Toxoplasma gondii IgG Serointensity Is Positively Associated With Frailty.

BACKGROUND: Persistent inflammation related to aging ("inflammaging") is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty. METHODS: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome. RESULTS: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant. CONCLUSIONS: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.

Longitude-based time zone partitions and rates of suicide.

BACKGROUND: Increasing evidence suggests that conditions with decreased morning and increased evening light exposure, including shift work, daylight-saving time, and eveningness, are associated with elevated mortality and suicide risk. Given that the alignment between the astronomical, biological, and social time varies across a time zone, with later-shifted daylight exposure in the western partition, we hypothesized that western time zone partitions would have higher suicide rates than eastern partitions. METHODS: United States (U.S.) county-level suicide and demographic data, from 2010 to 2018, were obtained from a Centers for Disease Control database. Using longitude and latitude, counties were sorted into the western, middle, or eastern partition of their respective time zones, as well as the northern and southern halves of the U.S. Linear regressions were used to estimate the associations between suicide rates and time zone partitions, adjusting for gender, race, ethnicity, age group, and unemployment rates. RESULTS: Data were available for 2872 counties. Across the U.S., western partitions had statistically significantly higher rates of suicide compared to eastern partitions and averaged up to two additional yearly deaths per 100,000 people (p < .001). LIMITATIONS: Ecological design and limited adjustment for socioeconomic factors. CONCLUSIONS: To our knowledge, this is the first study of the relationship between longitude-based time zone partitions and suicide. The results were consistent with the hypothesized elevated suicide rates in the western partitions, and concordant with previous reports on cancer mortality and transportation fatalities. The next step is to retest the hypothesis with individual-level data, accounting for latitude, photoperiodic changes, daylight-saving time, geoclimatic variables, physical and mental health indicators, as well as socioeconomic adversity and protection.

Impact of a Targeted Intervention on Hepatitis C Care Among African Americans With Serious Mental Illness.

OBJECTIVE: This study aimed to update findings on the continuum of care for hepatitis C virus (HCV) infection with follow-up data for individuals with serious mental illness and to identify predictors of decisions to decline vaccination. METHODS: The screening, testing, immunization, risk reduction, and referral (STIRR) intervention has been shown to increase testing and immunization rates. Prevalence of HCV diagnoses, HCV continuum of care, and hepatitis A (HAV) and B (HBV) vaccination were evaluated with laboratory results and chart review. RESULTS: The prevalence of HCV was 15% (N=40 of 270 African Americans receiving the STIRR intervention). Of the 40 individuals identified as having HCV, 75% (N=30) accepted referral to treatment, of whom 47% (N=14) achieved sustained virologic response. Nearly 68% (N=155) of those eligible received at least partial HAV/HBV vaccination. CONCLUSIONS: The STIRR intervention facilitated access to treatment for HCV and high acceptance of hepatitis vaccination. Avoidance proved to be a significant factor in decisions to decline vaccination.

Evaluating the heterogeneous effect of a modifiable risk factor on suicide: The case of vitamin D deficiency.

OBJECTIVES: To illustrate the use of machine learning methods to search for heterogeneous effects of a target modifiable risk factor on suicide in observational studies. The illustration focuses on secondary analysis of a matched case-control study of vitamin D deficiency predicting subsequent suicide. METHODS: We describe a variety of machine learning methods to search for prescriptive predictors; that is, predictors of significant variation in the association between a target risk factor and subsequent suicide. In each case, the purpose is to evaluate the potential value of selective intervention on the target risk factor to prevent the outcome based on the provisional assumption that the target risk factor is causal. The approaches illustrated include risk modeling based on the super learner ensemble machine learning method, Least Absolute Shrinkage and Selection Operator (Lasso) penalized regression, and the causal forest algorithm. RESULTS: The logic of estimating heterogeneous intervention effects is exposited along with the illustration of some widely used methods for implementing this logic. CONCLUSIONS: In addition to describing best practices in using the machine learning methods considered here, we close with a discussion of broader design and analysis issues in planning an observational study to investigate heterogeneous effects of a modifiable risk factor.

A 12-Week Evidence-Based Education Project to Reduce Cardiovascular and Metabolic Risk in Adults With Serious Mental Illness in the Integrated Care Setting.

