Multidisciplinary barriers to addressing tobacco cessation during an inpatient psychiatric hospitalization.

Tobacco use and resultant health complications disproportionately impact individuals with psychiatric disorders. Inpatient psychiatric hospitalizations provide an opportunity to initiate tobacco treatment. In this study, electronic medical record review identified demographic and clinical information, smoking status, and tobacco cessation treatment offered for adults hospitalized on two acute, non-smoking psychiatric units in Massachusetts from January 2016 to March 2018. We additionally conducted semi-structured interviews with 15 inpatient nursing, psychiatry, psychology and social work providers regarding their tobacco cessation treatment practices and perceived facilitators and barriers to addressing tobacco use on psychiatric inpatient units. Chart review identified 1099 of 3140 (35%) people admitted reporting daily tobacco smoking. On discharge, 5 (0.005%) of inpatient smokers received a prescription for varenicline, 43 (0.04%) for dual-nicotine replacement therapy, 211 (19.2%) for nicotine patch, and 5 (0.005%) for bupropion. Barriers to inpatient smoking cessation treatment initiation identified in qualitative interviews included: 1) smoking cessation as low priority, 2) smoking cessation as the responsibility of outpatient providers, 3) lack of education about tobacco treatment, and 4) treatment discussions framed as preventing withdrawal. Given the potential to impact a large percentage of psychiatric tobacco users, future interventions should investigate provision of tobacco cessation counseling and pharmacotherapy in inpatient settings, with interventions that take into account the barriers and opportunities presented in this study.

Neural predictors of 12-month weight loss outcomes following bariatric surgery.

BACKGROUND/OBJECTIVES: Despite the effectiveness of bariatric surgery, there is still substantial variability in long-term weight outcomes and few factors with predictive power to explain this variability. Neuroimaging may provide a novel biomarker with utility beyond other commonly used variables in bariatric surgery trials to improve prediction of long-term weight-loss outcomes. The purpose of this study was to evaluate the effects of sleeve gastrectomy (SG) on reward and cognitive control circuitry postsurgery and determine the extent to which baseline brain activity predicts weight loss at 12-month postsurgery. SUBJECTS/METHODS: Using a longitudinal design, behavioral, hormone and neuroimaging data (during a desire for palatable food regulation paradigm) were collected from 18 patients undergoing SG at baseline (<1 month prior) and 12-month post-SG. RESULTS: SG patients lost an average of 29.0% of their weight (percentage of total weight loss (%TWL)) at 12-month post-SG, with significant variability (range: 16.0-43.5%). Maladaptive eating behaviors (uncontrolled, emotional and externally cued eating) improved (P<0.01), in parallel with reductions in fasting hormones (acyl ghrelin, leptin, glucose, insulin; P<0.05). Brain activity in the nucleus accumbens (NAcc), caudate, pallidum and amygdala during desire for palatable food enhancement vs regulation decreased from baseline to 12 months (P (family-wise error (FWE))<0.05). Dorsolateral and dorsomedial prefrontal cortex activity during desire for palatable food regulation (vs enhancement) increased from baseline to 12 months (P(FWE)<0.05). Baseline activity in the NAcc and hypothalamus during desire for palatable food enhancement was significantly predictive of %TWL at 12 months (P (FWE)<0.05), superior to behavioral and hormone predictors, which did not significantly predict %TWL (P>0.10). Using stepwise linear regression, left NAcc activity accounted for 54% of the explained variance in %TWL at 12 months. CONCLUSIONS: Consistent with previous obesity studies, reward-related neural circuit activity may serve as an objective, relatively robust predictor of postsurgery weight loss. Replication in larger studies is necessary to determine true effect sizes for outcome prediction.

Salience network coupling is linked to both tobacco smoking and symptoms of attention deficit hyperactivity disorder (ADHD).

