Background: COVID-19 has challenged the resilience of the health care information system, which has affected our ability to achieve the global goal of health and well-being. The pandemic has resulted in a number of recent cyberattacks on hospitals, pharmaceutical companies, the US Department of Health and Human Services, the World Health Organization and its partners, and others. Objective: The aim of this review was to identify key cybersecurity challenges, solutions adapted by the health sector, and areas of improvement needed to counteract the recent increases in cyberattacks (eg, phishing campaigns and ransomware attacks), which have been used by attackers to exploit vulnerabilities in technology and people introduced through changes to working practices in response to the COVID-19 pandemic. Methods: A scoping review was conducted by searching two major scientific databases (PubMed and Scopus) using the search formula “(covid OR healthcare) AND cybersecurity.” Reports, news articles, and industry white papers were also included if they were related directly to previously published works, or if they were the only available sources at the time of writing. Only articles in English published in the last decade were included (ie, 2011-2020) in order to focus on current issues, challenges, and solutions. Results: We identified 9 main challenges in cybersecurity, 11 key solutions that health care organizations adapted to address these challenges, and 4 key areas that need to be strengthened in terms of cybersecurity capacity in the health sector. We also found that the most prominent and significant methods of cyberattacks that occurred during the pandemic were related to phishing, ransomware, distributed denial-of-service attacks, and malware. Conclusions: This scoping review identified the most impactful methods of cyberattacks that targeted the health sector during the COVID-19 pandemic, as well as the challenges in cybersecurity, solutions, and areas in need of improvement. We provided useful insights to the health sector on cybersecurity issues during the COVID-19 pandemic as well as other epidemics or pandemics that may materialize in the future.

T-wave alternans (TWA) reflects every-other-beat alterations in the morphology of the electrocardiogram ST segment or T wave in the setting of a constant heart rate, hence, in the absence of heart rate variability. It is believed to be associated with the dispersion of repolarization and has been used as a non-invasive marker for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death as numerous studies have shown. This review aims to provide up-to-date review on both experimental and simulation studies in elucidating possible mechanisms underlying the genesis of TWA at the cellular level, as well as the genesis of spatially concordant/discordant alternans at the tissue level, and their transition to cardiac arrhythmia. Recent progress and future perspectives in antiarrhythmic therapies associated with TWA are also discussed.

Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, I_Kr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology. The ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate I_Kr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the I_Kr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC₅₀) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue. At the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD₉₀), whereas quinidine caused a significant prolongation of APD₉₀. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide. The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients.

Background: Health information systems (HISs) are continuously targeted by hackers, who aim to bring down critical health infrastructure. This study was motivated by recent attacks on health care organizations that have resulted in the compromise of sensitive data held in HISs. Existing research on cybersecurity in the health care domain places an imbalanced focus on protecting medical devices and data. There is a lack of a systematic way to investigate how attackers may breach an HIS and access health care records. Objective: This study aimed to provide new insights into HIS cybersecurity protection. We propose a systematic, novel, and optimized (artificial intelligence–based) ethical hacking method tailored specifically for HISs, and we compared it with the traditional unoptimized ethical hacking method. This allows researchers and practitioners to identify the points and attack pathways of possible penetration attacks on the HIS more efficiently. Methods: In this study, we propose a novel methodological approach to ethical hacking in HISs. We implemented ethical hacking using both optimized and unoptimized methods in an experimental setting. Specifically, we set up an HIS simulation environment by implementing the open-source electronic medical record (OpenEMR) system and followed the National Institute of Standards and Technology’s ethical hacking framework to launch the attacks. In the experiment, we launched 50 rounds of attacks using both unoptimized and optimized ethical hacking methods. Results: Ethical hacking was successfully conducted using both optimized and unoptimized methods. The results show that the optimized ethical hacking method outperforms the unoptimized method in terms of average time used, the average success rate of exploit, the number of exploits launched, and the number of successful exploits. We were able to identify the successful attack paths and exploits that are related to remote code execution, cross-site request forgery, improper authentication, vulnerability in the Oracle Business Intelligence Publisher, an elevation of privilege vulnerability (in MediaTek), and remote access backdoor (in the web graphical user interface for the Linux Virtual Server). Conclusions: This research demonstrates systematic ethical hacking against an HIS using optimized and unoptimized methods, together with a set of penetration testing tools to identify exploits and combining them to perform ethical hacking. The findings contribute to the HIS literature, ethical hacking methodology, and mainstream artificial intelligence–based ethical hacking methods because they address some key weaknesses of these research fields. These findings also have great significance for the health care sector, as OpenEMR is widely adopted by health care organizations. Our findings offer novel insights for the protection of HISs and allow researchers to conduct further research in the HIS cybersecurity domain.

Short QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS. Therefore, in this study, we used computational modeling to assess the effects of amiodarone, class III anti-arrhythmic agent, on human ventricular electrophysiology in SQT3. The ten Tusscher et al. model for the human ventricular action potentials (APs) was modified to incorporate I K1 formulations based on experimental data of Kir2.1 channels (including WT, WT-D172N and D172N conditions). The modified cell model was then implemented to construct one-dimensional (1D) and 2D tissue models. The blocking effects of amiodarone on ionic currents were modeled using IC50 and Hill coefficient values from literatures. Effects of amiodarone on APD, ERP and pseudo-ECG traces were computed. Effects of the drug on the temporal and spatial vulnerability of ventricular tissue to genesis and maintenance of re-entry were measured, as well as on the dynamic behavior of re-entry. Amiodarone prolonged the ventricular cell APD and decreased the maximal voltage heterogeneity (δV) among three difference cells types across transmural ventricular wall, leading to a decreased transmural heterogeneity of APD along a 1D model of ventricular transmural strand. Amiodarone increased cellular ERP, prolonged QT interval and decreased the T-wave amplitude. It reduced tissue’s temporal susceptibility to the initiation of re-entry and increased the minimum substrate size necessary to sustain re-entry in the 2D tissue. At the therapeutic-relevant concentration of amiodarone, the APD and ERP at the single cell level were increased significantly. The QT interval in pseudo-ECG was prolonged and the re-entry in tissue was prevented. This study provides further evidence that amiodarone may be a potential pharmacological agent for preventing arrhythmogenesis for SQT3 patients.