Costs of a Train-the-Trainer Program to Teach Primary Care Faculty Mental Health Care.

BACKGROUND: Mental health care must improve in this country. With the worsening shortage of psychiatrists and other mental health professionals, the next generation of physicians in primary care will need to be better trained in mental health care. OBJECTIVES: We estimate the direct cost of implementing an evidence-based Train-the-Trainer (3T) program to disseminate mental health training to allopathic medical school faculty; once trained, faculty can teach a much-enhanced curriculum of mental health care to medical students and residents. METHODS: A combination of published standardized unit costs and an activity-based costing approach is used to estimate the direct costs (labor and nonlabor) for implementing the 3T program. RESULTS: The estimated direct cost of implementing the 3T program at one prototypical school, including the 12-month start-up period (1.1 million) and 18-month rollout period (8.6 million), is ∼9.7 million dollars. CONCLUSIONS: Successfully adopted in all US allopathic medical schools, the 3T program will provide over 3800 attitudinally competent and mental health skills-qualified primary care faculty members. They would then be available to train nearly 100,000 medical students per year and 55,000 primary care residents to be as competent in basic mental health care as in medical care. This 3T program will begin to meet the needs each year for the millions of adults with major mental disorders that now are largely unrecognized and untreated.

Relationship of cognitive measures to mRNA levels in lymphocytes from patients with schizophrenia and controls.

Patients with schizophrenia show substantial cognitive deficits and abnormalities in neurotransmitter-related levels of mRNA in brain or peripheral blood lymphocytes. However, the relationship of cognitive deficits as measured by the MATRICS battery and mRNA levels in brain or lymphocytes has not been sufficiently explored. We measured levels of methylation or neurotransmitter-related mRNAs in lymphocytes of 38 patients with chronic schizophrenia (CSZ) and 33 non-psychotic controls (controls) by qPCR using TaqMan probes. We assessed cognitive function in these patients and controls with the MATRICS battery. We used correlation analysis and scatter plots to assess the relationship of lymphocyte mRNA levels to MATRICS domain and composite scores. CSZ subjects had a consistently negative correlation between mRNA levels in lymphocytes and MATRICS cognitive variables of speed of processing, attention-vigilance, working memory, visual learning, and overall composite score. It is uncertain whether these negative correlations represent a causative relation between specific mRNA levels and cognitive deficits. Controls had either positive correlations or non-significant correlations between mRNA and most of the MATRICS variables. There were statistically significant differences in the correlations between mRNA and MATRICS variables between CSZ vs controls for several mRNAs (DNMT1, DNMT3A, BDNF, NR3C1, FPRF3, CNTNAP2). Our data show a different relationship between mRNA levels in peripheral blood lymphocytes and MATRICS cognitive variables in CSZ vs controls. The substantive significance of these differences needs further investigation.

Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes.

Introduction: People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies. Methods: In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin' Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression. Results: Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor. Discussion: Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.

Specific and common functional connectivity deficits in drug-free generalized anxiety disorder and panic disorder: A data-driven analysis.

Evidence of comparing neural network differences between anxiety disorder subtypes is limited, while it is crucial to reveal the pathogenesis of anxiety disorders. The present study aimed to investigate specific and common resting-state functional connectivity (FC) networks in generalized anxiety disorder (GAD), panic disorder (PD), and healthy controls (HC). We employed the gRAICAR algorithm to decompose the resting-state fMRI into independent components and align the components across 61 subjects (22 GAD, 18 PD and 21 HC). The default mode network and precuneus network exhibited GAD-specific aberrance, the anterior default mode network showed atypicality specific to PD, and the right fronto-parietal network showed aberrance common to GAD and PD. Between GAD-specific networks, FC between bilateral dorsolateral prefrontal cortex (DLPFC) was positively correlated with interoceptive sensitivity. In the common network, altered FCs between DLPFC and angular gyrus, and between orbitofrontal cortex and precuneus, were positively correlated with anxiety severity and interoceptive sensitivity. The pathological mechanism of PD could closely relate to the dysfunction of prefrontal cortex, while GAD could involve more extensive brain areas, which may be related to fear generalization.

Interventions for providers to promote a patient-centred approach in clinical consultations.

