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The periocular region is challenging for cosmetic laser surgeons. Surgery and laser resurfacing have traditionally been used to correct periorbital lines and wrinkles. Although effective, the associated downtime with these methods has made many people reluctant to decide for such treatments. More recently, the non-ablative long-pulse 2940 nm Er:YAG laser is being used to improve the structure and function and hence the appearance of skin in the periorbital region. The objective of this study is to evaluate the safety and efficacy of long-pulse 2940 nm Er:YAG laser for non-ablative treatment of periorbital static wrinkles and skin laxity. This is a prospective analysis of 30 patients treated for periorbital rejuvenation using three sessions of non-ablative long-pulse Er:YAG laser over a 3-month period. All patients were assessed according to Fitzpatrick’s classification of periorbital wrinkles to class I, II, or III and were treated with 2940 nm Er:YAG laser using a fluence of 3.75 J/cm2, a repetition rate of 1.7–2 Hz, and with the SMOOTH™ pulse mode (250 ms). The treatment sessions were performed on each patient, 4 weeks apart. Patient improvement was assessed before each laser session as well as at 12 months after the final treatment. Blind photographic evaluations were performed by three independent physicians using unlabeled before and after photos arranged in non-chronological order. Reviewers were asked to determine the before and after photos. Patients were asked to answer a questionnaire measuring satisfaction 4 weeks after each session, and to report any adverse reactions. There was statistically and clinically significant improvement in the Fitzpatrick classification of the periorbital wrinkles. Blinded evaluators correctly identified the before and after photos in all cases. All patients reported mild edema and erythema, which persisted for 1 to 2 days, and superficial peeling of the skin for 4 to 6 days after each laser treatment. No long-term adverse effects were reported. The non-ablative long-pulse 2940 nm Er:YAG laser seems to be a safe and effective treatment for periocular rejuvenation with minimal and tolerable adverse reaction. The improvement attained from the laser sessions was persisting after 1 year denoting the long-term efficacy of the procedure.

Worldwide, early intervention services for young people with recent-onset psychosis have been associated with improvements in outcomes, including reductions in hospitalization, symptoms, and improvements in treatment engagement and work/school participation. States have received federal mental health block grant funding to implement team-based, multi-element, evidence-based early intervention services, now called coordinated specialty care (CSC) in the USA. New York State’s CSC program, OnTrackNY, has grown into a 23-site, statewide network, serving over 1800 individuals since its 2013 inception. A state-supported intermediary organization, OnTrackCentral, has overseen the growth of OnTrackNY. OnTrackNY has been committed to quality improvement since its inception. In 2019, OnTrackNY was awarded a regional hub within the National Institute of Mental Health-sponsored Early Psychosis Intervention Network (EPINET). The participation in the national EPINET initiative reframes and expands OnTrackNY’s quality improvement activities. The national EPINET initiative aims to develop a learning healthcare system (LHS); OnTrackNY’s participation will facilitate the development of infrastructure, including a systematic approach to facilitating stakeholder input and enhancing the data and informatics infrastructure to promote quality improvement. Additionally, this infrastructure will support practice-based research to improve care. The investment of the EPINET network to build regional and national LHSs will accelerate innovations to improve quality of care.

N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonists such as ketamine have demonstrated efficacy in both major depressive disorder (MDD) and bipolar disorder depression (BP-D). We have previously reported that reduction in Glx (glutamate + glutamine) in the ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC), measured by proton magnetic resonance spectroscopy (1H MRS) at 3T during a ketamine infusion, mediates the relationship of ketamine dose and blood level to improvement in depression. In the present study, we assessed the impact of D-cycloserine (DCS), an oral NMDAR antagonist combined with lurasidone in BP-D on both glutamate and Glx. Subjects with DSM-V BP-D-I/II and a Montgomery-Asberg Depression Rating Scale (MADRS) score>17, underwent up to three 1H MRS scans. During Scan 1, subjects were randomized to receive double-blind lurasidone 66 mg or placebo. During Scan 2, all subjects received single-blind DCS 950 mg + lurasidone 66 mg, followed by 4 weeks of open label phase of DCS+lurasidone and an optional Scan 3. Five subjects received lurasidone alone and three subjects received placebo for Scan 1. Six subjects received DCS+lurasidone during Scan 2. There was no significant baseline or between treatment-group differences in acute depression improvement or glutamate response. In Scan 2, after a dose of DCS+lurasidone, peak change in glutamate correlated negatively with improvement from baseline MADRS (r = −0.83, p = 0.04). There were no unexpected adverse events. These preliminary pilot results require replication but provide further support for a link between antidepressant effect and a decrease in glutamate by the NMDAR antagonist class of antidepressants.

Glutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were conducted contemporaneously. 95 healthy volunteers were randomized to POMA and 63 to TS-134. High-dose POMA significantly reduced ketamine-induced BPRS total symptoms within and between-groups (p d = −0.41; p = 0.04, d = −0.44, respectively), but neither POMA dose significantly suppressed ketamine-induced dACC pharmacoBOLD. In contrast, low-dose TS-134 led to moderate to large within and between group reductions in both BPRS positive symptoms (p = 0.02, d = −0.36; p = 0.008, d = −0.82, respectively) and dACC pharmacoBOLD (p = 0.004, d = −0.56; p = 0.079, d = −0.50, respectively) using pooled across-study placebo data. High-dose POMA exerted significant effects on clinical symptoms, but not on target engagement, suggesting a higher dose may yet be needed, while the low dose of TS-134 showed evidence of symptom reduction and target engagement. These results support further investigation of mGluR2/3 and other glutamate-targeted treatments for schizophrenia.

