EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series

<p>Abstract</p> <p>Background</p> <p>This paper presents a case study that demonstrates the evolution of a project entitled "Enhancing QUality-of-care In Psychosis" (EQUIP) that began approximately when the U.S. Department of Veterans Affairs' Quality Enhancement Research Initiative (QUERI), and implementation science were emerging. EQUIP developed methods and tools to implement chronic illness care principles in the treatment of schizophrenia, and evaluated this implementation using a small-scale controlled trial. The next iteration of the project, EQUIP-2, was further informed by implementation science and the use of QUERI tools.</p> <p>Methods</p> <p>This paper reports the background, development, results and implications of EQUIP, and also describes ongoing work in the second phase of the project (EQUIP-2). The EQUIP intervention uses implementation strategies and tools to increase the adoption and implementation of chronic illness care principles. In EQUIP-2, these strategies and tools are conceptually grounded in a stages-of-change model, and include clinical and delivery system interventions and adoption/implementation tools. Formative evaluation occurs in conjunction with the intervention, and includes developmental, progress-focused, implementation-focused, and interpretive evaluation.</p> <p>Results</p> <p>Evaluation of EQUIP provided an understanding of quality gaps <it>and </it>how to address related problems in schizophrenia. EQUIP showed that solutions to quality problems in schizophrenia differ by treatment domain and are exacerbated by a lack of awareness of evidence-based practices. EQUIP also showed that improving care requires creating resources for physicians to help them easily implement practice changes, plus intensive education as well as product champions who help physicians use these resources. Organizational changes, such as the addition of care managers and informatics systems, were shown to help physicians with identifying problems, making referrals, and monitoring follow-up. In EQUIP-2, which is currently in progress, these initial findings were used to develop a more comprehensive approach to implementing and evaluating the chronic illness care model.</p> <p>Discussion</p> <p>In QUERI, small-scale projects contribute to the development and enhancement of hands-on, action-oriented service-directed projects that are grounded in current implementation science. This project supports the concept that QUERI tools can be useful in implementing complex care models oriented toward evidence-based improvement of clinical care.</p

Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

How and When Socially Entrepreneurial Nonprofit Organizations Benefit From Adopting Social Alliance Management Routines to Manage Social Alliances?

Social alliance is defined as the collaboration between for-profit and nonprofit organizations. Building on the insights derived from the resource-based theory, we develop a conceptual framework to explain how socially entrepreneurial nonprofit organizations (SENPOs) can improve their social alliance performance by adopting strategic alliance management routines. We test our framework using the data collected from 203 UK-based SENPOs in the context of cause-related marketing campaign-derived social alliances. Our results confirm a positive relationship between social alliance management routines and social alliance performance. We also find that relational mechanisms, such as mutual trust, relational embeddedness, and relational commitment, mediate the relationship between social alliance management routines and social alliance performance. Moreover, our findings suggest that different types of social alliance motivation can influence the impact of social alliance management routines on different types of the relational mechanisms. In general, we demonstrate that SENPOs can benefit from adopting social alliance management routines and, in addition, highlight how and when the social alliance management routines–social alliance performance relationship might be shaped. Our study offers important academic and managerial implications, and points out future research directions

Comparison of results from tests of association in unrelated individuals with uncollapsed and collapsed sequence variants using tiled regression

Tiled regression is an approach designed to determine the set of independent genetic variants that contribute to the variation of a quantitative trait in the presence of many highly correlated variants. In this study, we evaluate the statistical properties of the tiled regression method using the Genetic Analysis Workshop 17 data in unrelated individuals for traits Q1, Q2, and Q4. To increase the power to detect rare variants, we use two methods to collapse rare variants and compare the results with those from the uncollapsed data. In addition, we compare the tiled regression method to traditional tests of association with and without collapsed rare variants. The results show that collapsing rare variants generally improves the power to detect associations regardless of method, although only variants with the largest allelic effects could be detected. However, for traditional simple linear regression, the average estimated type I error is dependent on the trait and varies by about three orders of magnitude. The estimated type I error rate is stable for tiled regression across traits

Humanized Mouse Model of Ovarian Cancer Recapitulates Patient Solid Tumor Progression, Ascites Formation, and Metastasis

Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγnull (NSG) mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts) i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma

Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year prospective observational study

<p>Abstract</p> <p>Background</p> <p>This study of chronically ill patients with schizophrenia aimed to identify patients who achieve sustained favorable long-term outcome - when the outcome incorporates severity of symptoms, level of functioning, and use of acute care services - and to identify the best baseline predictors of achieving this sustained favorable long-term outcome.</p> <p>Methods</p> <p>Using data from the United States Schizophrenia Care and Assessment Program (US-SCAP) (N = 2327), a large 3-year prospective, multisite, observational study of individuals treated for schizophrenia in the US, a hierarchical cluster analysis was performed to group patients based upon baseline symptom severity. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) scores, level of functioning, and use of acute care services. Level of functioning reflected patient-reported productivity and clinician-rated occupational role functioning. Use of acute care services reflected self-reported psychiatric hospitalization and emergency service use. Change of health state was determined over the 3-year period. A patient was classified as having a sustained favorable long-term outcome if their health state values had the closest distance to the defined "best baseline cluster" at each point over the length of the study. Stepwise logistic regression was used to determine baseline predictors of sustained favorable long-term outcome.</p> <p>Results</p> <p>At baseline, 5 distinct health state clusters were identified, ranging from "best" to "worst." Of 1635 patients with sufficient data, only 157 (10%) experienced sustained favorable long-term outcome during the 2-years postbaseline. The baseline predictors associated with sustained favorable long-term outcome included better quality of life, more daily activities, patient-reported clearer thinking from medication, better global functioning, being employed, not being a victim of a crime, not having received individual therapy, and not having received help with shopping and leisure activities.</p> <p>Conclusions</p> <p>Only a small percentage of patients achieved sustained favorable long-term outcome in this study, suggesting there continues to be a great need for improvement in the treatment of schizophrenia. Findings suggest that clinicians could make early projections of health states and identify those patients more likely to achieve favorable long-term outcomes enabling early therapeutic interventions to enhance benefits for patients.</p

Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005

<p>Abstract</p> <p>Background</p> <p>Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.</p> <p>Methods</p> <p>A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005.</p> <p>Results</p> <p>Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.</p> <p>Conclusion</p> <p>The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.</p

Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers

BACKGROUND: We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. METHODS: Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. RESULTS: A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. CONCLUSIONS: These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis