Enhancing assertive community treatment with cognitive behavioral social skills training for schizophrenia: study protocol for a randomized controlled trial

BACKGROUND: Schizophrenia leads to profound disability in everyday functioning (e.g., difficulty finding and maintaining employment, housing, and personal relationships). Medications can effectively reduce positive symptoms (e.g., hallucinations and delusions), but they do not meaningfully improve daily life functioning. Psychosocial evidence-based practices (EBPs) improve functioning, but these EBPs are not available to most people with schizophrenia. The field must close the research and service delivery gap by adapting EBPs for schizophrenia to facilitate widespread implementation in community settings. Our hybrid effectiveness and implementation study represents an initiative to bridge this divide. In this study we will test whether an existing EBP (i.e., Cognitive Behavioral Social Skills Training (CBSST)) modified to work in practice settings (i.e., Assertive Community Treatment (ACT) teams) commonly available to persons with schizophrenia results in better consumer outcomes. We will also identify key factors relevant to developing future CBSST implementation strategies. METHODS/DESIGN: For the effectiveness study component, persons with schizophrenia will be recruited from existing publicly funded ACT teams operating in community settings. Participants will be randomized to one of the 2 treatments (ACT alone or ACT + Adapted CBSST) and followed longitudinally for 18 months with assessments every 18 weeks after baseline (5 in total). The primary outcome domain is psychosocial functioning (e.g., everyday living skills and activities related to employment, education, and housing) as measured by self-report, testing, and observation. Additional outcome domains of interest include mediators of change in functioning, symptoms, and quality of services. Primary analyses will be conducted using linear mixed-effects models for continuous data. The implementation study component consists of a structured, mixed qualitative-quantitative methodology (i.e., Concept Mapping) to characterize and assess the implementation experience from multiple stakeholder perspectives in order to inform future implementation initiatives. DISCUSSION: Adapting CBSST to fit into the ACT service delivery context found throughout the United States creates an opportunity to substantially increase the number of persons with schizophrenia who could have access to and benefit from EBPs. As part of the implementation learning process training materials and treatment workbooks have been revised to promote easier use of CBSST in the context of brief community-based ACT visits. TRIAL REGISTRATION: ClinicalTrials.gov NCT02254733. Date of registration: 25 April 2014

Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches

BACKGROUND: Emerging animal and zoonotic diseases and increasing international trade have resulted in an increased demand for veterinary surveillance systems. However, human and financial resources available to support government veterinary services are becoming more and more limited in many countries world-wide. Intuitively, issues that present higher risks merit higher priority for surveillance resources as investments will yield higher benefit-cost ratios. The rapid rate of acceptance of this core concept of risk-based surveillance has outpaced the development of its theoretical and practical bases. DISCUSSION: The principal objectives of risk-based veterinary surveillance are to identify surveillance needs to protect the health of livestock and consumers, to set priorities, and to allocate resources effectively and efficiently. An important goal is to achieve a higher benefit-cost ratio with existing or reduced resources. We propose to define risk-based surveillance systems as those that apply risk assessment methods in different steps of traditional surveillance design for early detection and management of diseases or hazards. In risk-based designs, public health, economic and trade consequences of diseases play an important role in selection of diseases or hazards. Furthermore, certain strata of the population of interest have a higher probability to be sampled for detection of diseases or hazards. Evaluation of risk-based surveillance systems shall prove that the efficacy of risk-based systems is equal or higher than traditional systems; however, the efficiency (benefit-cost ratio) shall be higher in risk-based surveillance systems. SUMMARY: Risk-based surveillance considerations are useful to support both strategic and operational decision making. This article highlights applications of risk-based surveillance systems in the veterinary field including food safety. Examples are provided for risk-based hazard selection, risk-based selection of sampling strata as well as sample size calculation based on risk considerations

Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas aeruginosa through Tyrosine Phosphatase TpbA (PA3885)

With the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing based on homoserine lactones was found to influence biofilm formation. Here we discern a mechanism by which quorum sensing controls biofilm formation by screening 5850 transposon mutants of P. aeruginosa PA14 for altered biofilm formation. This screen identified the PA3885 mutant, which had 147-fold more biofilm than the wild-type strain. Loss of PA3885 decreased swimming, abolished swarming, and increased attachment, although this did not affect production of rhamnolipids. The PA3885 mutant also had a wrinkly colony phenotype, formed pronounced pellicles, had substantially more aggregation, and had 28-fold more exopolysaccharide production. Expression of PA3885 in trans reduced biofilm formation and abolished aggregation. Whole transcriptome analysis showed that loss of PA3885 activated expression of the pel locus, an operon that encodes for the synthesis of extracellular matrix polysaccharide. Genetic screening identified that loss of PelABDEG and the PA1120 protein (which contains a GGDEF-motif) suppressed the phenotypes of the PA3885 mutant, suggesting that the function of the PA3885 protein is to regulate 3,5-cyclic diguanylic acid (c-di-GMP) concentrations as a phosphatase since c-di-GMP enhances biofilm formation by activating PelD, and c-di-GMP inhibits swarming. Loss of PA3885 protein increased cellular c-di-GMP concentrations; hence, PA3885 protein is a negative regulator of c-di-GMP production. Purified PA3885 protein has phosphatase activity against phosphotyrosine peptides and is translocated to the periplasm. Las-mediated quorum sensing positively regulates expression of the PA3885 gene. These results show that the PA3885 protein responds to AHL signals and likely dephosphorylates PA1120, which leads to reduced c-di-GMP production. This inhibits matrix exopolysaccharide formation, which leads to reduced biofilm formation; hence, we provide a mechanism for quorum sensing control of biofilm formation through the pel locus and suggest PA3885 should be named TpbA for tyrosine phosphatase related to biofilm formation and PA1120 should be TpbB

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions

Efficacy of Bupropion for Relapse Prevention in Smokers With and Without a Past History of Major Depression

BACKGROUND: This study evaluated the efficacy of bupropion for relapse prevention in smokers with and without a past history of major depressive disorder. Changes in depressive symptoms were also examined. DESIGN: Data were gathered prospectively from a randomized, double-blind relapse prevention trial of bupropion conducted at five study sites. A total of 784 smokers (54% female, 97% white) were enrolled. Using the Structured Clinical Interview for Depression, 17% of the subjects reported a past history of major depressive disorder at baseline. All subjects received open-label bupropion SR (300 mg/d) for 7 weeks. Subjects abstinent from smoking at the end of 7 weeks (N= 429) were randomized to bupropion SR (300 mg/d) or placebo for the remainder of the year and followed for 1 year off medication. The primary outcome measures were median time to relapse to smoking and the 7-day point-prevalence smoking abstinence rate. Self-reported abstinence from smoking was verified by expired air carbon monoxide. The Beck Depression Inventory was used to assess depressive symptoms at baseline and at weeks 8 and 12. RESULTS: Median time to relapse did not differ by past history of major depressive disorder. Bupropion was associated with higher point-prevalence smoking abstinence at the end of medication compared to placebo (P= .007), independent of a past history of major depressive disorder. Moreover, change in depressive symptoms during the double-blind phase did not differ for those with and without a past history of major depressive disorder. CONCLUSIONS: Extended use of bupropion for relapse prevention is effective for smokers with and without a history of major depression