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) symptoms, even those below diagnostic threshold, enhance the likelihood of nicotine dependence, suggesting a neurobiological link between disorders. Of particular interest is the salience network (SN), which mediates attention to salient internal/external stimuli to guide behavior and is anchored by the dorsal anterior cingulate cortex (dACC) and bilateral anterior insula (AI). Disrupted interactions between the SN and the default mode (DMN) and central executive networks (CEN) have been noted in both ADHD and nicotine dependence. Further, enhanced intra-SN coupling between the dACC-AI influences aspects of nicotine dependence such as reactivity to smoking cues. METHODS: To identify links between SN functional connectivity and ADHD symptoms in nicotine dependence, we compared 21 nicotine dependent individuals with 17 non-smokers on ADHD symptoms as measured by the ADHD self-report scale (ASRS) and resting state intra and inter-SN functional connectivity. RESULTS: Relative to healthy controls, nicotine dependent individuals had significantly higher ASRS scores and greater dACC-AI coupling. No group differences were noted on inter-SN network coupling. A significant association was found between ASRS and dACC-AI coupling both in the entire cohort and specifically when evaluating nicotine dependent individuals alone. CONCLUSIONS: The greater ASRS scores in nicotine dependent individuals is in line with existent literature and the stronger dACC-AI coupling in smokers further supports the role of this network in nicotine dependence. The significant association between dACC-AI coupling and ASRS suggests that intra-SN coupling strength may impact neurocognitive functioning associated with both ADHD symptoms and nicotine dependence.

Revisiting the role of the insula and smoking cue-reactivity in relapse: A replication and extension of neuroimaging findings.

INTRODUCTION: The ability to direct smoking cessation treatment based on neuroscientific findings holds incredible promise. However, there is a strong need for consistency across studies to confirm neurobiological targets. While our prior work implicated enhanced insula reactivity to smoking cues in tobacco smoking relapse vulnerability, this finding has not been confirmed. METHOD: Using functional magnetic resonance imaging (fMRI), we evaluated the pre-cessation brain reactivity to smoking vs. neutral cues in nicotine dependent smokers who were and were not able to maintain subsequent abstinence. RESULTS: Of the 23 (7 women) individuals assessed, 13 relapsed and there were no demographic differences between those who did and did not relapse. However, smokers who relapsed showed enhanced reactivity to smoking cues in the right insula and dorsal striatum, showing significant overlap between our current and prior work despite methodological differences, including the fact that our previous work only included women. CONCLUSION: The current work supports our prior results and builds on the concept that the insula and dorsal striatum work in concert to maintain nicotine dependence. Specifically, dorsal striatal-mediated habitual responding may be triggered both by the external drug-associated cues, and the insula-mediated internal states that provide additional context motivating drug use. This replicated finding also mirrors preclinical work that finds the same individualized distinction, as only some rodents attribute incentive salience to drug cues and are more likely to reinstate drug seeking after extinction. To effectively treat addiction, these individual characteristics and their underlying neurobiological foundations must be considered.

Prospective association between tobacco smoking and death by suicide: a competing risks hazard analysis in a large twin cohort with 35-year follow-up.

BACKGROUND: The relationship between smoking and suicide remains controversial. METHOD: A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case-control design. RESULTS: Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31-5.22] than light smokers (HR 2.30, 95% CI 1.61-3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43-4.59), adjusting for depressive symptoms, alcohol and sedative-hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06-23.8]. CONCLUSIONS: Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development.

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.

A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

UNLABELLED: This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. METHOD: This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. RESULTS: Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. CONCLUSION: Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

Opioid antagonists for smoking cessation.

