The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.OBJECTIVE To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.DATA SOURCES A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.STUDY SELECTION Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.DATA EXTRACTION AND SYNTHESIS Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis. PASI 75,90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline. MAIN OUTCOMES AND MEASURES RESULTSSixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses. CONCLUSIONS AND RELEVANCEThis study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.

OBJECTIVES:The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis (UC) has been reported up to week 52 from the placebo-controlled trials ULTRA (Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab) 1 and 2. Up to 4 years of data for adalimumab-treated patients from ULTRA 1, 2, and the open-label extension ULTRA 3 are presented.METHODS:Remission per partial Mayo score, remission per Inflammatory Bowel Disease Questionnaire (IBDQ) score, and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208. Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline. Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing, respectively. As observed, last observation carried forward (LOCF) and nonresponder imputation (NRI) were used to report efficacy. Adverse events were reported for any adalimumab-treated patient.RESULTS:A total of 600/1,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies. Of these, 199 patients remained on adalimumab after 4 years of follow-up. Rates of remission per partial Mayo score, remission per IBDQ score, mucosal healing, and corticosteroid discontinuation at week 208 were 24.7%, 26.3%, 27.7% (NRI), and 59.2% (observed), respectively. Of the patients who were followed up in ULTRA 3 (588/1,094), a total of 360 patients remained on adalimumab 3 years later. Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6% and 59.9% of patients, respectively (NRI). Adverse event rates were stable over time.CONCLUSIONS:Remission, mucosal healing, and improved quality of life were maintained in patients with moderately to severely active UC with long-term adalimumab therapy, for up to 4 years. No new safety signals were reported.

IMPORTANCE Noninfectious uveitis (NIU) is a collection of intraocular inflammatory disorders that may be associated with significant visual impairment. To our knowledge, few studies have investigated NIU prevalence overall or stratified by inflammation location, severity, presence of systemic conditions, age, or sex. OBJECTIVE To estimate NIU prevalence using a large, retrospective, administrative claims database. DESIGN, SETTING, AND PARTICIPANTS This analysis used the OptumHealth Reporting and Insights database to estimate 2012 NIU prevalence. Analysis was conducted in September 2016. The large administrative insurance claims database includes 14 million privately insured individuals in 69 self-insured companies spanning diverse industries. Included in the study were patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and continuous enrollment in a health plan for all of 2012 and categorized by inflammation site. MAIN OUTCOMES AND MEASURES We estimated overall NIU prevalence by inflammation site, severity, sex, and age. Patients with anterior NIU were categorized by the presence of systemic conditions. RESULTS Of the approximately 4 million eligible adult patients, approximately 2.1 million were women, and of the 932 260 children, 475 481 were boys. The adult prevalence of NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and 75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The prevalences of noninfectious intermediate, posterior, and panuveitis were, for adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7) per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3 (95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The prevalence of NIU increased with age and was higher among adult females than males. Application of these estimates to the US population suggests that NIU affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21 879 children (95% CI, 19 360-24 626) in 2015. CONCLUSIONS AND RELEVANCE The estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5-124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was estimated using administrative claims from a commercially insured population, which may have a different prevalence than other segments of the US population. A better understanding of the prevalence of NIU will help to determine the number of patients affected.

Objective-Euthymic bipolar disorder (BD) youths have a deficit in face emotion labeling that is present across multiple emotions. Recent research indicates that youths at familial risk for BD, but without a history of mood disorder, also have a deficit in face emotion labeling, suggesting that such impairments may be an endophenotype for BD. It is unclear if this deficit in at-risk youths is present across all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BD become manifest.Method-37 patients with pediatric BD, 25 unaffected children with a first-degree relative with BD, and 36 typically developing youths were administered the Emotional Expression Multimorph Task, a computerized behavioral task which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, disgust).Results-Repeated measures analysis of covariance revealed that, compared to healthy youths, patients and at-risk youths required significantly more intense emotional information to identify and correctly label face emotions. Patients with BD and at-risk youths did not differ from each other. Group-by-emotion interactions were not significant, indicating that the group effects did not differ based on the facial emotion.Conclusions-Youths at risk for BD demonstrate non-specific deficits in face emotion recognition, similar to patients with the illness. Further research is needed to determine if such deficits meet all criteria for an endophenotype.

Noninfectious intermediate uveitis, posterior uveitis, or panuveitis, particularly persistent disease, is associated with a substantial risk of ocular complications. Optimal treatment initiatives remain imperative to reduce the ocular complication-related burden of NIIPPU.

While much is known about the neural regions recruited in the human brain when a dominant motor response becomes inappropriate and must be stopped, less is known about the regions that support switching to a new, appropriate, response. Using functional magnetic resonance imaging with two variants of the stop-signal paradigm that require either stopping altogether or switching to a different response, we examined the brain systems involved in these two forms of executive control. Both stopping trials and switching trials showed common recruitment of the right inferior frontal gyrus, presupplementary motor area, and midbrain. Contrasting switching trials with stopping trials showed activation similar to that observed on response trials (where the initial response remains appropriate and no control is invoked), whereas there were no regions that showed significantly greater activity for stopping trials compared with switching trials. These results show that response switching can be supported by the same neural systems as response inhibition, and suggest that the same mechanism of rapid, nonselective response inhibition that is thought to support speeded response stopping can also support speeded response switching when paired with execution of the new, appropriate, response.

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We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimer's disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroimage. Author manuscript; available in PMC 2012 June 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.