Region-based analysis of sensory processing using diffusion tensor imaging.

The caudate nucleus has been thought to be involved in the control of motor commands by the cerebrum, and recent studies suggest that it may play a role in the control of attachment behavior, cognition, emotion, and mental functions. Implied by the basal ganglia's involvement in the execution, planning and control of movement, the caudate nucleus functions in a situation-dependent manner where processing of external stimuli is important on the basis of learning and memory. Sensory processing, which determines the response to external stimuli, has been shown to be related to various brain regions but it remains unknown how sensory processing is associated with the structure of the caudate nucleus and white matter microstructures of the caudate. Using four diffusion parameters derived from diffusion tensor imaging (DTI) (i.e., fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), and radial diffusivity (RD)) and the Adolescent/Adult Sensory Profile (AASP) questionnaire of 99 healthy subjects [42 males and 57 females; mean age:26.9 years, standard deviation 6.9], we investigated the relationship between white matter structure in the caudate nucleus and sensory processing. In consistent with what had been suggested by the results of previous studies, we found significant correlations between AD, MD and tactile sensation. Furthermore, we found a significant correlation between AD, MD and tactile sensory avoidance, the AASP sub-scores regarding the tactile senses. To the best of our knowledge, this is the first study to show that DTI diffusion parameters correlate with AASP scores in specific brain regions.

Guided internet-based cognitive behavioral therapy for obsessive-compulsive disorder: A multicenter randomized controlled trial in Japan.

Few studies have compared the effectiveness of internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) with treatment as usual (TAU). We investigated the effectiveness of guided ICBT for patients with OCD. This prospective, randomized, controlled, assessor-blinded, multicenter clinical trial was conducted at three facilities in Japan from January 2020 to March 2021. Thirty-one patients with OCD as the primary diagnosis participated in the trial and were randomly assigned to either the intervention group or the control group. The primary outcome was the Yale-Brown obsessive-compulsive scale score; the assessors were blinded. Results of the analysis of covariance among the groups were significantly different between the groups (p < 0.01, effect size Cohen's d = 1.05), indicating the superiority of guided ICBT. The results suggest that guided ICBT is more effective than TAU for treating OCD. RCT REGISTRATION: UMIN Clinical Trials Registry (UMIN000039375).

The effects of epigenetic age and its acceleration on surface area, cortical thickness, and volume in young adults.

DNA methylation age has been used in recent studies as an epigenetic marker of accelerated cellular aging, whose contribution to the brain structural changes was lately acknowledged. We aimed to characterize the association of epigenetic age (i.e. estimated DNA methylation age) and its acceleration with surface area, cortical thickness, and volume in healthy young adults. Using the multi-tissue method (Horvath S. DNA methylation age of human tissues and cell types. 2013. Genome Biol 14), epigenetic age was computed with saliva sample. Epigenetic age acceleration was derived from residuals after adjusting epigenetic age for chronological age. Multiple regression models were computed for 148 brain regions for surface area, cortical thickness, and volume using epigenetic age or accelerated epigenetic age as a predictor and controlling for sex. Epigenetic age was associated with surface area reduction of the left insula. It was also associated with cortical thinning and volume reduction in multiple regions, with prominent changes of cortical thickness in the left temporal regions and of volume in the bilateral orbital gyri. Finally, accelerated epigenetic age was negatively associated with right cuneus gyrus volume. Our findings suggest that understanding the mechanisms of epigenetic age acceleration in young individuals may yield valuable insights into the relationship between epigenetic aging and the cortical change and on the early development of neurocognitive pathology among young adults.

Liver resection is associated with good outcomes for hepatocellular carcinoma patients beyond the Barcelona Clinic Liver Cancer criteria: A multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