BACKGROUND: The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. Smokers report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking. OBJECTIVES: To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group specialized register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of MEDLINE using 'Narcotic antagonists' and smoking terms in March 2006. We also contacted investigators, when possible, for information on unpublished studies. SELECTION CRITERIA: We considered randomized controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included in the meta-analysis only those trials which reported data on abstinence for a minimum of six months. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psycho-biological mediating variables associated with nicotine dependence. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was cotinine- or carbon monoxide-verified abstinence from smoking after at least six months follow up in patients smoking at baseline. Where appropriate, we performed meta-analysis using a fixed-effect model (Mantel-Haenszel odds ratios). MAIN RESULTS: Four trials of naltrexone met inclusion criteria for meta-analyses for long-term cessation. All four trials failed to detect a significant difference in quit rates between naltrexone and placebo. In a pooled analysis there was no significant effect of naltrexone on long-term abstinence, and confidence intervals were wide (odds ratio 1.26, 95% confidence interval 0.80 to 2.01). No trials of naloxone or buprenorphine reported long-term follow up. AUTHORS' CONCLUSIONS: Based on limited data from four trials it is not possible to confirm or refute whether naltrexone helps smokers quit. The confidence intervals are compatible with both clinically significant benefit and possible negative effects of naltrexone in promoting abstinence. Data from larger trials of naltrexone are needed to settle the question of efficacy for smoking cessation.

An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia.

OBJECTIVE: We conducted this 6-week open-label trial to examine the effects of adjunctive aripiprazole in clozapine-treated subjects on weight, lipid and glucose metabolism, as well as positive and negative symptoms of schizophrenia. METHOD: Ten clozapine-treated subjects received aripiprazole augmentation; eight completed the 6-week trial and two ended at week 4. Eighty percent were male, the mean age was 38.7 +/- 8.9 years and the mean clozapine dose was 455 +/- 83 mg daily. RESULTS: There was a significant decrease in weight (P = 0.003), body mass index (P = 0.004), fasting total serum cholesterol (P = 0.002) and total triglycerides (P = 0.04) comparing baseline to study endpoint. There was no significant change in total Positive and Negative Syndrome Scale scores. CONCLUSION: This combination may be useful for clozapine-associated medical morbidity and must be studied in placebo-controlled double-blind randomized trials to determine efficacy and safety.

A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia.

The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.

Augmentation strategies in the treatment of schizophrenia.

Use of augmenting agents in schizophrenia is a common practice in response to resistant symptoms or comorbid illness. Increasingly, clinicians are combining more than one antipsychotic agent, despite a lack of evidence from controlled studies to support this approach. A rationale can be made for adding higher-potency agents to clozapine in an attempt to optimize D2 dopamine receptor blockade, but this strategy requires further study before it should be adopted in clinical practice. Older reports have explored the use of antidepressants, mood stabilizers, and anxiolytics as augmenting agents. These agents appear to improve comorbid affective or anxiety symptoms, but earlier evidence of improvement in psychotic or negative symptoms has not been replicated consistently. Glutamatergic agents acting at the glycine coagonist site of the N-methyl-d-aspartate receptor, including glycine, d-cycloserine, and d-serine, have demonstrated impressive therapeutic effects for negative symptoms when added to conventional neuroleptic agents, but do not appear to enhance clozapine efficacy. Given the high rates of symptom persistence and disability associated with schizophrenia, the need for augmentation strategies is great, but no approach has clearly emerged as effective for a substantial portion of patients. Although certain approaches may prove helpful for individual patients, augmentation should not be used unless monotherapy has been optimized, and should not be continued long-term unless benefits are clear.

Placebo-controlled trial of glycine added to clozapine in schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the effects of high-dose oral glycine on positive and negative symptoms and cognitive function when added to clozapine in adults with schizophrenia. METHOD: The authors conducted a double-blind, placebo-controlled, parallel-group trial of 60 g/day of glycine added to clozapine for 8 weeks in 30 adults with schizophrenia. Clinical ratings were performed every 2 weeks. RESULTS: Twenty-seven patients completed the trial. Glycine augmentation of clozapine produced no statistically significant change in positive or negative symptoms or cognitive functioning. No subjects showed clinically significant worsening of clinical ratings. CONCLUSIONS: These data, combined with data from previous trials with D-cycloserine and glycine, suggest that agonists at the glycine site may be less effective when combined with clozapine than they are when combined with conventional antipsychotics.

A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia.

