Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Minimal energy cost to initialize a bit with tolerable error.

Landauer's principle imposes a fundamental limit on the energy cost to perfectly initialize a classical bit, which is only reached under the ideal operation with infinitely long time. The question on the cost in the practical operation for a bit has been raised under the constraint by the finiteness of operation time. We discover a raise-up of energy cost by L^{2}(ε)/τ from the Landaeur's limit (k_{B}Tln2) for a finite-time τ initialization of a bit with an error probability ε. The thermodynamic length L(ε) between the states before and after initializing in the parametric space increases monotonously as the error decreases. For example, in the constant dissipation coefficient (γ_{0}) case, the minimal additional cost is 0.997k_{B}T/(γ_{0}τ) for ε=1% and 1.288k_{B}T/(γ_{0}τ) for ε=0.1%. Furthermore, the optimal protocol to reach the bound of minimal energy cost is proposed for the bit initialization realized via a finite-time isothermal process.

Geodesic Path for the Minimal Energy Cost in Shortcuts to Isothermality.

Shortcuts to isothermality are driving strategies to steer the system to its equilibrium states within finite time, and enable evaluating the impact of a control promptly. Finding the optimal scheme to minimize the energy cost is of critical importance in applications of this strategy in pharmaceutical drug tests, biological selection, and quantum computation. We prove the equivalence between designing the optimal scheme and finding the geodesic path in the space of control parameters. Such equivalence allows a systematic and universal approach to find the optimal control to reduce the energy cost. We demonstrate the current method with examples of a Brownian particle trapped in controllable harmonic potentials.

Risk assessment of venous thromboembolism and bleeding in COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. More and more reports highlight the risk of venous thromboembolism (VTE) in COVID-19. Our study aims to identify in-hospital VTE risk and bleeding risk in COVID-19 patients. METHODS: We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE patients. RESULTS: Our findings identified that 23 (16.7%) patients with COVID-19 were at high risk for VTE according to Padua prediction score and 9 (6.5%) patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. Fifteen critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in all 15 [100%] patients) and hemorrhage (Improve score more than 7 points in 9 [60.0%] patients). Thrombotic events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed with deep vein thrombosis by ultrasound 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means that the incidence of VTE among critically ill patients was 20%. One major hemorrhage happened in critically ill patients during VTE treatment. CONCLUSION: Critically ill patients with COVID-19 suffered both a high risk of thrombosis and bleeding risks. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.

The factors of fiducial marker motions and individual margin assessment in postoperative breast cancer radiotherapy.

Background: As a surrogate for the breast tumor bed, individual fiducial markers frequently move during radiotherapy. This study aimed to classify the motions and calculate the individualized target margin. Methods: The mammary basal diameters (D) and heights (H) were measured to represent breast sizes for 15 patients after breast-conserving surgery. The clinical target volume (CTV) was divided into 4 quadrants by a coordinate system with the center of mass of the tumor bed as the origin. The lateral, anteroposterior, and craniocaudal motions of markers were calculated (MLR, MAP, MSI) based on the difference of the setup errors between the spine matching and the fiducial markers matching. The distances between markers and the innermost, foremost, and uppermost borders of CTV (DSLR, DSAP, DSSI) were recorded. Results: In the first quadrant, MAP was strongly correlated with D×H (r>0.80) when D×H <99.89 cm2. Both MLR and MAP were positively linearly related to DSLR, DSAP, DSSI (r>0.85, R2>0.75). MSI was also positively linearly correlated with DSAP and DSLR (r>0.90, R2>0.80). In the fourth quadrant with D×H <90.71 cm2, only MLR and DSLR showed a linear positive correlation (r>0.90, R2>0.75), whereas the others showed linear negative correlations (r>-0.90, R2>0.80). The planning target volume (PTV) margin varied significantly between the first and fourth quadrant (P<0.05), and the largest margin was 12.4 mm in the craniocaudal direction of the first quadrant with D×H ≥99.89 cm2. Conclusions: Fiducial motion is susceptible to breast size and fiducial position, and the individualized PTV margins should take the above factors into account.

Correlation between the γ passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer.

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

Cancer risk assessment in modern radiotherapy workflow with medical big data.

Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose-response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI.

Radiological Assessment of the Effect of Congenital C3-4 Synostosis on Adjacent Segments.

STUDY DESIGN: Retrospective case series. PURPOSE: To assess the effect of non-kyphotic aligned congenital C3-4 synostosis on the adjacent segment in 10 patients. OVERVIEW OF LITERATURE: In the cervical spine, fusion disease at the adjacent motion segments may be a risk factor for potential neurological compromise and death. METHODS: Radiograms of 10 patients 13 to 69 years of age presenting with neck/shoulder discomfort or pain with or without trauma history were examined. C3-4 synostosis was found incidentally in all patients on routine examination radiographs of cervical spine. RESULTS: Adjacent segment disease (ASD) was not found in the three patients younger than 39 years of age. Five of the 10 (50%) patients, including a 67-year-old man, did not develop spondylosis in any of the cervical mobile segments. Spondylosis was observed only in the caudal 1-2 mobile segments in the remaining five patients. The youngest was a 40-year-old male who had spondylosis in the two caudal mobile segments (C4-5 and C5-6). Spondylosis was limited to the two close caudal mobile segments and was not in the cranial segments. Flaring of the lower part of synostotic vertebra associated with advanced narrowed degenerate disc was evident in five patients. CONCLUSIONS: Mobile segment spondylosis in the individuals with congenital monosegment C3-4 synostosis over age of 40 years may be a natural manifestation of aging and is not solely an adjacent segment disease directly and fully related with congenital C3-4 synostosis.

Radiographic assessment of congenital C2-3 synostosis.

PURPOSE: To evaluate the morphologies of congenital C2-3 synostosis in 25 patients. METHODS: Radiographs of 11 males and 14 females aged 5 to 74 years with congenital C2-3 synostosis were reviewed. All cases were found incidentally on radiographs when presenting with neck/shoulder discomfort/pain. RESULTS: 13 of the patients had spondylosis in 21 segments: C1-2 (n=1) and C3-4 (n=1), C4-5 (n=7), C5-6 (n=9), and C6-7 (n=3). Of whom 12 had normal sagittal alignment and one had kyphotic synostosis (who developed compensatory hyperlordosis of the caudal mobile segments and subsequent spondylosis at C3-4 and C5 retrolisthesis). The remaining 12 patients had no spondylosis and had normal sagittal alignment, but had other associated pathologies including disc herniation at C3-4, C1 ring hypoplasia, and calcification of the nuchal ligament. CONCLUSION: Normally aligned congenital synostosis of C2-3 is rarely associated with a junctional problem, whereas a kyphotic synostosis is associated with a caudal junctional problem. Spondylosis developing after age 40 years is not associated with C2-3 synostosis.