BACKGROUND: Communication problems in health care may arise as a result of healthcare providers focusing on diseases and their management, rather than people, their lives and their health problems. Patient-centred approaches to care delivery in the patient encounter are increasingly advocated by consumers and clinicians and incorporated into training for healthcare providers. However, the impact of these interventions directly on clinical encounters and indirectly on patient satisfaction, healthcare behaviour and health status has not been adequately evaluated. OBJECTIVES: To assess the effects of interventions for healthcare providers that aim to promote patient-centred care (PCC) approaches in clinical consultations. SEARCH METHODS: For this update, we searched: MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), and CINAHL (EbscoHOST) from January 2000 to June 2010. The earlier version of this review searched MEDLINE (1966 to December 1999), EMBASE (1985 to December 1999), PsycLIT (1987 to December 1999), CINAHL (1982 to December 1999) and HEALTH STAR (1975 to December 1999). We searched the bibliographies of studies assessed for inclusion and contacted study authors to identify other relevant studies. Any study authors who were contacted for further information on their studies were also asked if they were aware of any other published or ongoing studies that would meet our inclusion criteria. SELECTION CRITERIA: In the original review, study designs included randomized controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series studies of interventions for healthcare providers that promote patient-centred care in clinical consultations. In the present update, we were able to limit the studies to randomized controlled trials, thus limiting the likelihood of sampling error. This is especially important because the providers who volunteer for studies of PCC methods are likely to be different from the general population of providers. Patient-centred care was defined as a philosophy of care that encourages: (a) shared control of the consultation, decisions about interventions or management of the health problems with the patient, and/or (b) a focus in the consultation on the patient as a whole person who has individual preferences situated within social contexts (in contrast to a focus in the consultation on a body part or disease). Within our definition, shared treatment decision-making was a sufficient indicator of PCC. The participants were healthcare providers, including those in training. DATA COLLECTION AND ANALYSIS: We classified interventions by whether they focused only on training providers or on training providers and patients, with and without condition-specific educational materials. We grouped outcome data from the studies to evaluate both direct effects on patient encounters (consultation process variables) and effects on patient outcomes (satisfaction, healthcare behaviour change, health status). We pooled results of RCTs using standardized mean difference (SMD) and relative risks (RR) applying a fixed-effect model. MAIN RESULTS: Forty-three randomized trials met the inclusion criteria, of which 29 are new in this update. In most of the studies, training interventions were directed at primary care physicians (general practitioners, internists, paediatricians or family doctors) or nurses practising in community or hospital outpatient settings. Some studies trained specialists. Patients were predominantly adults with general medical problems, though two studies included children with asthma. Descriptive and pooled analyses showed generally positive effects on consultation processes on a range of measures relating to clarifying patients' concerns and beliefs; communicating about treatment options; levels of empathy; and patients' perception of providers' attentiveness to them and their concerns as well as their diseases. A new finding for this update is that short-term training (less than 10 hours) is as successful as longer training.The analyses showed mixed results on satisfaction, behaviour and health status. Studies using complex interventions that focused on providers and patients with condition-specific materials generally showed benefit in health behaviour and satisfaction, as well as consultation processes, with mixed effects on health status. Pooled analysis of the fewer than half of included studies with adequate data suggests moderate beneficial effects from interventions on the consultation process; and mixed effects on behaviour and patient satisfaction, with small positive effects on health status. Risk of bias varied across studies. Studies that focused only on provider behaviour frequently did not collect data on patient outcomes, limiting the conclusions that can be drawn about the relative effect of intervention focus on providers compared with providers and patients. AUTHORS' CONCLUSIONS: Interventions to promote patient-centred care within clinical consultations are effective across studies in transferring patient-centred skills to providers. However the effects on patient satisfaction, health behaviour and health status are mixed. There is some indication that complex interventions directed at providers and patients that include condition-specific educational materials have beneficial effects on health behaviour and health status, outcomes not assessed in studies reviewed previously. The latter conclusion is tentative at this time and requires more data. The heterogeneity of outcomes, and the use of single item consultation and health behaviour measures limit the strength of the conclusions.

Effects of transcranial direct current stimulation on brain changes and relation to cognition in patients with schizophrenia: a fMRI study.