BACKGROUND: Liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria remains controversial. Strict candidate selection is crucial to achieve optimal results in this population. This study explored postoperative outcomes and developed a preoperative predictive formula to identify patients most likely to benefit from liver resection. METHODS: In total, 382 patients who underwent liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria between 2000 and 2017 were identified from a multicenter database with the Hiroshima Surgical study group of Clinical Oncology. An overall survival prediction model was developed, and patients were classified by risk status. RESULTS: The 5-year overall survival after curative resection was 50.0%. Overall survival multivariate analysis identified that a high a-fetoprotein level, macrovascular invasion, and high total tumor burden were independent prognostic risk factors; these factors were used to formulate risk scores. Patients were divided into low-, moderate-, and high-risk groups; the 5-year overall survival was 65.7%, 49.5%, and 17.0% (P < .001), and the 5-year recurrence-free survival was 31.3%, 26.2%, and 0%, respectively (P < .001). The model performance was good (C-index, 0.76). Both the early and extrahepatic recurrence increased with higher risk score. CONCLUSION: The prognosis of patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria depended on a high a-fetoprotein level, macrovascular invasion, and high total tumor burden, and risk scores based on these factors stratified the prognoses. Liver resection should be considered in patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria with a low or moderate-risk score.

Relationship between sensory characteristics and cortical thickness/volume in autism spectrum disorders.

Individuals with autism spectrum disorders (ASDs) exhibit atypical sensory characteristics, impaired social skills, deficits in verbal and nonverbal communication, and restricted and repetitive behaviors. The relationship between sensory characteristics and brain morphological changes in ASD remains unclear. In this study, we investigated the association between brain morphological changes and sensory characteristics in individuals with ASD using brain image analysis and a sensory profile test. Forty-three adults with ASD and 84 adults with typical development underwent brain image analysis using FreeSurfer. The brain cortex was divided into 64 regions, and the cortical thickness and volume of the limbic system were calculated. The sensory characteristics of the participants were evaluated using the Adolescent/Adult Sensory Profile (AASP). Correlation analysis was performed for cortical thickness, limbic area volume, and AASP scores. In the ASD group, there was a significant positive correlation between visual sensory sensitivity scores and the right lingual cortical thickness (r = 0.500). There were also significant negative correlations between visual sensation avoiding scores and the right lateral orbitofrontal cortical thickness (r = -0.513), taste/smell sensation avoiding scores and the right hippocampal volume (r = -0.510), and taste/smell sensation avoiding scores and the left hippocampal volume (r = -0.540). The study identified associations among the lingual cortical thickness, lateral orbitofrontal cortical thickness, and hippocampal volume and sensory characteristics. These findings suggest that brain morphological changes may trigger sensory symptoms in adults with ASD.

Elucidation of the relationship between sensory processing and white matter using diffusion tensor imaging tractography in young adults.

Sensory processing and behaviors are altered during the development of connectivity between the sensory cortices and multiple brain regions in an experience-dependent manner. To reveal the relationship between sensory processing and brain white matter, we investigated the association between the Adolescent/Adult Sensory Profile (AASP) and neural connectivity in the white matter tracts of 84 healthy young adults using diffusion tensor imaging (DTI). We observed a positive relationship between AASP scores (i.e., sensory sensitivity, sensation avoiding, activity level)/subscores (i.e., sensory sensitivity-activity level, sensation avoiding-touch) and DTI parameters in the cingulum-cingulate gyrus bundle (CCG) and between AASP subscores (i.e., sensory sensitivity-auditory) and a diffusion parameter in the uncinate fasciculus (UNC). The diffusion parameters that correlated with AASP scores/subscores and AASP quadrant scores (i.e., sensory avoiding and sensitivity) were axonal diffusivity (AD) and mean diffusivity (MD) in the CCG and MD in the UNC. Moreover, the increased sensory avoiding and sensitivity scores represent the sensitization of sensory processing, and the level of diffusivity parameters indicates white matter microstructure variability, such as axons and myelin from diffusivity of water molecules. Thus, the present study suggests that the CCG and UNC are critical white matter microstructures for determining the level of sensory processing in young adults.

Laparoscopic versus open limited liver resection for hepatocellular carcinoma with liver cirrhosis: a propensity score matching study with the Hiroshima Surgical study group of Clinical Oncology (HiSCO).