BACKGROUND: Individuals with serious mental illness (SMI) such as schizophrenia spectrum disorders, severe bipolar disorder, or severe recurrent major depressive disorder have a shorter life expectancy compared with those in the general population. This is largely due to the higher rates of diabetes, hyperlipidemia, and hypertension. Treatment adherence, diet, exercise, and weight management are modifiable risk factors for these cardiometabolic conditions, yet the use of educational lifestyle interventions is not common practice in the clinical setting. AIM: The purpose of this project was to evaluate a 12-week evidence-based diabetes prevention education program integrated into a primary care behavioral health setting for adults with SMI, diabetes, or prediabetes, and who were overweight or obese. METHOD: This project utilized a pretest-posttest intervention design. Outcomes for this project included diabetes knowledge, self-care, and health indicators (blood pressure, hemoglobin A1C, weight, body mass index, and medication adherence). The project also addressed feasibility and acceptability of the program in this setting. RESULTS: Project outcomes showed a reduction in weight, waist circumference, hemoglobin A1C, and blood pressure. Outcomes also indicated an improvement in participants' self-knowledge and self-care. CONCLUSIONS: There was a high attendance rate and overall acceptability and feasibility described by participants. This project highlights the important role that primary care providers can play in providing health education to patients with SMI.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Creating a 'reverse' integrated primary and mental healthcare clinic for those with serious mental illness.

Individuals with serious mental illness (SMI) are more likely to experience preventable medical health issues, such as diabetes, hyperlipidemia, obesity, and cardiovascular disease, than the general population. To further compound this issue, these individuals are less likely to seek preventative medical care. These factors result in higher usage of expensive emergency care, lower quality of care, and lower life expectancy. This manuscript presents literature that examines the health disparities this population experiences, and barriers to accessing primary care. Through the identification of these barriers, we recommend that the field of family medicine work in collaboration with the field of mental health to implement 'reverse' integrated care (RIC) systems, and provide primary care services in the mental health settings. By embedding primary care practitioners in mental health settings, where individuals with SMI are more likely to present for treatment, this population may receive treatment for somatic care by experts. This not only would improve the quality of care received by patients, but would also remove the burden of managing complex somatic care from providers trained in mental health. The rationale for this RIC system, as well as training and policy reforms, are discussed.

Integrated Care and the Behavioral Health Home: A New Program to Help Improve Somatic Health Outcomes for Those With Serious Mental Illness.

Research indicates that individuals with serious mental illness (SMI) consistently have lower access to primary care and much higher rates of preventable somatic health problems, like diabetes, hypertension, and hyperlipidemia. These higher rates of preventable somatic health problems result in poorer quality of life, lower life expectancy, and higher use of expensive emergency care. With this growing awareness and the recent health care reform, a new program, called the Behavioral Health Home (BHH), has been created to reduce barriers that individuals with SMI face when trying to access primary care. This report provides information on the how these health disparities were well documented at a university-based psychiatric clinical program and the creation of a BHH to help address these health needs. Lessons learned from initial implementation and future directions of the BHH are discussed.

Preliminary Results From a Newly Established Behavioral Health Home: Early Identification of Glucose Metabolism Disorders in Individuals With Serious Mental Illness.

OBJECTIVE: Individuals with serious mental illness (SMI) have higher rates of preventable diseases such as diabetes in comparison to the general population. While multifaceted, these high rates of preventable diseases in the population with SMI may be partially attributed to limited access to primary care. A new program, the Behavioral Health Home (BHH), which allows for the delivery of somatic care coordination and population-based care, may provide this population with the much needed somatic coordination and education it requires. METHODS: The impact of the population-based health management program of the BHH identification and severity rating of glucose metabolism disorders was assessed during the initial 10 months of the BHH. RESULTS: Multiple patients were identified who either were not having hemoglobin A1c (HbA1c) levels drawn per recommended guidelines for individuals prescribed antipsychotic medications or were within diabetic range but did not have a diagnosis of diabetes. Mixed results occurred in regard to patients' HbA1c levels while engaging in the BHH. CONCLUSION: This case study provides some initial evidence for the utility of the BHH in regard to identifying patients who need preventive care.

Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder.

CONTEXT: The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder. OBJECTIVE: Because α4ß2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4ß2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans. DESIGN: A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4ß2-specific effects while minimizing adverse effects. SETTING: Outpatient clinics. PARTICIPANTS: A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline. MAIN OUTCOME MEASURES: Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention. RESULTS: A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose). CONCLUSIONS: Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits.