Unintended consequences of reducing QT-alert overload in a computerized physician order entry system

Purpose: After complaints of too many low-specificity drug-drug interaction (DDI) alerts on QT prolongation, the rules for QT alerting in the Dutch national drug database were restricted in 2007 to obviously QT-prolonging drugs. The aim of this virtual study was to investigate whether this adjustment would improve the identification of patients at risk of developing Torsades de Pointes (TdP) due to QT-prolonging drug combinations in a computerized physician order entry system (CPOE) and whether these new rules should be implemented. Methods: During a half-year study period, inpatients with overridden DDI alerts regarding QT prolongation and with an electrocardiogram recorded before and within 1 month of the alert override were included if they did not have a ventricular pacemaker and did not use the low-risk combination cotrimoxazole and tacrolimus. QT-interval prolongation and the risk of developing TdP were calculated for all patients and related to the number of patients for whom a QT-alert would be generated in the new situation with the restricted database. Results: Forty-nine patients (13%) met the inclusion criteria. In this study population, knowledge base-adjustment would reduce the number of alerts by 53%. However, the positive predictive value of QT alerts would not change (31% before and 30% after) and only 47% of the patients at risk of developing TdP would be identified in CPOEs using the adjusted knowledge base. Conclusion: The new rules for QT alerting would result in a poorer identification of patients at risk of developing TdP than the old rules. This is caused by the many non-drug-related risk factors for QT prolongation not being incorporated in CPOE alert generation. The partial contribution of all risk factors should be studied and used to create clinical rules for QT alerting with an acceptable positive predictive value

Struggles over access to the Muslim public sphere: Multiple publics and discourses on agency, belonging and citizenship (Introduction to the Themed Section)

Abstract This introductory essay provides the context for the articles in this Themed Section. Despite the diversity in locations, historical backgrounds and contemporary processes of change, all contributors to this Themed Section focus on the struggle of Muslim groups over access to an emergent Muslim public sphere. They highlight the contestations of and shifts in the notions of agency, belonging, and citizenship in nation-states with Muslim communities within its borders. The introduction consists of two parts. The first part reviews the notion of the public sphere as conceptualized by Habermas and critiqued by scholars of a diversity of backgrounds. In relation to the concept of the Muslim public sphere, three aspects of critique are given closer c

A System Dynamics Approach for Hospital Waste Management in a City in a Developing Country: The Case of Nablus, Palestine

Hospitals and health centers provide a variety of healthcare services and normally generate hazardous waste as well as general waste. General waste has a similar nature to that of municipal solid waste and therefore could be disposed of in municipal landfills. However, hazardous waste poses risks to public health, unless it is properly managed. The hospital waste management system encompasses many factors, i.e., number of beds, number of employees, level of service, population, birth rate, fertility rate, and not in my back yard (NIMBY) syndrome. Therefore, this management system requires a comprehensive analysis to determine the role of each factor and its influence on the whole system. In this research, a hospital waste management simulation model is presented based on the system dynamics technique to determine the interaction among these factors in the system using a software package, ithink. This model is used to estimate waste segregation as this is important in the hospital waste management system to minimize risk to public health. Real data has been obtained from a case study of the city of Nablus, Palestine to validate the model. The model exhibits wastes generated from three types of hospitals (private, charitable, and government) by considering the number of both inpatients and outpatients depending on the population of the city under study. The model also offers the facility to compare the total waste generated among these different types of hospitals and anticipate and predict the future generated waste both infectious and non-infectious and the treatment cost incurred

An Integrated Decision Making Approach for Adaptive Shared Control of Mobility Assistance Robots

© 2016, Springer Science+Business Media Dordrecht. Mobility assistance robots provide support to elderly or patients during walking. The design of a safe and intuitive assistance behavior is one of the major challenges in this context. We present an integrated approach for the context-specific, on-line adaptation of the assistance level of a rollator-type mobility assistance robot by gain-scheduling of low-level robot control parameters. A human-inspired decision-making model, the drift-diffusion Model, is introduced as the key principle to gain-schedule parameters and with this to adapt the provided robot assistance in order to achieve a human-like assistive behavior. The mobility assistance robot is designed to provide (a) cognitive assistance to help the user following a desired path towards a predefined destination as well as (b) sensorial assistance to avoid collisions with obstacles while allowing for an intentional approach of them. Further, the robot observes the user long-term performance and fatigue to adapt the overall level of (c) physical assistance provided. For each type of assistance a decision-making problem is formulated that affects different low-level control parameters. The effectiveness of the proposed approach is demonstrated in technical validation experiments. Moreover, the proposed approach is evaluated in a user study with 35 elderly persons. Obtained results indicate that the proposed gain-scheduling technique incorporating ideas of human decision-making models shows a general high potential for the application in adaptive shared control of mobility assistance robots

Empiric Antibiotic Therapy for Staphylococcus aureus Bacteremia May Not Reduce In-Hospital Mortality: A Retrospective Cohort Study

Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence factors in the infecting strain.We conducted a retrospective cohort study of adult patients admitted to a tertiary-care facility from January 1, 2003 to June 30, 2007, who had S. aureus bacteremia. Time to appropriate therapy was measured from blood culture collection to the receipt of antibiotics with in vitro activity to the infecting organism. Cox proportional hazard models were used to measure the association between receipt of appropriate empiric therapy and in-hospital mortality, statistically adjusting for patient and pathogen characteristics.Among 814 admissions, 537 (66%) received appropriate empiric therapy. Those who received appropriate empiric therapy had a higher hazard of 30-day in-hospital mortality (Hazard Ratio (HR): 1.52; 95% confidence interval (CI): 0.99, 2.34). A longer time to appropriate therapy was protective against mortality (HR: 0.79; 95% CI: 0.60, 1.03) except among the healthiest quartile of patients (HR: 1.44; 95% CI: 0.66, 3.15).Appropriate empiric therapy was not associated with decreased mortality in patients with S. aureus bacteremia except in the least ill patients. Initial broad antibiotic selection may not be widely beneficial

In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

<p>Abstract</p> <p>Background</p> <p>Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer.</p> <p>Methods</p> <p>Anaesthetized CD rats were mechanically ventilated and 10⁶human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection.</p> <p>Results</p> <p>After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p < 0.05). The same degree of impairment was achieved by inhibition of P- and L-selectins via animal treatment with fucoidan (p < 0.05) and also by inhibition of the Thomson-Friedenreich (TF)-antigen (p < 0.05).</p> <p>Conclusions</p> <p>These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.</p

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance

Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral). Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. The study presented here is designed to inform about people's perceptions regarding cholera and about socioeconomic and behavioural factors determining anticipated and actual oral cholera vaccine acceptance in Zanzibar. Its pre- and post-intervention design using a mixed-methods approach on different stakeholder levels in communities at high risk of cholera outbreaks will ensure the collection of locally valid data relevant for public health action and planning

Methods for evaluating delivery systems for scaling-up malaria control intervention

BACKGROUND: Despite increased resources over the past few years the coverage of malaria control interventions is still inadequate to reach national and international targets and achieve the full potential of the interventions to improve population health. One of the reasons for this inadequate coverage of efficacious interventions is the limited understanding of the optimum delivery systems of the interventions in different contexts. Although there have been debates about how to deliver interventions, the methods for evaluating the effectiveness of different delivery systems have rarely been discussed. Delivery of interventions is relatively complex and a thorough evaluation would need to look holistically at multiple steps in the delivery process and at multiple factors influencing the process. A better understanding of the strength of the evidence on delivery system effectiveness is needed in order to optimise delivery of efficacious interventions. METHODS: A literature review was conducted of methods used to evaluate delivery systems for insecticide treated nets, intermittent preventive treatment in pregnant women, and treatment for malaria in children. RESULTS: The methodology of delivery system evaluations varied. There were inconsistencies between objectives and methods of the evaluations including inappropriate outcome measures and unnecessary controls. There were few examples where the delivery processes were adequately described, or measured. We propose a cross sectional observational study design with attribution of the outcomes to a specific delivery system as an appropriate method for evaluating delivery systems at scale. CONCLUSIONS: The proposed evaluation framework is adaptable to natural experiments at scale, and can be applied using data from routine surveys such as the Demographic and Health Surveys, modified by the addition of one to two questions for each intervention. This framework has the potential to enable wider application of rigorous evaluations and thereby improve the evidence base on which decisions about delivery systems for malaria control and other public health interventions are taken