BACKGROUND: Laparoscopic liver resection (LLR) has evolved as a safe and effective alternative to conventional open liver resection (OLR) for malignant lesions. However, LLR in cirrhotic patients remains challenging. This study analyzed the perioperative and oncological outcomes of LLR for hepatocellular carcinoma (HCC) with cirrhosis compared with OLR using propensity score matching. METHODS: A multicenter retrospective analysis of records of patients who underwent limited liver resection for HCC and were histologically diagnosed with liver cirrhosis between January 2009 and December 2017 in the eight institutions belonging to the Hiroshima Surgical study group of Clinical Oncology was performed. The patients were divided into two groups: the LLR and OLR groups. After propensity score matching, we compared clinicopathological features and outcomes. RESULTS: In total 256 patients with histological liver cirrhosis who underwent limited liver resection for HCC were included in this study; 58 patients had undergone LLR, and the remaining 198 patients OLR. The number of tumors was higher, tumor size was larger, and difficulty score was significantly higher in the OLR group before propensity matching. After the matching, the data of the well-matched 58 patients in each group were evaluated; the intraoperative blood loss was lower in the LLR group (p = 0.004), and incidence of the postoperative complications was significantly higher in the OLR group (p = 0.019). The duration of the postoperative hospital stay was significantly shorter in the LLR group (p < 0.001). There were no differences between two groups in overall survival and recurrent-free survival. CONCLUSIONS: LLR decreased the incidences of postoperative complications, shortened the duration of postoperative hospital stay. Thus, LLR is a safe and feasible procedure even in patients with cirrhosis.

Short-term outcomes of laparoscopic surgery in octogenarians with colorectal cancer: a single-institution analysis.

PURPOSE: The number of elderly patients with colorectal cancer (CRC) treated with surgery has gradually increased. The aim of this study was to evaluate the short-term outcomes in patients ≥80 years of age who underwent laparoscopic or open surgery for CRC using a propensity score-matched analysis to make uniform the patient background characteristics affecting the postoperative morbidity and mortality. METHODS: We compared the short-term outcomes of open vs. laparoscopic surgery in patients with CRC ≥80 years of age between 2010 and 2015. Fifty-two patients undergoing laparoscopic colectomy for CRC were matched to 52 patients undergoing open colectomy with respect to gender, age, body mass index, performance status, prognostic nutritional index, Charlson Comorbidity Index score, tumor-node-metastasis stage, and tumor location. The operative time, blood loss, length of hospital stay, and postoperative complications were investigated. RESULTS: Blood loss was less during laparoscopic surgery than during open surgery (40 vs. 140 ml, p < 0.001). In the laparoscopic surgery group, the hospital stay was shorter (11 vs. 14 days, p < 0.001) and the morbidity rate lower (21.2 vs. 40.4%) than in the open surgery group. The mortality for both groups was similar (0 vs. 1.9% for laparoscopic surgery vs. open surgery). CONCLUSION: Laparoscopic surgery in octogenarians with CRC is a safe, low-invasive alternative to open surgery with less blood loss and a shorter hospital stay.

Complete pathological response of multiple huge liver metastases of colon cancer: a case report.

We report a case of a pathological complete response (pCR) with chemotherapy for multiple huge liver metastases from colon cancer. A 59-year-old woman presented with anorexia and weight loss. Laboratory tests revealed elevated liver enzyme levels and tumor markers. A computed tomography/positron emission tomography-computed tomography scan revealed a transverse colon tumor and unresectable liver masses measuring 9.0 cm in maximum diameter in segments 7 and 8, with another mass in segment 6. She underwent laparoscopic colectomy and was administered FOLFOX + BV. After 11-cycles of chemotherapy, the liver masses became resectable with a partial response, so hepatectomy was performed. On the final histopathological analysis, all lesions were fibrotic without any viable cancer cells. The patient is alive without recurrence 2 years after resection. We believe this is the largest tumor of unresectable colorectal liver metastasis (CRLM) that has ever resulted in pCR with chemotherapy. FOLFOX + Bev was thus found to be an effective treatment for unresectable CRLM.

Single-incision laparoscopic excision of a chylous mesenteric cyst: A case report.

INTRODUCTION: Chylous mesenteric cysts are rare intra-abdominal lesions located in the mesentery of the gastrointestinal tract and may extend from the base of the mesentery into the retroperitoneum. The treatment is the complete removal of the cyst PRESENTATION OF CASE: A 49-year-old female presented with abdominal pain. Abdominal computed tomography showed a 5.0-cm-diameter intraabdominal, homogenous cystic lesion located on the mesentery of the small intestine. Single-incision laparoscopic surgery was performed for complete resection. DISCUSSION: Only a handful of cases of laparoscopic surgery for a mesenteric cyst have been reported, and no reports have been published regarding single-incision laparoscopic surgery for a mesenteric cyst. CONCLUSION: We report the first known case of a chylous mesenteric cyst that was successfully treated by single-incision laparoscopic surgery.

