Safety-critical medical device development using the UPP2SF model translation tool

Software-based control of life-critical embedded systems has become increasingly complex, and to a large extent has come to determine the safety of the human being. For example, implantable cardiac pacemakers have over 80,000 lines of code which are responsible for maintaining the heart within safe operating limits. As firmware-related recalls accounted for over 41% of the 600,000 devices recalled in the last decade, there is a need for rigorous model-driven design tools to generate verified code from verified software models. To this effect, we have developed the UPP2SF model-translation tool, which facilitates automatic conversion of verified models (in UPPAAL) to models that may be simulated and tested (in Simulink/Stateflow). We describe the translation rules that ensure correct model conversion, applicable to a large class of models. We demonstrate how UPP2SF is used in themodel-driven design of a pacemaker whosemodel is (a) designed and verified in UPPAAL (using timed automata), (b) automatically translated to Stateflow for simulation-based testing, and then (c) automatically generated into modular code for hardware-level integration testing of timing-related errors. In addition, we show how UPP2SF may be used for worst-case execution time estimation early in the design stage. Using UPP2SF, we demonstrate the value of integrated end-to-end modeling, verification, code-generation and testing process for complex software-controlled embedded systems. © 2014 ACM.

Implant healing in experimental animal models of diabetes.

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices.

The Barriers to the Integration of the Uterine Balloon Tamponade into South Africa and Ghana's Health Systems for the Management of Postpartum Hemorrhage

Background

Postpartum hemorrhage is the most significant contributor to maternal mortality globally, claiming 140,000 lives annually. Postpartum hemorrhage is a leading cause of maternal death in South Africa, with the literature indicating that 80 percent of the postpartum hemorrhage deaths in South Africa are avoidable. Ghana, as of 2010, witnesses 2700 maternal deaths annually, primarily because of poor quality of care in health facilities and services being difficult to access. As per WHO recommendations, uterotonics are integral to treating postpartum hemorrhage as soon as it is diagnosed. In case of persistent bleeding or limited availability of uterotonics, the uterine balloon tamponade (UBT) can be used as a second line of defense. If both these measures are unable to counter the bleeding, providers must perform surgical interventions. Literature on the UBT, as one tool in the protocol to address postpartum hemorrhage, has shown it to have success rates ranging from 60 to 100 percent. Despite the potential to lower the number of postpartum hemorrhage deaths in South Africa and Ghana, the UBT has not been incorporated widely in South Africa and Ghana. The aim of this study is to describe the barriers involved with integrating the UBT into South Africa and Ghana’s health systems to address postpartum hemorrhage.

Methods

The study took place in multiple sites in South Africa (Cape Town, Johannesburg, Durban and Mpumalanga) and in Accra, Ghana. South Africa and Ghana were selected because postpartum hemorrhage contributes greatly to their maternal mortality numbers and there is potential in both countries to lower those rates through greater use of the UBT. A total of 25 participants were interviewed through purposive sampling, snowball sampling and participant referrals, and included various categories of stakeholders integral to the integration process of a medical device. Individual in-depth interviews were used for data collection, with interview questions being tailored to each stakeholder category. The focus of the interviews was on the protocol used to counter postpartum hemorrhage, the frequency with which the UBT is used as part of the protocol, and the process of integrating it into the South Africa and Ghana’s health systems. The data collected were coded using NVivo and analyzed using content analysis.

Results

The barriers to integration of the uterine balloon tamponade to address postpartum hemorrhage in South Africa and Ghana were evident on the political, economic and health delivery levels. The results indicated that the barriers to integration in South Africa included the low recognition of postpartum hemorrhage as a problem, the lack of clarity surrounding the role of the Medicines Control Council as a regulatory body for medical devices, and low awareness of the UBT as an intervention to control postpartum hemorrhage. The barriers in Ghana were the cash constraints experienced by the Ghana Health Services to fund medical devices, a heavy reliance on donors for funding, and the lack of consistent knowledge on processes involving clinical trials for new medical devices in Ghana.

Conclusion

Existing literature on methods to counter postpartum hemorrhage to reduce maternal mortality has focused on and emphasized the efficacy of the UBT. Despite overwhelming evidence supporting the use of the UBT, many health systems across the world, particularly low-income countries, do not have access to the device owing to numerous barriers in integrating the device into obstetric care. This study illustrates the need to focus on incorporating the UBT into health systems for greater availability to health workers and its use as standard of care. Ultimately, this study can be used as a stepping-stone for more research on this subject, providing evidence to influence policymakers to integrate the UBT into their protocols for postpartum hemorrhage response.