Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections.

Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus aureus infections. AB-SA01 contains three naturally occurring, obligately lytic myoviruses related to Staphylococcus phage K. AB-SA01 component phages have been sequenced and contain no identifiable bacterial virulence or antibiotic resistance genes. In vitro, AB-SA01 killed 94.5% of 401 clinical Staphylococcus aureus isolates, including methicillin-resistant and vancomycin-intermediate ones for a total of 95% of the 205 known multidrug-resistant isolates. The spontaneous frequency of resistance to AB-SA01 was ≤3 × 10-9, and resistance emerging to one component phage could be complemented by the activity of another component phage. In both neutropenic and immunocompetent mouse models of acute pneumonia, AB-SA01 reduced lung S. aureus populations equivalently to vancomycin. Overall, the inherent characteristics of AB-SA01 component phages meet regulatory and generally accepted criteria for human use, and the preclinical data presented here have supported production under good manufacturing practices and phase 1 clinical studies with AB-SA01.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Establishing an Integrated Health Care Clinic in a Community Mental Health Center: Lessons Learned.

Integrating primary care with behavioral health services at community mental health centers is one response to the disparity in mortality and morbidity experienced by adults with serious mental illnesses and co-occurring substance use disorders. Many integration models have been developed in response to the Primary and Behavioral Health Care Integration (PBHCI) initiative of the Substance Abuse and Mental Health Services Administration (SAMHSA). One model is a primary care clinic co-located within the mental health center. The Connecticut Mental Health Center (CMHC) Wellness Center is one such co-located clinic developed as a partnership between CMHC and a Federally Qualified Health Center (FQHC). In this article, we describe the process of developing this on-site clinic along with lessons learned during implementation. We review different aspects of building and maintaining such a clinic and outline lessons learned from both successes and challenges. We briefly describe the demographics and health characteristics of the patient population served in this clinic. We make recommendations for providers and agencies that are considering or are already developing a model for integrating care. Finally, we briefly review status of our clinic after completion of grant funding.

The Connecticut Latino Behavioral Health System: A culturally informed community-academic collaboration.

The Connecticut Latino Behavioral Health System (LBHS) represents a culturally informed community-academic collaboration that includes agencies focused on mental health, addictions, behavioral health within community health centers, and social rehabilitation; the Yale University Department of Psychiatry; and the Connecticut Department of Mental Health and Addiction Services. The core mission of the LBHS is to expand and enhance the provision of recovery-oriented, and culturally and linguistically appropriate, services to the monolingual Spanish-speaking community in parts of South Central Connecticut. This article outlines the rationale and need for such a collaboration to meet the needs of an underrepresented and underserved ethnic minority group. The process by which these entities came together to develop and successfully implement systemic strategies is described in the context of 2 overarching priorities: (a) workforce development, and (b) access to services. The authors also highlight lessons learned that have informed the decision-making process since the inception of the LBHS, and future directions to ensure that it is prepared to meet changing consumer needs and systemic priorities. (PsycINFO Database Record

High throughput peptide mass fingerprinting and protein macroarray analysis using chemical printing strategies.

We describe a chemical printer that uses piezoelectric pulsing for rapid, accurate, and non-contact microdispensing of fluid for proteomic analysis of immobilized protein macroarrays. We demonstrate protein digestion and peptide mass fingerprinting analysis of human plasma and platelet proteins direct from a membrane surface subsequent to defined microdispensing of trypsin and matrix solutions, hence bypassing multiple liquid-handling steps. Detection of low abundance, alkaline proteins from whole human platelet extracts has been highlighted. Membrane immobilization of protein permits archiving of samples pre-/post-analysis and provides a means for subanalysis using multiple chemistries. This study highlights the ability to increase sequence coverage for protein identification using multiple enzymes and to characterize N-glycosylation modifications using a combination of PNGase F and trypsin. We also demonstrate microdispensing of multiple serum samples in a quantitative microenzyme-linked immunosorbent assay format to rapidly screen protein macroarrays for pathogen-derived antigens. We anticipate the chemical printer will be a major component of proteomic platforms for high throughput protein identification and characterization with widespread applications in biomedical and diagnostic discovery.