Supported employment for adults with severe mental illness.

BACKGROUND: People who suffer from severe mental disorder experience high rates of unemployment. Supported employment is an approach to vocational rehabilitation that involves trying to place clients in competitive jobs without any extended preparation. The Individual placement and support (IPS) model is a carefully specified form of supported employment. OBJECTIVES: 1. To review the effectiveness of supported employment compared with other approaches to vocational rehabilitation or treatment as usual.2. Secondary objectives were to establish how far:(a) fidelity to the IPS model affects the effectiveness of supported employment,(b) the effectiveness of supported employment can be augmented by the addition of other interventions. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (February 2010), which is compiled by systematic searches of major databases, handsearches and conference proceedings. SELECTION CRITERIA: All relevant randomised clinical trials focusing on people with severe mental illness, of working age (normally 16 to 70 years), where supported employment was compared with other vocational approaches or treatment as usual. Outcomes such as days in employment, job stability, global state, social functioning, mental state, quality of life, satisfaction and costs were sought. DATA COLLECTION AND ANALYSIS: Two review authors (YK and KK) independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated mean difference (MD) between groups and its 95% (CI). We employed a fixed-effect model for analyses. A random-effects model was also employed where heterogeneity was present. MAIN RESULTS: A total of 14 randomised controlled trials were included in this review (total 2265 people). In terms of our primary outcome (employment: days in competitive employment, over one year follow-up), supported employment seems to significantly increase levels of any employment obtained during the course of studies (7 RCTs, n = 951, RR 3.24 CI 2.17 to 4.82, very low quality of evidence). Supported employment also seems to increase length of competitive employment when compared with other vocational approaches (1 RCT, n = 204, MD 70.63 CI 43.22 to 94.04, very low quality evidence). Supported employment also showed some advantages in other secondary outcomes. It appears to increase length (in days) of any form of paid employment (2 RCTs, n = 510, MD 84.94 CI 51.99 to 117.89, very low quality evidence) and job tenure (weeks) for competitive employment (1 RCT, n = 204, MD 9.86 CI 5.36 to 14.36, very low quality evidence) and any paid employment (3 RCTs, n = 735, MD 3.86 CI -2.94 to 22.17, very low quality evidence). Furthermore, one study indicated a decreased time to first competitive employment in the long term for people in supported employment (1 RCT, n = 204, MD -161.60 CI -225.73 to -97.47, very low quality evidence). A large amount of data were considerably skewed, and therefore not included in meta-analysis, which makes any meaningful interpretation of the vast amount of data very difficult. AUTHORS' CONCLUSIONS: The limited available evidence suggests that supported employment is effective in improving a number of vocational outcomes relevant to people with severe mental illness, though there appears to exist some overall risk of bias in terms of the quality of individual studies. All studies should report a standard set of vocational and non-vocational outcomes that are relevant to the consumers and policy-makers. Studies with longer follow-up should be conducted to answer or address the critical question about durability of effects.

Duloxetine versus other anti-depressive agents for depression.

BACKGROUND: Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. OBJECTIVES: To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. SEARCH METHODS: MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. MAIN RESULTS: A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55). AUTHORS' CONCLUSIONS: Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies were sponsored by the drug industry manufacturing duloxetine. As for all other new investigational compounds, the potential for overestimation of treatment effect due to sponsorship bias should be borne in mind. In the present review no trials reported economic outcomes. Given that several SSRIs and the great majority of antidepressants are now available as generic formulation (only escitalopram, desvenlafaxine and duloxetine are still on patent), more comprehensive economic estimates of antidepressant treatment effect should be considered to better inform healthcare policy.

Mirtazapine versus other antidepressive agents for depression.

