METHODS/DESIGN: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.

DISCUSSION: This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.

TRIAL REGISTRATION AND URL: NCT: NCT01427608.

We have presented a consensus statement forged by the panel through discussion during a 2-day meeting and the article-writing process. We have identified practical problems that sometimes arise in connection with providing additional safeguards for groups labeled as vulnerable and offered recommendations on how we might better balance concerns for protection with concerns for justice and participant autonomy.

METHODS: In 2002-2003, clinical interviewers met with 86 high-risk inpatients with co-occurring mental and substance use disorders (excluding schizophrenia) to carefully elicit the patients' global rating of their risk of behaving violently and to complete two brief risk assessment tools-the Clinically Feasible Iterative Classification Tree (ICT-CF) and the Modified Screening Tool (MST). Two months after discharge, patients were reinterviewed in the community to assess their involvement in violence.

RESULTS: Patients' self-perceptions of risk performed quite well in predicting serious violence (area under the curve [AUC]=.74, sensitivity=50%), particularly compared with the ICT-CF (AUC=.59, sensitivity=40%) and the MST (AUC=.66, sensitivity=30%). Self-perceived risk also added significant incremental utility to these tools in predicting violence.

CONCLUSIONS: Patients' self-perceptions hold promise as a method for improving risk assessment in routine clinical settings. Assuming it replicates and generalizes beyond the research context, this finding encourages a shift away from unaided clinical judgment toward a feasible method of risk assessment built on patient collaboration.

We sought to test this hypothesis in a group of 41 psychiatric patients who received standard magnetic resonance imaging and a psychometric protocol including aggression and impulsivity measures. Whole amygdala volumes were not associated with aggression or impulsivity, but significant correlations were found when dorsal/ventral amygdalae were analyzed separately. Specifically, left and right ventral amygdala volume was positively associated with motor impulsivity, and left dorsal amygdala was negatively associated with aggression.

Results are discussed in terms of an activation and control model of brain-behavior relations. Potential relevance to the continuum of amygdala hyper- to hypo-activation and aggression is discussed.

METHODS: Phosphorus Magnetic Resonance Spectroscopy ((31)P MRS) was used to determine pH, phopshocreatine (PCr) and inorganic phosphate (Pi) levels in 8 subjects with BD and 8 healthy comparison subjects (HCS) ages 11 to 20 years old.

RESULTS: There was no significant difference in pH between the patients and HCS. However, frontal pH values for patients with BD increased with age, contrary to studies of HCS and the pH values in the frontal lobe correlated negatively with the YMRS values. Global Pi was significantly lower in subjects with BD compared with HCS. There were no significant differences in PCr between the groups. Global PCr-to-Pi ratio (PCr/Pi) was significantly higher in subjects with BD compared with HCS.

CONCLUSIONS: The change in Pi levels for the patients with BD coupled with the no difference in PCr levels, suggest an altered mitochondrial phosphorylation. However, our findings require further investigation of the underlying mechanisms with the notion that a mitochondrial dysfunction may manifest itself differently in children than that in adults.

LIMITATIONS: Further investigations with larger patient populations are necessary to draw further conclusions.

METHODS: A total of 45 patients received six monthly assessments; 21 also received integrated group therapy (IGT), focusing simultaneously on BPD and substance dependence, while 24 did not receive IGT. Patients reported at intake their current reasons for initiating substance use (including BPD symptoms) and the effects of substance use on those symptoms.

RESULTS: Nearly all patients initiated substance use because of at least one BPD symptom, especially depression (77.8%) and racing thoughts (57.8%); most (66.7%) reported improvement in at least one BPD symptom as a result of substance use. Among patients reporting substance-induced improvement in BPD symptoms, those receiving IGT reported fewer days of drug use over the 6-month study period than those not receiving IGT; this difference was not significant among patients without substance-induced improvement in BPD symptoms.

LIMITATIONS: The study is limited by its small sample size and by the potential inaccuracy of self-reports regarding the effects of substance use on mood.

CONCLUSIONS: Substance dependent patients who report that substance use improves their BPD symptoms may benefit from treatment that focuses simultaneously on both disorders.

METHOD: A randomized controlled trial compared 20 weeks of integrated group therapy or group drug counseling with 3 months of posttreatment follow-up. Sixty-two patients with bipolar disorder and current substance dependence, treated with mood stabilizers for >or=2 weeks, were randomly assigned to integrated group therapy (N=31) or group drug counseling (N=31). The primary outcome measure was the number of days of substance use. The primary mood outcome was the number of weeks ill with a mood episode.

