Brief, Web-Based Interventions to Motivate Smokers With Schizophrenia: Randomized Trial.

BACKGROUND: In-person motivational interventions increase engagement with evidence-based cessation treatments among smokers with schizophrenia, but access to such interventions can be limited because of workforce shortages and competing demands in mental health clinics. The use of digital technology to deliver interventions can increase access, but cognitive impairments in schizophrenia may impede the use of standard digital interventions. We developed an interactive, multimedia, digital motivational decision support system for smokers with schizophrenia (Let's Talk About Smoking). We also digitalized a standard educational pamphlet from the National Cancer Institute (NCI Education). Both were tailored to reduce cognitive load during use. OBJECTIVE: We conducted a randomized trial of Let's Talk About Smoking versus NCI Education to test whether the interactive motivational intervention was more effective and more appealing than the static educational intervention for increasing use of smoking cessation treatment, quit attempts, and abstinence among smokers with schizophrenia, accounting for the level of cognitive functioning. METHODS: Adult smokers with schizophrenia (n=162) were enrolled in the study from 2014 to 2015, randomly assigned to intervention condition, and assessed in person at 3- and 6-month follow-ups. Interventions were delivered on a laptop computer in a single session. All participants had access to standard, community-delivered cessation treatments during follow-up. Multivariate models were used to evaluate outcomes. RESULTS: Treatment initiation outcomes were not different between intervention conditions (27/84 [32%] for Let's Talk About Smoking vs 36/78 [46%] for NCI Education; odds ratio [OR] 0.71 [95% CI 0.37-1.33]); 38.9% (63/162) of participants initiated treatment. Older age (OR 1.03 [95% CI 1.00-1.07]; P=.05), higher education (OR 1.21 [95% CI 1.04-1.41]; P=.03), and fewer positive symptoms (OR 0.87 [95% CI 0.80-0.96]; P=.01) predicted cessation treatment initiation, whereas level of cognition did not. The mean satisfaction and usability index score was higher for Let's Talk About Smoking versus NCI Education (8.9 [SD 1.3] vs 8.3 [SD 2.1]; t120.7=2.0; P=.045). Quit attempts (25/84, 30% vs 36/78, 46%; estimate [Est]=-0.093, SE 0.48; P=.85) and abstinence (1/84, 1% vs 6/78, 7%; χ21=3.4; P=.07) were not significantly different between intervention conditions. Cognitive functioning at baseline (Est=1.47, SE 0.47; P=.002) and use of any behavioral or medication cessation treatment (Est=1.43, SE 0.47; P=.003) predicted quit attempts with self-reported abstinence over the 6-month follow-up. CONCLUSIONS: The interactive, multimedia intervention was not more effective than the static, text-based intervention among smokers with schizophrenia. Both tailored digital interventions resulted in levels of treatment engagement and quit attempts that were similar to findings from previous studies of in-person interventions, confirming the potential role of digital interventions to educate and motivate smokers with schizophrenia to use cessation treatment and to quit smoking. These findings indicate that additional cessation treatment is needed after brief education or motivational interventions, and that cessation treatment should be adjusted for people with cognitive impairment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02086162; https://clinicaltrials.gov/show/NCT02086162.

A Comparative Effectiveness Trial of Two Patient-Centered Interventions for Women with Unmet Social Needs: Personalized Support for Progress and Enhanced Screening and Referral.

Background: Despite recent widespread acceptance that unmet social needs are critically relevant to health, limited guidance exists about how best to address them in the context of women's health care delivery. We aimed to evaluate two interventions: enhanced screening and referral (ESR), a screening intervention with facilitated referral and follow-up calls, and personalized support for progress (PSP), a community health worker intervention tailored to women's priorities. Materials and Methods: Women >18 years were screened for presence of elevated depressive symptoms in three women's health clinics serving primarily Medicaid-eligible patients. If eligible and interested, we enrolled and randomized women to ESR or PSP. Pre- and postintervention assessments were conducted. Primary outcomes were satisfaction, depression, and quality of life (QOL). Planned analyses of subgroup differences were also explored. Results: A total of 235 participants were randomized; 54% identified as African American, 19% as White, and 15% as Latina. Participant mean age was 30 years; 77% reported annual incomes below US $20,000/year; and 30% were pregnant at enrollment. Participants in both arms found the interventions satisfactory and improved for depression (p < 0.001). There were no differences between groups for the primary outcomes. Subgroups reporting greater improvement in QOL in PSP compared with ESR included participants who at baseline reported anxiety (p = 0.05), lack of access to depression treatment (p = 0.02), pain (p = 0.04), and intimate partner violence (p = 0.02). Conclusions: Clinics serving women with unmet social needs may benefit from offering PSP or ESR. Distinguishing how best to use these interventions in practice is the next step.

