receiving usual care. Time-to-event data was constructed from routine medical records. Effect trajectory of CCM on psychiatric hospitalization was simulated from an extended Cox model over one year of implementation support. Covariate risk contributions were estimated from subset stratified Cox models without using simulation. Ratios of hazard ratios (RHR) allowed comparison by trial arm for HTE analysis, also without simulation. No standard Cox proportional hazards models were used for either estimating the time-course or heterogeneity of treatment effect. RESULTS: The effect of CCM implementation support increased most rapidly immediately after implementation start and grew more gradually throughout the rest of the study. On the final study day, psychiatric hospitalization rates in the treatment arm were 17% to 49% times lower than controls, with adjustment for all model covariates (HR 0.66; 95% CI 0.51-0.83). Our analysis of HTE favored usual care for those with a history of prior psychiatric hospitalization (RHR 4.92; 95% CI 3.15-7.7) but favored CCM for those with depression (RHR 0.61; 95% CI: 0.41-0.91). Having a single medical diagnosis, compared to having none, favored CCM (RHR 0.52; 95% CI 0.31-0.86). CONCLUSION: Reduction of psychiatric hospitalization is evident immediately after start of CCM implementation support, but assessments may be better timed once the effect size begins to stabilize, which may be as early as six months. HTE findings for CCM can guide future research on utility of CCM in specific populations.

Effects of the psychotomimetic benzomorphan N-allylnormetazocine (SKF 10,047) on prepulse inhibition of startle in mice.

N-allylnormetazocine (NANM; SKF 10,047) is a benzomorphan opioid that produces psychotomimetic effects. (+)-NANM is the prototypical agonist for the sigma-1 (σ1) receptor, and there is a widespread belief that the hallucinogenic effects of NANM and other benzomorphan derivatives are mediated by interactions with σ1 sites. However, NANM is also an agonist at the κ opioid receptor (KOR) and binds to the PCP site located within the channel pore of the NMDA receptor, interactions that could potentially contribute to the effects of NANM. NMDA receptor antagonists such as phencyclidine (PCP) and ketamine are known to disrupt prepulse inhibition (PPI) of acoustic startle, a measure of sensorimotor gating, in rodents. We recently found that racemic NANM disrupts PPI in rats, but it is not clear whether the effect is mediated by blockade of the NMDA receptor, or alternatively whether interactions with KOR and σ1 receptors are involved. The present studies examined whether NANM and its stereoisomers alter PPI in C57BL/6J mice, and tested whether the effects on PPI are mediated by KOR or σ1 receptors. Racemic NANM produced a dose-dependent disruption of PPI (3-30mg/kg SC). (+)-NANM also disrupted PPI, whereas (-)-NANM was ineffective. Pretreatment with the selective KOR antagonist nor-binaltorphimine (10mg/kg SC) or the selective σ1 antagonist NE-100 (1mg/kg IP) failed to attenuate the reduction in PPI produced by racemic NANM. We also found that the selective KOR agonist (-)-U-50,488H (10-40mg/kg SC) had no effect on PPI. These findings confirm that NANM reduces sensorimotor gating in rodents, and indicate that the effect is mediated by interactions with the PCP receptor and not by activation of KOR or σ1 receptors. This observation is consistent with evidence indicating that the σ1 receptor is not linked to hallucinogenic or psychotomimetic effects.

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

OBJECTIVE: This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). BACKGROUND: Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. METHODS: Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. RESULTS: Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17), drug violations (HR 2.44 95% CI: 2.00-2.98), non-violent violations (HR 2.14 95% CI: 1.73-2.64), violent and serious violations (HR 1.88 95% CI: 1.45-2.43), and technical violations (HR 1.86 95% CI: 1.37-2.53). CONCLUSIONS: Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice.

Although it is well established that hallucinogens act as 5-HT(2A) and 5-HT(2C) receptor agonists, little is known about the relative contributions of 5-HT(2A) and 5-HT(2C) receptors to the acute behavioral effects of these drugs. The behavioral pattern monitor was used to characterize the effects of the hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on locomotor and investigatory behavior in mice. Studies were also conducted to assess the contributions of 5-HT(2A) and 5-HT(2C) receptors to the behavioral effects of DOI. DOI produced an inverted U-shaped dose-response function, with lower doses (0.625-5.0 mg/kg) increasing and higher doses (> or =10 mg/kg) decreasing locomotor activity. The increase in locomotor activity induced by 1.0 mg/kg DOI was absent in 5-HT(2A) receptor KO mice, suggesting the involvement of 5-HT(2A) receptors. The reduction in locomotor activity produced by 10 mg/kg DOI was potentiated in 5-HT(2A) KO mice and attenuated by pretreatment with the selective 5-HT(2C/2B) antagonist SER-082. These data indicate that the decrease in locomotor activity induced by 10 mg/kg DOI is mediated by 5-HT(2C) receptors, an interpretation that is supported by the finding that the selective 5-HT(2C) agonist WAY 161,503 produces reductions in the locomotor activity that are potentiated in 5HT(2A) KO mice. These results show for the first time that 5-HT(2A) and 5-HT(2C) receptors both contribute to the effects of DOI on locomotor activity in mice. Furthermore, these data also suggest that 5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity.

A Kappa Opioid Model of Atypical Altered Consciousness and Psychosis: U50488, DOI, AC90179 Effects on Prepulse Inhibition and Locomotion in Mice.

Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system - the serotonin sub-type associated with classical psychedelics - were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.