RESULTS: Intention-to-treat analysis revealed significantly fewer days of substance use for integrated group therapy patients during treatment and follow-up. Groups were similar in the number of weeks ill with bipolar disorder during treatment and follow-up, although integrated group therapy patients had more depressive and manic symptoms.

CONCLUSIONS: Integrated group therapy, a new treatment developed specifically for patients with bipolar disorder and substance dependence, appears to be a promising approach to reduce substance use in this population.

METHODS: Patients with current bipolar disorder and substance dependence who were prescribed mood stabilizers (n=105) completed a 27-item version of the HDRS that was subjected to item and principal components analyses. Preliminary validity analysis consisted of comparing the derived total and component scores to the depressed mood indicators from the Addiction Severity Index (ASI).

RESULTS: Eleven items representing two related components labeled "melancholia" and "anxiety" were retained. The 11-item HDRS total and component scores were higher for those who reported serious depression, serious anxiety, cognitive problems, and suicidal ideation on the ASI than for those who did not report these problems.

LIMITATIONS: We conducted the analyses with a relatively small sample of patients who were primarily white and were diagnosed with bipolar I disorder, thus limiting the generalizability of findings. Moreover, we obtained limited data regarding construct validity of the 11-item scale.

CONCLUSIONS: Our psychometric evaluation of the HDRS led us to retain 11 items representing primarily melancholic and neurovegetative symptoms of depression. These findings suggest that sample-specific item characteristics of the HDRS need to be evaluated prior to using this scale to assess depressive symptom severity among patients with complex diagnostic and treatment characteristics.

METHODS: The Canadian ACS2, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) were used to obtain data on 10,667 non-ST segment elevation acute coronary syndrome (NSTEACS) patients between 2002 and 2008. Multivariable analysis was used to examine the relationships between the number of vascular beds affected and both in-hospital coronary angiography and in-hospital mortality. The ACS2 registry (2002-2003) included physician-reported reasons for non-invasive management, which were stratified by vascular disease burden.

RESULTS: Patients with more vascular disease had higher GRACE risk scores at presentation, but less frequently received antiplatelet agents and angiography. The most common reason in the ACS2 registry for patients who did not undergo angiography was "not high enough risk." There was an independent inverse relationship between the extent of vascular disease and in-hospital angiography. Patients with higher vascular disease burden had higher unadjusted in-hospital mortality. In multivariable analysis, patients with 1 vascular territory affected had the lowest and those with 3 vascular beds affected had the highest adjusted in-hospital mortality. In the ACS2 registry, patients with more extensive vascular disease had higher rates of 1-year mortality and death/re-infarction (both p for trend <0.001).

CONCLUSIONS: NSTEACS patients with more vascular disease received less intensive treatment, with an associated worse outcome. This undertreatment might be partly mediated by physicians' underestimation of patient risk. More aggressive risk factor modification and intensive ACS therapies may improve the outcome of these high-risk patients.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Aims: To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy.

Methods: Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models.

Results: Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, pp=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization.

Conclusions: This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.

Objective: Medical and dental providers are not addressing prenatal oral health (POH) with patients despite knowledge of the risks. The objective of this study was to determine how training in dental schools and OB/Gyn residencies may contribute to this paradox.

Methods: We conducted a national survey of 60 dental school deans and 240 obstetrics and gynecology residency program directors. Questions assessed the number of hours of POH education, topics addressed, awareness of guidelines, and barriers to including more POH training.

Results: Response rates were 53% and 40% for dental schools and OB/Gyn residencies, respectively. 94% of dental schools provide some POH education, with 61% of schools offering 3+ hours. Only 39% of OB/Gyn residencies provide some POH education, most only 1-2 hours. 65% of dental programs and 45% of OB/Gyn residencies are aware of current POH evidence-based guidelines. Those OB/Gyn residency programs with POH training were three times as likely to expose their residents to these guidelines. A similar trend was observed for dental schools. Barriers to POH education include space in the curriculum and competing clinical priorities. 76% of OB/Gyn directors affirmed the importance of addressing oral health needs among prenatal patients; however, only 23% agreed that the ACGME should add POH competencies. The majority of respondents agreed they would add more POH education if the American College of Obstetrics and Gynecology issued a policy statement or practice bulletin.

