Designing A Standard-Based Approach for Security of Healthcare Systems

Healthcare systems in recent years have had the highest cost of breaches. Data security is one of the most obstacles encountered in the healthcare system, which could cancel the integrity, availability, and confidentiality of medical data. These breaches are expected to increase in the future. Therefore, it has become necessary to develop systems that provide full protection for patients. Healthcare systems security can be improved greatly by involving security requirements in the early phases of system implementation. Usually, the security requirements are only handled from a technical viewpoint during the implementation phases. When building security in the implementation phase, this leads to weakness in system security and an increase in violations. So, this research paper is aimed to improve the security of healthcare systems, by focusing on security requirements in the early phase, and making the healthcare systems less vulnerable to hacking or any external threat by restricting access to healthcare systems. This research paper proposes designing a standard-based approach to the security of the healthcare system, which analyzes and combines system and software security requirements required to gain a secure healthcare system architecture. Both types of security requirements are designed in the healthcare architecture based on the COSMIC ISO/IEC 19761 standards. A case study is introduced for the proposed standard-based approach experimented by using the system and software security requirements specifications to protect the pharmacy system in the healthcare system from ransomware

Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation

<p>Abstract</p> <p>Background</p> <p>Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.</p> <p>Methods</p> <p>Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.</p> <p>Results</p> <p>After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.</p> <p>Conclusions</p> <p>Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.</p

Digital technologies: Innovations that transform the face of drug development

Abstract Recently, digital health technologies (DHTs) and digital biomarkers have gained a lot of traction in clinical investigations, motivating sponsors, investigators, and regulators to discuss and implement integrated approaches for deploying DHTs. These new tools present new and unique challenges for optimal technology integration in clinical trial processes, including operational, ethical, and regulatory issues. In this paper, we gathered different perspectives to discuss challenges and perspectives from three different stakeholders: industry, US regulators, and a public‐private partnership consortium. The complexities of DHT implementation, which include regulatory definitions, defining the scope of validation experiments, and the need for partnerships between BioPharma and the technology sectors, are highlighted. Most of these challenges are related to translation of DHT‐derived measures into endpoints that are meaningful to clinicians and patients, participant safety, training, and retention and privacy of data. The example of the Wearable Assessments in the Clinic and Home in PD (WATCH‐PD) study is discussed as an example that demonstrated the advantages of pre‐competitive collaborations, which include early regulatory feedback, data sharing, and multistakeholder alignment. Future advances in DHTs are expected to spur device‐agnostic measured development and incorporate patient reported outcomes in drug development. More efforts are needed to define validation experiments for a defined context of use, incentivize data sharing and development of data standards. Multistakeholder collaborations via precompetitive consortia will help facilitate broad acceptance of DHT‐enabled measures in drug development

Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

Alzheimer's disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes Aβ clearance across BBB

Inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h between α-tocopherol and ezetimibe

Tocopherol is used not only as an ethical drug but also as a supplement. In 2008, it was reported that alpha-tocopherol is partly transported via an intestinal cholesterol transporter, Niemann-Pick C1-Like 1 (NPC1L1). Ezetimibe, a selective inhibitor of NPC1L1, is administered for a long time to inhibit cholesterol absorption and there is a possibility that the absorption of alpha-tocopherol is also inhibited by ezetimibe. This study investigated the influence of ezetimibe on the absorption of alpha-tocopherol with single administration and long-term administration. An approach to avoid its undesirable consequence was also examined. alpha-Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of alpha-tocopherol and tissue concentrations were investigated. The plasma concentration of alpha-tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of alpha-tocopherol was prevented by an administration interval of 4 h. In a group of rats administered for 2 months with a 4 h interval, not only the plasma concentration but also the liver concentration was increased compared with those in a group with concurrent combination intake of alpha-tocopherol and ezetimibe. The absorption of alpha-tocopherol was inhibited by ezetimibe. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Attention should be paid to the use of ezetimibe and components of NPC1L1 substrates such as alpha-tocopherol. Copyright (C) 2016 John Wiley & Sons, Ltd