We studied brain changes during an N-back task before and after 10 sessions of transcranial direct current stimulation (tDCS) and its relation to cognitive changes. This was a double-blind, sham-controlled, randomized study of tDCS in 27 patients with schizophrenia. They performed an N-back task in a 3 T scanner before and after receiving the 10 tDCS sessions. Cognitive performance outside the fMRI session was assessed using the MATRICS Consensus Cognitive Battery and other tests at baseline and several time points after 10 sessions of tDCS. During the N-back task performed during fMRI scans, comparing the 0-back vs. the 2-back task, the active tDCS group demonstrated a significantly increased activation in the right fusiform, left middle frontal, left inferior frontal gyrus (opercular part) and right inferior frontal gyrus (triangular part) and reduced activation in the left posterior cingulum gyrus with most of these results primarily due to increases in activation during the 0-back rather than 2-back task. There were also significant positive or negative correlations between some of the brain changes and cognitive performance. tDCS modulated prefrontal activation at low working memory load or attention mode, but default mode network at higher working memory load. Changes in brain activation measured during the N-back task were correlated with some dimensions of cognitive function immediately after 10 tDCS sessions and at follow-up times. The results support tDCS could offer a potential novel approach for modulating cortical activity and its relation to cognitive function.

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

Background: Cannabis use is a component risk factor for the manifestation of schizophrenia. The biological effects of cannabis include effects on epigenetic systems, immunological parameters, in addition to changes in cannabinoid receptors 1 and 2, that may be associated with this risk. However, there has been limited study of the effects of smoked cannabis on these biological effects in human peripheral blood cells. We analyzed the effects of two concentrations of tetrahydrocannabinol (THC) vs. placebo in lymphocytes of a subset of participants who enrolled in a double-blind study of the effects of cannabis on driving performance (outcome not the focus of this study). Methods: Twenty four participants who regularly use cannabis participated in an experiment in which they smoked cannabis cigarettes (5.9 or 13.4% THC) or placebo (0.02%) ad libitum. Blood samples were drawn at baseline and several times after smoking. Lymphocytes were separated and stored at -80°C for further analysis. Samples were analyzed for mRNA content for cannabinoid receptors 1 (CB1) and 2 (CB2), methylation and demethylating enzymes (DNMT, TET), glucocorticoid receptor (NRC3) and immunological markers (IL1B, TNFα) by qPCR using TaqMan probes. The results were correlated with THC whole blood levels during the course of the day, as well as THCCOOH baseline levels. Statistical analyses used analysis of variance and covariance and t-tests, or non-parametric equivalents for those values which were not normally distributed. Results: There were no differences in background baseline characteristics of the participants except that the higher concentration THC group was older than the low concentration and placebo groups, and the low concentration THC group had higher baseline CB2 mRNA levels. Both the 5.9 and 13.4% THC groups showed increased THC blood levels that then decreased toward baseline within the first hour. However, there were no significant differences between THC blood levels between the 5.9 and 13.4% groups at any time point. At the 4-h time point after drug administration the 13.4% THC group had higher CB2 (P = 0.021) and DNMT3A (P = 0.027) mRNA levels than the placebo group. DNMT1 mRNA levels showed a trend in the same direction (P = 0.056). The higher 13.4% THC group had significantly increased CB2 mRNA levels than the 5.9% concentration group at several post drug administration time points and showed trends for difference in effects for between 5.9 and 13.4% THC groups for other mRNAs. TET3 mRNA levels were higher in the 13.4% THC group at 55 min post-cannabis ingestion. When the high and lower concentration THC groups were combined, none of the differences in mRNA levels from placebo remained statistically significant. Changes in THC blood levels were not related to changes in mRNA levels. Conclusion: Over the time course of this study, CB2 mRNA increased in blood lymphocytes in the high concentration THC group but were not accompanied by changes in immunological markers. The changes in DNMT and TET mRNAs suggest potential epigenetic effects of THC in human lymphocytes. Increases in DNMT methylating enzymes have been linked to some of the pathophysiological processes in schizophrenia and, therefore, should be further explored in a larger sample population, as one of the potential mechanisms linking cannabis use as a trigger for schizophrenia in vulnerable individuals. Since the two THC groups did not differ in post-smoking blood THC concentrations, the relationship between lymphocytic changes and the THC content of the cigarettes remains to be determined.

A Novel Expert Coaching Model in Urology, Aimed at Accelerating the Learning Curve in Robotic Prostatectomy.

INTRODUCTION/BACKGROUND: The surgical residency model assumes that upon completion, a surgeon is ready to practice and grow independently. However, many surgeons fail to improve after reaching proficiency, which in certain instances has correlated with worse clinical outcomes. Coaching addresses this problem and furthers surgeons' education post-residency. Currently, surgical coaching programs focus on medical students and residents, and have been shown to improve residents' and medical students' technical and non-technical abilities. Coaching programs also increase the accuracy of residents, fellows, and attendings in self-assessing their surgical ability. Despite the potential benefits, coaching remains underutilized and poorly studied. We developed an expert-led, face-to-face, video-based surgical coaching program at a tertiary medical center among specialized attending surgeons. Our goal was to evaluate the feasibility of such a program, measure surgeons' attitudes towards internal peer coaching, determine whether surgeons found the sessions valuable and educational, and to subjectively self-assess changes in operative technique. METHODS/MATERIALS: Surgeons who perform robot-assisted laparoscopic prostatectomies were chosen and grouped by number of cases completed: junior (<100 cases), intermediate (100-500 cases), and senior (>500 cases). Surgeons were scheduled for 3 1-hour coaching sessions 1-2 months apart (February-October 2019), meeting individually with the coach (PS), an expert Urologic Oncologist with thousands of cases of experience performing radical prostatectomy. He received training on coaching methodology prior to beginning the coaching program. Before each session, surgeons selected 1 of their recent intraoperative videos to review. During sessions, the coach led discussion on topics chosen by the surgeon (i.e. neurovascular bundle dissection, apical dissection, bladder neck); together, they developed goals to achieve before the next session. Subsequent sessions included presentation and discussion of a case occurring subsequent to the prior session. Sessions were coded by discussion topics and analyzed based on level of experience. Surgeons completed a survey evaluating the experience. RESULTS: All 6 surgeons completed 3 sessions. Five surgeons completed the survey; most respondents evaluated themselves as having improved in desired areas and feeling more confident performing the discussed steps of the operation. Discussed surgical principles varied by experience group; when subjectively quantifying the difficulty of surgical steps, the more difficult steps were discussed by the higher experience groups compared to the junior surgeons. The senior surgeons also focused more on oncologic potency, continence outcomes, and more theory-driven questions while the junior surgeons tended to focus more on anatomic and technique-based questions such as tissue handling and the use of cautery and clips. Overall, the surgeons thought this program provoked critical discussion and subsequently modified their technique, and "agreed" or "strongly agreed" that they would seek further sessions. CONCLUSIONS: Surgical coaching at a large medical center is not only feasible but was rated positively by surgeons across all levels of experience. Coaching led to subjective self-improvement and increased self-confidence among most surgeons. Surgeons also felt that this program offered a safe space to acquire new skills and think critically after finishing residency/fellowship. Themes discussed and takeaways from the sessions varied based on surgeon experience level. While further research is needed to more objectively quantify the impact coaching has on surgeon metrics and patient outcomes, the results of this study supports the initial "proof-of-concept" of peer-based surgical coaching and its potential benefits in accelerating the learning curve for surgeons' post-residency.

Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN: PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS: Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS: Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.

Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial.

Sulforaphane has been reported to possibly improve core symptoms associated with autism spectrum disorders from mostly small size studies. Here we present results of a larger randomized clinical trial (N = 108) in China. There were no significant changes in caregiver rated scales between sulforaphane and placebo groups. However, clinician rated scales showed a significant improvement in the sulforaphane group, and one third of participants showed at least a 30% decrease in score by 12 weeks treatment. The effects of sulforaphane were seen across the full range of intelligence and greater in participants over 10 years. Sulforaphane was safe and well-tolerated even for young children. The inconsistent results between caregiver and clinician rated scales suggest more clinical trials are needed to confirm our findings.