BACKGROUND: Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice. OBJECTIVES: The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults. SEARCH METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group's specialised register (CCDANCTR), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response to treatment. The secondary outcomes included dropouts and individual adverse events.Meta-analyses were conducted using the random-effects model. MAIN RESULTS: A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR 1.57, 95% CI 1.30 to 1.88) and at the end of acute-phase treatment (OR 1.19, 95% CI 1.01 to 1.39). Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor (venlafaxine only, two trials, n = 415) at two weeks (OR 2.29, 95% CI 1.45 to 3.59) and at the end of acute-phase treatment (OR 1.53, 95% CI 1.03 to 2.25).In terms of dropouts, there was no robust evidence to detect a difference between mirtazapine and other antidepressants. Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction. AUTHORS' CONCLUSIONS: Some statistically significant and possibly clinically meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression. Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment. Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants, although the adverse event profile of mirtazapine is unique.

Distinct neuropsychological profiles of three major symptom dimensions in obsessive-compulsive disorder.

Recent neuroimaging studies have suggested that different symptom dimensions are mediated by partially distinct neural systems in obsessive-compulsive disorder (OCD). However, the correlations between neuropsychological profiles and symptom dimensions in OCD are unknown. The aim of this study was to examine the extent to which OCD symptom dimensions were associated with episodic memory and attention and executive functions. The symptom dimensions of 63 patients with OCD were assessed using both the Padua Inventory and the Y-BOCS symptom checklist. Then, we administered the Logical Memory (LM) subset of the Wechsler Memory Scale-Revised (WMR-R) test and evaluated inhibition (Stroop test, Trail Making test) and cognitive flexibility (Digit Symbol test, Letter Fluency, and Category Fluency). While associations were observed between scores on the contamination/cleaning dimension and better performances on the LM and Trail Making tests, associations were also observed between scores on the aggressive/checking dimension and poorer performances on the Trail Making test. In addition, we found that scores on the symmetry/ordering dimension were associated with poorer performances on the LM and Trail Making tests. Our results support the hypothesis that different symptoms may represent distinct and partially overlapping neurocognitive networks in OCD patients.

Fluvoxamine versus other anti-depressive agents for depression.

BACKGROUND: Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. OBJECTIVES: Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. SELECTION CRITERIA: We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. DATA COLLECTION AND ANALYSIS: Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. MAIN RESULTS: A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). AUTHORS' CONCLUSIONS: We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles.

Sulpiride augmentation for schizophrenia.

BACKGROUND: Sulpiride may be used in combination with other antipsychotic drugs in the hope of augmenting effectiveness - especially for those whose schizophrenia has proved resistant to treatment. OBJECTIVES: To evaluate the effects of sulpiride augmentation versus monotherapy for people with schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: All relevant randomised clinical trials (RCTs). DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a fixed-effect model. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model. MAIN RESULTS: We included three short-term and one long-term trial (total N=221). All participants had schizophrenia that was either treatment-resistant or with prominent negative symptoms. All studies compared sulpiride plus clozapine with clozapine (+/- placebo), were small and at considerable risk of bias.Short-term data of 'no clinically significant response' in global state tended to favour sulpiride augmentation of clozapine compared with clozapine alone (n=193, 3 RCTs, RR 0.58 CI 0.3 to 1.09).People allocated to sulpiride plus clozapine had more movement disorders (n=70, 1 RCT, RR 48.24 CI 3.05 to 762.56) and an increase in serum prolactin (skewed data, 1 RCT), but less incidence of hypersalivation (n=162, 3 RCTs, RR 0.49 CI 0.29 to 0.83) and less weight gain (n=64, 1 RCT, RR 0.30 CI 0.09 to 0.99). The augmentation of clozapine by sulpiride also caused less appetite loss (n=70, 1 RCT, RR 0.09 CI 0.01 to 0.70, NNT 4 CI 4 to 12, Z=2.31, P=0.02) and less abdominal distension (n=70, 1 RCT, RR 0.10 CI 0.01 to 0.78, NNT 5 CI 4 to 19, Z=2.20, P=0.03).Long-term data showed no significant difference in global state (n=70, 1 RCT, RR 0.67 CI 0.42 to 1.08) and relapse (n=70, 1 RCT, RR 0.85 CI 0.5 to 1.3). AUTHORS' CONCLUSIONS: Sulpiride plus clozapine is probably more effective than clozapine alone in producing clinical improvement in some people whose illness has been resistant to other antipsychotic drugs including clozapine. However, much more robust data are needed.

