433 research outputs found

    Analyzing The Impact Of Social Factors On Homelessness: A Fuzzy Cognitive Map Approach

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    Background The forces which affect homelessness are complex and often interactive in nature. Social forces such as addictions, family breakdown, and mental illness are compounded by structural forces such as lack of available low-cost housing, poor economic conditions, and insufficient mental health services. Together these factors impact levels of homelessness through their dynamic relations. Historic models, which are static in nature, have only been marginally successful in capturing these relationships. Methods Fuzzy Logic (FL) and fuzzy cognitive maps (FCMs) are particularly suited to the modeling of complex social problems, such as homelessness, due to their inherent ability to model intricate, interactive systems often described in vague conceptual terms and then organize them into a specific, concrete form (i.e., the FCM) which can be readily understood by social scientists and others. Using FL we converted information, taken from recently published, peer reviewed articles, for a select group of factors related to homelessness and then calculated the strength of influence (weights) for pairs of factors. We then used these weighted relationships in a FCM to test the effects of increasing or decreasing individual or groups of factors. Results of these trials were explainable according to current empirical knowledge related to homelessness. Results Prior graphic maps of homelessness have been of limited use due to the dynamic nature of the concepts related to homelessness. The FCM technique captures greater degrees of dynamism and complexity than static models, allowing relevant concepts to be manipulated and interacted. This, in turn, allows for a much more realistic picture of homelessness. Through network analysis of the FCM we determined that Education exerts the greatest force in the model and hence impacts the dynamism and complexity of a social problem such as homelessness. Conclusions The FCM built to model the complex social system of homelessness reasonably represented reality for the sample scenarios created. This confirmed that the model worked and that a search of peer reviewed, academic literature is a reasonable foundation upon which to build the model. Further, it was determined that the direction and strengths of relationships between concepts included in this map are a reasonable approximation of their action in reality. However, dynamic models are not without their limitations and must be acknowledged as inherently exploratory

    A phase I dose-escalation study of MEDI-575, a PDGFRα monoclonal antibody, in adults with advanced solid tumors

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    PURPOSE: The purpose of the study was to evaluate safety and determine the maximum tolerated dose (MTD) of MEDI-575, a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor-α (PDGFRα), in patients with advanced solid tumors. METHODS: This phase I multicenter, open-label, single-arm study enrolled adults in a 3 + 3 dose escalation design to receive MEDI-575 (3, 6, 9, 12, or 15 mg/kg) once weekly (QW) until toxicity or disease progression occurred. One 0.5-mg/kg dose was given before the first dose in the 3-mg/kg cohort to determine pharmacokinetics (PK) and pharmacodynamics under unsaturated conditions. After completion of dose escalation in the QW cohorts, patients were enrolled in two additional cohorts and received MEDI-575 25 or 35 mg/kg every 3 weeks (Q3W). Secondary measures included assessments of PK, immunogenicity, and antitumor activity. RESULTS: A total of 35 patients received MEDI-575 QW (n = 23) or Q3W (n = 12). Most treatment-related adverse events were grade 1 or 2 in severity across all dose levels, with fatigue (n = 12) and nausea (n = 8) being reported most frequently. With no reports of dose-limiting toxicities (DLTs), the MTD was not reached. MEDI-575 exhibited a nonlinear PK profile and increased plasma platelet-derived growth factor-AA levels in a dose-dependent manner with limited immunogenicity. Stable disease was reported as the best tumor response in 9 of 29 evaluable patients; however, no objective responses were reported. CONCLUSION: Administration of MEDI-575 QW or Q3W resulted in a favorable safety profile, including a lack of DLTs, but without evidence of antitumor activity in patients with refractory solid tumors

    Toward Evaluation of Disseminated Effects of Medications for Opioid Use Disorder within Provider-Based Clusters Using Routinely-Collected Health Data

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    Routinely-collected health data can be employed to emulate a target trial when randomized trial data are not available. Patients within provider-based clusters likely exert and share influence on each other’s treatment preferences and subsequent health outcomes and this is known as dissemination or spillover. Extending a framework to replicate an idealized two-stage randomized trial using routinely-collected health data, an evaluation of disseminated effects within provider-based clusters is possible. In this paper, we propose a novel application of causal inference methods for dissemination to retrospective cohort studies in administrative claims data and evaluate the impact of the normality of the random effects distribution for the cluster-level propensity score on estimation of the causal parameters. An extensive simulation study was conducted to study the robustness of the methods under different distributions of the random effects. We applied these methods to evaluate baseline prescription for medications for opioid use disorder among a cohort of patients diagnosed opioid use disorder and adjust for baseline confounders using information obtained from an administrative claims database. We discuss future research directions in this setting to better address unmeasured confounding in the presence of disseminated effects

    GaPP: a pilot randomised controlled trial of the efficacy of action of gabapentin for the management of chronic pelvic pain in women: study protocol

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    <p><b>Introduction:</b> Chronic pelvic pain (CPP) affects >1 million UK women. Annual healthcare costs are estimated at >£150 million. Proven interventions for CPP are limited, and treatment is often unsatisfactory. Gabapentin is increasingly prescribed due to reports of effectiveness in other chronic pain conditions, but there are insufficient data supporting value in CPP specifically. The mechanism by which gabapentin exerts its analgesic action is unknown. Given the prevalence and costs of CPP, the authors believe that a large, multicentre, placebo-controlled, double-blind randomised controlled trial to evaluate the efficacy of gabapentin in management of CPP is required. The focus of this study is a pilot to inform planning of a future randomised controlled trial.</p> <p><b>Methods and analysis:</b> The authors plan to perform a two-arm, parallel, randomised controlled pilot trial. The authors aim to recruit 60 women with CPP in NHS Lothian and NHS Grampian (UK) and randomise them to gabapentin or placebo. Response to treatment will be monitored by questionnaire compared at 0, 3 and 6 months. The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness and acceptability to participants of the proposed methods of recruitment, randomisation, drug treatments and assessment tools and to perform a pretrial cost-effectiveness assessment of treatment with gabapentin.</p> <p><b>Ethics and dissemination:</b> Ethical approval has been obtained from the Scotland A Research Ethics Committee (LREC 12/SS/0005). Data will be presented at international conferences and published in peer-reviewed journals.</p&gt

    Automated detection and tracking of marine mammals : a novel sonar tool for monitoring effects of marine industry

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    Funding: The work was funded under the Scottish Government Demonstration Strategy (Project no. USA/010/14)and as part of the Department of Energy and Climate Change’s Offshore Energy Strategic Environmental Assessment programme, with additional resources from the Natural Environment Research Council (grant numbers: NE/R014639/1 and SMRU1001).1. Many marine industries may pose acute risks to marine wildlife. For example, tidal turbines have the potential to injure or kill marine mammals through collisions with turbine blades. However, the quantification of collision risk is currently limited by a lack of suitable technologies to collect long‐term data on marine mammal behaviour around tidal turbines. 2. Sonar provides a potential means of tracking marine mammals around tidal turbines. However, its effectiveness for long‐term data collection is hindered by the large data volumes and the need for manual validation of detections. Therefore, the aim here was to develop and test automated classification algorithms for marine mammals in sonar data. 3. Data on the movements of harbour seals were collected in a tidally energetic environment using a high‐frequency multibeam sonar on a custom designed seabed‐mounted platform. The study area was monitored by observers to provide visual validation of seals and other targets detected by the sonar. 4. Sixty‐five confirmed seals and 96 other targets were detected by the sonar. Movement and shape parameters associated with each target were extracted and used to develop a series of classification algorithms. Kernel support vector machines were used to classify targets (seal vs. nonseal) and cross‐validation analyses were carried out to quantify classifier efficiency. 5. The best‐fit kernel support vector machine correctly classified all the confirmed seals but misclassified a small percentage of non‐seal targets (~8%) as seals. Shape and non‐spectral movement parameters were considered to be the most important in achieving successful classification. 6. Results indicate that sonar is an effective method for detecting and tracking seals in tidal environments, and the automated classification approach developed here provides a key tool that could be applied to collecting long‐term behavioural data around anthropogenic activities such as tidal turbines.PostprintPeer reviewe

    Developmental Evaluation of the CHOICE+ Champion Training Program

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    Context: Mealtimes in residential care homes are important for social engagement and can encourage resident relationships. Yet, training programs to improve mealtime care practices in residential care settings remain limited in learning approaches and scope. Objectives: To determine whether a one-day Champion Training session would improve participants’ knowledge, skills, and confidence to implement a relationship-centred mealtime program (CHOICE+) in their homes. Methods: The study employed a pre-/post-test design to evaluate a train-the-trainer model using paper-based questionnaires. Thirty-four participants attended the training session; 25 participants completed pre/post training questionnaires based on Kirkpatrick’s evaluation model. Training included: 1) program implementation manual, 2) best-practices document, 3) educational resources and evaluation tools, 4) presentation on theory-based implementation strategies and behaviour change techniques, and 5) group discussion on applying strategies and techniques, problem-solving for implementation facilitators and barriers. Findings: More than half of attendees worked as Food Service Managers or Registered Dietitians. Participants identified several organizational factors that could impact their home’s readiness to implement CHOICE+, though they felt training to be acceptable and feasible for their homes. Participants reported increase in knowledge (8.4 ± 1.1), confidence (8.3 ± 1.4), and commitment (8.8 ± 1.4) to implement the relationship-centred mealtime program. There was no association with pre-training readiness, leadership, or home characteristics. Limitations: Generalizability is limited due to small sample size. Follow-up interviews on results of training could not be conducted due COVID-19 pandemic research restrictions. Implications: Champion Leader training is an effective and feasible learning approach to up-skill staff on change management and relationship-centred mealtime practices in residential care

    Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

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    BackgroundRecurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population.Methods/designIn this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care.DiscussionIf this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings.Trial registrationClinicalTrials.gov Identifier NCT01763203

    Has increased clinical experience with methotrexate reduced the direct costs of medical management of ectopic pregnancy compared to surgery?