Sulforaphane Effects on Cognition and Symptoms in First and Early Episode Schizophrenia: A Randomized Double-Blind Trial.

Objective: Cognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia. Methods: This double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects. Results: A total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory (F = 5.68, P = 0.004), reasoning-problem solving (F = 2.82, P = 0.063), and verbal learning (F = 3.56, P = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated. Conclusion: Although the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia.

Behaviorally defined patient-centered communication--a narrative review of the literature.

BACKGROUND: Touted by some as reflecting a better medical model and cited by the influential IOM report in 2000 as one of the six domains of quality care, patient-centered medicine has yet to fully establish its scientific attributes or to become mainstream. One proposed reason is failure to behaviorally define what the term 'patient-centered' actually means. OBJECTIVES: (1) To identify patient-centered articles among all reported randomized controlled trials (RCT); (2) to identify those with specific behaviorally defined interventions; (3) to identify commonalities among the behavioral definitions; and (4) to evaluate the relationship of the well-defined RCTs to patient outcomes. DATA SOURCES: Medline from April 2010 to 1975. ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: RCTs having any specific, behaviorally defined patient-centered skill(s) in an intervention with some patient outcome involving real adult patients and providers in real clinical situations. APPRAISAL AND SYNTHESIS METHODS: Critical appraisal via narrative review. RESULTS: The prevalence of any mention of patient-centeredness among 327,219 RCTs was 0.50% (1,475 studies), from which we identified only 13 studies (0.90%) where there were behaviorally-defined patient-centered skills in an intervention. Although there were too few studies to make clinical recommendations, we identified common features of the behavioral definitions used: all went well beyond identifying individual skills. Rather, skills were grouped, prioritized, and sequenced by virtually all, often describing a stepwise patient-centered approach to, variously, gather data, address emotions, or inform and motivate. LIMITATIONS: The inherent subjectivity of our method for identifying behaviorally-defined studies could under- or over-represent truly replicable such studies considerably. Also, studies were few and very heterogeneous with interventions of widely differing intensity and foci. CONCLUSIONS AND IMPLICATIONS: RCTs identified as patient-centered were rare, and <1% of these were behaviorally defined and, therefore, possibly replicable. There were many common behavioral definitions in the studies reported, and these can guide us in identifying agreed-upon patient-centered interventions, the immediate next-step in advancing the field.

Differential sensory gating functions between smokers and non-smokers among drug-naive first episode schizophrenic patients.

Although an acute effect of cigarette smoking and nicotine on sensory gating of schizophrenias has been investigated in published papers, the chronic effect of cigarette smoking on this phenomenon has not yet been reported. We report the effects of chronic cigarette smoking, without new acute exposure before testing, on sensory gating using the P50 auditory evoked potential in a group of drug-naive first episode schizophrenic smokers and healthy smokers. Sensory gating was evaluated using auditory P50 suppression elicited using the conditioning (S1)-testing (S2) paradigm. Fifty six male drug-naive first episode schizophrenic patients were compared to 41 healthy male controls. Patients were classified into subgroups of current smokers (n=18) and non-smokers (n=38) to explore the effects of smoking on sensory gating. All subjects did not smoke a cigarette for at least 1h prior to testing. Schizophrenic patients showed an increased S2 amplitude and a poorer sensory gating as measured by both S2/S1 ratio and S1-S2 difference of P50 amplitude, as compared to healthy controls. However, smokers showed an increased S1 amplitude and better sensory gating than did non-smokers both in schizophrenia patients and healthy controls. Our findings support a sensory gating deficit among first episode schizophrenic patients. However, it was less pronounced among schizophrenic patients who were current cigarette smokers, suggesting a positive effect of chronic cigarette smoking on ameliorating this sensory gating deficit in schizophrenia. Our findings of the present study present new evidence supporting the self-medication hypothesis of self-medication by cigarette smoking in schizophrenia to possibly ameliorate pre-existing functional deficits.

Making the biopsychosocial model more scientific-its general and specific models.

Some aver that the biopsychosocial (BPS) model is not fully scientific because it lacks a method to produce BPS information. To resolve this criticism, I propose that we think in terms of general and specific BPS models. What most understand to be the model is the general BPS model. It simply indicates that all patients be understood in biological, psychological, and social terms without specifying a method or sources of BPS information. Its fundamental function is to guide medicine away from the effete, 17th century disease-only model in clinical care, teaching, and research. Considerable population-based research data also support its scientific status. Less well understood, but of greater relevance to the clinician, is the specific BPS model, which describes the BPS features unique to an individual patient. The specific model, however, requires an interviewing method to achieve this, the method critics believe lacking. In this article, I review how medical communication scholars have established a method to acquire individualized BPS data on each patient. Research identified the patient-centered interviewing (PCI) method to do this. After much progress over several decades, the field was able to test the PCI in several randomized controlled trials-and confirmed it to be evidence-based. Therefore, by definition, because the patient-centered interview defines the specific BPS model in each patient, the model itself is evidence-based. This means we now can, for the first time, identify a scientific BPS model for every individual patient. Joining this scientific support with much existing data for the general model, we now have a fully scientific BPS model.

Effects of transcranial electrical stimulation on working memory in patients with schizophrenia: A systematic review and meta-analysis.

To investigate the immediate and lasting effects of transcranial electrical stimulation (tES) on working memory (WM) in schizophrenia. We performed a literature search to identify randomized controlled trials (RCTs) evaluating the ability of tES to ameliorate WM. Twelve studies were included: 215 patients in the active stimulation group and 214 in the sham stimulation group. Meta-analysis demonstrated a significant efficacy of tES on WM in follow up, a summary of one or more assessments weeks after the last tES session (standardized mean difference (SMD) 0.33, 95% confidence interval (CI) 0.04 to 0.62; p = 0.02; n = 190, 4 studies; I2 = 33%) compared to sham tES, while non-significant results were observed for WM assessed immediately after the last tES session (SMD 0.14, 95% CI -0.12 to 0.41; p = 0.30; n = 417, 11 studies; I2 = 41%) in schizophrenia. There was no significant difference between the two groups in tolerability and dropouts. Evidence of low quality indicates that effects of tES on WM in schizophrenia may appear a few weeks after the last tES session, but not always be present when tested immediately after the last tES session. Further large-scale RCTs with a parallel-group design, sample size estimation and a longer follow-up period are needed.

Concordance of Immune-Related Markers in Lymphocytes and Prefrontal Cortex in Schizophrenia.

Schizophrenia is a severe neuropsychiatric disorder associated with a wide array of transcriptomic and neurobiochemical changes. Genome-wide transcriptomic profiling conducted in postmortem brain have provided novel insights into the pathophysiology of this disorder, and identified biological processes including immune/inflammatory-related responses, metabolic, endocrine, and synaptic function. However, few studies have investigated whether similar changes are present in peripheral tissue. Here, we used RNA-sequencing to characterize transcriptomic profiles of lymphocytes in 18 nonpsychotic controls and 19 individuals with schizophrenia. We identified 2819 differentially expressed transcripts (P nominal < .05) in the schizophrenia group when compared to controls. Bioinformatic analyses conducted on a subset of 293 genes (P nominal < .01 and |log2 FC| > 0.5) highlighted immune/inflammatory responses as key biological processes in our dataset. Differentially expressed genes in lymphocytes were highly enriched in gene expression profiles associated with cortex layer 5a and immune cells. Thus, we investigated whether the changes in transcripts levels observed in lymphocytes could also be detected in the prefrontal cortex (PFC, BA10) in a second replication cohort of schizophrenia subjects. Remarkably, mRNA levels detected in the PFC and lymphocytes were in strong agreement, and measurements obtained using RNA-sequencing positively correlated with data obtained by reverse transcriptase-quantitative polymerase chain reaction analysis. Collectively, our work supports a role for immune dysfunction in the pathogenesis of schizophrenia and suggests that peripheral markers can be used as accessible surrogates to investigate putative central nervous system disruptions.

Gene Expression Of Methylation Cycle And Related Genes In Lymphocytes And Brain Of Patients With Schizophrenia And Non-Psychotic Controls.