Supported employment for adults with severe mental illness.

This is the protocol for a review and there is no abstract. The objectives are as follows: To review the effectiveness of supported employment compared to other approached to vocational rehabilitation and treatment as usual.Secondary objectives are to establish how far: fidelity to the IPS model affects the effectiveness of supported employment,the effectiveness of supported employment can be augmented by the addition of other interventions.

Safety reporting and adverse-event profile of mirtazapine described in randomized controlled trials in comparison with other classes of antidepressants in the acute-phase treatment of adults with depression: systematic review and meta-analysis.

BACKGROUND: Mirtazapine has a unique mechanism of antidepressant action, and thus is thought to have a different profile of adverse events from that of other antidepressants. OBJECTIVE: To present a methodologically rigorous systematic review of the adverse event profile of mirtazapine and point to possible problems with safety reporting in randomized controlled trials (RCTs) of the acute-phase treatment of major depression in adults with mirtazapine in comparison with other types of antidepressant. METHODS: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register was electronically searched using the following search terms: 'depress*', 'dysthymi*', 'adjustment disorder*', 'mood disorder*', 'affective disorder', 'affective symptoms' and 'mirtazapine'. Pharmaceutical companies and experts in this field were contacted, and the reference lists of the relevant RCTs were checked, for additional data. No language restriction was imposed. Two authors independently assessed the quality of trials for inclusion in the review. Disagreements were resolved by consensus. Two authors independently extracted data on adverse events. Disagreements were resolved by consensus. The adequacy of safety reporting was assessed by one author. Regarding the adequacy of safety reporting, the qualitative and quantitative parameters of safety reporting were determined. Regression analyses were conducted to assess characteristics of trials influencing safety reporting. The primary and secondary outcomes in the systematic review of the adverse events associated with mirtazapine were defined as the proportion of patients having each of 43 adverse events listed in the modified version of the WHO Adverse Reaction Terminology, and the proportion of patients experiencing at least one adverse event, respectively. Meta-analyses were conducted for these outcomes. RESULTS: Twenty-five RCTs involving 4842 patients were identified as meeting our inclusion criteria. With regard to safety reporting, only two trials and no trials were rated as 'adequate' in terms of the reporting of clinical adverse events and laboratory-determined toxicity, respectively. The proportion of text in the results sections of the study reports devoted to safety reporting was a mean of 22%. No associations were observed between the adequacy of safety reporting and any characteristics of the trials; however, sample size over 100 participants in total and over 50 subjects in a study arm, double blindness and sponsorship by the company marketing mirtazapine were significantly associated with a greater number of reported adverse events in mirtazapine recipients. In terms of individual adverse events, mirtazapine was significantly less likely to cause hypertension or tachycardia (risk ratio [RR] 0.51) and tremor (RR 0.43) than tricyclic antidepressants (TCAs). In comparison with selective serotonin uptake inhibitors (SSRIs), mirtazapine was significantly more likely to cause weight gain or increased appetite (RR 3.68), increased salivation (RR 3.66), somnolence (RR 1.62) and fatigue (RR 1.45), but less likely to cause flatulence (RR 0.26), sweating (RR 0.28), sexual dysfunction (RR 0.34), tremor (RR 0.37), nausea or vomiting (RR 0.40), sleep disturbance (RR 0.55) and diarrhoea (RR 0.61). In comparison with the serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine, mirtazapine was significantly more likely to cause fatigue (RR 2.02), but less likely to cause sleep disturbance (RR 0.03), sweating (RR 0.03) and constipation (RR 0.25). Relative to trazodone, mirtazapine was significantly more likely to cause weight gain or increased appetite (RR 4.00). Approximately 70% of patients treated with mirtazapine experienced at least one adverse event, with no significant difference in comparison with other antidepressants. CONCLUSIONS: The study confirmed the paucity of adequate safety reporting in trials comparing mirtazapine with other types of antidepressant in the acute-phase treatment of depression in adults. Based on the available evidence, mirtazapine appears to have a unique adverse-event profile. Using these findings, clinicians can inform their patients, not only of the simple frequency of adverse events with mirtazapine, but also of the relative difference in the frequency of adverse events in comparison with that of other antidepressants, to aid pragmatic clinical decisions.