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China.

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China.

Cannabinoid exposure during pregnancy and its impact on immune function.

Cannabinoids are the most commonly abused illicit drugs worldwide. While cannabis can be beneficial for certain heath conditions, abuse of potent synthetic cannabinoids has been on the rise. Exposure to cannabinoids is also prevalent in women of child-bearing age and pregnant women. These compounds can cross the placental barrier and directly affect the fetus. They mediate their effects primarily through G-protein coupled cannabinoid receptors, CB1 and CB2. In addition to significant neurological effects, cannabinoids can trigger robust immunomodulation by altering cytokine levels, causing apoptosis of lymphoid cells and inducing suppressor cells of the immune system. Profound effects of cannabinoids on the immune system as discussed in this review, suggest that maternal exposure during pregnancy could lead to dysregulation of innate and adaptive immune system of developing fetus and offspring potentially leading to weakening of immune defenses against infections and cancer later in life. Emerging evidence also indicates the underlying role of epigenetic mechanisms causing long-lasting impact following cannabinoid exposure in utero.

Characteristics and Predictors of Intention to use Cessation Treatment among Smokers with Schizophrenia: Young Adults Compared to Older Adults.

BACKGROUND: Over half of young adults with schizophrenia smoke. Quitting before age 30 could prevent some of the disparate morbidity and mortality due to smoking-related diseases. However, little research has addressed smoking in this group nor evaluated strategies to help young adults with schizophrenia quit smoking. METHODS: We compared demographic and smoking-related characteristics of young adults and those over 30 years of age among 184 smokers with schizophrenia. With a series of regression models, we assessed whether age, gender, smoking characteristics, social norms, attitudes, and perceived behavioral control predicted intention to quit smoking and to use cessation treatments. RESULTS: Young adults had smoked for fewer years, had lower nicotine dependence, and had lower breath carbon monoxide levels than those over 30, yet awareness of the harms of smoking and readiness to quit were similar between groups. Attitudes about smoking, attitudes about cessation treatment, social norms for cessation treatment, and perceived behavioral control for cessation treatment significantly predicted intention to use cessation treatment. Age was not a predictor of intention to quit, nor to use cessation treatment. CONCLUSIONS: Young adults with schizophrenia are amenable to smoking cessation intervention. Increasing awareness of the safety, efficacy and access to cessation treatments among smokers with schizophrenia and also among those in their social network may improve use of effective cessation treatment. These strategies may enhance the standard educational approach (increasing awareness of harms). Research is needed to evaluate such intervention strategies in smokers with schizophrenia of all ages.

Human glial chimeric mice reveal astrocytic dependence of JC virus infection.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease triggered by infection with the human gliotropic JC virus (JCV). Due to the human-selective nature of the virus, there are no animal models available to investigate JCV pathogenesis. To address this issue, we developed mice with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These results indicate that the principal CNS targets for JCV infection are astrocytes and GPCs and that infection is associated with progressive mutation, while demyelination is a secondary occurrence, following T antigen-triggered oligodendroglial apoptosis. More broadly, this study provides a model by which to further assess the biology and treatment of human-specific gliotropic viruses.

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia.

OBJECTIVES: The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. METHODS: Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1ß, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1ß, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. CONCLUSIONS: Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.

Changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia.

OBJECTIVE: The present study aimed to examine the changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia. METHODS: Sixty-two drug naïve, first-episode schizophrenia (SZ group) and 60 healthy individuals (control group) were enrolled in the study. Serum interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and body weight were measured at baseline for both groups, and repeated for the SZ group at five different time points during 6-month risperidone treatment. RESULTS: At baseline, serum IL-1ß, IL-6, and TNF-α levels in the SZ group (53.28 ± 12.62, 33.98 ± 14.13, 50.08 ± 12.86 pg/mL, respectively) were significantly higher than those in the control group (23.49 ± 15.27, 15.53 ± 7.16, 32.12 ± 15.23 pg/mL, respectively) (p's < 0.001). Within the SZ group, serum IL-1ß levels decreased significantly at 2 weeks (48.02 ± 16.00 pg/mL, p < 0.01) and 1 month (44.70 ± 16.63 pg/mL, p < 0.001), but then gradually increased at 2 months (48.49 ± 18.87 pg/mL), 3 months (50.59 ± 18.48 pg/mL) and 6 months (53.64 ± 16.22 pg/mL) to the levels comparable to baseline; serum IL-6 levels changed significantly over the course of treatment (p = 0.001), but reached the levels comparable to baseline at 6 months (37.13 ± 13.23 pg/mL); serum levels of TNF-α increased significantly at 3 months (55.02 ± 16.69 pg/mL, p < 0.01) and 6 months (58.69 ± 13.57 pg/mL, p < 0.001); steady and significant weight gain was observed at each follow-up time point (p's < 0.001), from 56.71 ± 9.25 kg at baseline to 62.72 ± 9.53 kg at 6 months. CONCLUSIONS: Risperidone treatment is associated with changes in serum pro-inflammatory cytokines levels and weight. There is an initial anti-inflammatory effect that reduces with treatment, potentially due to its weight gain side effect.

Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight.

OBJECTIVE: The study was to examine the levels of adiponectin (APN) and other cytokines, and body metabolism in drug naïve, first episode schizophrenia patients with normal weight. METHODS: Ninety-six drug naïve, first episode schizophrenia patients with normal weight (SZ group), 60 healthy individuals with normal weight (control group), and 60 overweight or obese but otherwise healthy individuals (obesity group) were enrolled in the study. Serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and APN were measured using enzyme linked immunosorbent assay (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels were measured using the enzymatic colorimetric method. RESULTS: Serum levels of IL-1ß, IL-6 and TNF-α in both the SZ group and the obesity group were significantly higher than those in the control group (p's<0.001). There were no significant differences between the SZ group and the obesity group on those cytokines (p's>0.05). In addition, the levels of APN were significantly higher in the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01) compared with the control group. Further, there were significant positive relationships between levels of APN and levels of other cytokines within the SZ group (p's<0.05); in contrast, there were significant negative relationships between levels of APN and levels of other cytokines within the obesity group (p's<0.05). Fasting serum levels of glucose, LDL, triglycerides and total cholesterol were significantly higher, and fasting serum levels of HDL were significantly lower in the obesity group compared with the other two groups (p's<0.01). There were no significant differences in any of the metabolic parameters between the control group and the SZ group (p's>0.05). CONCLUSIONS: Drug naïve, first episode schizophrenia patients with normal weight seem to present an up-regulated inflammatory status as reflected by elevated levels of IL-1ß, IL-6, and TNF-α. APN may play a unique pro-inflammatory role in this patient population. Implications of the findings in relation to the pathogenesis of schizophrenia and the vulnerability for metabolic problems were discussed.

Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients.

BACKGROUND: The duration, severity, and cause of hypotension after intravenous amiodarone has not been well characterized in anesthetized cardiac surgical patients. Because amiodarone is tolerated in patients with advanced cardiac disease, we hypothesized that left ventricular systolic performance is preserved despite hypotension during amiodarone loading. METHODS: In a prospective double-blind trial, 30 patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive intravenous amiodarone (n = 15) or placebo (n = 15). Cardiac output (CO), mixed venous oxygen saturation (SVO), arterial blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP]), pulmonary artery pressure, and central venous pressure (CVP) were recorded. Transesophageal echocardiographic left ventricular end-diastolic area (EDA), end-systolic area (ESA), fractional area change (FAC), and end-systolic wall stress (ESWS) were measured every 5 minutes. RESULTS: Mean arterial pressure, SBP, and DBP decreased over time after drug administration in both groups (p < 0.05). At 6 minutes, amiodarone decreased the MAP by 14 mm Hg (p = 0.004) and placebo decreased the MAP by 4 mm Hg. The change in MAP, SBP, and DBP between groups was statistically different for the first 15 minutes after drug administration. Hypotension requiring intervention occurred in 3 of 15 after amiodarone and 0 of 15 after placebo (p = 0.22). The mean heart rate was 11.5 beats per minute less after amiodarone (p < 0.02), but pulmonary artery pressure, CVP, SVO, and FAC were not different between groups. CONCLUSIONS: Intravenous amiodarone decreased heart rate and caused a significant, but transient decrease in arterial pressure in the first 15 minutes after administration. Left ventricular performance was maintained suggesting that selective arterial vasodilation was the primary cause of drug-induced hypotension.