Conclusions: The majority of dental schools teach POH but clinical exposure is limited. Less than half of OB/Gyn residencies include POH training. Future efforts should include distribution of POH guidelines/consensus statements to educators and learners, increasing exposure of dental students to pregnant patients, and developing faculty expertise in residencies.

Purpose: The purpose of this study was to determine whether there is a difference in gene expression in epicardial fat of patients with and without coronary artery disease and if there is a difference, whether these differentially expressed genes participate in the inflammatory pathways.

Methods: EAT and paired subcutaneous adipose tissue (SAT) samples collected from cardiac surgery patients with and without coronary disease were fixed for microscopy and frozen for RNA extraction. RNA was hybridized to Affymetrix Human Gene 1.0 ST chips. We used an unbiased approach to identify genes highly and differentially expressed in EAT vs. SAT (FC>3.0). The probe intensities for these resultant genes were then correlated with the severity of atherosclerosis in each patient as determined by the Gensini score.

Results: 35 genes were differentially expressed in EAT at >3.0 fold change (p<0.05). Of these, 14 genes were significantly correlated with the degree of atherosclerosis, quantified by Gensini score. Integrin αvβ8 (ITGB8) and transglutaminase 2 (TGM2) were both more highly expressed in EAT than in SAT (p<0.009) for all patients. Expression of ITGB8 had the strongest positive correlation (r=0.94, p<0.01), while TGM2 had the strongest negative correlation (r=-0.80, p<0.01) (Fig. 1). Importantly, expression of neither ITGB8 nor TG2 in SAT correlated with the extent of atherosclerosis.

Conclusions: Using an unbiased whole genome approach, we identified ITGB8 and TG2 as genes whose expression is correlated with CAD severity. ITGB8 has been previously shown to be expressed by fibroblasts and functions to activate TGFβ. TGFβ signaling has also been correlated with advanced atherosclerosis. We speculate that EAT expression of ITGB8 may have pro-inflammatory effects, possibly by activating TGFβ, and stimulating recruitment of dendritic cells or T cells to secondary lymphoid organs in EAT. Whether or not this is the case is a goal of future studies.

Purpose: The purpose of this study was to evaluate the intraoperative, postoperative, and total opioid consumption of patients undergoing total hip and knee replacements in an effort to develop a multi-modal approach to decrease opioid consumption, minimize adverse effects secondary to narcotic administration, and to achieve better pain control. This MMA was achieved by administering oxycodone, gabapentin, celecoxib, and acetaminophen starting before surgical incision.

Methods: The study sample consisted of 192 patients undergoing total hip and knee replacements over a 10-month period between June 2012 and March 2013 at UMASS Memorial performed by five orthopedic surgeons. The main objective was to record intraoperative, postoperative, total opioid consumption, and patient satisfaction amongst these patients. Furthermore, the patients were subdivided based on the type of procedure (hip vs knee), type of anesthetic (general vs spinal), and the presence or absence of an indwelling catheter to deliver anesthetic (catheter vs no catheter).

Results: The data showed a large variability among the surgeons in regards to the amount of opioid used intraoperatively, postoperatively and total opioid consumption. In terms of type of anesthetic, the patients undergoing spinal anesthesia used statistically significantly less opioids intraoperatively but not postoperatively, compared to general anesthesia. As for catheter use with general and spinal anesthesia, surprisingly, there was no significant difference in opioid consumption compared to the non-catheter counterpart. Furthermore, there seems to be no correlation between body mass index (BMI) and intraoperative or postoperative opioid use. Patient satisfaction was another variable that showed no correlation with opioid use intraoperatively or postoperatively. In terms of age, the data suggests that older patients use less opioids postoperatively in both hip and knee replacements.

Conclusions: Our results quantitatively show spinal anesthesia to be far superior than general anesthesia in both joint replacements. Spinal anesthesia provides better pain control intraoperatively which allows one to use less opioids, thereby minimizing the adverse side effects of narcotic administration which include respiratory depression, urinary retention, nausea and post-operative ileus to name just a few. One surgeon’s patients required significantly less opioids intraoperatively compared to the rest of the surgeons. Further studies might warrant examining this surgeon’s technique or the demographics of his patient population to determine how better pain control and less opioid consumption could be achieved across all joints with all participating surgeons.