Some of the biochemical abnormalities underlying schizophrenia, involve differences in methylation and methylating enzymes, as well as other related target genes. We present results of a study of differences in mRNA expression in peripheral blood lymphocytes (PBLs) and post-mortem brains of chronic schizophrenics (CSZ) and non-psychotic controls (NPC), emphasizing the differential effects of sex and antipsychotic drug treatment on mRNA findings. We studied mRNA expression in lymphocytes of 61 CSZ and 49 NPC subjects using qPCR assays with TaqMan probes to assess levels of DNMT, TET, GABAergic, NR3C1, BDNF mRNAs, and several additional targets identified in a recent RNA sequence analysis. In parallel we studied DNMT1 and GAD67 in samples of brain tissues from 19 CSZ, 26 NPC. In PBLs DNMT1 and DNMT3A mRNA levels were significantly higher in male CSZ vs NPC. No significant differences were detected in females. The GAD1, NR3C1 and CNTNAP2 mRNA levels were significantly higher in CSZ than NPC. In CSZ patients treated with clozapine, GAD-1 related, CNTNAP2, and IMPA2 mRNAs were significantly higher than in CSZ subjects not treated with clozapine. Differences between CSZ vs NPC in these mRNAs was primarily attributable to the clozapine treatment. In the brain samples, DNMT1 was significantly higher and GAD67 was significantly lower in CSZ than in NPC, but there were no significant sex differences in diagnostic effects. These findings highlight the importance of considering sex and drug treatment effects in assessing the substantive significance of differences in mRNAs between CSZ and NPC.

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) in first-episode schizophrenia patients: Rationale and trial design.

Accumulated studies have investigated pharmacological interventions for first-episode schizophrenia (FES) patients. However, studies on subsequent treatment steps, which are essential to guide clinicians, are largely missing. This Sequential Multiple-Assignment Randomized Trials comparing Antipsychotic Treatments (SMART-CAT) program intends to evaluate the effectiveness of commonly used antipsychotic drugs in FES patients. The major goals of this study are to examine: 1) what would be the optimal subsequent sequential treatment if the first antipsychotic drug failed; 2) whether clozapine could be used in those first-trial failed and have superior efficacy compared to other atypical antipsychotics. In this article we will report the detail protocol of SMART-CAT. The SMART-CAT is a randomized controlled clinical multicenter trial in which 9 institutions in China will participate. A total of 720 FES patients will be enrolled and followed up for 12 months in this study. The trial includes three treatment phases (each phase lasting for 8 weeks) and a naturalistic follow-up phase; participants who do well on an assigned treatment will remain on that treatment for the duration of the 12-month treatment period, while non-responders will move to the next phase of the study to receive a new treatment. Phase 1 is a randomized controlled trial; patients will be randomly assigned to one of the treatments with oral olanzapine, risperidone, amisulpride, aripiprazole or perphenazine. Subjects who fail to respond after 8 weeks will enter the phase 2 randomization. Phase 2 is an equipoise-stratified randomization trial, and patients will be randomly assigned to oral olanzapine, amisulpride or clozapine for 8 weeks. Subjects who fail to respond after phase 2 will enter an open label trial (phase 3); patients who receive clozapine in phase 2 and fail to respond will be assigned to an extended clozapine treatment or modified electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAs not previously used in phase 1 and 2 (Phase 3B). The primary outcome for the treatment phase is the treatment efficacy rate, which is defined as at least 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score. We hypothesize that clozapine is more therapeutically effective than any other SGAs to patients who failed to meet efficacy criteria in Phase 1, and earlier treatment with clozapine can improve the functional outcomes of schizophrenia patients. As for the naturalistic follow-up phase, time to all-cause treatment failure, marked by its discontinuation is selected as the primary outcome, since it reflects both efficacy and side effects. The all-cause discontinuation is defined as discontinuing for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons. The results of the SMART-CAT trial will provide evidence for the selection of antipsychotics in FES patients who fail to respond to the first trial of an antipsychotic drug. It will also provide evidence for the efficacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs. The study is based on the combination of sequential therapy and dynamic therapy, which can be more suitable to assess the effectiveness of treatment options in the real-world clinical setting. As a result, we hope that this study can provide guidance for an optimal treatment algorithm in first-episode schizophrenia patients. Trial registration: ID NCT03510325 in ClinicalTrials.gov.