We tested two metabotropic glutamate receptor 2/3 (mGluR2/3) agonist prodrugs – pomaglumetad (POMA) and TS-134 – including a high-dose of POMA that was four times the dose tested in the failed phase schizophrenia III trials – in two proof of mechanism, Phase Ib studies using identical pharmacoBOLD target-engagement methodology.The POMA study was a double-blind, NIMH-sponsored, 10-day study of 80 or 320 mg/d POMA or placebo (1:1:1 ratio), designed to detect d>0.8 sd between-group effect-size differences. The TS-134 study was a single-blind, industry-sponsored, 6-day study of 20 or 60 mg/d TS-134 or placebo (5:5:2 ratio), designed to permit effect-size estimation for future studies. Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and Brief Psychiatric Rating Scale (BPRS).95 healthy controls were randomized to POMA and 63 to TS-134. High-dose POMA had significant within and between-group reduction in ketamine-induced BPRS total symptoms (pHigh-dose POMA exerted significant effects on clinical symptoms, but not on target engagement, suggesting a higher dose may yet be needed. TS-134 20 mg showed evidence of symptom reduction and target engagement, indicating a curvilinear dose-response curve. These results warrant further investigation of mGluR2/3 and other glutamate-targeted treatments for schizophrenia.

Despite their theoretical rationale, nicotinic alpha-7 acetylcholine (nα(7)) receptor agonists, have largely failed to demonstrate efficacy in placebo-controlled trials in schizophrenia. AVL-3288 is a nα(7) positive allosteric modulator (PAM), which is only active in the presence of the endogenous ligand (acetylcholine), and thus theoretically less likely to cause receptor desensitization. We evaluated the efficacy of AVL-3288 in a Phase 1b, randomized, double-blind, placebo-controlled, triple cross-over study. Twenty-four non-smoking, medicated, outpatients with schizophrenia or schizoaffective disorder and a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) ≥62 were randomized. Each subject received 5 days of AVL-3288 (10, 30 mg) and placebo across three separate treatment weeks. The primary outcome measure was the RBANS total scale score, with auditory P50 evoked potential suppression the key target engagement biomarker. Secondary outcome measures include task-based fMRI (RISE task), mismatch negativity, the Scale for the Assessment of Negative Symptoms of Schizophrenia (SANS) and the Brief Psychiatric Rating Scale (BPRS). Twenty-four subjects were randomized and treated without any clinically significant treatment emergent adverse effects. Baseline RBANS (82 ± 17) and BPRS (41 ± 13) scores were consistent with moderate impairment. Primary outcomes were negative, with non-significant worsening for both active groups vs. placebo in the P50 and minimal between group changes on the RBANS. In conclusion, the results did not indicate efficacy of the compound, consistent with most prior results for the nα(7) target.

The medical and health-related educational system in Egypt has advantages and limitations. Medical education includes a unique system of three-year community-based public health training, but better planning and collaboration among schools could notably increase new physicians' knowledge of cancer detection and prevention. Nurses and pharmacists exert great influence in the provision of health care. Yet, their training includes neither cancer education nor information about prevention. The medical and health-related educational system in Egypt has many limitations, but it has the structure and inherent ability to achieve cancer education goals.

THE IMMUNOGENICITY AND SAFETY OF A NOVEL STAPHYLOCOCCUS AUREUS VACCINE (V710) IN ADULTS WITH END-STAGE RENAL DISEASE RECEIVING HEMODIALYSIS -A PHASE IIA STUDY Moustafa Moustafa, John Buerkert, Tarek Sobeih, Claude Galphin, Gaspar Barreto-Torrella, George Aronoff, Jonathan Hartzel, Elizabeth Brown, Steven Smugar, Nicholas Kartsonis, Dalya Guris South Carolina Nephrology & Hypertension Center, Orangeburg, SC; Columbia Nephrology Associates, PA, Columbia, SC; Nephrology Associates, Chattanooga, TN; Nephrology Associates of South Miami PA, Miami, FL; University of Louisville, Louisville, KY; Merck Sharp & Dohme Corp., Whitehouse Station, NJ Patients with ESRD on hemodialysis are at increased risk for severe S. aureus infections, including septicemia. In Phase I studies, V710, a vaccine containing a surface protein (IsdB) was immunogenic after a single dose in healthy adults. This Phase II study was a randomized, double-blind, placebo-controlled study in adults aged 18-80 years with ESRD on hemodialysis (N=206 randomized, 201 vaccinated). Patients were randomized to receive V710 as a 60-μg dose (with or without adjuvant) or a 90-μg dose (with adjuvant) or placebo. Patients received two doses 28 days apart (V710/V710; V710/placebo; placebo/placebo), and a third dose at Day 180. Blood samples were collected at different intervals through Day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 doses of V710 would have a ≥2.5-fold rise in anti-IsdB IgG titers 28 days after the second dose (i.e., Day 56) compared to baseline. All 3 grou ps receiving 2 doses of V710 had significant increases of anti-IsdB titers (15.1-18.9-fold) from baseline (p