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    <p>Abstract</p> <p>Background</p> <p>There is a debate about the cost-efficiency of methotrexate for the management of ectopic pregnancy (EP), especially for patients presenting with serum human chorionic gonadotrophin levels of >1500 IU/L. We hypothesised that further experience with methotrexate, and increased use of guideline-based protocols, has reduced the direct costs of management with methotrexate.</p> <p>Methods</p> <p>We conducted a retrospective cost analysis on women treated for EP in a large UK teaching hospital to (1) investigate whether the cost of medical management is less expensive than surgical management for those patients eligible for both treatments and (2) to compare the cost of medical management for women with hCG concentrations 1500–3000 IU/L against those with similar hCG concentrations that elected for surgery. Three distinct treatment groups were identified: (1) those who had initial medical management with methotrexate, (2) those who were eligible for initial medical management but chose surgery (‘elected’ surgery) and (3) those who initially ‘required’ surgery and did not meet the eligibility criteria for methotrexate. We calculated the costs from the point of view of the National Health Service (NHS) in the UK. We summarised the cost per study group using the mean, standard deviation, median and range and, to account for the skewed nature of the data, we calculated 95% confidence intervals for differential costs using the nonparametric bootstrap method.</p> <p>Results</p> <p>Methotrexate was £1179 (CI 819–1550) per patient cheaper than surgery but there were no significant savings with methotrexate in women with hCG >1500 IU/L due to treatment failures.</p> <p>Conclusions</p> <p>Our data support an ongoing unmet economic need for better medical treatments for EP with hCG >1500 IU/L.</p

    MSH2 and MSH6 in mismatch repair system account for soybean (Glycine max (L.) Merr.) tolerance to cadmium Toxicity by determining DNA damage response

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    Our aim was to investigate DNA mismatch repair (MMR) genes regulating cadmium tolerance in two soybean cultivars. Cultivars Liaodou 10 (LD10, Cd-sensitive) and Shennong 20 (SN20, Cd-tolerant) seedlings were grown hydroponically on Murashige and Skoog (MS) media containing 0–2.5 mg·L–1 Cd for 4 days. Cd stress induced less random amplified polymorphism DNA (RAPD) polymorphism in LD10 than in SN20 roots, causing G1/S arrest in LD10 and G2/M arrest in SN20 roots. Virus-induced gene silencing (VIGS) of MLH1 in LD10-TRV-MLH1 plantlets showed markedly diminished G1/S arrest but enhanced root length/area under Cd stress. However, an increase in G1/S arrest and reduction of G2/M arrest occurred in SN20-TRV-MSH2 and SN20-TRV-MSH6 plantlets with decreased root length/area under Cd stress. Taken together, we conclude that the low expression of MSH2 and MSH6, involved in the G2/M arrest, results in Cd-induced DNA damage recognition bypassing the MMR system to activate G1/S arrest with the assistance of MLH1. This then leads to repressed root growth in LD10, explaining the intervarietal difference in Cd tolerance in soybean

    Gabapentin for the Management of Chronic Pelvic Pain in Women (GaPP1): A Pilot Randomised Controlled Trial

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    Chronic pelvic pain (CPP) affects 2.1–24% of women. Frequently, no underlying pathology is identified, and the pain is difficult to manage. Gabapentin is prescribed for CPP despite no robust evidence of efficacy. We performed a pilot trial in two UK centres to inform the planning of a future multicentre RCT to evaluate gabapentin in CPP management. Our primary objective was to determine levels of participant recruitment and retention. Secondary objectives included estimating potential effectiveness, acceptability to participants of trial methodology, and cost-effectiveness of gabapentin. Women with CPP and no obvious pelvic pathology were assigned to an increasing regimen of gabapentin (300-2700mg daily) or placebo. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to six months. The analyses by treatment group were by intention-to-treat. Interviews were conducted to evaluate women’s experiences of the trial. A probabilistic decision analytical model was used to estimate cost-effectiveness. Between September 2012–2013, 47 women (34% of those eligible) were randomised (22 to gabapentin, 25 to placebo), and 25 (53%) completed six-month follow-up. Participants on gabapentin had less pain (BPI difference 1.72 points, 95% CI:0.07–3.36), and an improvement in mood (HADS difference 4.35 points, 95% CI:1.97–6.73) at six months than those allocated placebo. The majority of participants described their trial experience favorably. At the UK threshold for willingness-to-pay, the probabilities of gabapentin or no treatment being cost-effective are similar. A pilot trial assessing gabapentin for CPP was feasible, but uncertainty remains, highlighting the need for a large definitive trial
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