BACKGROUND: D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor, has previously been shown to improve negative symptoms when added to conventional antipsychotics and, in one preliminary dose-finding study, worsened negative symptoms when added to clozapine. METHODS: Seventeen schizophrenia outpatients treated with clozapine were assigned in random order to 6-week trials of D-cycloserine 50 mg/day and placebo in a crossover design separated by a 1 week placebo washout. RESULTS: Eleven patients competed the 13-week study. D-Cycloserine significantly worsened ratings of negative symptoms compared to placebo but did not significantly affect ratings of psychotic symptoms. CONCLUSIONS: The differing effects of D-cycloserine on negative symptoms when added to clozapine compared to conventional antipsychotics suggests that activation of the glycine recognition site may play a role in clozapine's efficacy for negative symptoms.

Negative symptoms in schizophrenia: neurobiological models and treatment response.

Evidence from lesioning studies and neuroimaging has linked negative symptoms to dysfunction of the prefrontal cortex, the limbic system, and the basal ganglia. Although such symptoms have been most strongly associated with dopaminergic hypoactivity in the prefrontal cortex, other neurotransmitters including norepinephrine, serotonin, and the excitatory amino acids may also play a role. In some patients moderate doses of conventional neuroleptics clearly improve negative symptoms; the response of such symptoms is relatively greater with clozapine and probably with certain serotonin-dopamine antagonists. Recent studies demonstrating improvement of negative symptoms when conventional neuroleptics are augmented with selective serotonin-reuptake inhibitors or with agents active at the glycine-modulatory site of the glutamatergic N-methyl-D-aspartate receptor complex suggest that further amelioration of primary negative symptoms may be possible through pharmacological strategies involving multiple neurotransmitter systems.

Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics.

To examine whether serum excitatory amino acid concentrations change with clozapine treatment and whether these changes correlate with improvement in negative symptoms, serum excitatory amino acids were measured and clinical scales administered in seven subjects with schizophrenia before and after switching from conventional neuroleptics to clozapine. Clozapine treatment was associated with increased serum glutamate and aspartate concentrations. Clinical improvement was negatively correlated with baseline glycine concentrations. These results support the hypothesis that clozapine acts at least in part by increasing glutamatergic activity.

Evaluation of connective tissue cell responses to orthopaedic implant materials.

We have developed an in vitro cell culture model to examine the interaction between connective tissue cells and orthopaedic implant biomaterials. Human connective tissue cells grown on different materials exhibit distinct responses in terms of attachment, morphology, proliferative capacity and matrix biosynthesis. Our results closely complement in vivo observations concerning biocompatibility and demonstrate the usefulness of this in vitro system for evaluating biomaterials. More importantly, this model can be used to define the specific cellular and biochemical processes that are responsible for the local tissue responses to orthopaedic implant materials.

Immediate chest roentgenography following fiberoptic bronchoscopy.

It is a common practice for some clinicians to obtain a chest roentgenogram immediately following FOB in an attempt to detect complications of the procedure, particularly pneumothorax; however, the roentgenogram adds substantially to the cost of FOB. It was our clinical impression that the diagnostic and therapeutic value of immediate chest roentgenography was minimal. Therefore, we reviewed 130 chest roentgenograms taken immediately after bronchoscopy that were obtained over 36 months. One hundred fourteen (88 percent) were unchanged from the most recent roentgenogram before bronchoscopy. Ten (8 percent) showed an increase in alveolar infiltrate due to bronchoalveolar lavage or hemorrhage. Five (4 percent) had changes presumably unrelated to the procedure. Only one patient had a pneumothorax on the roentgenogram taken immediately after bronchoscopy; however, the patient was symptomatic, and the pneumothorax was detected by fluoroscopy prior to the chest roentgenogram. Management of the patient's condition was not altered in a single case based upon findings on the chest roentgenogram. We conclude that the immediately postbronchoscopic chest roentgenogram rarely provides clinically useful information or detects a complication that is not suspected clinically; furthermore, it appears to have minimal impact, if any, on the management of a patient's condition.